2024
Kobayashi, Yuya; Hiraoka, Kotaro; Itabashi, Ryo; Saito, Takuya; Kawabata, Yuichi; Yazawa, Yukako; Funaki, Yoshihito; Furumoto, Shozo; Okamura, Nobuyuki; Furukawa, Katsutoshi; Ishiki, Aiko; Arai, Hiroyuki; Yanai, Kazuhiko; Tashiro, Manabu; Sekijima, Yoshiki
Amyloid accumulation in cases of suspected comorbid cerebral amyloid angiopathy and isolated cortical venous thrombosis Journal Article
In: J Neurol Sci, vol. 457, pp. 122892, 2024, ISSN: 1878-5883.
@article{pmid38266518,
title = {Amyloid accumulation in cases of suspected comorbid cerebral amyloid angiopathy and isolated cortical venous thrombosis},
author = {Yuya Kobayashi and Kotaro Hiraoka and Ryo Itabashi and Takuya Saito and Yuichi Kawabata and Yukako Yazawa and Yoshihito Funaki and Shozo Furumoto and Nobuyuki Okamura and Katsutoshi Furukawa and Aiko Ishiki and Hiroyuki Arai and Kazuhiko Yanai and Manabu Tashiro and Yoshiki Sekijima},
doi = {10.1016/j.jns.2024.122892},
issn = {1878-5883},
year = {2024},
date = {2024-02-01},
journal = {J Neurol Sci},
volume = {457},
pages = {122892},
abstract = {BACKGROUND AND AIM: The differentiation of isolated cortical venous thrombosis (ICVT) from cerebral amyloid angiopathy (CAA) can be difficult because both diseases share similar neurological symptoms and imaging findings. N-methyl-C-2-(4'-methylaminophenyl)-6-hydroxybenzo-thiazole (C-PiB) positron emission tomography (PET) functions as a diagnostic modality for CAA by detecting amyloid deposition. The present prospective study evaluated amyloid deposition using C-PiB-PET in consecutive patients with suspected ICVT.
METHOD: This study was a prospective observational study. Patients who attended or were hospitalized between May 2019 and March 2020 were included in the analysis. Consecutive patients who met the criteria for suspicion of ICVT were enrolled in the study, and the clinical course, symptoms, imaging findings (including magnetic resonance imaging), and the C-PiB-PET findings of each case were analyzed.
RESULTS: The study cohort included four patients (64-82 years of age, all women). In one younger patient, C-PiB-PET afforded no findings suggestive of CAA, whereas the remaining three patients exhibited C-PiB-PET findings suggestive of CAA.
CONCLUSION: Although C-PiB-PET would be a reasonable modality for distinguishing ICVT from CAA, especially in younger patients, it might be difficult to differentiate ICVT from CAA in elderly patients because of the potential deposition of amyloid.
CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ Unique identifier: UMIN 000037101.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND AIM: The differentiation of isolated cortical venous thrombosis (ICVT) from cerebral amyloid angiopathy (CAA) can be difficult because both diseases share similar neurological symptoms and imaging findings. N-methyl-C-2-(4'-methylaminophenyl)-6-hydroxybenzo-thiazole (C-PiB) positron emission tomography (PET) functions as a diagnostic modality for CAA by detecting amyloid deposition. The present prospective study evaluated amyloid deposition using C-PiB-PET in consecutive patients with suspected ICVT.
METHOD: This study was a prospective observational study. Patients who attended or were hospitalized between May 2019 and March 2020 were included in the analysis. Consecutive patients who met the criteria for suspicion of ICVT were enrolled in the study, and the clinical course, symptoms, imaging findings (including magnetic resonance imaging), and the C-PiB-PET findings of each case were analyzed.
RESULTS: The study cohort included four patients (64-82 years of age, all women). In one younger patient, C-PiB-PET afforded no findings suggestive of CAA, whereas the remaining three patients exhibited C-PiB-PET findings suggestive of CAA.
CONCLUSION: Although C-PiB-PET would be a reasonable modality for distinguishing ICVT from CAA, especially in younger patients, it might be difficult to differentiate ICVT from CAA in elderly patients because of the potential deposition of amyloid.
CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ Unique identifier: UMIN 000037101.
METHOD: This study was a prospective observational study. Patients who attended or were hospitalized between May 2019 and March 2020 were included in the analysis. Consecutive patients who met the criteria for suspicion of ICVT were enrolled in the study, and the clinical course, symptoms, imaging findings (including magnetic resonance imaging), and the C-PiB-PET findings of each case were analyzed.
RESULTS: The study cohort included four patients (64-82 years of age, all women). In one younger patient, C-PiB-PET afforded no findings suggestive of CAA, whereas the remaining three patients exhibited C-PiB-PET findings suggestive of CAA.
CONCLUSION: Although C-PiB-PET would be a reasonable modality for distinguishing ICVT from CAA, especially in younger patients, it might be difficult to differentiate ICVT from CAA in elderly patients because of the potential deposition of amyloid.
CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ Unique identifier: UMIN 000037101.
Ando, Soichi; Fujimoto, Toshihiko; Sudo, Mizuki; Watanuki, Shoichi; Hiraoka, Kotaro; Takeda, Kazuko; Takagi, Yoko; Kitajima, Daisuke; Mochizuki, Kodai; Matsuura, Koki; Katagiri, Yuki; Nasir, Fairuz Mohd; Lin, Yuchen; Fujibayashi, Mami; Costello, Joseph T; McMorris, Terry; Ishikawa, Yoichi; Funaki, Yoshihito; Furumoto, Shozo; Watabe, Hiroshi; Tashiro, Manabu
The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise Journal Article
In: J Physiol, vol. 602, no. 3, pp. 461–484, 2024, ISSN: 1469-7793.
@article{pmid38165254,
title = {The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise},
author = {Soichi Ando and Toshihiko Fujimoto and Mizuki Sudo and Shoichi Watanuki and Kotaro Hiraoka and Kazuko Takeda and Yoko Takagi and Daisuke Kitajima and Kodai Mochizuki and Koki Matsuura and Yuki Katagiri and Fairuz Mohd Nasir and Yuchen Lin and Mami Fujibayashi and Joseph T Costello and Terry McMorris and Yoichi Ishikawa and Yoshihito Funaki and Shozo Furumoto and Hiroshi Watabe and Manabu Tashiro},
doi = {10.1113/JP285173},
issn = {1469-7793},
year = {2024},
date = {2024-02-01},
journal = {J Physiol},
volume = {602},
number = {3},
pages = {461--484},
abstract = {Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [ C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [ C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [ C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [ C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.
2023
Shinagawa, Kiyotsugu; Hatta, Taku; Watanuki, Shoichi; Yamamoto, Nobuyuki; Tashiro, Manabu; Itoi, Eiji
In: J Shoulder Elbow Surg, vol. 32, no. 2, pp. 392–400, 2023, ISSN: 1532-6500.
@article{pmid36206980,
title = {The quantification of muscle activities during arm elevation following reverse shoulder arthroplasty or superior capsular reconstruction for irreparable rotator cuff tears using positron emission tomography},
author = {Kiyotsugu Shinagawa and Taku Hatta and Shoichi Watanuki and Nobuyuki Yamamoto and Manabu Tashiro and Eiji Itoi},
doi = {10.1016/j.jse.2022.08.020},
issn = {1532-6500},
year = {2023},
date = {2023-02-01},
journal = {J Shoulder Elbow Surg},
volume = {32},
number = {2},
pages = {392--400},
abstract = {BACKGROUND: Reverse shoulder arthroplasty (RSA) and superior capsular reconstruction (SCR) are recognized as surgical options for an irreparable rotator cuff tear. However, the postoperative changes of the muscle activity patterns remain unclear. The purpose of this study was to investigate the quantified muscle activities on shoulder elevation in patients treated with RSA or SCR using fluorine-18-labelled fluorodeoxyglucose-positron emission tomography.
METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups.
RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group.
CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Reverse shoulder arthroplasty (RSA) and superior capsular reconstruction (SCR) are recognized as surgical options for an irreparable rotator cuff tear. However, the postoperative changes of the muscle activity patterns remain unclear. The purpose of this study was to investigate the quantified muscle activities on shoulder elevation in patients treated with RSA or SCR using fluorine-18-labelled fluorodeoxyglucose-positron emission tomography.
METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups.
RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group.
CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.
METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups.
RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group.
CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.
Morito, Takahiro; Harada, Ryuichi; Iwata, Ren; Ishikawa, Yoichi; Okamura, Nobuyuki; Kudo, Yukitsuka; Furumoto, Shozo; Yanai, Kazuhiko; Tashiro, Manabu
In: PLoS One, vol. 18, no. 6, pp. e0287047, 2023, ISSN: 1932-6203.
@article{pmid37315033,
title = {Evaluation of 18F labeled glial fibrillary acidic protein binding nanobody and its brain shuttle peptide fusion proteins using a neuroinflammation rat model},
author = {Takahiro Morito and Ryuichi Harada and Ren Iwata and Yoichi Ishikawa and Nobuyuki Okamura and Yukitsuka Kudo and Shozo Furumoto and Kazuhiko Yanai and Manabu Tashiro},
doi = {10.1371/journal.pone.0287047},
issn = {1932-6203},
year = {2023},
date = {2023-01-01},
journal = {PLoS One},
volume = {18},
number = {6},
pages = {e0287047},
abstract = {Astrogliosis is a crucial feature of neuroinflammation and is characterized by the significant upregulation of glial fibrillary acidic protein (GFAP) expression. Hence, visualizing GFAP in the living brain of patients with damaged central nervous system using positron emission tomography (PET) is of great importance, and it is expected to depict neuroinflammation more directly than existing neuroinflammation imaging markers. However, no PET radiotracers for GFAP are currently available. Therefore, neuroimaging with antibody-like affinity proteins could be a viable strategy for visualizing imaging targets that small molecules rarely recognize, such as GFAP, while we need to overcome the challenges of slow clearance and low brain permeability. The E9 nanobody, a small-affinity protein with high affinity and selectivity for GFAP, was utilized in this study. E9 was engineered by fusing a brain shuttle peptide that facilitates blood-brain barrier permeation via two different types of linker domains: E9-GS-ApoE (EGA) and E9-EAK-ApoE (EEA). E9, EGA and EEA were radiolabeled with fluorine-18 using cell-free protein radiosynthesis. In vitro autoradiography showed that all radiolabeled proteins exhibited a significant difference in neuroinflammation in the brain sections created from a rat model constructed by injecting lipopolysaccharide (LPS) into the unilateral striatum of wildtype rats, and an excess competitor displaced their binding. However, exploratory in vivo PET imaging and ex vivo biodistribution studies in the rat model failed to distinguish neuroinflammatory lesions within 3 h of 18F-EEA intravenous injection. This study contributes to a better understanding of the characteristics of small-affinity proteins fused with a brain shuttle peptide for further research into the use of protein molecules as PET tracers for imaging neuropathology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Astrogliosis is a crucial feature of neuroinflammation and is characterized by the significant upregulation of glial fibrillary acidic protein (GFAP) expression. Hence, visualizing GFAP in the living brain of patients with damaged central nervous system using positron emission tomography (PET) is of great importance, and it is expected to depict neuroinflammation more directly than existing neuroinflammation imaging markers. However, no PET radiotracers for GFAP are currently available. Therefore, neuroimaging with antibody-like affinity proteins could be a viable strategy for visualizing imaging targets that small molecules rarely recognize, such as GFAP, while we need to overcome the challenges of slow clearance and low brain permeability. The E9 nanobody, a small-affinity protein with high affinity and selectivity for GFAP, was utilized in this study. E9 was engineered by fusing a brain shuttle peptide that facilitates blood-brain barrier permeation via two different types of linker domains: E9-GS-ApoE (EGA) and E9-EAK-ApoE (EEA). E9, EGA and EEA were radiolabeled with fluorine-18 using cell-free protein radiosynthesis. In vitro autoradiography showed that all radiolabeled proteins exhibited a significant difference in neuroinflammation in the brain sections created from a rat model constructed by injecting lipopolysaccharide (LPS) into the unilateral striatum of wildtype rats, and an excess competitor displaced their binding. However, exploratory in vivo PET imaging and ex vivo biodistribution studies in the rat model failed to distinguish neuroinflammatory lesions within 3 h of 18F-EEA intravenous injection. This study contributes to a better understanding of the characteristics of small-affinity proteins fused with a brain shuttle peptide for further research into the use of protein molecules as PET tracers for imaging neuropathology.
2022
Corales, Laarni Grace; Inada, Hitoshi; Hiraoka, Kotaro; Araki, Shun; Yamanaka, Shinya; Kikkawa, Takako; Osumi, Noriko
The subcommissural organ maintains features of neuroepithelial cells in the adult mouse Journal Article
In: J Anat, vol. 241, no. 3, pp. 820–830, 2022, ISSN: 1469-7580.
@article{pmid35638289,
title = {The subcommissural organ maintains features of neuroepithelial cells in the adult mouse},
author = {Laarni Grace Corales and Hitoshi Inada and Kotaro Hiraoka and Shun Araki and Shinya Yamanaka and Takako Kikkawa and Noriko Osumi},
doi = {10.1111/joa.13709},
issn = {1469-7580},
year = {2022},
date = {2022-09-01},
journal = {J Anat},
volume = {241},
number = {3},
pages = {820--830},
abstract = {The subcommissural organ (SCO) is a part of the circumventricular organs located in the dorsocaudal region of the third ventricle at the entrance of the aqueduct of Sylvius. The SCO comprises epithelial cells and produces high molecular weight glycoproteins, which are secreted into the third ventricle and become part of Reissner's fibre in the cerebrospinal fluid. Abnormal development of the SCO has been linked with congenital hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid in the brain. In the present study, we characterized the SCO cells in the adult mouse brain to gain insights into the possible role of this brain region. Immunohistochemical analyses revealed that expression of Pax6, a transcription factor essential for SCO differentiation during embryogenesis, is maintained in the SCO at postnatal stages from P0 to P84. SCO cells in the adult brain expressed known neural stem/progenitor cell (NSPC) markers, Sox2 and vimentin. The adult SCO cells also expressed proliferating marker PCNA, although expression of another proliferation marker Ki67, indicating a G /M phase, was not detected. The SCO cells did not incorporate BrdU, a marker for DNA synthesis in the S phase. Therefore, the SCO cells have a potential for proliferation but are quiescent for cell division in the adult. The SCO cells also expressed GFAP, a marker for astrocytes or NSPCs, but not NeuN (for neurons). A few cells positive for Iba1 (microglia), Olig2 (for oligodendrocytes) and PDGFRα (oligodendrocyte progenitors) existed within or on the periphery of the SCO. These findings revealed that the SCO cells have a unique feature as secretory yet immature neuroepithelial cells in the adult mouse brain.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The subcommissural organ (SCO) is a part of the circumventricular organs located in the dorsocaudal region of the third ventricle at the entrance of the aqueduct of Sylvius. The SCO comprises epithelial cells and produces high molecular weight glycoproteins, which are secreted into the third ventricle and become part of Reissner's fibre in the cerebrospinal fluid. Abnormal development of the SCO has been linked with congenital hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid in the brain. In the present study, we characterized the SCO cells in the adult mouse brain to gain insights into the possible role of this brain region. Immunohistochemical analyses revealed that expression of Pax6, a transcription factor essential for SCO differentiation during embryogenesis, is maintained in the SCO at postnatal stages from P0 to P84. SCO cells in the adult brain expressed known neural stem/progenitor cell (NSPC) markers, Sox2 and vimentin. The adult SCO cells also expressed proliferating marker PCNA, although expression of another proliferation marker Ki67, indicating a G /M phase, was not detected. The SCO cells did not incorporate BrdU, a marker for DNA synthesis in the S phase. Therefore, the SCO cells have a potential for proliferation but are quiescent for cell division in the adult. The SCO cells also expressed GFAP, a marker for astrocytes or NSPCs, but not NeuN (for neurons). A few cells positive for Iba1 (microglia), Olig2 (for oligodendrocytes) and PDGFRα (oligodendrocyte progenitors) existed within or on the periphery of the SCO. These findings revealed that the SCO cells have a unique feature as secretory yet immature neuroepithelial cells in the adult mouse brain.
Ariga, Kana; Tashiro, Manabu
Change in the graphics of journal articles in the life sciences field: analysis of figures and tables in the journal "Cell" Journal Article
In: Hist Philos Life Sci, vol. 44, no. 3, pp. 33, 2022, ISSN: 1742-6316.
@article{pmid35918565,
title = {Change in the graphics of journal articles in the life sciences field: analysis of figures and tables in the journal "Cell"},
author = {Kana Ariga and Manabu Tashiro},
doi = {10.1007/s40656-022-00516-9},
issn = {1742-6316},
year = {2022},
date = {2022-08-01},
journal = {Hist Philos Life Sci},
volume = {44},
number = {3},
pages = {33},
abstract = {The purpose of this study is to examine how trends in the use of images in modern life science journals have changed since the spread of computer-based visual and imaging technology. To this end, a new classification system was constructed to analyze how the graphics of a scientific journal have changed over the years. The focus was on one international peer-reviewed journal in life sciences, Cell, which was founded in 1974, whereby 1725 figures and 160 tables from the research articles in Cell were sampled. The unit of classification was defined as a graphic and the figures and tables were divided into 5952 graphics. These graphics were further classified into hierarchical categories, and the data in each category were aggregated every five years. The following categories were observed: (1) data graphics, (2) explanation graphics, and (3) hybrid graphics. Data graphics increased by more than sixfold between 1974 and 2014, and some types of data graphics including mechanical reproduction images and bar charts displayed notable changes. The representation of explanatory graphics changed from hand-painted illustrations to diagrams of Bezier-curves. It is suggested that in addition to the development of experimental technologies such as fluorescent microscopy and big data analysis, continuously evolving application software for image creation and researchers' motivation to convince reviewers and editors have influenced these changes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The purpose of this study is to examine how trends in the use of images in modern life science journals have changed since the spread of computer-based visual and imaging technology. To this end, a new classification system was constructed to analyze how the graphics of a scientific journal have changed over the years. The focus was on one international peer-reviewed journal in life sciences, Cell, which was founded in 1974, whereby 1725 figures and 160 tables from the research articles in Cell were sampled. The unit of classification was defined as a graphic and the figures and tables were divided into 5952 graphics. These graphics were further classified into hierarchical categories, and the data in each category were aggregated every five years. The following categories were observed: (1) data graphics, (2) explanation graphics, and (3) hybrid graphics. Data graphics increased by more than sixfold between 1974 and 2014, and some types of data graphics including mechanical reproduction images and bar charts displayed notable changes. The representation of explanatory graphics changed from hand-painted illustrations to diagrams of Bezier-curves. It is suggested that in addition to the development of experimental technologies such as fluorescent microscopy and big data analysis, continuously evolving application software for image creation and researchers' motivation to convince reviewers and editors have influenced these changes.
Fukudo, Shin; Kano, Michiko; Sato, Yasuhiro; Muratsubaki, Tomohiko; Kanazawa, Motoyori; Tashiro, Manabu; Yanai, Kazuhiko
Histamine Neuroimaging in Stress-Related Disorders Journal Article
In: Curr Top Behav Neurosci, vol. 59, pp. 113–129, 2022, ISSN: 1866-3370.
@article{pmid35156186,
title = {Histamine Neuroimaging in Stress-Related Disorders},
author = {Shin Fukudo and Michiko Kano and Yasuhiro Sato and Tomohiko Muratsubaki and Motoyori Kanazawa and Manabu Tashiro and Kazuhiko Yanai},
doi = {10.1007/7854_2021_262},
issn = {1866-3370},
year = {2022},
date = {2022-01-01},
journal = {Curr Top Behav Neurosci},
volume = {59},
pages = {113--129},
abstract = {Although histamine plays a major role in animal models of stress-related disorders, human neuroimaging data are sparse. Histamine H1 receptors in the human brain were first imaged by Professor Kazuhiko Yanai in 1992 by using C-doxepin, a potent ligand of H1 receptors, and positron emission tomography (PET). Subsequent work revealed that H1 receptors are reduced in the prefrontal and anterior cingulate cortices in patients with major depressive disorders. A sex difference in H1 receptor binding in the brain has also been found, with women exhibiting more abundant H1 receptor binding than men. Moreover, female patients with anorexia nervosa show higher H1 receptor binding in the amygdala and lentiform nucleus. These studies also found an inverse correlation of depression scores with H1 receptor binding. Histamine is considered to play a major role in the pathophysiology of irritable bowel syndrome (IBS), a representative disorder of brain-gut interactions. Along these lines, hypnotic suggestion dramatically changes the waveforms of viscerosensory cerebral evoked potentials in response to electrical rectal stimulation and these changes are modified by the administration of H1 antagonist. The direction of the H1 antagonist-induced changes in the viscerosensory cerebral evoked potentials differs between IBS patients and healthy controls. Thus, histamine likely plays an important role in stress-related disorders. Further histamine brain imaging studies of humans are warranted.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Although histamine plays a major role in animal models of stress-related disorders, human neuroimaging data are sparse. Histamine H1 receptors in the human brain were first imaged by Professor Kazuhiko Yanai in 1992 by using C-doxepin, a potent ligand of H1 receptors, and positron emission tomography (PET). Subsequent work revealed that H1 receptors are reduced in the prefrontal and anterior cingulate cortices in patients with major depressive disorders. A sex difference in H1 receptor binding in the brain has also been found, with women exhibiting more abundant H1 receptor binding than men. Moreover, female patients with anorexia nervosa show higher H1 receptor binding in the amygdala and lentiform nucleus. These studies also found an inverse correlation of depression scores with H1 receptor binding. Histamine is considered to play a major role in the pathophysiology of irritable bowel syndrome (IBS), a representative disorder of brain-gut interactions. Along these lines, hypnotic suggestion dramatically changes the waveforms of viscerosensory cerebral evoked potentials in response to electrical rectal stimulation and these changes are modified by the administration of H1 antagonist. The direction of the H1 antagonist-induced changes in the viscerosensory cerebral evoked potentials differs between IBS patients and healthy controls. Thus, histamine likely plays an important role in stress-related disorders. Further histamine brain imaging studies of humans are warranted.
2021
Ezura, Michinori; Kikuchi, Akio; Okamura, Nobuyuki; Ishiki, Aiko; Hasegawa, Takafumi; Harada, Ryuichi; Watanuki, Shoichi; Funaki, Yoshihito; Hiraoka, Kotaro; Baba, Toru; Sugeno, Naoto; Yoshida, Shun; Kobayashi, Junpei; Kobayashi, Michiko; Tano, Ohito; Ishiyama, Shun; Nakamura, Takaaki; Nakashima, Ichiro; Mugikura, Shunji; Iwata, Ren; Taki, Yasuyuki; Furukawa, Katsutoshi; Arai, Hiroyuki; Furumoto, Shozo; Tashiro, Manabu; Yanai, Kazuhiko; Kudo, Yukitsuka; Takeda, Atsushi; Aoki, Masashi
F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies Journal Article
In: Front Aging Neurosci, vol. 13, pp. 761010, 2021, ISSN: 1663-4365.
@article{pmid34912209,
title = {F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies},
author = {Michinori Ezura and Akio Kikuchi and Nobuyuki Okamura and Aiko Ishiki and Takafumi Hasegawa and Ryuichi Harada and Shoichi Watanuki and Yoshihito Funaki and Kotaro Hiraoka and Toru Baba and Naoto Sugeno and Shun Yoshida and Junpei Kobayashi and Michiko Kobayashi and Ohito Tano and Shun Ishiyama and Takaaki Nakamura and Ichiro Nakashima and Shunji Mugikura and Ren Iwata and Yasuyuki Taki and Katsutoshi Furukawa and Hiroyuki Arai and Shozo Furumoto and Manabu Tashiro and Kazuhiko Yanai and Yukitsuka Kudo and Atsushi Takeda and Masashi Aoki},
doi = {10.3389/fnagi.2021.761010},
issn = {1663-4365},
year = {2021},
date = {2021-01-01},
journal = {Front Aging Neurosci},
volume = {13},
pages = {761010},
abstract = {We aimed to determine whether tau deposits and monoamine oxidase B (MAO-B) detection using F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional F-THK5351 retention was associated with the cognitive function in CBS and PSP. Measurement of the tau deposits and MAO-B density in the brain using F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We aimed to determine whether tau deposits and monoamine oxidase B (MAO-B) detection using F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional F-THK5351 retention was associated with the cognitive function in CBS and PSP. Measurement of the tau deposits and MAO-B density in the brain using F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.
2020
Matsuzawa, Gaku; Sano, Hirotaka; Yamamoto, Nobuyuki; Kurokawa, Daisuke; Watanuki, Shoichi; Tashiro, Manabu; Itoi, Eiji
In: Skeletal Radiol, vol. 49, no. 11, pp. 1839–1847, 2020, ISSN: 1432-2161.
@article{pmid32533204,
title = {Muscle activities during shoulder internal rotation differ in arm position: a preliminary quantitative analysis using positron emission tomography},
author = {Gaku Matsuzawa and Hirotaka Sano and Nobuyuki Yamamoto and Daisuke Kurokawa and Shoichi Watanuki and Manabu Tashiro and Eiji Itoi},
doi = {10.1007/s00256-020-03490-0},
issn = {1432-2161},
year = {2020},
date = {2020-11-01},
journal = {Skeletal Radiol},
volume = {49},
number = {11},
pages = {1839--1847},
abstract = {OBJECTIVE: To investigate the muscle activity patterns of the glenohumeral joint during internal rotation both with the arm at 0° and 90° of abduction using 2-deoxy-2-[F] fluoro-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI).
MATERIALS AND METHODS: Six healthy male volunteers underwent PET examination after performing active glenohumeral internal rotation exercise using an elastic band both with the arm at 0° and 90° of abduction. As a control, PET scan under resting condition was also performed. The exercise was performed before and after 18 fluorodeoxyglucose injection. Each PET image was fused to the corresponding MRI to identify each muscle. The standardized uptake value (SUV) of each muscle was compared between the two arm positions.
RESULTS: With the arm at 0° of abduction, the SUV increased significantly after exercise both in the middle and inferior 1/3 of the subscapularis, which were significantly higher than that of the superior 1/3 of the subscapularis (P < 0.05). The SUV of the inferior 1/3 of the subscapularis was significantly higher at 90° of abduction than at 0° of abduction and was significantly higher than that of the superior 1/3 at 90° of abduction (P < 0.01). The SUV after exercise in the inferior infraspinatus and teres minor increased.
CONCLUSIONS: The middle and inferior parts of the subscapularis are the main shoulder internal rotators in 0° of abduction, whereas the inferior part of the subscapularis is the main internal rotator in 90° of abduction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To investigate the muscle activity patterns of the glenohumeral joint during internal rotation both with the arm at 0° and 90° of abduction using 2-deoxy-2-[F] fluoro-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI).
MATERIALS AND METHODS: Six healthy male volunteers underwent PET examination after performing active glenohumeral internal rotation exercise using an elastic band both with the arm at 0° and 90° of abduction. As a control, PET scan under resting condition was also performed. The exercise was performed before and after 18 fluorodeoxyglucose injection. Each PET image was fused to the corresponding MRI to identify each muscle. The standardized uptake value (SUV) of each muscle was compared between the two arm positions.
RESULTS: With the arm at 0° of abduction, the SUV increased significantly after exercise both in the middle and inferior 1/3 of the subscapularis, which were significantly higher than that of the superior 1/3 of the subscapularis (P < 0.05). The SUV of the inferior 1/3 of the subscapularis was significantly higher at 90° of abduction than at 0° of abduction and was significantly higher than that of the superior 1/3 at 90° of abduction (P < 0.01). The SUV after exercise in the inferior infraspinatus and teres minor increased.
CONCLUSIONS: The middle and inferior parts of the subscapularis are the main shoulder internal rotators in 0° of abduction, whereas the inferior part of the subscapularis is the main internal rotator in 90° of abduction.
MATERIALS AND METHODS: Six healthy male volunteers underwent PET examination after performing active glenohumeral internal rotation exercise using an elastic band both with the arm at 0° and 90° of abduction. As a control, PET scan under resting condition was also performed. The exercise was performed before and after 18 fluorodeoxyglucose injection. Each PET image was fused to the corresponding MRI to identify each muscle. The standardized uptake value (SUV) of each muscle was compared between the two arm positions.
RESULTS: With the arm at 0° of abduction, the SUV increased significantly after exercise both in the middle and inferior 1/3 of the subscapularis, which were significantly higher than that of the superior 1/3 of the subscapularis (P < 0.05). The SUV of the inferior 1/3 of the subscapularis was significantly higher at 90° of abduction than at 0° of abduction and was significantly higher than that of the superior 1/3 at 90° of abduction (P < 0.01). The SUV after exercise in the inferior infraspinatus and teres minor increased.
CONCLUSIONS: The middle and inferior parts of the subscapularis are the main shoulder internal rotators in 0° of abduction, whereas the inferior part of the subscapularis is the main internal rotator in 90° of abduction.
Oyama, Senri; Hosoi, Ayumu; Ibaraki, Masanobu; McGinnity, Colm J; Matsubara, Keisuke; Watanuki, Shoichi; Watabe, Hiroshi; Tashiro, Manabu; Shidahara, Miho
Error propagation analysis of seven partial volume correction algorithms for [F]THK-5351 brain PET imaging Journal Article
In: EJNMMI Phys, vol. 7, no. 1, pp. 57, 2020, ISSN: 2197-7364.
@article{pmid32926222,
title = {Error propagation analysis of seven partial volume correction algorithms for [F]THK-5351 brain PET imaging},
author = {Senri Oyama and Ayumu Hosoi and Masanobu Ibaraki and Colm J McGinnity and Keisuke Matsubara and Shoichi Watanuki and Hiroshi Watabe and Manabu Tashiro and Miho Shidahara},
doi = {10.1186/s40658-020-00324-9},
issn = {2197-7364},
year = {2020},
date = {2020-09-01},
journal = {EJNMMI Phys},
volume = {7},
number = {1},
pages = {57},
abstract = {BACKGROUND: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome.
METHODS: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR.
RESULTS: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions.
CONCLUSIONS: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome.
METHODS: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR.
RESULTS: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions.
CONCLUSIONS: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.
METHODS: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR.
RESULTS: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions.
CONCLUSIONS: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.
Meguro, Mitsue; Meguro, Kenichi; Takahashi, Kyoko; Yamaguchi, Satoshi; Tashiro, Manabu
In: Psychogeriatrics, vol. 20, no. 2, pp. 149–155, 2020, ISSN: 1479-8301.
@article{pmid31456337,
title = {Alzheimer's deterioration in intellectual and neurobiological staging supports the retrogenesis model: a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal glucose metabolism. A retrospective data analysis from the Tajiri Project},
author = {Mitsue Meguro and Kenichi Meguro and Kyoko Takahashi and Satoshi Yamaguchi and Manabu Tashiro},
doi = {10.1111/psyg.12478},
issn = {1479-8301},
year = {2020},
date = {2020-03-01},
journal = {Psychogeriatrics},
volume = {20},
number = {2},
pages = {149--155},
abstract = {BACKGROUND: Alzheimer disease (AD) patients demonstrate various clinical features reminiscent of children (the retrogenesis model). The Binet test is available for assessing mental development and deterioration. However, neuroimaging correlations remain to be clarified. Although AD patients also manifest social judgment disability, there are few cognitive tests, contrary to so many memory tests. Among the database, we noticed that the Binet test includes the subscale of social judgement using illogical sentences and pictures. The aim of this study is to clarify the neuroimaging correlations for the Binet test, especially for the illogical questions.
METHODS: Forty participants were selected from the database of the Tajiri Project. The Tanaka-Binet test was used to evaluate the mental age and the basic age. The latter is the age level at which the patient can completely accomplish all questions at the immediately lower age level and is used for calculating the mental age. Using the subtests of illogical sentences/pictures, logical judgment abilities were assessed. Using magnetic resonance imaging, we performed four-grade visual evaluation for cortical atrophy. The cerebral metabolic rate for glucose (CMRglc) was measured using an autoradiographic method of F-fluoreodeoxyglucose - positron emission tomography (FDG-PET).
RESULTS: There was a significant Spearman's correlation between the clinical stage and the basic age. Degree of frontal, temporal and hippocampal atrophy were correlated with the basic age. The entire grey matter and frontal and temporal CMRglc were associated with the basic age. The illogical sentences scores were correlated with the bilateral temporal, hippocampal and the left parieto-temporal CMRglc, whereas the illogical picture scores were correlated with the right parieto-temporal CMRglc.
CONCLUSIONS: We found that frontal and temporal atrophy as well as hypometabolism were associated with the basic age. Regarding the illogical judgment, the current PET data analysis disclosed that there may be a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal areas.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Alzheimer disease (AD) patients demonstrate various clinical features reminiscent of children (the retrogenesis model). The Binet test is available for assessing mental development and deterioration. However, neuroimaging correlations remain to be clarified. Although AD patients also manifest social judgment disability, there are few cognitive tests, contrary to so many memory tests. Among the database, we noticed that the Binet test includes the subscale of social judgement using illogical sentences and pictures. The aim of this study is to clarify the neuroimaging correlations for the Binet test, especially for the illogical questions.
METHODS: Forty participants were selected from the database of the Tajiri Project. The Tanaka-Binet test was used to evaluate the mental age and the basic age. The latter is the age level at which the patient can completely accomplish all questions at the immediately lower age level and is used for calculating the mental age. Using the subtests of illogical sentences/pictures, logical judgment abilities were assessed. Using magnetic resonance imaging, we performed four-grade visual evaluation for cortical atrophy. The cerebral metabolic rate for glucose (CMRglc) was measured using an autoradiographic method of F-fluoreodeoxyglucose - positron emission tomography (FDG-PET).
RESULTS: There was a significant Spearman's correlation between the clinical stage and the basic age. Degree of frontal, temporal and hippocampal atrophy were correlated with the basic age. The entire grey matter and frontal and temporal CMRglc were associated with the basic age. The illogical sentences scores were correlated with the bilateral temporal, hippocampal and the left parieto-temporal CMRglc, whereas the illogical picture scores were correlated with the right parieto-temporal CMRglc.
CONCLUSIONS: We found that frontal and temporal atrophy as well as hypometabolism were associated with the basic age. Regarding the illogical judgment, the current PET data analysis disclosed that there may be a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal areas.
METHODS: Forty participants were selected from the database of the Tajiri Project. The Tanaka-Binet test was used to evaluate the mental age and the basic age. The latter is the age level at which the patient can completely accomplish all questions at the immediately lower age level and is used for calculating the mental age. Using the subtests of illogical sentences/pictures, logical judgment abilities were assessed. Using magnetic resonance imaging, we performed four-grade visual evaluation for cortical atrophy. The cerebral metabolic rate for glucose (CMRglc) was measured using an autoradiographic method of F-fluoreodeoxyglucose - positron emission tomography (FDG-PET).
RESULTS: There was a significant Spearman's correlation between the clinical stage and the basic age. Degree of frontal, temporal and hippocampal atrophy were correlated with the basic age. The entire grey matter and frontal and temporal CMRglc were associated with the basic age. The illogical sentences scores were correlated with the bilateral temporal, hippocampal and the left parieto-temporal CMRglc, whereas the illogical picture scores were correlated with the right parieto-temporal CMRglc.
CONCLUSIONS: We found that frontal and temporal atrophy as well as hypometabolism were associated with the basic age. Regarding the illogical judgment, the current PET data analysis disclosed that there may be a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal areas.
Hiraoka, Kotaro; Inada, Hitoshi; Yanai, Kazuhiko; Osumi, Noriko
Bone Morphogenetic Proteins Inhibit Ciliogenesis of Ependymal Cells in Vitro Journal Article
In: Tohoku J Exp Med, vol. 252, no. 3, pp. 199–208, 2020, ISSN: 1349-3329.
@article{pmid33087680,
title = {Bone Morphogenetic Proteins Inhibit Ciliogenesis of Ependymal Cells in Vitro},
author = {Kotaro Hiraoka and Hitoshi Inada and Kazuhiko Yanai and Noriko Osumi},
doi = {10.1620/tjem.252.199},
issn = {1349-3329},
year = {2020},
date = {2020-01-01},
journal = {Tohoku J Exp Med},
volume = {252},
number = {3},
pages = {199--208},
abstract = {Ependymal cells have an essential role in regulating the dynamics of the cerebrospinal fluid flow by the movement of their multiple cilia. Impaired generation or function of cilia could cause hydrocephalus due to the disordered dynamics of the cerebrospinal fluid flow. However, molecular bases regulating differentiation of the ependymal cells and their ciliogenesis have not been fully elucidated. We report here that bone morphogenetic proteins (BMPs), growth factors orchestrating tissue architecture throughout the body, inhibit ciliogenesis during ependymal cell differentiation in primary cell culture. Previous in vitro study has reported that ectopic expression of Smad6 and Smad7 promotes differentiation of embryonic stem cells into multi-ciliated ependymal-like cells. Since Smad6 and Smad7 have been known as the intracellular inhibitory factors of the BMP signaling pathway, the activation of the pathway could cause a deficit in ciliogenesis of ependymal cells. To examine whether activation of the pathway affects ciliogenesis, we investigated the effects of two BMPs, BMP2 and BMP4, on the ependymal differentiation of the primary cultured cells prepared from the neonatal mouse brain. Supplementation of BMP2 or BMP4 in culture media significantly reduced the number of cells with multiple cilia among the total cells, while most of the cells expressed FoxJ1, a master regulator of ciliogenesis. Activation of the pathway was confirmed by the phosphorylation of intracellular Smad1/5/8, downstream factors of the BMP receptors. These in vitro results suggest that inhibition of the BMP signaling pathway might be essential for ciliogenesis during the ependymal cell differentiation in vivo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ependymal cells have an essential role in regulating the dynamics of the cerebrospinal fluid flow by the movement of their multiple cilia. Impaired generation or function of cilia could cause hydrocephalus due to the disordered dynamics of the cerebrospinal fluid flow. However, molecular bases regulating differentiation of the ependymal cells and their ciliogenesis have not been fully elucidated. We report here that bone morphogenetic proteins (BMPs), growth factors orchestrating tissue architecture throughout the body, inhibit ciliogenesis during ependymal cell differentiation in primary cell culture. Previous in vitro study has reported that ectopic expression of Smad6 and Smad7 promotes differentiation of embryonic stem cells into multi-ciliated ependymal-like cells. Since Smad6 and Smad7 have been known as the intracellular inhibitory factors of the BMP signaling pathway, the activation of the pathway could cause a deficit in ciliogenesis of ependymal cells. To examine whether activation of the pathway affects ciliogenesis, we investigated the effects of two BMPs, BMP2 and BMP4, on the ependymal differentiation of the primary cultured cells prepared from the neonatal mouse brain. Supplementation of BMP2 or BMP4 in culture media significantly reduced the number of cells with multiple cilia among the total cells, while most of the cells expressed FoxJ1, a master regulator of ciliogenesis. Activation of the pathway was confirmed by the phosphorylation of intracellular Smad1/5/8, downstream factors of the BMP receptors. These in vitro results suggest that inhibition of the BMP signaling pathway might be essential for ciliogenesis during the ependymal cell differentiation in vivo.
Stokholm, M Gersel; Iranzo, A; Østergaard, K; Serradell, M; Otto, M; Svendsen, K Bacher; Garrido, A; Vilas, D; Fedorova, T D; Santamaria, J; Møller, A; Gaig, C; Hiraoka, K; Brooks, D J; Okamura, N; Borghammer, P; Tolosa, E; Pavese, N
Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder Journal Article
In: Eur J Neurol, vol. 27, no. 4, pp. 644–652, 2020, ISSN: 1468-1331.
@article{pmid31725927,
title = {Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder},
author = {M Gersel Stokholm and A Iranzo and K Østergaard and M Serradell and M Otto and K Bacher Svendsen and A Garrido and D Vilas and T D Fedorova and J Santamaria and A Møller and C Gaig and K Hiraoka and D J Brooks and N Okamura and P Borghammer and E Tolosa and N Pavese},
doi = {10.1111/ene.14127},
issn = {1468-1331},
year = {2020},
date = {2020-01-01},
journal = {Eur J Neurol},
volume = {27},
number = {4},
pages = {644--652},
abstract = {BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies.
METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels ( C-donepezil PET) and nigrostriatal dopaminergic function ( F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment.
RESULTS: The C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level.
CONCLUSION: Reduced neocortical C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies.
METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels ( C-donepezil PET) and nigrostriatal dopaminergic function ( F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment.
RESULTS: The C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level.
CONCLUSION: Reduced neocortical C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.
METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels ( C-donepezil PET) and nigrostriatal dopaminergic function ( F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment.
RESULTS: The C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level.
CONCLUSION: Reduced neocortical C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.
2019
Islam, Md Shahidul; Watanuki, Shoichi; Tashiro, Manabu; Watabe, Hiroshi
Error evaluation of the D-shuttle dosimeter technique in positron emission tomography study Journal Article
In: Radiol Phys Technol, vol. 12, no. 4, pp. 363–373, 2019, ISSN: 1865-0341.
@article{pmid31420776,
title = {Error evaluation of the D-shuttle dosimeter technique in positron emission tomography study},
author = {Md Shahidul Islam and Shoichi Watanuki and Manabu Tashiro and Hiroshi Watabe},
doi = {10.1007/s12194-019-00530-w},
issn = {1865-0341},
year = {2019},
date = {2019-12-01},
journal = {Radiol Phys Technol},
volume = {12},
number = {4},
pages = {363--373},
abstract = {The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with F-FDG solution, and then, the phantom was imaged for 1 h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1-5 cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was - 15.0% and - 19.7% for the 1 cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with F-FDG solution, and then, the phantom was imaged for 1 h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1-5 cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was - 15.0% and - 19.7% for the 1 cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study.
Nishiyama, Yoshihiro; Kinuya, Seigo; Kato, Takashi; Kayano, Daiki; Sato, Shuhei; Tashiro, Manabu; Tatsumi, Mitsuaki; Hashimoto, Teisuke; Baba, Shingo; Hirata, Kenji; Yoshimura, Mana; Yoneyama, Hiroto
Nuclear medicine practice in Japan: a report of the eighth nationwide survey in 2017 Journal Article
In: Ann Nucl Med, vol. 33, no. 10, pp. 725–732, 2019, ISSN: 1864-6433.
@article{pmid31236776,
title = {Nuclear medicine practice in Japan: a report of the eighth nationwide survey in 2017},
author = {Yoshihiro Nishiyama and Seigo Kinuya and Takashi Kato and Daiki Kayano and Shuhei Sato and Manabu Tashiro and Mitsuaki Tatsumi and Teisuke Hashimoto and Shingo Baba and Kenji Hirata and Mana Yoshimura and Hiroto Yoneyama},
doi = {10.1007/s12149-019-01382-5},
issn = {1864-6433},
year = {2019},
date = {2019-10-01},
journal = {Ann Nucl Med},
volume = {33},
number = {10},
pages = {725--732},
abstract = {OBJECTIVE: Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years.
METHODS: The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2017, to all nuclear medicine institutes. The total numbers for the year 2017 were then estimated.
RESULTS: A total of 1132 institutes responded to the survey, including 351 PET centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1332 in total, with 7.0% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 88.2 and 23.6%, respectively. The number of single-photon tracer studies in 2017 was 1.08 million which means a decrease in 5.7% in 5 years and 23.6% in 10 years. All but neurotransmitter system, sentinel lymph node, and liver scintigraphy decreased. Bone scintigraphy was a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%) in order. SPECT studies showed an increase from 47.2% to 63.5%. PET centers have also increased from 295 to 389, as compared to the last survey. The 112 PET centers have installed one or two in-house cyclotrons. PET studies showed 24.5% increase in 5 years, with oncology accounting for 88.9%. F-FDG accounted for 98.2% (630,570 examinations). PET examinations using C-methionine have decreased, with 2440 examinations in 2017. PET examinations using N-NH have been increasing, with 2363 examinations in 2017. The number of PET studies using C-PIB was 904. I-radioiodine targeted therapies showed an increase in 5 years (23.1%), including 4487 patients for thyroid cancer. Out-patient thyroid bed ablation therapy with 1,110 MBq of I accounted for 36.6% of cancer patients. The number of admission rooms increased from 135 to 157 in 5 years. The number of Ra targeted therapies for castration-resistant metastatic prostate cancer was 1194 patients.
CONCLUSIONS: Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study and radionuclide targeted therapy have steadily increased.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years.
METHODS: The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2017, to all nuclear medicine institutes. The total numbers for the year 2017 were then estimated.
RESULTS: A total of 1132 institutes responded to the survey, including 351 PET centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1332 in total, with 7.0% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 88.2 and 23.6%, respectively. The number of single-photon tracer studies in 2017 was 1.08 million which means a decrease in 5.7% in 5 years and 23.6% in 10 years. All but neurotransmitter system, sentinel lymph node, and liver scintigraphy decreased. Bone scintigraphy was a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%) in order. SPECT studies showed an increase from 47.2% to 63.5%. PET centers have also increased from 295 to 389, as compared to the last survey. The 112 PET centers have installed one or two in-house cyclotrons. PET studies showed 24.5% increase in 5 years, with oncology accounting for 88.9%. F-FDG accounted for 98.2% (630,570 examinations). PET examinations using C-methionine have decreased, with 2440 examinations in 2017. PET examinations using N-NH have been increasing, with 2363 examinations in 2017. The number of PET studies using C-PIB was 904. I-radioiodine targeted therapies showed an increase in 5 years (23.1%), including 4487 patients for thyroid cancer. Out-patient thyroid bed ablation therapy with 1,110 MBq of I accounted for 36.6% of cancer patients. The number of admission rooms increased from 135 to 157 in 5 years. The number of Ra targeted therapies for castration-resistant metastatic prostate cancer was 1194 patients.
CONCLUSIONS: Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study and radionuclide targeted therapy have steadily increased.
METHODS: The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2017, to all nuclear medicine institutes. The total numbers for the year 2017 were then estimated.
RESULTS: A total of 1132 institutes responded to the survey, including 351 PET centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1332 in total, with 7.0% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 88.2 and 23.6%, respectively. The number of single-photon tracer studies in 2017 was 1.08 million which means a decrease in 5.7% in 5 years and 23.6% in 10 years. All but neurotransmitter system, sentinel lymph node, and liver scintigraphy decreased. Bone scintigraphy was a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%) in order. SPECT studies showed an increase from 47.2% to 63.5%. PET centers have also increased from 295 to 389, as compared to the last survey. The 112 PET centers have installed one or two in-house cyclotrons. PET studies showed 24.5% increase in 5 years, with oncology accounting for 88.9%. F-FDG accounted for 98.2% (630,570 examinations). PET examinations using C-methionine have decreased, with 2440 examinations in 2017. PET examinations using N-NH have been increasing, with 2363 examinations in 2017. The number of PET studies using C-PIB was 904. I-radioiodine targeted therapies showed an increase in 5 years (23.1%), including 4487 patients for thyroid cancer. Out-patient thyroid bed ablation therapy with 1,110 MBq of I accounted for 36.6% of cancer patients. The number of admission rooms increased from 135 to 157 in 5 years. The number of Ra targeted therapies for castration-resistant metastatic prostate cancer was 1194 patients.
CONCLUSIONS: Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study and radionuclide targeted therapy have steadily increased.
Inomata, Takato; Watanuki, Shoichi; Odagiri, Hayato; Nambu, Takeyuki; Karakatsanis, Nicolas A; Ito, Hiroshi; Watabe, Hiroshi; Tashiro, Manabu; Shidahara, Miho
In: Ann Nucl Med, vol. 33, no. 7, pp. 459–470, 2019, ISSN: 1864-6433.
@article{pmid30924048,
title = {A systematic performance evaluation of head motion correction techniques for 3 commercial PET scanners using a reproducible experimental acquisition protocol},
author = {Takato Inomata and Shoichi Watanuki and Hayato Odagiri and Takeyuki Nambu and Nicolas A Karakatsanis and Hiroshi Ito and Hiroshi Watabe and Manabu Tashiro and Miho Shidahara},
doi = {10.1007/s12149-019-01353-w},
issn = {1864-6433},
year = {2019},
date = {2019-07-01},
journal = {Ann Nucl Med},
volume = {33},
number = {7},
pages = {459--470},
abstract = {PURPOSES: Subject's motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol.
METHODS: A cylindrical phantom with two Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed.
RESULTS: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions.
CONCLUSIONS: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSES: Subject's motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol.
METHODS: A cylindrical phantom with two Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed.
RESULTS: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions.
CONCLUSIONS: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.
METHODS: A cylindrical phantom with two Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed.
RESULTS: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions.
CONCLUSIONS: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.
Rahman, Mahabubur; Watabe, Hiroshi; Shidahara, Miho; Watanuki, Shoichi; Tashiro, Manabu; Mori, Takefumi; Ito, Sadayoshi; Ohsaki, Yusuke
Renal statistical map for positron emission tomography with [O-15] water Journal Article
In: Am J Nucl Med Mol Imaging, vol. 9, no. 4, pp. 193–202, 2019, ISSN: 2160-8407.
@article{pmid31516765,
title = {Renal statistical map for positron emission tomography with [O-15] water},
author = {Mahabubur Rahman and Hiroshi Watabe and Miho Shidahara and Shoichi Watanuki and Manabu Tashiro and Takefumi Mori and Sadayoshi Ito and Yusuke Ohsaki},
issn = {2160-8407},
year = {2019},
date = {2019-01-01},
journal = {Am J Nucl Med Mol Imaging},
volume = {9},
number = {4},
pages = {193--202},
abstract = {Image statistics are frequently used for functional and molecular imaging research in which images from a patient group with a specific diagnosis are compared with images from a healthy control group who have been matched for demographic variables. The success of image statistics for brain imaging has encouraged us to develop a method for obtaining volumetrically normalized kidney to perform image statistics so that we can locally visualize the statistical significant difference comparing voxel by voxel between certain groups in terms kidney blood flow kinetic parameters. For the development of this evolutionary process, we first volumetrically normalized all subjects, which include healthy control (HC) and chronic renal failure (CRF) patients, O water PET image with respect to one HC subject's MRI image using affine transformation. Then O kinetic parametric images of normalized kidneys were obtained through the basis function method. Finally, the statistical map of these parametric images was produced using the threshold-free cluster enhancement based permutation method. Kinetic parameters of kidney namely, uptake rate constant (K), clearance rate constant (k) and blood volume (V), were found to be notably lower in CRF than those of in HC and k parameter was found to be more stable compared to K and V. The statistical map of these parametric images allowed us to visualize local significant differences statistically (P<0.05) between HC and CRF groups. Though PET and MRI techniques have enormous potentiality for functional and molecular imaging of kidney, these are, at best, in experimental level. It is speculated that statistical mapping of kidney could play a significant role in the successful implementation of functional and molecular kidney imaging. However, more research involving a larger sample size and improved normalization technique will be needed for the robustness of the process.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Image statistics are frequently used for functional and molecular imaging research in which images from a patient group with a specific diagnosis are compared with images from a healthy control group who have been matched for demographic variables. The success of image statistics for brain imaging has encouraged us to develop a method for obtaining volumetrically normalized kidney to perform image statistics so that we can locally visualize the statistical significant difference comparing voxel by voxel between certain groups in terms kidney blood flow kinetic parameters. For the development of this evolutionary process, we first volumetrically normalized all subjects, which include healthy control (HC) and chronic renal failure (CRF) patients, O water PET image with respect to one HC subject's MRI image using affine transformation. Then O kinetic parametric images of normalized kidneys were obtained through the basis function method. Finally, the statistical map of these parametric images was produced using the threshold-free cluster enhancement based permutation method. Kinetic parameters of kidney namely, uptake rate constant (K), clearance rate constant (k) and blood volume (V), were found to be notably lower in CRF than those of in HC and k parameter was found to be more stable compared to K and V. The statistical map of these parametric images allowed us to visualize local significant differences statistically (P<0.05) between HC and CRF groups. Though PET and MRI techniques have enormous potentiality for functional and molecular imaging of kidney, these are, at best, in experimental level. It is speculated that statistical mapping of kidney could play a significant role in the successful implementation of functional and molecular kidney imaging. However, more research involving a larger sample size and improved normalization technique will be needed for the robustness of the process.
Nakamura, Tadaho; Hiraoka, Kotaro; Harada, Ryuichi; Matsuzawa, Takuro; Ishikawa, Yoichi; Funaki, Yoshihito; Yoshikawa, Takeo; Tashiro, Manabu; Yanai, Kazuhiko; Okamura, Nobuyuki
Brain histamine H receptor occupancy after oral administration of desloratadine and loratadine Journal Article
In: Pharmacol Res Perspect, vol. 7, no. 4, pp. e00499, 2019, ISSN: 2052-1707.
@article{pmid31338198,
title = {Brain histamine H receptor occupancy after oral administration of desloratadine and loratadine},
author = {Tadaho Nakamura and Kotaro Hiraoka and Ryuichi Harada and Takuro Matsuzawa and Yoichi Ishikawa and Yoshihito Funaki and Takeo Yoshikawa and Manabu Tashiro and Kazuhiko Yanai and Nobuyuki Okamura},
doi = {10.1002/prp2.499},
issn = {2052-1707},
year = {2019},
date = {2019-01-01},
journal = {Pharmacol Res Perspect},
volume = {7},
number = {4},
pages = {e00499},
abstract = {Some histamine H receptor (HR) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second-generation antihistamine for treatment of allergic disorders. Its binding to brain HRs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain HR binding potential ratio (BPR), HR occupancy (HRO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [C]-doxepin, a PET tracer for HRs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPR and HRO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD], <0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059, = 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain HROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (=0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain HRs and did not induce any significant sedation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Some histamine H receptor (HR) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second-generation antihistamine for treatment of allergic disorders. Its binding to brain HRs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain HR binding potential ratio (BPR), HR occupancy (HRO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [C]-doxepin, a PET tracer for HRs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPR and HRO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD], <0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059, = 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain HROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (=0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain HRs and did not induce any significant sedation.
Ezura, M; Kikuchi, A; Ishiki, A; Okamura, N; Hasegawa, T; Harada, R; Watanuki, S; Funaki, Y; Hiraoka, K; Baba, T; Sugeno, N; Oshima, R; Yoshida, S; Kobayashi, J; Kobayashi, M; Tano, O; Nakashima, I; Mugikura, S; Iwata, R; Taki, Y; Furukawa, K; Arai, H; Furumoto, S; Tashiro, M; Yanai, K; Kudo, Y; Takeda, A; Aoki, M
Longitudinal changes in F-THK5351 positron emission tomography in corticobasal syndrome Journal Article
In: Eur J Neurol, vol. 26, no. 9, pp. 1205–1211, 2019, ISSN: 1468-1331.
@article{pmid30980575,
title = {Longitudinal changes in F-THK5351 positron emission tomography in corticobasal syndrome},
author = {M Ezura and A Kikuchi and A Ishiki and N Okamura and T Hasegawa and R Harada and S Watanuki and Y Funaki and K Hiraoka and T Baba and N Sugeno and R Oshima and S Yoshida and J Kobayashi and M Kobayashi and O Tano and I Nakashima and S Mugikura and R Iwata and Y Taki and K Furukawa and H Arai and S Furumoto and M Tashiro and K Yanai and Y Kudo and A Takeda and M Aoki},
doi = {10.1111/ene.13966},
issn = {1468-1331},
year = {2019},
date = {2019-01-01},
journal = {Eur J Neurol},
volume = {26},
number = {9},
pages = {1205--1211},
abstract = {BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with F-THK5351.
METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs).
RESULTS: The 1-year follow-up scan images revealed that F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional F-THK5351 retention in the NCs.
CONCLUSIONS: Longitudinal increases in F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with F-THK5351.
METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs).
RESULTS: The 1-year follow-up scan images revealed that F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional F-THK5351 retention in the NCs.
CONCLUSIONS: Longitudinal increases in F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.
METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs).
RESULTS: The 1-year follow-up scan images revealed that F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional F-THK5351 retention in the NCs.
CONCLUSIONS: Longitudinal increases in F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.
Kikkawa, Takako; Casingal, Cristine R; Chun, Seung Hee; Shinohara, Hiroshi; Hiraoka, Kotaro; Osumi, Noriko
The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder Journal Article
In: Brain Res, vol. 1705, pp. 95–103, 2019, ISSN: 1872-6240.
@article{pmid29499177,
title = {The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder},
author = {Takako Kikkawa and Cristine R Casingal and Seung Hee Chun and Hiroshi Shinohara and Kotaro Hiraoka and Noriko Osumi},
doi = {10.1016/j.brainres.2018.02.041},
issn = {1872-6240},
year = {2019},
date = {2019-01-01},
journal = {Brain Res},
volume = {1705},
pages = {95--103},
abstract = {Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
Kikkawa, Takako; Casingal, Cristine R; Chun, Seung Hee; Shinohara, Hiroshi; Hiraoka, Kotaro; Osumi, Noriko
The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder Journal Article
In: Brain Res, vol. 1705, pp. 95–103, 2019, ISSN: 1872-6240.
@article{pmid29499177b,
title = {The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder},
author = {Takako Kikkawa and Cristine R Casingal and Seung Hee Chun and Hiroshi Shinohara and Kotaro Hiraoka and Noriko Osumi},
doi = {10.1016/j.brainres.2018.02.041},
issn = {1872-6240},
year = {2019},
date = {2019-01-01},
journal = {Brain Res},
volume = {1705},
pages = {95--103},
abstract = {Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
2018
Nai, Ying-Hwey; Watanuki, Shoichi; Tashiro, Manabu; Okamura, Nobuyuki; Watabe, Hiroshi
Investigation of the quantitative accuracy of low-dose amyloid and tau PET imaging Journal Article
In: Radiol Phys Technol, vol. 11, no. 4, pp. 451–459, 2018, ISSN: 1865-0341.
@article{pmid30328073,
title = {Investigation of the quantitative accuracy of low-dose amyloid and tau PET imaging},
author = {Ying-Hwey Nai and Shoichi Watanuki and Manabu Tashiro and Nobuyuki Okamura and Hiroshi Watabe},
doi = {10.1007/s12194-018-0485-y},
issn = {1865-0341},
year = {2018},
date = {2018-12-01},
journal = {Radiol Phys Technol},
volume = {11},
number = {4},
pages = {451--459},
abstract = {With the increasing incidence of dementia worldwide, the frequent use of amyloid and tau positron emission tomography imaging requires low-dose protocols for the differential diagnoses of various neurodegenerative diseases and the monitoring of disease progression. In this study, we investigated the feasibility to reduce the PET dose without a significant loss of quantitative accuracy in 3D dynamic row action maximum likelihood algorithm-reconstructed PET images using [C]PIB and [F]THK5351. Eighteen cognitively normal young controls, cognitively normal elderly controls, and patients with probable Alzheimer's disease (n = 6 each), were included. Reduced doses were simulated by randomly sampling half and quarter of the full counts in list mode data for one independent realization at each simulated dose. Bias was evaluated between the reduced dose from the full dose of standardized uptake value ratio (SUVR), distribution volume ratio (DVR) from reference Logan, and non-displaceable binding potential (BP) from simplified reference tissue model (SRTM). DVR yielded the least bias at low dose compared to SUVR and BP, and thus, is highly recommended. The dose of [F]THK5351 and [C]PIB can be reduced to a quarter of the full dose using DVR for evaluation, whereas the dose can only be reduced to half and a quarter of the full dose for [F]THK5351 and [C]PIB using SUVR. BP showed inconsistent trend and large bias at low dose. The feasibility of dose reduction was dependent on the selected parameters of interest, reconstruction algorithms, reference regions, and to a lesser degree by motion effects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
With the increasing incidence of dementia worldwide, the frequent use of amyloid and tau positron emission tomography imaging requires low-dose protocols for the differential diagnoses of various neurodegenerative diseases and the monitoring of disease progression. In this study, we investigated the feasibility to reduce the PET dose without a significant loss of quantitative accuracy in 3D dynamic row action maximum likelihood algorithm-reconstructed PET images using [C]PIB and [F]THK5351. Eighteen cognitively normal young controls, cognitively normal elderly controls, and patients with probable Alzheimer's disease (n = 6 each), were included. Reduced doses were simulated by randomly sampling half and quarter of the full counts in list mode data for one independent realization at each simulated dose. Bias was evaluated between the reduced dose from the full dose of standardized uptake value ratio (SUVR), distribution volume ratio (DVR) from reference Logan, and non-displaceable binding potential (BP) from simplified reference tissue model (SRTM). DVR yielded the least bias at low dose compared to SUVR and BP, and thus, is highly recommended. The dose of [F]THK5351 and [C]PIB can be reduced to a quarter of the full dose using DVR for evaluation, whereas the dose can only be reduced to half and a quarter of the full dose for [F]THK5351 and [C]PIB using SUVR. BP showed inconsistent trend and large bias at low dose. The feasibility of dose reduction was dependent on the selected parameters of interest, reconstruction algorithms, reference regions, and to a lesser degree by motion effects.
Islam, Md Shahidul; Watanuki, Shoichi; Tashiro, Manabu; Watabe, Hiroshi
In: Med Phys, vol. 45, no. 10, pp. 4693–4703, 2018, ISSN: 2473-4209.
@article{pmid30098031,
title = {Internal radiation dose estimation using multiple D-shuttle dosimeters for positron emission tomography (PET): A validation study using NEMA body phantom},
author = {Md Shahidul Islam and Shoichi Watanuki and Manabu Tashiro and Hiroshi Watabe},
doi = {10.1002/mp.13124},
issn = {2473-4209},
year = {2018},
date = {2018-10-01},
journal = {Med Phys},
volume = {45},
number = {10},
pages = {4693--4703},
abstract = {PURPOSE: Internal radiation dosimetry plays an important role in ensuring the safe use of positron emission tomography (PET) technology and is a legal requirement in most countries. We propose a new technique to estimate the internal radiation dose in PET studies by means of multiple D-shuttle dosimeters attached on the body surface of the patient.
METHODS: Radioactivity in a source organ was estimated iteratively using measurements from multiple D-shuttle dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo simulation. To validate our technique, we performed a phantom study using a National Electrical Manufacturers Association (NEMA) body phantom. The fillable compartments (torso cavity and six spheres) of the phantom were filled with F-FDG mixed with pure water using an 800:1 sphere-to-background radioactivity concentration ratio. The radioactivity concentrations present in the torso cavity and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial radioactivities of the torso cavity and six spheres (treated as source organs) were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere), 7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and 0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA body phantom surface to obtain information on body surface dose and a mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code System (PHITS) Monte Carlo simulation code.
RESULTS: Radioactivity was estimated in 2 min intervals over a 110-min total dose time using our proposed technique. A significant correlation (R = 0.992) was found between actual radioactivity and estimated radioactivity at every 2 min interval for each source organ. The estimated initial radioactivity (mean with standard deviation) was 16.5 ± 0.311 MBq (torso cavity), 33.0 ± 0.624 MBq (37 mm sphere), 15.7 ± 0.189 MBq (28 mm sphere), 7.11 ± 0.738 MBq (22 mm sphere), 4.17 ± 0.083 MBq (17 mm sphere), 1.48 ± 0.469 MBq (13 mm sphere), and 0.865 ± 0.313 MBq (10 mm sphere), which were very close to the actual initial radioactivity measurements for each source organ.
CONCLUSIONS: The phantom study showed that our technique worked successfully. This technique could be used to estimate internal radiation dosimetry in a clinical PET study.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: Internal radiation dosimetry plays an important role in ensuring the safe use of positron emission tomography (PET) technology and is a legal requirement in most countries. We propose a new technique to estimate the internal radiation dose in PET studies by means of multiple D-shuttle dosimeters attached on the body surface of the patient.
METHODS: Radioactivity in a source organ was estimated iteratively using measurements from multiple D-shuttle dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo simulation. To validate our technique, we performed a phantom study using a National Electrical Manufacturers Association (NEMA) body phantom. The fillable compartments (torso cavity and six spheres) of the phantom were filled with F-FDG mixed with pure water using an 800:1 sphere-to-background radioactivity concentration ratio. The radioactivity concentrations present in the torso cavity and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial radioactivities of the torso cavity and six spheres (treated as source organs) were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere), 7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and 0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA body phantom surface to obtain information on body surface dose and a mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code System (PHITS) Monte Carlo simulation code.
RESULTS: Radioactivity was estimated in 2 min intervals over a 110-min total dose time using our proposed technique. A significant correlation (R = 0.992) was found between actual radioactivity and estimated radioactivity at every 2 min interval for each source organ. The estimated initial radioactivity (mean with standard deviation) was 16.5 ± 0.311 MBq (torso cavity), 33.0 ± 0.624 MBq (37 mm sphere), 15.7 ± 0.189 MBq (28 mm sphere), 7.11 ± 0.738 MBq (22 mm sphere), 4.17 ± 0.083 MBq (17 mm sphere), 1.48 ± 0.469 MBq (13 mm sphere), and 0.865 ± 0.313 MBq (10 mm sphere), which were very close to the actual initial radioactivity measurements for each source organ.
CONCLUSIONS: The phantom study showed that our technique worked successfully. This technique could be used to estimate internal radiation dosimetry in a clinical PET study.
METHODS: Radioactivity in a source organ was estimated iteratively using measurements from multiple D-shuttle dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo simulation. To validate our technique, we performed a phantom study using a National Electrical Manufacturers Association (NEMA) body phantom. The fillable compartments (torso cavity and six spheres) of the phantom were filled with F-FDG mixed with pure water using an 800:1 sphere-to-background radioactivity concentration ratio. The radioactivity concentrations present in the torso cavity and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial radioactivities of the torso cavity and six spheres (treated as source organs) were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere), 7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and 0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA body phantom surface to obtain information on body surface dose and a mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code System (PHITS) Monte Carlo simulation code.
RESULTS: Radioactivity was estimated in 2 min intervals over a 110-min total dose time using our proposed technique. A significant correlation (R = 0.992) was found between actual radioactivity and estimated radioactivity at every 2 min interval for each source organ. The estimated initial radioactivity (mean with standard deviation) was 16.5 ± 0.311 MBq (torso cavity), 33.0 ± 0.624 MBq (37 mm sphere), 15.7 ± 0.189 MBq (28 mm sphere), 7.11 ± 0.738 MBq (22 mm sphere), 4.17 ± 0.083 MBq (17 mm sphere), 1.48 ± 0.469 MBq (13 mm sphere), and 0.865 ± 0.313 MBq (10 mm sphere), which were very close to the actual initial radioactivity measurements for each source organ.
CONCLUSIONS: The phantom study showed that our technique worked successfully. This technique could be used to estimate internal radiation dosimetry in a clinical PET study.
Kikuchi, Asuka; Nasir, Fairuz Binti Mohammadi; Inami, Akie; Mohsen, Attayeb; Watanuki, Shoichi; Miyake, Masayasu; Takeda, Kazuko; Koike, Daigo; Ito, Takayasu; Sasakawa, Junpei; Matsuda, Rin; Hiraoka, Kotaro; Maurer, Marcus; Yanai, Kazuhiko; Watabe, Hiroshi; Tashiro, Manabu
In: Hum Psychopharmacol, vol. 33, no. 2, pp. e2655, 2018, ISSN: 1099-1077.
@article{pmid29532516,
title = {Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks},
author = {Asuka Kikuchi and Fairuz Binti Mohammadi Nasir and Akie Inami and Attayeb Mohsen and Shoichi Watanuki and Masayasu Miyake and Kazuko Takeda and Daigo Koike and Takayasu Ito and Junpei Sasakawa and Rin Matsuda and Kotaro Hiraoka and Marcus Maurer and Kazuhiko Yanai and Hiroshi Watabe and Manabu Tashiro},
doi = {10.1002/hup.2655},
issn = {1099-1077},
year = {2018},
date = {2018-01-01},
journal = {Hum Psychopharmacol},
volume = {33},
number = {2},
pages = {e2655},
abstract = {OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.
METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [ F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy.
RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.
CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.
METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [ F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy.
RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.
CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.
METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [ F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy.
RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.
CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.
Tanaka, Yukari; Kanazawa, Motoyori; Kano, Michiko; Tashiro, Manabu; Fukudo, Shin
In: PLoS One, vol. 13, no. 7, pp. e0199698, 2018, ISSN: 1932-6203.
@article{pmid29979696,
title = {Relationship between sympathoadrenal and pituitary-adrenal response during colorectal distention in the presence of corticotropin-releasing hormone in patients with irritable bowel syndrome and healthy controls},
author = {Yukari Tanaka and Motoyori Kanazawa and Michiko Kano and Manabu Tashiro and Shin Fukudo},
doi = {10.1371/journal.pone.0199698},
issn = {1932-6203},
year = {2018},
date = {2018-01-01},
journal = {PLoS One},
volume = {13},
number = {7},
pages = {e0199698},
abstract = {Corticotropin-releasing hormone (CRH) mediates stress responses in the brain-gut axis. Administration of CRH modulates brain activation, for example by controlling the autonomic nervous system in response to colorectal distention. Here, we investigated the relationship between sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to colorectal distention in patients with irritable bowel syndrome (IBS). We enrolled 32 patients with IBS (16 women and 16 men) and 32 healthy subjects (16 women and 16 men), and randomly divided them between CRH and saline injection groups. The patients randomly underwent no (0 mmHg), mild (20 mmHg), or strong (40 mmHg) colorectal distension. CRH (2 μg/kg) or saline was then administered via injection, and the distention protocol was repeated. The heart rate (HR) and HR variability (HRV; calculated as the low [LF] to high frequency [HF] peak ratio, LF/HF) were analyzed using electrocardiography. Plasma noradrenaline, adrenaline, adrenocorticotropic hormone (ACTH), and cortisol levels were measured at the time of each distention. Plasma adrenaline levels were shown to be associated with plasma ACTH levels in HCs injected with CRH during distention using structural equation modeling analysis. Patients with IBS injected with placebo during distention displayed a closer association between these two parameters than those injected with CRH. Generalized estimating equation analysis revealed a significant distention × group × drug interaction for HF power. Moreover, there was a strong correlation between adrenaline and HRV upon CRH injection in controls, but not patients with IBS. The relationship between HPA-sympathoadrenal responses and CRH levels during colorectal distention differs between patients with IBS and controls. Modulation of adrenal gland activity in response to ACTH stimulation may contribute to the brain-gut pathophysiology characteristic of IBS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Corticotropin-releasing hormone (CRH) mediates stress responses in the brain-gut axis. Administration of CRH modulates brain activation, for example by controlling the autonomic nervous system in response to colorectal distention. Here, we investigated the relationship between sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to colorectal distention in patients with irritable bowel syndrome (IBS). We enrolled 32 patients with IBS (16 women and 16 men) and 32 healthy subjects (16 women and 16 men), and randomly divided them between CRH and saline injection groups. The patients randomly underwent no (0 mmHg), mild (20 mmHg), or strong (40 mmHg) colorectal distension. CRH (2 μg/kg) or saline was then administered via injection, and the distention protocol was repeated. The heart rate (HR) and HR variability (HRV; calculated as the low [LF] to high frequency [HF] peak ratio, LF/HF) were analyzed using electrocardiography. Plasma noradrenaline, adrenaline, adrenocorticotropic hormone (ACTH), and cortisol levels were measured at the time of each distention. Plasma adrenaline levels were shown to be associated with plasma ACTH levels in HCs injected with CRH during distention using structural equation modeling analysis. Patients with IBS injected with placebo during distention displayed a closer association between these two parameters than those injected with CRH. Generalized estimating equation analysis revealed a significant distention × group × drug interaction for HF power. Moreover, there was a strong correlation between adrenaline and HRV upon CRH injection in controls, but not patients with IBS. The relationship between HPA-sympathoadrenal responses and CRH levels during colorectal distention differs between patients with IBS and controls. Modulation of adrenal gland activity in response to ACTH stimulation may contribute to the brain-gut pathophysiology characteristic of IBS.
Ishiki, Aiko; Harada, Ryuichi; Kai, Hideaki; Sato, Naomi; Totsune, Tomoko; Tomita, Naoki; Watanuki, Shoichi; Hiraoka, Kotaro; Ishikawa, Yoichi; Funaki, Yoshihito; Iwata, Ren; Furumoto, Shozo; Tashiro, Manabu; Sasano, Hironobu; Kitamoto, Tetsuyuki; Kudo, Yukitsuka; Yanai, Kazuhiko; Furukawa, Katsutoshi; Okamura, Nobuyuki; Arai, Hiroyuki
Neuroimaging-pathological correlations of [F]THK5351 PET in progressive supranuclear palsy Journal Article
In: Acta Neuropathol Commun, vol. 6, no. 1, pp. 53, 2018, ISSN: 2051-5960.
@article{pmid29958546,
title = {Neuroimaging-pathological correlations of [F]THK5351 PET in progressive supranuclear palsy},
author = {Aiko Ishiki and Ryuichi Harada and Hideaki Kai and Naomi Sato and Tomoko Totsune and Naoki Tomita and Shoichi Watanuki and Kotaro Hiraoka and Yoichi Ishikawa and Yoshihito Funaki and Ren Iwata and Shozo Furumoto and Manabu Tashiro and Hironobu Sasano and Tetsuyuki Kitamoto and Yukitsuka Kudo and Kazuhiko Yanai and Katsutoshi Furukawa and Nobuyuki Okamura and Hiroyuki Arai},
doi = {10.1186/s40478-018-0556-7},
issn = {2051-5960},
year = {2018},
date = {2018-01-01},
journal = {Acta Neuropathol Commun},
volume = {6},
number = {1},
pages = {53},
abstract = {Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.
Harada, Ryuichi; Ishiki, Aiko; Kai, Hideaki; Sato, Naomi; Furukawa, Katsutoshi; Furumoto, Shozo; Tago, Tetsuro; Tomita, Naoki; Watanuki, Shoichi; Hiraoka, Kotaro; Ishikawa, Yoichi; Funaki, Yoshihito; Nakamura, Tadaho; Yoshikawa, Takeo; Iwata, Ren; Tashiro, Manabu; Sasano, Hironobu; Kitamoto, Tetsuyuki; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka; Okamura, Nobuyuki
Correlations of F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease Journal Article
In: J Nucl Med, vol. 59, no. 4, pp. 671–674, 2018, ISSN: 1535-5667.
@article{pmid28864633,
title = {Correlations of F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease},
author = {Ryuichi Harada and Aiko Ishiki and Hideaki Kai and Naomi Sato and Katsutoshi Furukawa and Shozo Furumoto and Tetsuro Tago and Naoki Tomita and Shoichi Watanuki and Kotaro Hiraoka and Yoichi Ishikawa and Yoshihito Funaki and Tadaho Nakamura and Takeo Yoshikawa and Ren Iwata and Manabu Tashiro and Hironobu Sasano and Tetsuyuki Kitamoto and Kazuhiko Yanai and Hiroyuki Arai and Yukitsuka Kudo and Nobuyuki Okamura},
doi = {10.2967/jnumed.117.197426},
issn = {1535-5667},
year = {2018},
date = {2018-01-01},
journal = {J Nucl Med},
volume = {59},
number = {4},
pages = {671--674},
abstract = {Clinical PET studies using F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent F-THK5351 and C-Pittsburgh compound B PET before death. Regional in vivo F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Clinical PET studies using F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent F-THK5351 and C-Pittsburgh compound B PET before death. Regional in vivo F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain.
2017
Yanai, Kazuhiko; Yoshikawa, Takeo; Yanai, Ai; Nakamura, Tadaho; Iida, Tomomitsu; Leurs, Rob; Tashiro, Manabu
The clinical pharmacology of non-sedating antihistamines Journal Article
In: Pharmacol Ther, vol. 178, pp. 148–156, 2017, ISSN: 1879-016X.
@article{pmid28457804,
title = {The clinical pharmacology of non-sedating antihistamines},
author = {Kazuhiko Yanai and Takeo Yoshikawa and Ai Yanai and Tadaho Nakamura and Tomomitsu Iida and Rob Leurs and Manabu Tashiro},
doi = {10.1016/j.pharmthera.2017.04.004},
issn = {1879-016X},
year = {2017},
date = {2017-10-01},
journal = {Pharmacol Ther},
volume = {178},
pages = {148--156},
abstract = {We previously reported on brain H receptor occupancy measurements of antihistamines in human brain using [C]doxepin and positron emission tomography (PET). We proposed the use of brain H receptor occupancy to classify antihistamines objectively into three categories of sedating, less-sedating, and non-sedating antihistamines according to their sedative effects. Non-sedating antihistamines are recommended for the treatment of allergies such as pollinosis and atopic dermatitis because of their low penetration into the central nervous system. Physicians and pharmacists are responsible for fully educating patients about the risks of sedating antihistamines from pharmacological points of view. If a sedating antihistamine must be prescribed, its sedative effects should be thoroughly considered before choosing the drug. Non-sedating antihistamines should be preferentially used whenever possible as most antihistamines are equally efficacious, while adverse effects of sedating antihistamines can be serious. This review summarizes the pharmacological properties of clinically useful non-sedating antihistamines from the perspective of histamine function in the CNS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We previously reported on brain H receptor occupancy measurements of antihistamines in human brain using [C]doxepin and positron emission tomography (PET). We proposed the use of brain H receptor occupancy to classify antihistamines objectively into three categories of sedating, less-sedating, and non-sedating antihistamines according to their sedative effects. Non-sedating antihistamines are recommended for the treatment of allergies such as pollinosis and atopic dermatitis because of their low penetration into the central nervous system. Physicians and pharmacists are responsible for fully educating patients about the risks of sedating antihistamines from pharmacological points of view. If a sedating antihistamine must be prescribed, its sedative effects should be thoroughly considered before choosing the drug. Non-sedating antihistamines should be preferentially used whenever possible as most antihistamines are equally efficacious, while adverse effects of sedating antihistamines can be serious. This review summarizes the pharmacological properties of clinically useful non-sedating antihistamines from the perspective of histamine function in the CNS.
Shidahara, Miho; Thomas, Benjamin A; Okamura, Nobuyuki; Ibaraki, Masanobu; Matsubara, Keisuke; Oyama, Senri; Ishikawa, Yoichi; Watanuki, Shoichi; Iwata, Ren; Furumoto, Shozo; Tashiro, Manabu; Yanai, Kazuhiko; Gonda, Kohsuke; Watabe, Hiroshi
A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [F]THK5351 and [C]PIB Journal Article
In: Ann Nucl Med, vol. 31, no. 7, pp. 563–569, 2017, ISSN: 1864-6433.
@article{pmid28639126,
title = {A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [F]THK5351 and [C]PIB},
author = {Miho Shidahara and Benjamin A Thomas and Nobuyuki Okamura and Masanobu Ibaraki and Keisuke Matsubara and Senri Oyama and Yoichi Ishikawa and Shoichi Watanuki and Ren Iwata and Shozo Furumoto and Manabu Tashiro and Kazuhiko Yanai and Kohsuke Gonda and Hiroshi Watabe},
doi = {10.1007/s12149-017-1185-0},
issn = {1864-6433},
year = {2017},
date = {2017-08-01},
journal = {Ann Nucl Med},
volume = {31},
number = {7},
pages = {563--569},
abstract = {PURPOSE: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study.
METHODS: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [F]THK5351 and [C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data.
RESULTS: In regions of high uptake of [F]THK5351 and [C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition.
CONCLUSION: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study.
METHODS: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [F]THK5351 and [C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data.
RESULTS: In regions of high uptake of [F]THK5351 and [C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition.
CONCLUSION: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.
METHODS: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [F]THK5351 and [C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data.
RESULTS: In regions of high uptake of [F]THK5351 and [C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition.
CONCLUSION: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.
Inami, Akie; Ogura, Takeshi; Watanuki, Shoichi; Masud, Md Mehedi; Shibuya, Katsuhiko; Miyake, Masayasu; Matsuda, Rin; Hiraoka, Kotaro; Itoh, Masatoshi; Fuhr, Arlan W; Yanai, Kazuhiko; Tashiro, Manabu
In: Evid Based Complement Alternat Med, vol. 2017, pp. 4345703, 2017, ISSN: 1741-427X.
@article{pmid28167971,
title = {Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [F]FDG PET Study},
author = {Akie Inami and Takeshi Ogura and Shoichi Watanuki and Md Mehedi Masud and Katsuhiko Shibuya and Masayasu Miyake and Rin Matsuda and Kotaro Hiraoka and Masatoshi Itoh and Arlan W Fuhr and Kazuhiko Yanai and Manabu Tashiro},
doi = {10.1155/2017/4345703},
issn = {1741-427X},
year = {2017},
date = {2017-01-01},
journal = {Evid Based Complement Alternat Med},
volume = {2017},
pages = {4345703},
abstract = {. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [F]fluorodeoxyglucose ([F]FDG PET). . Twenty-one male volunteers were recruited for the present study. [F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. . Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. . Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [F]fluorodeoxyglucose ([F]FDG PET). . Twenty-one male volunteers were recruited for the present study. [F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. . Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. . Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.
Arakawa, Yuma; Nai, YingHwey; Shidahara, Miho; Furumoto, Shozo; Seki, Chie; Okamura, Nobuyuki; Tashiro, Manabu; Kudo, Yukitsuka; Yanai, Kazuhiko; Gonda, Kohsuke; Watabe, Hiroshi
In: J Nucl Med, vol. 58, no. 8, pp. 1285–1292, 2017, ISSN: 1535-5667.
@article{pmid28062596,
title = {Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand},
author = {Yuma Arakawa and YingHwey Nai and Miho Shidahara and Shozo Furumoto and Chie Seki and Nobuyuki Okamura and Manabu Tashiro and Yukitsuka Kudo and Kazuhiko Yanai and Kohsuke Gonda and Hiroshi Watabe},
doi = {10.2967/jnumed.116.183566},
issn = {1535-5667},
year = {2017},
date = {2017-01-01},
journal = {J Nucl Med},
volume = {58},
number = {8},
pages = {1285--1292},
abstract = {Our study aimed to develop a method to mathematically predict the kinetic parameters (influx rate constant), (efflux rate constant), and BP (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted time-activity curves of target and reference regions. We investigated 10 clinically applied amyloid PET radioligands: C-Pittsburgh compound B, C-BF-227, C-AZD2184, C-SB-13, F-FACT, F-florbetapir, F-florbetaben, F-flutemetamol, F-FDDNP, and F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. , , and BP were derived from the lipophilicity (log), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid β using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted , , BP, and SUVR for the healthy and AD groups were compared with the respective clinically observed values. The correlation between predicted and clinical kinetic parameters had an value of 0.73 for in the healthy group, 0.71 for in the AD group, 0.81 for in the healthy group, 0.85 for in the AD group, and 0.63 for BP in the AD group. The regression relationship between the predicted SUVR () and the clinical SUVR () for the healthy and the AD groups was = 2.73 - 2.11 ( = 0.72). The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Our study aimed to develop a method to mathematically predict the kinetic parameters (influx rate constant), (efflux rate constant), and BP (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted time-activity curves of target and reference regions. We investigated 10 clinically applied amyloid PET radioligands: C-Pittsburgh compound B, C-BF-227, C-AZD2184, C-SB-13, F-FACT, F-florbetapir, F-florbetaben, F-flutemetamol, F-FDDNP, and F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. , , and BP were derived from the lipophilicity (log), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid β using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted , , BP, and SUVR for the healthy and AD groups were compared with the respective clinically observed values. The correlation between predicted and clinical kinetic parameters had an value of 0.73 for in the healthy group, 0.71 for in the AD group, 0.81 for in the healthy group, 0.85 for in the AD group, and 0.63 for BP in the AD group. The regression relationship between the predicted SUVR () and the clinical SUVR () for the healthy and the AD groups was = 2.73 - 2.11 ( = 0.72). The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.
Ishiki, A; Harada, R; Okamura, N; Tomita, N; Rowe, C C; Villemagne, V L; Yanai, K; Kudo, Y; Arai, H; Furumoto, S; Tashiro, M; Furukawa, K
Tau imaging with [ F]THK-5351 in progressive supranuclear palsy Journal Article
In: Eur J Neurol, vol. 24, no. 1, pp. 130–136, 2017, ISSN: 1468-1331.
@article{pmid27797445,
title = {Tau imaging with [ F]THK-5351 in progressive supranuclear palsy},
author = {A Ishiki and R Harada and N Okamura and N Tomita and C C Rowe and V L Villemagne and K Yanai and Y Kudo and H Arai and S Furumoto and M Tashiro and K Furukawa},
doi = {10.1111/ene.13164},
issn = {1468-1331},
year = {2017},
date = {2017-01-01},
journal = {Eur J Neurol},
volume = {24},
number = {1},
pages = {130--136},
abstract = {BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [ F]THK-5351, which we have recently developed.
METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [ H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [ F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed.
RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [ H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [ F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
CONCLUSIONS: We conclude that [ F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [ F]THK-5351, which we have recently developed.
METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [ H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [ F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed.
RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [ H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [ F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
CONCLUSIONS: We conclude that [ F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [ H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [ F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed.
RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [ H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [ F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
CONCLUSIONS: We conclude that [ F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
Harada, Ryuichi; Furumoto, Shozo; Tago, Tetsuro; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Iwata, Ren; Tashiro, Manabu; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka; Okamura, Nobuyuki
Erratum to: Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351 Journal Article
In: Eur J Nucl Med Mol Imaging, vol. 44, no. 1, pp. 177, 2017, ISSN: 1619-7089.
@article{pmid27734120,
title = {Erratum to: Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351},
author = {Ryuichi Harada and Shozo Furumoto and Tetsuro Tago and Katsutoshi Furukawa and Aiko Ishiki and Naoki Tomita and Ren Iwata and Manabu Tashiro and Hiroyuki Arai and Kazuhiko Yanai and Yukitsuka Kudo and Nobuyuki Okamura},
doi = {10.1007/s00259-016-3547-6},
issn = {1619-7089},
year = {2017},
date = {2017-01-01},
journal = {Eur J Nucl Med Mol Imaging},
volume = {44},
number = {1},
pages = {177},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2016
Inubushi, Masayuki; Higashi, Tatsuya; Kuji, Ichiei; Sakamoto, Setsu; Tashiro, Manabu; Momose, Mitsuru
Introduction of nuclear medicine research in Japan
2016.
@{pmid27492625,
title = {Introduction of nuclear medicine research in Japan},
author = {Masayuki Inubushi and Tatsuya Higashi and Ichiei Kuji and Setsu Sakamoto and Manabu Tashiro and Mitsuru Momose},
doi = {10.1007/s00259-016-3468-4},
issn = {1619-7089},
year = {2016},
date = {2016-12-01},
journal = {Eur J Nucl Med Mol Imaging},
volume = {43},
number = {13},
pages = {2449--2452},
abstract = {There were many interesting presentations of unique studies at the Annual Meeting of the Japanese Society of Nuclear Medicine, although there were fewer attendees from Europe than expected. These presentations included research on diseases that are more frequent in Japan and Asia than in Europe, synthesis of original radiopharmaceuticals, and development of imaging devices and methods with novel ideas especially by Japanese manufacturers. In this review, we introduce recent nuclear medicine research conducted in Japan in the five categories of Oncology, Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that this article will encourage the participation of researchers from all over the world, in particular from Europe, in scientific meetings on nuclear medicine held in Japan.},
keywords = {},
pubstate = {published},
tppubtype = {}
}
There were many interesting presentations of unique studies at the Annual Meeting of the Japanese Society of Nuclear Medicine, although there were fewer attendees from Europe than expected. These presentations included research on diseases that are more frequent in Japan and Asia than in Europe, synthesis of original radiopharmaceuticals, and development of imaging devices and methods with novel ideas especially by Japanese manufacturers. In this review, we introduce recent nuclear medicine research conducted in Japan in the five categories of Oncology, Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that this article will encourage the participation of researchers from all over the world, in particular from Europe, in scientific meetings on nuclear medicine held in Japan.
Kikuchi, Akio; Okamura, Nobuyuki; Hasegawa, Takafumi; Harada, Ryuichi; Watanuki, Shoichi; Funaki, Yoshihito; Hiraoka, Kotaro; Baba, Toru; Sugeno, Naoto; Oshima, Ryuji; Yoshida, Shun; Kobayashi, Junpei; Ezura, Michinori; Kobayashi, Michiko; Tano, Ohito; Mugikura, Shunji; Iwata, Ren; Ishiki, Aiko; Furukawa, Katsutoshi; Arai, Hiroyuki; Furumoto, Shozo; Tashiro, Manabu; Yanai, Kazuhiko; Kudo, Yukitsuka; Takeda, Atsushi; Aoki, Masashi
In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET Journal Article
In: Neurology, vol. 87, no. 22, pp. 2309–2316, 2016, ISSN: 1526-632X.
@article{pmid27794115,
title = {In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET},
author = {Akio Kikuchi and Nobuyuki Okamura and Takafumi Hasegawa and Ryuichi Harada and Shoichi Watanuki and Yoshihito Funaki and Kotaro Hiraoka and Toru Baba and Naoto Sugeno and Ryuji Oshima and Shun Yoshida and Junpei Kobayashi and Michinori Ezura and Michiko Kobayashi and Ohito Tano and Shunji Mugikura and Ren Iwata and Aiko Ishiki and Katsutoshi Furukawa and Hiroyuki Arai and Shozo Furumoto and Manabu Tashiro and Kazuhiko Yanai and Yukitsuka Kudo and Atsushi Takeda and Masashi Aoki},
doi = {10.1212/WNL.0000000000003375},
issn = {1526-632X},
year = {2016},
date = {2016-11-01},
journal = {Neurology},
volume = {87},
number = {22},
pages = {2309--2316},
abstract = {OBJECTIVE: To determine whether F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS).
METHODS: We evaluated the in vitro binding of H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD).
RESULTS: H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism.
CONCLUSIONS: F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To determine whether F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS).
METHODS: We evaluated the in vitro binding of H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD).
RESULTS: H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism.
CONCLUSIONS: F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.
METHODS: We evaluated the in vitro binding of H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD).
RESULTS: H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism.
CONCLUSIONS: F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.
Meguro, Kenichi; Akanuma, Kyoko; Meguro, Mitsue; Yamaguchi, Satoshi; Ishii, Hiroshi; Tashiro, Manabu
In: Psychogeriatrics, vol. 16, no. 2, pp. 116–120, 2016, ISSN: 1479-8301.
@article{pmid26114837,
title = {Prevalence and prognosis of prodromal Alzheimer's disease as assessed by magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography in a community: reanalysis from the Osaki-Tajiri Project},
author = {Kenichi Meguro and Kyoko Akanuma and Mitsue Meguro and Satoshi Yamaguchi and Hiroshi Ishii and Manabu Tashiro},
doi = {10.1111/psyg.12131},
issn = {1479-8301},
year = {2016},
date = {2016-03-01},
journal = {Psychogeriatrics},
volume = {16},
number = {2},
pages = {116--120},
abstract = {BACKGROUND: Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and (18) F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated.
METHODS: Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging).
RESULTS: Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period.
DISCUSSION: The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and (18) F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated.
METHODS: Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging).
RESULTS: Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period.
DISCUSSION: The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD.
METHODS: Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging).
RESULTS: Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period.
DISCUSSION: The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD.
Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Tago, Tetsuro; Hiraoka, Kotaro; Watanuki, Shoichi; Shidahara, Miho; Miyake, Masayasu; Ishikawa, Yoichi; Matsuda, Rin; Inami, Akie; Yoshikawa, Takeo; Funaki, Yoshihito; Iwata, Ren; Tashiro, Manabu; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka
18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease Journal Article
In: J Nucl Med, vol. 57, no. 2, pp. 208–214, 2016, ISSN: 1535-5667.
@article{pmid26541774,
title = {18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease},
author = {Ryuichi Harada and Nobuyuki Okamura and Shozo Furumoto and Katsutoshi Furukawa and Aiko Ishiki and Naoki Tomita and Tetsuro Tago and Kotaro Hiraoka and Shoichi Watanuki and Miho Shidahara and Masayasu Miyake and Yoichi Ishikawa and Rin Matsuda and Akie Inami and Takeo Yoshikawa and Yoshihito Funaki and Ren Iwata and Manabu Tashiro and Kazuhiko Yanai and Hiroyuki Arai and Yukitsuka Kudo},
doi = {10.2967/jnumed.115.164848},
issn = {1535-5667},
year = {2016},
date = {2016-02-01},
journal = {J Nucl Med},
volume = {57},
number = {2},
pages = {208--214},
abstract = {Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives.
METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed.
RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117.
CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives.
METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed.
RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117.
CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed.
RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117.
CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
Tanaka, Yukari; Kanazawa, Motoyori; Kano, Michiko; Morishita, Joe; Hamaguchi, Toyohiro; Oudenhove, Lukas Van; Ly, Huynh Giao; Dupont, Patrick; Tack, Jan; Yamaguchi, Takuhiro; Yanai, Kazuhiko; Tashiro, Manabu; Fukudo, Shin
In: PLoS One, vol. 11, no. 7, pp. e0157347, 2016, ISSN: 1932-6203.
@article{pmid27448273,
title = {Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome},
author = {Yukari Tanaka and Motoyori Kanazawa and Michiko Kano and Joe Morishita and Toyohiro Hamaguchi and Lukas Van Oudenhove and Huynh Giao Ly and Patrick Dupont and Jan Tack and Takuhiro Yamaguchi and Kazuhiko Yanai and Manabu Tashiro and Shin Fukudo},
doi = {10.1371/journal.pone.0157347},
issn = {1932-6203},
year = {2016},
date = {2016-01-01},
journal = {PLoS One},
volume = {11},
number = {7},
pages = {e0157347},
abstract = {Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.
Kikuchi, Akio; Takeda, Atsushi; Sugeno, Naoto; Miura, Emiko; Kato, Kazuhiro; Hasegawa, Takafumi; Baba, Toru; Konno, Masatoshi; Oshima, Ryuji; Watanuki, Shoichi; Hiraoka, Kotaro; Tashiro, Manabu; Aoki, Masashi
Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy Journal Article
In: Intern Med, vol. 55, no. 14, pp. 1919–1922, 2016, ISSN: 1349-7235.
@article{pmid27432104,
title = {Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy},
author = {Akio Kikuchi and Atsushi Takeda and Naoto Sugeno and Emiko Miura and Kazuhiro Kato and Takafumi Hasegawa and Toru Baba and Masatoshi Konno and Ryuji Oshima and Shoichi Watanuki and Kotaro Hiraoka and Manabu Tashiro and Masashi Aoki},
doi = {10.2169/internalmedicine.55.5843},
issn = {1349-7235},
year = {2016},
date = {2016-01-01},
journal = {Intern Med},
volume = {55},
number = {14},
pages = {1919--1922},
abstract = {We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.
Harada, Ryuichi; Furumoto, Shozo; Tago, Tetsuro; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Iwata, Ren; Tashiro, Manabu; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka; Okamura, Nobuyuki
Characterization of the radiolabeled metabolite of tau PET tracer F-THK5351 Journal Article
In: Eur J Nucl Med Mol Imaging, vol. 43, no. 12, pp. 2211–2218, 2016, ISSN: 1619-7089.
@article{pmid27430946,
title = {Characterization of the radiolabeled metabolite of tau PET tracer F-THK5351},
author = {Ryuichi Harada and Shozo Furumoto and Tetsuro Tago and Katsutoshi Furukawa and Aiko Ishiki and Naoki Tomita and Ren Iwata and Manabu Tashiro and Hiroyuki Arai and Kazuhiko Yanai and Yukitsuka Kudo and Nobuyuki Okamura},
doi = {10.1007/s00259-016-3453-y},
issn = {1619-7089},
year = {2016},
date = {2016-01-01},
journal = {Eur J Nucl Med Mol Imaging},
volume = {43},
number = {12},
pages = {2211--2218},
abstract = {PURPOSE: F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties.
METHODS: Venous blood samples were collected from three human subjects after injection of F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples.
RESULTS: About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of F-THK5351. The isolated radiometabolite of F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples.
CONCLUSIONS: These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties.
METHODS: Venous blood samples were collected from three human subjects after injection of F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples.
RESULTS: About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of F-THK5351. The isolated radiometabolite of F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples.
CONCLUSIONS: These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.
METHODS: Venous blood samples were collected from three human subjects after injection of F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples.
RESULTS: About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of F-THK5351. The isolated radiometabolite of F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples.
CONCLUSIONS: These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.
Lockhart, Samuel N; Baker, Suzanne L; Okamura, Nobuyuki; Furukawa, Katsutoshi; Ishiki, Aiko; Furumoto, Shozo; Tashiro, Manabu; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka; Harada, Ryuichi; Tomita, Naoki; Hiraoka, Kotaro; Watanuki, Shoichi; Jagust, William J
Dynamic PET Measures of Tau Accumulation in Cognitively Normal Older Adults and Alzheimer's Disease Patients Measured Using [18F] THK-5351 Journal Article
In: PLoS One, vol. 11, no. 6, pp. e0158460, 2016, ISSN: 1932-6203.
@article{pmid27355840,
title = {Dynamic PET Measures of Tau Accumulation in Cognitively Normal Older Adults and Alzheimer's Disease Patients Measured Using [18F] THK-5351},
author = {Samuel N Lockhart and Suzanne L Baker and Nobuyuki Okamura and Katsutoshi Furukawa and Aiko Ishiki and Shozo Furumoto and Manabu Tashiro and Kazuhiko Yanai and Hiroyuki Arai and Yukitsuka Kudo and Ryuichi Harada and Naoki Tomita and Kotaro Hiraoka and Shoichi Watanuki and William J Jagust},
doi = {10.1371/journal.pone.0158460},
issn = {1932-6203},
year = {2016},
date = {2016-01-01},
journal = {PLoS One},
volume = {11},
number = {6},
pages = {e0158460},
abstract = {BACKGROUND: [18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.
METHODS: Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.
RESULTS: In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.
CONCLUSIONS: We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: [18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.
METHODS: Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.
RESULTS: In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.
CONCLUSIONS: We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.
METHODS: Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.
RESULTS: In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.
CONCLUSIONS: We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.
Inami, Akie; Matsuda, Rin; Grobosch, Thomas; Komamura, Hiroshi; Takeda, Kazuko; Yamada, Yusuke; Miyake, Masayasu; Hiraoka, Kotaro; Maurer, Marcus; Yanai, Kazuhiko; Tashiro, Manabu
In: Hum Psychopharmacol, vol. 31, no. 3, pp. 167–177, 2016, ISSN: 1099-1077.
@article{pmid26999510,
title = {A simulated car-driving study on the effects of acute administration of levocetirizine, fexofenadine, and diphenhydramine in healthy Japanese volunteers},
author = {Akie Inami and Rin Matsuda and Thomas Grobosch and Hiroshi Komamura and Kazuko Takeda and Yusuke Yamada and Masayasu Miyake and Kotaro Hiraoka and Marcus Maurer and Kazuhiko Yanai and Manabu Tashiro},
doi = {10.1002/hup.2524},
issn = {1099-1077},
year = {2016},
date = {2016-01-01},
journal = {Hum Psychopharmacol},
volume = {31},
number = {3},
pages = {167--177},
abstract = {OBJECTIVE: Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects.
METHODS: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed.
RESULTS: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation.
CONCLUSIONS: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects.
METHODS: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed.
RESULTS: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation.
CONCLUSIONS: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.
METHODS: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed.
RESULTS: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation.
CONCLUSIONS: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.
Sato, K; Shidahara, M; Watabe, H; Watanuki, S; Ishikawa, Y; Arakawa, Y; Nai, Y H; Furumoto, S; Tashiro, M; Shoji, T; Yanai, K; Gonda, K
Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards Journal Article
In: Phys Med Biol, vol. 61, no. 2, pp. 696–711, 2016, ISSN: 1361-6560.
@article{pmid26716872,
title = {Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards},
author = {K Sato and M Shidahara and H Watabe and S Watanuki and Y Ishikawa and Y Arakawa and Y H Nai and S Furumoto and M Tashiro and T Shoji and K Yanai and K Gonda},
doi = {10.1088/0031-9155/61/2/696},
issn = {1361-6560},
year = {2016},
date = {2016-01-01},
journal = {Phys Med Biol},
volume = {61},
number = {2},
pages = {696--711},
abstract = {The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.
Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko
Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry Journal Article
In: PLoS One, vol. 11, no. 6, pp. e0158153, 2016, ISSN: 1932-6203.
@article{pmid27355350,
title = {Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry},
author = {Kotaro Hiraoka and Akira Sumiyoshi and Hiroi Nonaka and Takako Kikkawa and Ryuta Kawashima and Noriko Osumi},
doi = {10.1371/journal.pone.0158153},
issn = {1932-6203},
year = {2016},
date = {2016-01-01},
journal = {PLoS One},
volume = {11},
number = {6},
pages = {e0158153},
abstract = {Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors.
K, Ariga; M, Tashiro
A History of Biological Illustrations in Japan Journal Article
In: J Nat Sic Illustration, vol. 48, iss. 3, pp. 3-8, 2016.
@article{nokeyb,
title = {A History of Biological Illustrations in Japan},
author = {Ariga K and Tashiro M},
year = {2016},
date = {2016-01-01},
journal = {J Nat Sic Illustration},
volume = {48},
issue = {3},
pages = {3-8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Akanuma, Kyoko; Meguro, Kenichi; Satoh, Masayuki; Tashiro, Manabu; Itoh, Masatoshi
In: Int J Neurosci, vol. 126, no. 1, pp. 39–45, 2016, ISSN: 1563-5279.
@article{pmid25567372,
title = {Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication},
author = {Kyoko Akanuma and Kenichi Meguro and Masayuki Satoh and Manabu Tashiro and Masatoshi Itoh},
doi = {10.3109/00207454.2014.992068},
issn = {1563-5279},
year = {2016},
date = {2016-01-01},
journal = {Int J Neurosci},
volume = {126},
number = {1},
pages = {39--45},
abstract = {Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.
2015
Sato, Hirotoshi; Ito, Chihiro; Hiraoka, Kotaro; Tashiro, Manabu; Shibuya, Katsuhiko; Funaki, Yoshihito; Yoshikawa, Takeo; Iwata, Ren; Matsuoka, Hiroo; Yanai, Kazuhiko
In: Psychopharmacology (Berl), vol. 232, no. 19, pp. 3497–3505, 2015, ISSN: 1432-2072.
@article{pmid26146015,
title = {Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers},
author = {Hirotoshi Sato and Chihiro Ito and Kotaro Hiraoka and Manabu Tashiro and Katsuhiko Shibuya and Yoshihito Funaki and Takeo Yoshikawa and Ren Iwata and Hiroo Matsuoka and Kazuhiko Yanai},
doi = {10.1007/s00213-015-4002-2},
issn = {1432-2072},
year = {2015},
date = {2015-10-01},
journal = {Psychopharmacology (Berl)},
volume = {232},
number = {19},
pages = {3497--3505},
abstract = {RATIONALE: Histamine H1 antagonists have hypnotic, appetite-promoting, and sedative side effects. Most second-generation antipsychotics have potent antagonistic effects on histamine H1 receptor (H1R). Positron emission tomography (PET) can measure the H1R occupancy (H1RO) in vivo, although there are no reports regarding antipsychotics.
OBJECTIVES: We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R.
METHODS: Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness.
RESULTS: The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations.
CONCLUSIONS: Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new-generation antipsychotics block the central histaminergic system in humans.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RATIONALE: Histamine H1 antagonists have hypnotic, appetite-promoting, and sedative side effects. Most second-generation antipsychotics have potent antagonistic effects on histamine H1 receptor (H1R). Positron emission tomography (PET) can measure the H1R occupancy (H1RO) in vivo, although there are no reports regarding antipsychotics.
OBJECTIVES: We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R.
METHODS: Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness.
RESULTS: The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations.
CONCLUSIONS: Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new-generation antipsychotics block the central histaminergic system in humans.
OBJECTIVES: We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R.
METHODS: Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness.
RESULTS: The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations.
CONCLUSIONS: Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new-generation antipsychotics block the central histaminergic system in humans.
Hiraoka, Kotaro; Narita, Wataru; Kikuchi, Hirokazu; Baba, Toru; Kanno, Shigenori; Iizuka, Osamu; Tashiro, Manabu; Furumoto, Shozo; Okamura, Nobuyuki; Furukawa, Katsutoshi; Arai, Hiroyuki; Iwata, Ren; Mori, Etsuro; Yanai, Kazuhiko
Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus Journal Article
In: J Neurol Sci, vol. 356, no. 1-2, pp. 124–128, 2015, ISSN: 1878-5883.
@article{pmid26095458,
title = {Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus},
author = {Kotaro Hiraoka and Wataru Narita and Hirokazu Kikuchi and Toru Baba and Shigenori Kanno and Osamu Iizuka and Manabu Tashiro and Shozo Furumoto and Nobuyuki Okamura and Katsutoshi Furukawa and Hiroyuki Arai and Ren Iwata and Etsuro Mori and Kazuhiko Yanai},
doi = {10.1016/j.jns.2015.06.029},
issn = {1878-5883},
year = {2015},
date = {2015-09-01},
journal = {J Neurol Sci},
volume = {356},
number = {1-2},
pages = {124--128},
abstract = {OBJECTIVES: In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery.
MATERIALS & METHODS: Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery.
RESULTS: Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH.
CONCLUSIONS: The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery.
MATERIALS & METHODS: Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery.
RESULTS: Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH.
CONCLUSIONS: The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.
MATERIALS & METHODS: Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery.
RESULTS: Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH.
CONCLUSIONS: The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.
Shidahara, Miho; Watabe, Hiroshi; Tashiro, Manabu; Okamura, Nobuyuki; Furumoto, Shozo; Watanuki, Shoichi; Furukawa, Katsutoshi; Arakawa, Yuma; Funaki, Yoshihito; Iwata, Ren; Gonda, Kohsuke; Kudo, Yukitsuka; Arai, Hiroyuki; Ishiwata, Kiichi; Yanai, Kazuhiko
Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain Journal Article
In: Nucl Med Biol, vol. 42, no. 9, pp. 734–744, 2015, ISSN: 1872-9614.
@article{pmid26093494,
title = {Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain},
author = {Miho Shidahara and Hiroshi Watabe and Manabu Tashiro and Nobuyuki Okamura and Shozo Furumoto and Shoichi Watanuki and Katsutoshi Furukawa and Yuma Arakawa and Yoshihito Funaki and Ren Iwata and Kohsuke Gonda and Yukitsuka Kudo and Hiroyuki Arai and Kiichi Ishiwata and Kazuhiko Yanai},
doi = {10.1016/j.nucmedbio.2015.05.001},
issn = {1872-9614},
year = {2015},
date = {2015-09-01},
journal = {Nucl Med Biol},
volume = {42},
number = {9},
pages = {734--744},
abstract = {INTRODUCTION: The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain.
METHODS: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients.
RESULTS: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different.
CONCLUSION: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain.
METHODS: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients.
RESULTS: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different.
CONCLUSION: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.
METHODS: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients.
RESULTS: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different.
CONCLUSION: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.
Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Hiraoka, Kotaro; Watanuki, Shoichi; Shidahara, Miho; Miyake, Masayasu; Ishikawa, Yoichi; Matsuda, Rin; Inami, Akie; Yoshikawa, Takeo; Tago, Tetsuro; Funaki, Yoshihito; Iwata, Ren; Tashiro, Manabu; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka
[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease Journal Article
In: Eur J Nucl Med Mol Imaging, vol. 42, no. 7, pp. 1052–1061, 2015, ISSN: 1619-7089.
@article{pmid25792456,
title = {[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease},
author = {Ryuichi Harada and Nobuyuki Okamura and Shozo Furumoto and Katsutoshi Furukawa and Aiko Ishiki and Naoki Tomita and Kotaro Hiraoka and Shoichi Watanuki and Miho Shidahara and Masayasu Miyake and Yoichi Ishikawa and Rin Matsuda and Akie Inami and Takeo Yoshikawa and Tetsuro Tago and Yoshihito Funaki and Ren Iwata and Manabu Tashiro and Kazuhiko Yanai and Hiroyuki Arai and Yukitsuka Kudo},
doi = {10.1007/s00259-015-3035-4},
issn = {1619-7089},
year = {2015},
date = {2015-06-01},
journal = {Eur J Nucl Med Mol Imaging},
volume = {42},
number = {7},
pages = {1052--1061},
abstract = {PURPOSE: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer.
METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks.
RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex.
CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer.
METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks.
RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex.
CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.
METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks.
RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex.
CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.
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