An EPIC Approach to Understanding Multiple Sclerosis

The following was written by Roland Henry, Ph.D., a Debbie and Andy Rachleff Distinguished Professor in Neurology and Professor in the Department of Radiology and Biomedical Imaging at UCSF, and Christopher Hess, M.D., Ph.D., an Associate Professor in the Department of Radiology and Biomedical Imaging at UCSF.

UCSF’s Multiple Sclerosis (MS) Research Group, the Department of Radiology’s Neuroradiology Section, and the Surbeck Laboratory for Advanced Imaging are partnering to advance the state of the art for imaging of multiple sclerosis.

MS is a story that unfolds in four dimensions, three dimensions of space and one dimension of time.  The quantitative MRI techniques used by our groups allow us to study the disease in each of these dimensions with high precision.  EPIC, a large-scale, multi-factorial observational study that has been ongoing since 2004, has permitted us to study the course of the disease in patients over time.

EPIC is a paramount project of the MS Research Group that is run by Stephen Hauser, MD and Bruce Cree, PhD, MD, with geneticists, immunologists and other investigators from the MS Clinic.

The study began with a cohort of 500 patients with MS studied on an annual basis. The project is now in its eighth year.  Patients are evaluated using direct clinical interaction, laboratory and blood markers, and MRI. The overarching goal of the EPIC study is to examine the relationship between genes and MRI in terms of understanding disease progression, predicting disease course and uncovering new concepts regarding disease mechanisms.  This approach facilitates understanding of genetic disease modifiers and gene expression as well as more complex immunological markers of the disease.

Together with the Surbeck Laboratory, under the direction of Sarah Nelson, PhD, we are using 7 Tesla (7T) MRI in some patients. This ultra-high field scanner provides much higher spatial and spectral resolution than 3 Tesla (3T) MRI, allowing the visualization of abnormalities that are difficult or impossible to see at lower magnetic fields.  For example, using 7T MRI we are now consistently able to see the precise location of lesions with respect to tiny vessels, identify lesions within the gray matter of the brain, and use new contrast mechanisms to study disease activity.

Using the high spectral sensitivity of 7T spectroscopy, we are also able to specifically probe the activity of a neurotransmitter called glutamate, which seems to be elevated in MS patients and may mediate some of the destructive effects of the disease. Damage in MS is also reflected in immune system activity that can be imaged at 7T in the form of phase imaging, which detects aspects of MS lesions not seen on other MR images.  Another brain molecule of interest, glutathione, helps to combat damaging processes in the brain and is reduced in MS patients due to these disease-related mechanisms.  Glutathione can only be quantified at the ultra-high fields, and we are able to measure this molecule in the brains of MS patients at 7T.

Several other important findings have resulted from the EPIC study, including relationships among the distribution of lesions in the brain, relations to gray matter atrophy in the brain, and the identification of genes that seem to be involved in the disease progression.

The EPIC study was recently expanded to include spinal cord imaging, as MS also frequently affects the spinal cord. The spinal cord is a particularly important part of the story because it is very difficult to understand patient symptoms without knowing what is occurring in the cord and brain together. The expanded research activity was made possible by the gift of a 3T MR scanner.  This scanner is unique in being specifically optimized for and dedicated solely to research studies in MS patients. The new images from this scanner allow us to better determine neuronal injury and loss within the spinal cord.

The research that has developed out of projects like the EPIC and other studies is having a dramatic effect on how we look at and interpret scans.  This program illustrates the potential for collaborations between UCSF departments to achieve research excellence.  (Dr. Henry, for example, is a faculty member in both departments.) Neuroradiologists in the UCSF Department of Radiology and Biomedical Imaging are now tailoring clinical imaging protocols to focus more specifically on MS instead of the previous more generalized brain MRI protocols.  Matching the imaging to the disease process permits visualization of lesions that have not previously been seen as well as understanding of how individual patients are responding to disease-modifying drugs, thus ensuring the optimal care of patients with MS.