Serial Diffusion Tensor MRI After Transient and Permanent Cerebral Ischemia in Nonhuman Primates

Abstract

Background and Purpose-We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point. Methods-Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, nϭ4 or permanent occlusion, nϭ3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis. Results-Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes.Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling. Conclusions-Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates.

How Does Water Diffusion in Human White Matter Change Following Ischemic Stroke?

“…3). On the other hand, a gradual increase in SIT2 has been demonstrated in ischemic lesions, 10,12,[16][17][18]20 which is consistent with the decline of DR2 observed in our Phase 2 (Fig. 4).…”

“…Human and animal studies show a decline in diŠusion anisotropy from a few hours after stroke onset, 9,[13][14][15][16][17][18] which has been attributed to vasogenic edema, membrane degradation, and cell lysis. 19 In the same time period, gradual increase in signal intensity on T2-weighted images (SIT2) has been demonstrated in ischemic lesions.…”

“…19 In the same time period, gradual increase in signal intensity on T2-weighted images (SIT2) has been demonstrated in ischemic lesions. 10,12,[16][17][18]20 The increased SIT2 has also been attributed to vasogenic edema and an increase in extracellular water. 15 However, concomitant decline in <ADC> seems to be contradictory to vasogenic edema.…”

Monitoring ischemic cerebral injury in spontaneously hypertensive rats by diffusion tensor imaging

“…Likewise, studies in animal models have shown correspondence between DTI measures and behavioral outcomes (8,10,62). chronic stages after ischemic injury (7,15,32,53). In order to determine whether the decrease in FA we observed in the ipsilateral IC and EC was due to demyelination or loss of axonal fibers, we next determined the axial and radial diffusivity values in each region.…”

An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade

“…18,[23][24][25][26] In canine stroke models, pial collateral recruitment was reported to be influenced by the following factors: vascular dynamics, systemic blood pressure and so on. 18,27 Besides, the occlusion site and the size of thrombus also had a certain impact on the infarct volume.…”