Longitudinal Magnetic Resonance Spectroscopy and T2 Measurements in a Mouse Model of Niemann-Pick Type C Disease

Introduction Niemann-Pick Type C (NPC) disease is a rare autosomal recessive neurodegenerative disease which involves impaired transport of intracellular lipids and accumulation of unesterified cholesterol in lysosomes and late endosomes in cells throughout the body [1]. NPC disease symptoms, including progressive ataxia, developmental dystonia, and dementia, often appear in the first decade of life, and the disease is often fatal by the end of the patient’s teenage years. No effective treatments are currently available, but several have been proposed and are in various stages of development and testing in animal models. Reliable and quantitative non-invasive imaging techniques that can track the progression and response to treatment of NPC disease will be valuable in both preclinical animal model studies and clinical studies. Abnormal myelination has been reported in a case study of clinical NPC disease using Diffusion Tensor Imaging (DTI) [2]. Dismyelination in a mouse model of NPC disease has been reported shortly after weaning at 23 days of age and quantified with DTI experiments [3], but required 3 hours of scan time. Magnetic resonance spectroscopy (MRS) has been used in studies of several mouse models of neurodegenerative diseases [4], and in clinical studies of Niemann-Pick Type C disease [5,6,7], but has not been reported in the NPC mouse model. In this work, a longitudinal study of T2 mapping and MRS measurements in a mouse model of NPC disease has been performed to examine T2 relaxation and brain metabolite levels as possible indicators of disease progression and response to therapy.