White-matter diffusion fMRI
Currently brain functional MRI (fMRI) measurements rely upon coupling of hemodynamic response to functional activation and are restricted almost exclusively to gray matter. These standard BOLD (Blood Oxygen Level Dependent) fMRI techniques are not applicable in white matter due to intrinsic physiologic differences between gray and white matter. However, since a number of neurological disorders originate with white-matter pathology, a non-invasive functional MR imaging technique applicable to white matter would be a valuable basic neuroscience and clinical diagnostic tool.
Recently, we have developed a technique called diffusion fMRI and demonstrated its utility for detecting white-matter activation. A completely reversible stimulus-induced decrease in the apparent diffusion coefficient (ADC) was observed in the optic nerves of normal mice with the application of a flashing-light visual stimulus. This phenomenon likely results from the osmotic after-effects of repetitive nerve impulses through the axonal fibers. We are continuing these investigations, initially targeting studies in subjects (both mouse models and patients) with optic neuritis, a commonly-encountered symptom of multiple sclerosis. However, with appropriately designed stimulus paradigms, this technique may ultimately be applied for the non-invasive assessment of white-matter function in health and disease throughout the CNS.