Abstract Body: Background: Early detection and intervention of cerebral ischemia is critical to improving patient outcomes. Optical brain pulse monitoring (OBPM) is a unique technique that offers non-invasive, continuous monitoring of brain hemodynamics via brain pulse waveform visualization. This method has the potential to identify ischemic changes and facilitate expeditious intervention. Here, we assessed OBPM signal changes during middle cerebral artery occlusion (MCAo) and following reperfusion in a clinically relevant sheep model to enable pre-clinical waveform characterization.

Methods: Eleven Merino wethers underwent MCAo for 4 hours followed by reperfusion for 6 hours. Brain tissue oxygen monitoring (PbtO₂; n=11) and OBPM (n=11) were performed in the MCAo hemisphere overlying the MCA territory, while intracranial pressure (ICP; n=11) and OBPM (n=6) were performed in the contralateral MCA territory. OBPM measurements were taken at baseline, MCAo, and following reperfusion. Magnetic resonance imaging (MRI) was used to measure infarct volume at 1 hour post reperfusion. Brain pulse waveforms were grouped into 5 classes by 3 blinded observers. Interrater agreement and frequency distributions were analyzed using Fleiss k and Fischer’s exact test, respectively. Generalized estimating equations (GEE) identified neuromonitoring changes (OBPM, StO₂%, PbtO₂, ICP) at each time point, adjusted with the Benjamini-Hochberg method.

Results: Observers were in moderate agreement (k=0.433; p<0.0001). Consensus classification of the OBP waveforms showed significant differences in the distribution of classes in the ipsilesional hemisphere over time (p=0.02), but not the contralesional hemisphere (p>0.99). One waveform class was observed only during MCAo. Reductions in brain pulse amplitude were found during MCAo when infarct volume was controlled for (p<0.05 for all time points). Slow wave activity was observed in the OBPM optical signal and was associated with changes in ICP and PbtO₂. OBPM StO₂% showed significant decreases in both ipsi- and contra-lesional hemispheres (p<0.001). A significant reduction in PbtO₂ (p< 0.001) was observed during MCAo.

Conclusion: MCAo was associated with distinct changes in the OBPM brain pulse waveform class and reductions in StO₂% in a sheep model. These findings demonstrate that the OBPM captures cerebrovascular signatures of MCAo identifiable by human observers or by a drop in StO₂%, providing an initial preclinical characterization of waveforms.