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
E-mail: Michael.Devouos@UTSouthwestern.edu
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):
N/A
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)
patient based
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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