Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging

Abstract

Background and Purpose— Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. Methods— MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. Results— ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. Conclusions— The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes.

White matter T2 hyperintensities and blood‐brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin‐2

“…Other studys suggest white matter is particularly vulnerable to injury by SAH, possible via multiple mechanisms including ischemia and trauma . In experimental cerebral ischemia, T2‐hyperintensity lesions appear 24 hours after transient middle cerebral artery occlusion . In contrast, in experimental traumatic brain injury, T2‐hyperintensity lesions are already recognized at 6 hours after onset .…”

“…13,14 In experimental cerebral ischemia, T2-hyperintensity lesions appear 24 hours after transient middle cerebral artery occlusion. 15 In contrast, in experimental traumatic brain injury, T2-hyperintensity lesions are already recognized at 6 hours after F I G U R E 3 Subarachnoid hemorrhage (SAH) induced expression of lipocalin-2 (LCN2) in white matter in WT mice. A, Examples of LCN2 immunoreactivity in white matter 4 h after a sham operation or after an SAH with (T2+) or without (T2−) a white matter T2 hyperintensity.…”

Translational MR Neuroimaging of Stroke and Recovery

“…In these cases, secondary delayed injury often occurs within hours, resulting in another reduction of ADC [41–43]. Ultimately, ADC in the lesion core will recover above baseline on a time scale of days as a result of vasogenic edema and loss of membrane structure.…”

Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke

“…Magnetic resonance imaging (MRI) can be used to visualize and quantify the infarct volume at multiple time points after stroke ( 67 ). This method can be applied to both animal models and stroke patients, and is arguably far more accurate than the determination of infarct volume by immunohistostaining such as NeuN immunostaining or cresyl violet staining ( 68 , 69 ), which cannot be achieved in humans. Stroke cavity size can also be determined in order to evaluate whether a therapy is promoting repair after stroke injury.…”