My research is focused mainly on changes in cerebral white matter integrity in normal and pathological aging and their impact on cognitive, behavioral, and functional decline in the elderly. I also have collaborated with other investigators at Brown to study white matter integrity in patients with psychiatric conditions and HIV infection. In addition, I have worked with colleagues in the Department of Computer Science to develop new methods for quantifying and visualizing higher order diffusion information derived from MRI data.
My neuroimaging efforts have focused on diffusion-tensor imaging (DTI), a magnetic resonance imaging (MRI) technique that provides indirect information about the microstructural integrity of white matter by measuring the magnitude and direction of water diffusion in cerebral tissue. DTI data can be displayed as two-dimensional maps of scalar parameters (i.e., no vector information), such as Trace (a measure of the magnitude of diffusion in an image voxel), and fractional anisotropy (a measure of the extent to which water diffusion is directionally restricted). These images can then be interrogated using either region-of-interest approaches or voxel-based methods to detect white matter differences between patients and healthy controls. DTI has repeatedly been shown to be sensitive to white matter changes that may fall below the threshold of detection on a conventional MRI. An alternative method of visualizing DTI data is to produce 3D models of white matter fibers. These computer-generated fibers can be interactively selected and measured for group comparisons a technique called quantitative tractography. The DTI work is done in close collaboration with David Laidlaw, Ph.D, and his colleagues in the Brown Department of Computer Science.
The majority of work to date has involved examining differences in frontal systems integrity and cognitive function in patients with mild cognitive impairment (MCI, or early Alzheimer's disease) and subcortical microvascular disease. Patients with MCI have impairments in memory and/or other cognitive functions but these do not produce sufficient functional decline to warrant a diagnosis of dementia. These patients are at increased risk for converting to Alzheimer's disease (or other forms of dementia) and there is evidence that those with executive cognitive impairment, which is supported by frontal systems, may be at greatest risk. DTI and detailed cognitive testing of frontal systems functions may be helpful for identifying these patients, who can then be targeted for more aggressive treatment.
The other main focus has been on patients with white matter injury from subcortical ischemic vascular disease. These patients have arteriosclerotic or other changes in the small arteries supplying the white matter and subcortical grey matter nuclei. These vessel changes can lead to hypoperfusive injury or completed lacunar infarction. The white matter injury is associated with cognitive dysfunction, particularly declines in speed of information processing and executive functions. My research on vascular white matter injury focuses on understanding the impact of disruption of specific white matter pathways on cognitive, behavioral, and functional impairment.
My work, particularly the focus on vascular white matter injury, is done at Butler Hospital in close collaboration with Stephen Salloway, M.D., professor of clinical neuroscience and Paul Malloy, Ph.D.. I work with other investigators at Brown including Ronald Cohen, Ph.D. who studies white matter injury in patients with HIV infection and with Benjamin Greenberg who studies patients with obsessive-compulsive disorder. I also work closely with Dr. Sean Deoni in the Department of Engineering who has a new MRI method for in vivo assessment of cerebral white matter myelin integrity.
A newly developing area of research is in blast-related traumatic brain injury.