Chun-Xia Li1, Yumei Yan1, Frank Tong2, Doty Kempf1, Stuart Zola1,3,4, Leonard Howell1,3, and Xiaodong Zhang 1
1Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, 2Department of Radiology, School of Medicine, Emory University, Atlanta, GA, United States, 3Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, United States, 4Atlanta Veterans Affairs Medical Center, Decatur, GA, United States
Synopsis
In the present study, adult
macaque monkeys were utilized to characterize the temporal changes of
DTI-derived diffusion indices in grey matter (GM) and white matter (WM) after
ischemic stroke. Our reults showed that mean diffusivity (MD), radial diffusivity (RD) and axial Diffusivity (AD) decreased
significantly in GM and WM immediately
post stroke while fractional
anisotropy (FA) remained unchanged until 48-hour post stroke. The results demonstrate the sensitivity and
robustness of MD, AD and RD to access the ischemic injury of GM and WM during
hyperacute stroke, and also reveal the temporal evolutiom of the WM and GM
microstructure following stroke onset.Introduction
Diffusion MRI is the most
sensitive and robust modality in stroke diagnosis [1-5],
and reveal different evolution pattern in grey matter (GM) and white matter
(WM) after stroke insult [4]. However, how the diffusivity indices changes during
hyper acute stroke, in particular in WM, remains not fully understood [6, 7]. In comparison with
rodents, non-human primates mimic most aspects of human neuroanatomy and are an
ideal model of stroke. Therefore, the purpose of the present study was to investigate the
temporal evolution of diffusivity indices in grey and white matter of monkey
brains after stroke insult.
Methods
Permanent
middle cerebral artery (MCA) occlusion was
induced in adult rhesus monkeys (n=5, 10-16 years old). The brain lesion was examined longitudinally with
diffusion tensor imaging (DTI) during the hyperacute phase (1-6 hours, n=5), 48
hours (n=4) and 96 hours (n=3) post occlusion. After the ischemic
occlusion surgery, animals were moved immediately into a 3T MRI clinical
scanner (MAGNETOM Trio, Siemens Healthcare) and scanned with a phased-array
8-channel knee coil (In vivo Inc., FL). DTI data was acquired with a
single-shot EPI sequence with the parameters: TR = 5000 ms / TE = 87 ms,
b-value = 1000 s/mm
2, 30 gradient directions, 1.5 mm isotropic
resolution, 4 repetitions. Also, MR angiography (MRA), T
1-weighted
images, T
2-weighted images were acquired for stroke lesion
validation purpose. In addition, each
animal received a pre-scan one week before surgery. Animals were sacrificed
immediately after their last
scans for histology. All the physiological parameters were recorded and
maintained in normal ranges. DTI data were prepared with the FSL software
(University of Oxford) for eddy-current distortion correction, co-registration,
acquired mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD)
and radial diffusivity (RD) maps and then processed with the Image J
1.49i software to define GM and WM regions of interest (ROIs). For each monkey,
the stroke-injured regions were identified with DWI images and MD maps and
cross-validated with corresponding T
2-weighted images. The white
matter bundles in the infarct territory were selected as ROI of WM. The ROIs in
stroke side and contralateral side is mirrored with each other. The results of pre-scan
and the corresponding contralateral side of each animal were used for
comparison purpose. The DTI-derived indices in the ROIs of lesion were compared
using repeated
ANOVA across each time point and paired t-test with contralateral side using
SPSS 22.0.
Results
The
temporal changes of MD (a), AD (b), RD (c) and FA (d) in grey and white matter of
macaque brains after stroke is shown in Figure 1. Compared to baseline or
contralateral side, MD, AD and RD of GM and WM decreased significantly after 2 hours
post stroke. In particular, AD of GM was reduced more than that of WM. The
recovery tendency in MD, AD and RD were seen 48 hours post stroke.
No obvious changes in FA of GM and
WM were seen during the entire hyper acute phase. Significant FA reduction was
observed 48 hours post stroke when compared to the contralateral side or baseline.
Discussion and conclusion
This study revealed the temporal
evolution of various diffusivity indices in ischemic GM and WM from 2 to 96
hours after stroke onset. Our results indicate that MD, RD and AD of GM and WM
are sensitive to the ischemic injury and all decreased significantly,
indicating concurrent degeneration processing in GM and WM during the hyperacute
phase. At 48 hours post stroke, the diffusivities started recovering while FA showed
significant reduction in WM and GM. As AD is more
related to axon integrity, its reduction may indicate the early response of
axonal degeneration during hyper acute stroke.
Also, AD and MD evolved very differently in GM and WM during hyper acute
stroke, indicating the tissue-specific difference after stroke insult, consistent
with previous clinical findings [4, 8].
In conclusion, the results demonstrate the
sensitivity and robustness of mean and axial diffusivities to detect the ischemic
injury of grey matter and white matter during hyperacute stroke, and also
reveal the temporal changes in grey and white matter following stroke onset.
Acknowledgements
No acknowledgement found.References
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