Yuguang Meng1 and Xiaodong Zhang1,2
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, 2Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory Univeristy, Atlanta, GA, United States
Synopsis
Conventional
diffusion tensor imaging (DTI) has been widely used to examine white matter connectivity
with neurological diseases but is limited in detecting pathways with crossing
fibers. As the crossing fibers are abundant in large and complicated brains
like human and non-human primate brains, the DTI tractography results may be
biased substantially. In stroke research, the integrity of corticospinal tract
(CST) plays a critical role in assessing the motor function. In this study, a compressed
sensing technique was explored to improve the CST delineation with conventional
DTI, and the feasibility was evaluated by using a monkey model of stroke.
Introduction
DTI
is a powerful tool to examine the white matter integrity and brain connectivity
but hindered by limited angular resolution to delineate the pathways with
crossing fibers. Although Q-ball imaging technique can resolve this issue by
using a large number of diffusion-encoding directions 1, its
application could be limited in preclinical and clinical studies due to increasing
scanning time and demand of high b values. The compressed sensing (CS) technique
has demonstrated its potential to improve the tractography of heathy human
brains scanned with traditional DTI and high angular resolution diffusion imaging
(HARDI) 2-3. As the corticospinal tract (CST) plays a critical role
in motor function and can be impaired by stroke, the stroke patients and animal
models are still widely scanned with traditional DTI 4. In the
present study, the compressed sensing technique was explored to assess the
detection ability of progressive alterations of the CST in the stroke monkey
brains scanned with conventional DTI.Methods
Healthy adult rhesus monkeys (n=4, 10-21 years
old) was induced with permanent middle cerebral artery (MCA) occlusion. DTI was
conducted on Day 0 (within 6 hours), Day 2 and Day 4 post occlusion on a 3T scanner. Animals were
sacrificed immediately after their last MRI scans for necropsy.
The DTI data were acquired with a single-shot EPI sequence with TE/TR = 80 ms/5
s, data matrix = 64 × 64, isotropic resolution = 1.5 mm, slice thickness = 1.5 mm,
30 gradient directions with b-value 1000 s/mm2. Structural T2-weighted
images were collected to identify the brain structure and infarction evolution.
DTI
data were analyzed with
conventional DTI tractography 5,
and further processed with the CS-based DTI approach (CS-DTI) by using the crossing
fiber angular resolution of intra-voxel structure (CFARI) algorism 3. A region-of-interest (ROI) was
separately placed in the left or right medulla manually drawn on the b0 diffusion-weighted
images, and the corticospinal fibers passing through each ROI were selected.
The tract volume of the CST was extracted for each hemisphere and examined
seperately. A two-way multivariate analysis of variance was performed for the
tract volume and the calculated fractional anisotropy (FA) in the CST
delineated with traditional DTI and
CS-DTI tractography, followed by post hoc comparisons between the two hemispheres
(contralateral vs. ipsilateral) or across all the time points (0, 2 and 4 days)
post stroke with Bonferroni correction.Results
The tractography
and statistical results were illustrated in Figure 1 and Figure 2 respectively.
By using conventional DTI tractography, reduction of the tract volumes in the
CST were seen in the ipsilateral hemisphere compared to those in the
contralateral hemisphere 4 days post occlusion (p < 0.05). Also, no
significant difference was observed in FA of the CST between the two hemispheres
at any time point post occlusion (p > 0.1). In contrast, by using CS-DTI
tractography, the tract volume reduction in the CST was observed 2 and 4 days
post occlusion (p < 0.05), and FA reduction in the CST was seen on 4 days
post-occlusion (p < 0.05). White matter lesion within or adjacent to the
infarct areas on Day 2 and Day 4 was verified with Luxol
fast blue stain 6.
With conventional
DTI, the tract volume of the CST in the ipsilateral hemisphere decreased
significantly from Day 0 to Day 4 post occlusion (p < 0.01), and no
significant FA change in the CST was seen between the time points post occlusion
(p > 0.05). In contrast, by using CS-DTI tractography, decrease of the tract
volume in the CST was observed from Day 0 to Day 2 post occlusion (p < 0.05),
and FA reduction was seen from Day 0 to Day 4 post occlusion as well (p <
0.01).
Discussion and Conclusion
The preliminary results demonstrated that the corticospinal fibers
missed by traditional DTI tractography could be substantially recovered by the
compressed sensing enhanced tractography approach. The tract volume and FA in
the CST derived from CS-DTI showed better sensitivity in detection of
early corticospinal fiber degeneration following stroke insult in the brain compared
to those from traditional DTI
tractography. In particular, our results showed the CST lesion could be
observed on Day 2 by examining the tract volume with CS-DTI while it was seen
on Day 4 with traditional DTI tractography,
suggesting the compressed sensing based fiber tracking approach may be useful
to enhance the assessment of the early damage or remodeling in the CST due to
stroke insult.
CST degeneration has been seen in stroke patients 7. Large animal
models like non-human primates (NHPs) show greater translational
potential in stroke research due to their similarity in brain anatomy and
physiology to human compared to rodent models, and DTI is still widely used in studies
of patients and animal models for its robustness and simplicity 8. Our
preliminary results suggest the CS-DTI tractography algorithm could improve the sensitivity
for detecting the CST injury in stroke brains and may be useful to exploit
the regular DTI data for comprehensively understanding the CST integrity in stroke
animals and patients and benefit the diagnosis of motor functions in the stroke
research.
Acknowledgements
No acknowledgement found.References
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