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Shinya Kagawa

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2 papers
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2

YNICL Journal 2019 Journal Article

Misery perfusion and amyloid deposition in atherosclerotic major cerebral artery disease

  • Hiroshi Yamauchi
  • Shinya Kagawa
  • Masaaki Takahashi
  • Naoya Oishi
  • Masahiro Ono
  • Tatsuya Higashi

Although experimental studies have shown that global cerebral hypoperfusion leads to amyloid deposition in the hemisphere with carotid artery occlusion in rodents, the results of such occurrence are controversial in humans. Hence, we aim to determine whether global cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increases in amyloid deposition in the hemisphere with atherosclerotic major cerebral artery disease in patients. We evaluated the distribution of β-amyloid plaques using positron emission tomography and a [18F]-pyridylbenzofuran derivative (18F-FPYBF-2) in 13 patients with unilateral atherosclerotic disease of the internal carotid artery (ICA) or middle cerebral artery (MCA) disease and no cortical infarction. The distribution volume ratio (DVR) of 18F- FPYBF-2 was calculated using dynamic data and Logan graphical analysis with reference tissue and was correlated with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and OEF, obtained from 15O-gas PET. The mean cortical value was calculated as the mean value within the frontal, posterior cingulate, precuneus, parietal, and lateral temporal cortical regions. Significant reductions in CBF and CMRO2 and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion compared with the contralateral hemisphere. There was no significant difference for 18F-FPYBF-2 DVR between hemispheres. The ipsilateral to contralateral ratio of the 18F- FPYBF-2 DVR was increased in 3 patients, while the ipsilateral to contralateral OEF ratio was increased in 4 patients. The incidence of an increased hemispheric DVR ratio was significantly higher in patients with an increased hemispheric OEF ratio (3/4) than in patients without (0/9) (p < 0. 02). Although the 18F- FPYBF-2 DVR in the ipsilateral hemisphere was positively correlated with OEF after adjustment for the 18F- FPYBF-2 DVR in the contralateral hemisphere using multiple regression analysis (p < 0. 05), the contribution rate of OEF was small (R2 = 5. 5%). Only one of the 4 patients with an increased hemispheric OEF ratio showed amyloid positivity based on the DVR value. In atherosclerotic major cerebral artery disease, misery perfusion accompanied only small increases of amyloid deposition at best. Misery perfusion was not associated with amyloid positivity.

YNIMG Journal 2013 Journal Article

Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with 18F-FAHA

  • Hsin-Hsien Yeh
  • Mei Tian
  • Rainer Hinz
  • Daniel Young
  • Alexander Shavrin
  • Uday Mukhapadhyay
  • Leo G. Flores
  • Julius Balatoni

Epigenetic modifications mediated by histone deacetylases (HDACs) play important roles in the mechanisms of different neurologic diseases and HDAC inhibitors (HDACIs) have shown promise in therapy. However, pharmacodynamic profiles of many HDACIs in the brain remain largely unknown due to the lack of validated methods for noninvasive imaging of HDAC expression-activity. In this study, dynamic PET/CT imaging was performed in 4 rhesus macaques using [18F]FAHA, a novel HDAC substrate, and [18F]fluoroacetate, the major radio-metabolite of [18F]FAHA, and fused with corresponding MR images of the brain. Quantification of [18F]FAHA accumulation in the brain was performed using a customized dual-tracer pharmacokinetic model. Immunohistochemical analyses of brain tissue revealed the heterogeneity of expression of individual HDACs in different brain structures and cell types and confirmed that PET/CT/MRI with [18F]FAHA reflects the level of expression-activity of HDAC class IIa enzymes. Furthermore, PET/CT/MRI with [18F]FAHA enabled non-invasive, quantitative assessment of pharmacodynamics of HDAC inhibitor SAHA in the brain.

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