Temporal evolution of diffusion indices in white matter and grey matter of macaque brains with ischemic stroke
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


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.


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.


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/mm2, 30 gradient directions, 1.5 mm isotropic resolution, 4 repetitions. Also, MR angiography (MRA), T1-weighted images, T2-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 T2-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.


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.


No acknowledgement found.


[1] Gillard, J.H et al. Br J Radiol (2011). [2] Lindenberg, R et al., Hum Brain Mapp (2012). [3] Bihel, E et al., Stroke (2011). [4] Munoz Maniega, S et al., J Neurol Neurosurg Psychiatry, (2004). [5] Wang, S et al., Stroke (2008). [6] Sorensen, A.G., et al., Radiology (1999). [7] Pamela W. Schaefer, A.K et al., Acute Ischemic Stroke Imaging and Intervention (2006). [8] M. M. Hirji et al., ISMRM (2010).


Temporal evolution of mean diffusivity (MD, figure a),axial diffusivity (AD, figure b), radial diffusivity (RD, figure c) and fractional anisotropy (FA, figure d) after stroke for grey matter (GM) and white matter (WM) in lesion (_stroke) and contralateral (_control) region.**, p<0.01; *, p<0.05; #,p=0.06 compared to contralateral region or corresponding baseline (Pre).

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)