Abstract
BackgroundSpatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI ‘tissue signatures’, (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures.ResultsAn improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis.ConclusionThese exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.
Highlights
Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood
Stroke model Analysis was conducted on two macaques with permanent middle cerebral artery occlusion (MCAo) and two macaques with 3-h transient MCAo
Tissue classifications In the permanent MCAo group, 48 % of the voxels with abnormal tissue signature were assigned to the Core tissue class. 41 % of the voxels were initially normal but became abnormal by 17 days (Growth)
Summary
Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI ‘tissue signatures’, (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. Diffusion-weighted imaging (DWI) is sensitive for the early detection of ischemic tissue injury due to stroke, Bouts et al BMC Neurosci (2015) 16:91 rodents have intrinsically different stroke evolution patterns than primates [3], serial studies using gyrencephalic primates may potentially provide more representative insight into human stroke [4]. The final aim of this study was to compare the MRI-determined tissue signatures with histopathology
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