Differential Recovery of Multimodal MRI and Behavior after Transient Focal Cerebral Ischemia in Rats

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Abstract
The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T2-weighted (T2WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n = 6) or sham operation (n = 6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T2 lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 24 h after ischemia. Transient middle cerebral artery occlusion produced lesions on DWI and PWI, which fully recovered by 30 mins after reperfusion. Ipsilesional fMRI responses to hypercapnia and forepaw stimulation were significantly impaired after ischemia and did not fully normalize until 3 and 24 h after tMCAO, respectively. No abnormalities were observed on imaging or TTC at 24 h despite significant behavioral dysfunctions including contralesional forelimb impairment and ipsilesional neglect. No MRI, behavioral, or TTC anomalies were observed in sham-operated rats. There were no significant correlations between MRI parameters, behavior, and TTC in either group. Together, these results suggest that normal findings on diffusion, perfusion, and T2 imaging shortly after transient ischemia may not indicate normal tissue status as indicated by fMRI and behavior, which may help explain the persistence of neurologic deficits in patients with normal conventional MRI after cerebral ischemia.