In Vivo Neuronal Fiber Tract Mapping in Mouse Using Diffusion Tensor Imaging: Detection of Central Nervous System Phenotypes in Twitcher Mice

Introduction Diffusion weighted magnetic resonance imaging is capable of early detection of cerebral injury. The visualization of water diffusion anisotropy in cerebral white matters has made diffusion tensor imaging (DTI) a promising tool for non-invasive in vivo neuronal fiber tract mapping. Globoid cell leukodystrophy (GLD) is a familial neurologic disorder caused by a deficiency of the lysosomal hydrolase galactosylceramidase. Characteristic features of GLD include demyelination and infiltration of macrophages. Light and electron microscopy features of the brain and peripheral nerves of twitcher mice closely resemble those of GLD in humans. This mutant is important not only for investigation of the pathogenesis of, and therapeutic approaches to GLD, but also as a model of spontaneous demyelination. Scoring systems based on hyper-intensities of T2 weighted images have been used in the evaluation of the progression of GLD and the outcome of therapeutic interventions. However, such scoring systems retain a subjective element. In the present study, we applied diffusion tensor imaging to identify neuronal fiber tracts in normal and twitcher mice. Conspicuous radiographic phenotypes in the twitcher mouse brain were detected and quantified based on relative anisotropy.