Medical Student Research Fellowship for Summer 2006
Mentor: Dr. Michael D. Devous, Sr.
Department: Radiology / Nuclear Medicine Center
Room number: E6.120
Mail Code: 9061
Phone number: 214 648-3315
Project title: Various - see below
Human subjects IRB approved project number (where applicable):
N/A (student will be working with data already collected)
Animal subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Brief Description of Project:
1. Network systems in speech and language
Functional Brain Imaging has been used to study speech and language processing in normal controls and in cochlear implant subjects under a variety of conditions. These data provide insight into the disturbances in the neuroanatomical substrate of speech and language as modified by deafness and its restoration following cochlear implantation. This project will focus on identifying neural networks associated with successful speech perception in normal subjects and with a range of speech perception performance in cochlear implant patients.
2. Voxel-based morphometry of hippocampus in the diagnosis of Alzheimer's Disease
This project focuses on anatomic measures from very-high-resolution MRI images obtained at 3T to assess the degree of hippocampal atrophy present in patients relative to age-matched controls. In addition to ADC funding, the technical aspects of voxel-based morphometry are being co-developed with support from UTD and UTA engineering graduate students and with support form the Gulf War Syndrome project.
3. Volumetric measures of leukoariosis in the assessment of vascular risk factors for Alzheimer's Disease
Leukoariosis leads to changes on T2-weighted MRI images that provide evidence of white matter vascular disease. This process is thought to represent a significant risk factor in Alzheimer's Disease for more rapid progression and treatment resistance. Quantitation of the volume of leukoariosis is a new measure being examined for its negative prognostic value. In addition to ADC funding, the technical aspects of voxel-based morphometry are being co-developed with support from UTD and UTA engineering graduate students.
4. Post mortem volumetric MRI
One important activity of the ADC is post mortem examination of the brain in patients in the various clinical cohorts. It is of substantial interest to provide MRI images for measurement of both hippocampal atrophy and leukoariosis in donor brains for comparison to pathologic examination. Techniques to accomplish such imaging in ex vivo brains are being developed by the Neuroimaging Core with simultaneous support from UT Southwestern and UTD cognitive neuroscience graduate students as well as UTD and UTA engineering graduate students.
5. Diffusion Tensor Imaging and resting state fMRI to assess connectivity failure in Alzheimer's Disease
Diffusion tensor imaging is an important advance in MRI techniques that provides images of white matter tracts in vivo by measuring the directional tendencies of diffusion of water along myelinated fibers (anisotropy). Such tractograms provide evidence of alterations in structural connectivity between gray matter regions. In parallel, it is possible to measure the temporal and spatial covariance of the MRI signal in gray matter during resting-state fMRI as a means of assessing functional connectivity in living humans. Measures of both structural and functional connectivity are key to assessing the pathological sequelae of neuronal dysfunction in neurodegenerative disease. These new techniques are of substantial value in numerous functional brain imaging projects and thus their development is simultaneously sponsored by the ADC and by the Gulf War and Traumatic Brain Injury grants, as well as by graduate students from UT Southwestern, UTD and UTA.
6. Development of Arterial Spin Labeling MRI perfusion measures to assess vasodilatory reserve in Alzheimer's Disease
A major theme of the ADC is to measure the effects of underlying vascular disease on disease progression and response to putative therapeutic agents. One substantial means for assessing such effects is to measure the vasodilatory reserve, in a manner similar to cardiac stress imaging. This has been done for some time by Dr. Fred Bonte using SPECT and the cerebral vasodilator acetazolamide. It is of interest to determine if MRI perfusion techniques can be used in place of SPECT for both baseline and vasodilated rCBF studies. This project focuses on simultaneous MRI and SPECT studies (SPECT tracer injected during MRI and then imaged later) to validate the MRI techniques. The least invasive of the MRI perfusion techniques is referred to as Arterial Spin Labeling. This work is also supported by the ADC, Gulf War and Traumatic Brain Injury grants, as well as by graduate students from UTSW, UTD and UTA.
7. Evaluation OF Diffuse Axonal Injury in Patients with Traumatic Brain Injury Using Diffusion Tensor Imaging
The hyposthesis of this project is that a novel imaging technique, Diffusion Tensor Magnetic Resonance Imaging (DTI) is a more reliable indicator of Diffuse Axonal Injury (DAI) than standard structural MRI. Being able to identify specific subtypes of traumatic brain injury (TBI) may facilitate the design of clinical trials by stratifying patients more likely to respond to a given therapy and may be useful as a surrogate outcome measure.
8. Neuroimaging in the study of dopaminergic degeneration in Parkinsonian Syndrome
We have developed a three-dimensional quantitation scheme for the assessment of binding potential for a dopamine transporter imaging agent that will be used in the phase 3 trial (in collaboration with GE Healthcare, M. Devous, PI). Similarly, we are collaborating with Guilford Pharmaceuticals in a phase 2 and a phase 3 study of a novel neuroprotectant drug that could lead to nerve regeneration in Parkinsonian patients in combination with another dopamine transporter imaging agent (M. Devous and R. Dewey, co-PIs). These projects will explore quantitative analysis of dopamine transporter binding as a diagnostic agent, a marker of disease progression, and as a means to monitor response to therapeutic intervention.
Previous Research Activities or Publications with Medical Students:
I have an ongoing research program that involves a number of students and faculty. This has derived in part from students contacted in the following teaching environments:
1) Functional Brain Imaging, subsection of MS-4 Radiology, 1984- present
2) Functional Brain Imaging in Psychiatry, PGY-2 and 3 Psychiatry lectures, 1998-present
3) Course Director and faculty member: Advanced fMRI Training Course, January 2002.
4) Fundamentals of Functional Brain Imaging, graduate lecture course for the Radiological Sciences Program
5) Advanced Principles of Functional Brain Imaging, graduate lecture course
6) Laboratory Rotation, Functional Brain Imaging, Biomedical Engineering Program
7) Course Director and faculty member: The Brain Imaging Practica.
Further, I have had the following medical students and fellows working in my lab:
Robert W. Kowatch, M.D., Ph.D., Trained (1995-2000) as a consequence of a K07 training grant (K07-MH01057-01) (MD Devous, mentor) focusing on functional brain imaging studies of pediatric patients with mood disorders.
Madhukar H. Trivedi, M.D. Trained (1991-1994) in functional brain imaging (MD Devous, mentor) as a consequence of both a NARSAD fellowship and NIH/NIMH Minority Supplement to the MHCRC
John R. Debus, M.D. Trained (1988-1990) in functional brain imaging (MD Devous, mentor) as a consequence of a NARSAD fellowship.
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