We assessed the regional brain atrophy in mouse lemur primates from 4.7Tesla T2-weighted magnetic resonance images. Thirty animals aged from 1.9 to 11.3 years were imaged. Sixty one percent of the 23 animals older than 3 years involved in the study displayed an atrophy process. Cross sectional analysis suggests that the atrophy follows a gradual pathway, starting in the frontal region then involving the temporal and/or the parietal part of the brain and finally the occipital region. Histological evaluation of five animals selected according to various stages of atrophy suggested that extracellular amyloid deposits and tau pathology can not explain by themselves this atrophy and that intracellular amyloid deposition is more closely linked to this pathology. This Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript study suggests that most of the age-related atrophy occurring in mouse lemurs is caused by one clinical, evolving, pathological process. The ability to follow this pathology non invasively by MRI will allow to further characterize it and evaluate its relationship with neuropathological lesions that are involved in human diseases such as Alzheimer.

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Age-related regional cerebral atrophy was evaluated in a small lissencephalic primate, model of cerebral aging. Twelve mouse lemurs (Microcebus murinus), ages 1.9 -10.9 years (maximum life span: 12 years), were studied. 3D inversion-recovery fast spin-echo MR images (isotropic resolution ‫؍‬ 234 m) were recorded at 4.7 T with a surface coil actively decoupled from the transmitting birdcage probe. The surface coil-related sensitivity gradient was corrected by normalization with images from an agar and NaCl phantom. An automatic statistical segmentation technique based on a classification-maximization algorithm was tested on digital phantoms that mimicked the brain and applied to the 3D brain images. Segmented 3D maps that displayed gray matter, white matter, and cerebro-spinal fluid (CSF) voxels were computed. The ventricles and peri-encephalic spaces were categorized into 14 regions, defined on brain atlases on the basis of cytoarchitectural and anatomical criteria. The volume of CSF voxels belonging to each of these regions was calculated as an index of regional atrophy. Dilation of the mammillary fossa was an early event in the aging process. CSF accumulation within the occipital, parieto-temporal, temporal, and frontal ventral peri-encephalic spaces was particularly marked in the oldest animals that also displayed ophthalmologic alterations.Magn Reson Med 50:984 -992, 2003.