量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Introduction Mild cerebral hypoperfusion events are relevant in aged individuals. It has been reported that decreased cerebral blood flow can accelerate Alzheimer's disease (AD) related pathologies but the underlying mechanism has been still unclear. Positron emission tomography (PET) visualizes various physiological conditions including amyloid beta(Abeta) deposition quantitatively. [11C]PIB is a PET imaging probe for Abeta plaques and PIB-PET can also detect the progression of Abeta amyloidosis with aging in living AD model mice1. Since [11C]PIB has adequate blood-brain barrier permeability2, rate constant for radiotracer delivery from plasma (K1) is considered to correlate with regional cerebral blood flow (rCBF). Thus Abeta deposition and rCBF can be evaluated simultaneously with a single PIB-PET scan, and application of this method to an AD animal model with local cerebral hypoperfusion would reveal the impact of lowered rCBF on the Abeta plaque formation. In this study, unilateral hypoperfusion model was made on wild-type mice, and PIB-PET scan was performed to evaluate target-to-cerebellum ratio of K1 (R1) as an index reflecting rCBF.
Methods All of the following animal procedures were performed under anesthesia with 1.5% (v/v) isoflurane. The left common carotid artery (lCCA) of a C57BL/6J mouse aged 10-33 weeks (n=13) was isolated from the adjacent vagus nerve and ligated with a 6-0 silk suture. Sixty-minute [11C]PIB-PET scans were performed 2 hours to 6 weeks after the surgery. Some mice underwent repeated PET scans twice or three times on different days to longitudinally monitor rCBF alternations. R1 was estimated by a simplified reference tissue model (SRTM) analysis3. To compare R1 with rCBF ratio to the cerebellum, a subset of mice underwent perfusion MRI with a 7T scanner on the same day of PET measurements.
Results and Conclusion Within 2 weeks after the surgery, [11C]PIB uptake was significantly decreased in the ipsilateral cerebral hemisphere. As there was no left-right difference in cerebellar radiotracer uptake, cerebellar rCBF was unlikely to be affected by the lCCA ligation. At 6 weeks, this difference between the ipsilateral and contralateral cerebral hemispheres was notably diminished. Though R1 values were underestimated by about 20% relative to rCBF ratios obtained from perfusion MRI data, they exhibited a reasonable correlation. The present data support that R1 can be used as an alternative to rCBF, and this method would be applicable to AD model mice.
\n1)Maeda J, et al., J Neurosci ; 27(41):10957-68, 2007
2)Bacskai BJ, et al., Proc Natl Acad Sci U S A.;100(21):12462-7, 2003.
3)Lammertsma AA, et al., Neuroimage ; 4 :153-8, 1996.
Evaluation of regional cerebral blood flow using [11C]PIB in unilateral cerebral hypoperfusion model mice
