<div>
<p> Essential
tremor (ET) is one of the most common movement disorders, characterized by
kinetic tremor in the upper extremities with additional cranial tremor often
present in the neck or jaw. While it is well established that ET is primarily a
cerebellar disorder, recent investigations have shown more widespread
pathological effects throughout the brain. Furthermore, the neurodegenerative
nature of ET is still disputed and requires additional investigation.
Additionally, the link between ET and Parkinson’s disease (PD) is of special
interest, as it can be challenging to clinically differentiate these diseases.</p>
<p> While
post-mortem studies have helped to further the pathological understanding of
these diseases, non-invasive in-vivo techniques allow for more accurate
diagnosis in the clinic. With a more accurate diagnosis comes a more targeted
treatment, and hopefully an improved remediation of the disease. My thesis
seeks to further investigate the neurodegenerative hypothesis of ET as well as
explore magnetic resonance imaging (MRI) biomarkers for potential differences
in ET and PD. </p>
<p>These aims will be accomplished in
three steps. First, gray matter volume loss in the cerebellum was investigated
using voxel-based morphometry and the Spatially Unbiased Infra-Tentorial
Template (SUIT) atlas on a lobule level. High resolution 3D T1-weighted MRI
images were acquired on 47 ET cases and 36 controls. The cerebellum was
segmented into 34 lobules using the SUIT atlas. Percent gray matter was
calculated as the ratio of lobule gray matter volume divided by total lobule
volume. No significant differences were identified between ET cases and
controls in any of the 34 lobules. However, nine lobules had significantly
decreased percent gray matter in ET cases with head or jaw tremor (n = 27)
compared to controls. Also, 11 lobules had significantly decreased percent gray
matter in ET cases with voice tremor (n = 22) compared to controls. This result
confirms, with increased regional accuracy, gray matter volume loss in the
cerebellum of ET cases.</p>
<p>Second, gray matter volume loss
beyond the cerebellum, in the cerebrum, was investigated using voxel-based
morphometry. High resolution 3D T1-weighted MRI images were acquired on 47 ET
cases and 36 controls for processing in SPM12. The processing steps of SPM12
were updated to include a higher resolution atlas and set of tissue probability
maps to optimize the segmentation and normalization of each subject image.
After segmentation, normalization, and smoothing, a voxel-wise statistical
analysis was performed to identify clusters of gray matter volume in ET cases
compared to controls. ET cases showed decreased gray matter volume in the
bilateral superior temporal region and the anterior and posterior cingulate
cortex. These results, in combination with previous work provide support of
wide-spread neurodegeneration in ET using optimized methodology.</p>
<p>Third, we applied T2* mapping to
determine relative iron concentrations in the substantia nigra (SN) and globus
pallidus (GP) in ET and PD cases. Three separate studies were independently
investigated to validate the reproducibility and detectability of group
differences using T2* mapping. The first study (ET study) acquired T2* maps on
21 ET cases and 12 matched controls, the second study (PD study 1) acquired T2*
maps on 10 PD cases and 7 controls, and the third study (PD study 2) acquired
T2* maps on 21 PD cases and 17 controls. Regions of interest (ROIs) were manually
placed in the SN and GP for each subject and group differences were calculated
independently for each study using a linear regression model with age and sex
as covariates. A significant decrease in T2* was found in PD study 1 and PD
study 2 in the right SN in PD cases compared to their respective controls,
indicating increased iron deposition. No significant difference was found in
the ET group compared to their respective controls in the SN. No significant
differences were found in any of the three studies in the GP. These results
provide evidence for a difference in brain iron regulation in the pathology of
ET and PD.</p>
<p>Together, these thesis aims provide
additional evidence in support of the neurodegenerative hypothesis of ET using
updated methodology and present a quantitative imaging difference between
groups of ET and PD cases. </p>
</div>
<br>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/8035598 |
| Date | 11 June 2019 |
| Creators | Eric M Cameron (6630587) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Differentiation_and_Evaluation_of_Disease_Progression_in_Essential_Tremor_Utilizing_MRI_Biomarkers/8035598 |
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