SignificanceCurrent clinical care following ischemic stroke provides intermittent assessments, potentially missing early detection of neurological deterioration. Optical imaging offers the potential for a continuous, portable alternative to the current combination of physical exams and radiological imaging. However, optical imaging technology has lacked the crucial combination of portability, resolution, and coverage required to assess spatially distributed brain function.AimHere, we present a proof-of-principle study that applies recent advancements in portable high-density diffuse optical tomography (HD-DOT) instrumentation and a functional connectivity analysis strategy to assess spatially distributed brain connectivity. Point-of-care brain health assessments with these tools may inform clinical care and our understanding of brain injury throughout acute stages of stroke recovery.ApproachWe measured spatially distributed cortical oxygenation with HD-DOT within the intensive care unit in N=13 patients with ischemic stroke within the first 72-h since last known normal. To assess brain function integrity, we developed a Similarity metric of functional connectivity (FC) through comparisons to FC in a healthy young adult population. To assess the sensitivity of this FC Similarity metric to disruptions caused by stroke, we compared these data with FC Similarity assessed in an older healthy cohort. We administered the NIH Stroke Scale to stroke patients to evaluate the potential of the FC Similarity metric to inform the severity of functional disruptions.ResultsThe FC Similarity metric applied to HD-DOT data in both acute stroke patients and healthy older controls exhibited a significant sensitivity to the presence of a stroke (Cohen’s d=1.5, p=1.2×10−3) and a significant relationship with the degree of neurological disruption as measured by the NIH Stroke Scale (R2=0.69, p=4.7×10−4).ConclusionsWe present a proof-of-principle for HD-DOT and the FC Similarity metric for assessing brain function during the acute stage of ischemic stroke recovery at the point-of-care.