Differentiation of the Infarct Core from Ischemic Penumbra within the First 4.5 Hours, Using Diffusion Tensor Imaging-Derived Metrics: A Rat Model

Abstract

Objective: To investigate whether the diffusion tensor imaging-derived metrics are capable of differentiating the ischemic penumbra (IP) from the infarct core (IC), and determining stroke onset within the first 4.5 hours.

Materials and methods: All procedures were approved by the local animal care committee. Eight of the eleven rats having permanent middle cerebral artery occlusion were included for analyses. Using a 7 tesla magnetic resonance system, the relative cerebral blood flow and apparent diffusion coefficient maps were generated to define IP and IC, half hour after surgery and then every hour, up to 6.5 hours. Relative fractional anisotropy, pure anisotropy (rq) and diffusion magnitude (rL) maps were obtained. One-way analysis of variance, receiver operating characteristic curve and nonlinear regression analyses were performed.

Results: The evolutions of tensor metrics were different in ischemic regions (IC and IP) and topographic subtypes (cortical, subcortical gray matter, and white matter). The rL had a significant drop of 40% at 0.5 hour, and remained stagnant up to 6.5 hours. Significant differences (p < 0.05) in rL values were found between IP, IC, and normal tissue for all topographic subtypes. Optimal rL threshold in discriminating IP from IC was about -29%. The evolution of rq showed an exponential decrease in cortical IC, from -26.9% to -47.6%; an rq reduction smaller than 44.6% can be used to predict an acute stroke onset in less than 4.5 hours.

Conclusion: Diffusion tensor metrics may potentially help discriminate IP from IC and determine the acute stroke age within the therapeutic time window.

Keywords: Diffusion magnitude; Diffusion tensor imaging; Infarct core; Ischemic penumbra; Pure anisotropy.

Fig. 1. Serial L (A), q (B), FA (C), and T2WI (D) maps of rat for demonstrating spatiotemporal evolutions.

L and q maps showed significant hypointensities on ischemic lesion, while FA maps displayed initial elevation (red arrows) of ischemia with later reduction (white arrows) by 6.5 hours. T2WI showed progressively minor increased intensity in ischemia areas, over time. FA = fractional anisotropy, T2WI = T2-weighted imaging

Fig. 2. Temporal evolutions of rL (A), rq (B), and rFA (C) in cortical (left column), subcortical GM (middle column), and WM regions (right column), respectively.

^*Indicates significant difference between IP and NT (p < 0.05), ^†Represents significant difference between IP and IC (p < 0.05). Error bars are ± SEM. GM = gray matter, IC = infarct core, IP = ischemic penumbra, NT = normal tissue, WM = white matter

Fig. 3. ROC curves in discriminating IP from IC (blue curves) and NT (red curves) for cortical (A), subcortical GM (B), and WM (C) using rL values. Gray areas indicate range for eight rats.

GM = gray matter, IC = infarct core, IP = ischemic penumbra, NT = normal tissue, ROC = receiver operating characteristic, WM = white matter

Fig. 4. IC (red) and IP (green) regions defined by perfusion-diffusion mismatch (A) and proposed L-defined method (B) rat at 90 min after MCAo. 24 hr-T2WIs are also displayed to show final infarct regions (C).

Severe edema extending to normal hemisphere is observed in 24 hr-T2WIs. IC = infarct core, IP = ischemic penumbra, MCAo = middle cerebral artery occlusion, T2WI = T2-weighted imaging

Fig. 5. Relationship between rq value and time after stroke for cortical IC.

Solid curve represents empirical relationship, i.e., elapsed time = 1.636 x exp (-0.115 × rq value), estimated by nonlinear regression analysis. Red dashed lines indicate that 4.5-hr stroke onset can be identified by 44.6% reduction of rq value. Error bars are ± SEM. IC = infarct core