Cerebral microcirculation mapped by echo particle tracking velocimetry quantifies the intracranial pressure and detects ischemia

Zeng Zhang,Anush Sridharan,Todd J. Kilbaugh,Joseph Katz,Misun Hwang

doi:10.1038/s41467-022-28298-5

Abstract

Affecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP). It is the leading cause for brain surgery in newborns, often causing long-term neurologic disabilities or even death. Since conventional invasive ICP monitoring is risky, early neurosurgical interventions could benefit from noninvasive techniques. Here we use clinical contrast-enhanced ultrasound (CEUS) imaging and intravascular microbubble tracking algorithms to map the cerebral blood flow in hydrocephalic pediatric porcine models. Regional microvascular perfusions are quantified by the cerebral microcirculation (CMC) parameter, which accounts for the concentration of micro-vessels and flow velocity in them. Combining CMC with hemodynamic parameters yields functional relationships between cortical micro-perfusion and ICP, with correlation coefficients exceeding 0.85. For cerebral ischemia cases, the nondimensionalized cortical micro-perfusion decreases by an order of magnitude when ICP exceeds 50% of the MAP. These findings suggest that CEUS-based CMC measurement is a plausible noninvasive method for assessing the ICP and detecting ischemia.

Highlights

Affecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP)
These findings suggest that a parameter that accounts for the cerebral micro-perfusion, including the density of micro-vessels and the velocity in them, could be used as a potential marker for ICP and ischemia associated with hydrocephalus
When the lactate to pyruvate (L/P) ratio obtained from cerebral microdialysis exceeds the ischemic threshold, there is a significant decrease in the cortical cerebral microcirculation (CMC)

Summary

Introduction

Affecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP). Animal studies have shown that the increased capillary resistance due to an elevated ICP causes non-nutritive thoroughfare channel shunt flow, which leads to tissue hypoxia[20] These findings suggest that a parameter that accounts for the cerebral micro-perfusion, including the density of micro-vessels and the velocity in them, could be used as a potential marker for ICP and ischemia associated with hydrocephalus. When the lactate to pyruvate (L/P) ratio obtained from cerebral microdialysis exceeds the ischemic threshold, there is a significant decrease in the cortical CMC These findings suggest that the CEUS-based CMC measurements could potentially serve as a noninvasive tool for evaluating the ICP level and detecting brain ischemia in neonatal hydrocephalus

Methods

Results

Conclusion