Neimann-Pick type C (NPC) disease is a genetic disorder affecting the intracellular trafficking and metabolism of cholesterol and shingolipids. This abnormality results in the acculmulation of unesterified choleterol within the cell which results severe neuronal degeneration in the brain. We are trying to develop novel brain MRI methodology that can be used to accurately and non-invasively detect the presence and progression of NPC disease. Such a methodology will allow for non-invasive, quantitative assessment of therapies aimed at arresting or reversing the effects of this disease and help speed development of therpies as well as add value to clinical trials.

Diffusion-Weighted MRI in NPC
The diffusion of water in brain tissue is extremely sensitive to the cellular architecture and integrity of the tissue. Because of this, diffusion-weighted MRI (DWMRI) can play a valuable role in the diagnosis, evaluation, and understanding of neurodegenerative diseases. In particular, Diffusion Tensor Imaging (DTI), which measures the anisotropy of water diffusion in the brain can be used to assess white matter integrity. Because of the dysmyelination characteristic of NPC disease, we are applying DTI methods to study NPC patients as well as a mouse model of the disease.

Quantitative T2 relaxation MRI in mouse models of NPC
T2 relaxation times are heavily influenced by the rotational mobility of water molecules in tissue. Water in myelinated white matter has restricted rotational mobility, compared to water in other brain tissue, and typically has very small values of T2. Deficient myelination will tend to increase the rotational mobility of water and therefor increase T2 times. Because of this, our lab is working on the development of novel radial MRI techniques and image reconstruction algorithms to rapidly and accurately measure T2 relaxation in brain tissue.

This work is funded by the National Institutes of Health grant EB000343 (National Institute for Biomedical Imaging and Bioengineering) and the Ara Parseghian Medical Research Foundation (APMRF).

Relevant Publications
Trouard et al. Diffusion tensor imaging in Niemann-Pick Type C disease. Pediatr Neurol. 2005
Ahmad et al. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann-Pick C mice. J Neurosci Res. 2005
Bascunan et al. Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C. J Appl Genet. 2004
Theilmann et al. View-ordering in radial fast spin-echo imaging. Magn Reson Med. 2004
Altbach et al. Processing of radial fast spin-echo data for obtaining T2 estimates from a single k-space data set. Magn Reson Med. 2005