Cerebral microvascular markers of intracranial pressure in acute and subacute porcine hydrocephalus model

Abstract

Hydrocephalus affects 1.1% of infants, resulting in abnormal accumulation of cerebrospinal fluid and elevated intracranial pressure (ICP). Elevated ICP can occur prior to detectable morphological changes using computed tomography, resulting in delayed diagnosis and treatment. To improve early diagnosis, we propose vascular imaging using ultrasound localization microscopy (ULM) and ultrafast Doppler to measure cerebral blood flow changes due to acute to subacute elevations in ICP. We performed a pre-clinical study on a neonatal porcine model with 30 min, 8 h, 12 h, and 24 h ICP elevations while performing brain ultrasound measurements in hourly intervals. Ultrafast plane-wave ultrasound imaging was implemented using the Verasonics Vantage-256 and GE IC59D curved array probe at 400Hz frame rate. Lumason contrast agent was infused into each animal, providing tracers for ULM and enhancing the ultrafast Doppler imaging. Based on preliminary analysis, ultrafast Doppler showed reduced total cerebral blood volume after acute ICP elevation. ULM showed highly correlated parabolic reductions in cortical microcirculation with increasing ICP. Drastic reductions in cerebral microcirculation but less so in microcirculation accompanied microdialysis evidence of brain ischemia. Additionally, there were spatiotemporal changes in cerebral microvascular flow with varying ICP durations that warrant additional investigations using ultrafast ultrasound imaging.