Tracking brain volume changes in C57BL/6J and ApoE-deficient mice in a model of neurodegeneration: A 5-week longitudinal micro-MRI study

Magnetic resonance imaging (MRI)-based volume measurements of brain structu res are useful indicators of pending cognitive decline in humans suffering from neurodegenerative diseases. Transgenic mouse models that mimic the cli nical conditions of these disorders have been developed. Noninvasive method s that can follow progression and regression of relevant pathology in these mice are therefore in great demand. In this study we tested whether high-r esolution MRI (micro-MRI) in a mouse model of neurodegeneration (cerebral i schemia) could reliably track development of brain atrophy. We first establ ished that diffusion imaging at a spatial resolution of 1.6 X 10(-3) mm(3) allowed superior visualization of forebrain, ventricles, and dorsal hippoca mpus in the mouse brain compared to either T2*- or Tl-weighted MR imaging. Using this predetermined protocol we subsequently scanned C56BL/6J (C57) an d ApoE-deficient (ApoE(-/-)) mice before and after ischemia. Four groups we re studied: C57/sham (n = 9), ApoE(-/-)/sham (n = 9), C57/ischemia (n = 9), and ApoE(-/-)/ischemia (n = 11). All mice received a baseline 3D diffusion scan. One week later C57/ischemia and ApoE-/-/ischemia mice were exposed t o 10 min of ischemia and scanned again on the 3rd and 30th postischemic day . The C57/sham and ApoE(-/-)/sham mice served as controls and were scanned at corresponding time points. Diffusion images of ApoE(-/-)/ischemia mice o n the 3rd postischemic day revealed multiple localized high signal intensit y areas. An increase in ventricle and a decrease in dorsal hippocampal volu mes (which included the associated cortex laterally) at 30 days confirmed b rain atrophy in C57 mice after ischemia. Excessive mortality of ApoE(-/-)/i schemia mice restricted statistical analysis, but ventricle enlargement pos tischemia was demonstrated. Our results show that volume changes in the bra in of a 30-g mouse can be tracked by micro-MRI in a model of neurodegenerat ion. Clearly the ability to follow progression of pathology in mice will gr eatly aid our understanding of neurodegenerative diseases and facilitate th e many possibilities to intervene pharmacologically. (C) 2001 Academic Pres s.