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 structures are useful indicators of pending cognitive decline in humans suffering from neurodegenerative diseases. Transgenic mouse models that mimic the clinical conditions of these disorders have been developed. Noninvasive methods that can follow progression and regression of relevant pathology in these mice are therefore in great demand. In this study we tested whether high-resolution MRI (micro-MRI) in a mouse model of neurodegeneration (cerebral ischemia) could reliably track development of brain atrophy. We first established that diffusion imaging at a spatial resolution of 1.6 x 10(-3) mm(3) allowed superior visualization of forebrain, ventricles, and dorsal hippocampus in the mouse brain compared to either T2*- or T1-weighted MR imaging. Using this predetermined protocol we subsequently scanned C56BL/6J (C57) and ApoE-deficient (ApoE(-/-)) mice before and after ischemia. Four groups were 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 to 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 on the 3rd postischemic day revealed multiple localized high signal intensity areas. An increase in ventricle and a decrease in dorsal hippocampal volumes (which included the associated cortex laterally) at 30 days confirmed brain atrophy in C57 mice after ischemia. Excessive mortality of ApoE(-/-)/ischemia mice restricted statistical analysis, but ventricle enlargement postischemia was demonstrated. Our results show that volume changes in the brain of a 30-g mouse can be tracked by micro-MRI in a model of neurodegeneration. Clearly the ability to follow progression of pathology in mice will greatly aid our understanding of neurodegenerative diseases and facilitate the many possibilities to intervene pharmacologically.
McDaniel
B
B
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Sheng
H
H
Warner
D S
DS
Hedlund
L W
LW
Benveniste
H
H
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D001931:Brain Mapping; D002552:Cerebral Ventricles / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D007089:Image Enhancement; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008853:Microscopy; D019636:Neurodegenerative Diseases / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology
D001057:Apolipoproteins E