Neuroimaging of demyelination and remyelination models

Small-animal magnetic resonance imaging is becoming an increasingly utilized noninvasive tool in the study of animal models of MS including the most commonly used autoimmune, viral, and toxic models. Because most MS models are induced in rodents with brains and spinal cords of a smaller magnitude than humans, small-animal MRI must accomplish much higher resolution acquisition in order to generate useful data. In this review, we discuss key aspects and important differences between high field strength experimental and human MRI. We describe the role of conventional imaging sequences including T1, T2, and proton density-weighted imaging, and we discuss the studies aimed at analyzing blood-brain barrier (BBB) permeability and acute inflammation utilizing gadolinium-enhanced MRI. Advanced MRI methods, including diffusion-weighted and magnetization transfer imaging in monitoring demyelination, axonal damage, and remyelination, and studies utilizing in vivo T1 and T2 relaxometry, provide insight into the pathology of demyelinating diseases at previously unprecedented details. The technical challenges of small voxel in vivo MR spectroscopy and the biologically relevant information obtained by analysis of MR spectra in demyelinating models is also discussed. Novel cell-specific and molecular imaging techniques are becoming more readily available in the study of experimental MS models. As a growing number of tissue restorative and remyelinating strategies emerge in the coming years, noninvasive monitoring of remyelination will be an important challenge in small-animal imaging. High field strength small-animal experimental MRI will continue to evolve and interact with the development of new human MR imaging and experimental NMR techniques.