Despite the devastating global impact of ischemic stroke, there are few Food and Drug Administration (FDA) approved treatments, none of which are capable of regenerating or replacing infarcted brain tissue. Recently, our group demonstrated that induced pluripotent stem cell derived neural stem cells (iNSCs) are a regenerative and neuroprotective cell replacement therapy in an ischemic stroke porcine model that closely resembles human stroke pathophysiology. Historically, intracerebral stem cell transplantations have been largely guided by the injury site without taking individual neuroanatomical structures and their functions into consideration. Utilizing magnetic resonance imaging (MRI), the current study aims to identify key structures lesioned by a permanent middle cerebral artery occlusion (MCAO) that impact stroke recovery in a preclinical porcine model and determine an ideal transplantation location for future stroke iNSC transplant studies. A porcine MRI brain atlas was registered to identify stroke lesion location, and linear regressions between infarcted brain structures and functional data were completed to evaluate the predictive capacity of individual brain structure lesion on neurological outcome. MCAO resulted in prominent lesion volumes and decreased white matter integrity. Highly lesioned brain structures included the insular cortex, somatosensory cortices, visual cortices, temporal gyri, and putamen. MCAO severely impaired translational gait parameters, decreased voluntary movement in open field testing, and resulted in increased modified Rankin Scale (mRS) scoring. Linear regression analysis determined that lesions in the secondary visual cortex, claustrum, amygdala, and superior temporal gyrus were highly prognostic of overall gait and behavioral outcomes. This regression analysis approach identified neuroanatomical structures that were predictive of stroke outcome, and these structures may be key iNSC transplantation locations to facilitate optimal functional recovery.
Multiparametric classification of sub‐acute ischemic stroke recovery with ultrafast diffusion,
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Na, and MPIO‐labeled stem cell MRI at 21.1 T
