Prolongation of the T2 relaxation time, an increase in T2-weighted signal intensity (T2-SI), and a decrease in the apparent diffusion coefficient (ADC) calculated from diffusion-weighted images (DWI) on magnetic resonance imaging (MRI) are conventional indicators of the vasogenic (interstitial) or cytotoxic (cellular) cerebral edema that develops after ischemic stroke. However, these parameters obtained on stroke imaging have not given us a precise threshold at which we can determine the viability or vulnerability of the tissue, allowing us to decide on an intervention that will help reversible tissue in the acute phase. Here, we introduce a new indicator-the essential diffusion coefficient or EDC, calculated from the T2-SI and ADC-that permits detection of irreversible brain damage after induction of experimental, focal cerebral ischemia. Our three-vessel occlusion (3-VO) method (Yang et al. Eur Neurol 71:4-18, 2014) was applied to investigate early changes on 7-T MRI. In the 3-VO model, which targets only a part of the cortex, animals seldom die at least within 24 h. The T2-SI and the ADC value were monitored, starting at 60 min after reperfusion, and every 30-60 min, for 10 h after the induction of focal ischemia. The region of interest (ROI) was set in each of the following: (1) the ischemic core (the dead zone); (2) the medial border area (the dying/dead mixed zone, including the ischemic penumbra); (3) the lateral border area (the surviving zone after the ischemic stress, where the rCBF is above the threshold for death); and (4) The intact area (outside the ischemic zone). The diagnosis was made by histological analysis performed 24 h after reperfusion. Significant increases in the T2-SI were observed, in ROI-1 at 1 h, in ROI-2 at 2.5 h, and in ROI-3 at 4 h post-reperfusion (1.10, 1.11, or 1.11; > 1.10, respectively, p < 0.001). Significant reductions in the ADC were also observed in ROI-1, ROI-2, and ROI-3, at 1 h post-reperfusion (0.55, 0.52, or 0.58; < 0.60, respectively, p < 0.001), indicating that both types of cerebral edema develop simultaneously in the acute phase. In the EDC analysis, from 5.0 h post-reperfusion, the value in the dying/dead zone (ROI-1 and ROI-2) was consistently reduced to < 50%, showing repeated, significant differences from the value in the surviving zone (ROI-3). A reduction in the EDC to below 50% indicated irreversible tissue damage, with transformation to cerebral infarction. We could detect a sign of cerebral infarction (initial necrosis-like irreversible lesion) as early as 5.25 h after the onset of ischemia. Although the biological time that depends on the body weight must be different between mice and humans, the earliest irreversible tissue damage or tissue destruction (to have achieved the risk of hemorrhagic transformation) that progressed after invisible or silent cell death in the ultra-acute phase, seems to occur at a similar time point.
Keywords: Brain imaging; Cellular edema; Diagnosis; EDC; Irreversible tissue damage.