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P4‐294: MR imaging of arterial dysfunction in a mouse model of Alzheimer's disease
Author(s) -
Grand'Maison Marilyn,
Ho MingKai,
Hebert Francois,
Bedell Barry
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.08.075
Subject(s) - magnetic resonance imaging , medicine , cerebral amyloid angiopathy , cerebral arteries , perivascular space , pathology , cerebral blood flow , nuclear medicine , perfusion , anatomy , radiology , cardiology , disease , dementia
Background: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) has demonstrated regional cerebral hypoperfusion in Alzheimer’s disease (AD) patients, as well as murine models of AD. It is well-recognized that cerebral arteries undergo microstructural changes in AD, including deposition of b-amyloid (i.e. cerebral amyloid angiopathy) and loss of smooth muscle cells, resulting in cerebrovascular dysfunction. While compromised arterial function can be assessed in mouse brain by several techniques, these methods are restricted to focal regions of the cortical surface. In order to assess the entire arterial system, we have employed a novel, non-invasive, quantitative approach based on in vivo 3D MRI data. Methods:MR image volumes were acquired from 3-5 month-old (young) and 18-20 month-old (aged) APP transgenic (TG) and wild-type (WT) mice. Whole-brain anatomical images and 3D MR arteriograms were acquired on a 7T animal MRI system. TheMRI data was processed using a fully-automated pipeline. In order to derive quantitative information from the arteriogram, we utilized a region-of-interest (ROI)-based approach. The ROI labels (vessel segments) were mapped from a standardized atlas in reference space to each mouse brain MRI volume in native space via atlas-based segmentation. We then derived a quantitative measure, the "arterial index", which is related to the apparent arterial cerebral blood volume (CBV a), for each ROI. Results: Young APP TG mice demonstrated significantly reduced arterial indices relative to WT mice in the distal segments of major cerebral arteries, including middle cerebral, posterior cerebral, and azygos pericallosal arteries (with the exception of the retrosplenial branch), while the proximal segments and the internal carotid were largely unaffected. The pterygopalatine artery demonstrated a higher arterial index in the young TG relative to WTmice. The retrosplenial branch of the azygos pericallosal artery showed greater age-related reduction in the arterial index in TG compared to WT mice. Conclusions: We have demonstrated regional differences in arterial function as a function of genotype (TG vs. WT) and age (young vs. aged). The arterial index may complement conventional ASL perfusion MRI measures, and could potentially serve as a powerful, novel imaging biomarker for the assessment of disease evolution and therapeutic intervention in pre-clinical and clinical studies.