Because the brain is enclosed in a rigid skull, an increase in intracranial pressure may impede cerebral blood flow (CBF) and lead to cerebral ischemia. Continuous intracranial pressure (ICP) monitoring is recommended in a wide range of disorders, including traumatic brain injury (TBI), intracerebral and subarachnoid hemorrhage, hydrocephalus, benign intracranial hypertension, meningitis, stroke, acute liver failure, etc. The gold standard technique for ICP monitoring is done using an intracranial catheter connected to a pressure transducer. This invasive technique carries risks of hemorrhage and infection. Noninvasive monitoring of ICP will avoid complications and be helpful as a screening tool in the management of patients when invasive ICP monitoring is not immediately available, and will aid in identifying patients who may need invasive monitoring. Current non-invasive methods are less accurate than the invasive methods and are not suitable for continuous monitoring. The transcranial Doppler ultrasonography (TCD) pulsatility index (PI) depend on the interplay between cerebrovascular resistance (CVR), cerebral perfusion pressure (CPP), pulse amplitude of arterial blood pressure (pABP), compliance of the cerebral arteries and heart rate. As a result PI is not an accurate estimator of ICP. While near-infrared spectroscopy (NIRS) can monitor cerebral blood volume (CBV) and hemoglobin oxygenation (SO2) continuously at the bedside, ICP correlates only loosely with its indirectly derived estimates of cerebrovascular reactivity and cerebral blood flow, and without sufficient independence from other hemodynamic parameters to provide an accurate ICP surrogate. We propose to use an alternative non-invasive optical method, diffuse correlation spectroscopy (DCS), to measure pulsatile cerebral blood flow (pCBF), and from that to estimate ICP, CPP and CVR. The concept is based on the principle that the pressure-axis intercept in the pulsatile pressure-flow relationship curve, i.e. the criticl closing pressure (CrCP), is directly related to ICP. The main advantages of using DCS are that it directly measures blood flow, not blood flow velocity as TCD, or blood volume as NIRS, and it measures CBF in cortical microvessels which have lower tension and are more passive and susceptible to pressure changes than large arteries as measured with TDC. The challenge is to measure DCS signals fast enough to detect the pulsatile BF. The purpose of this R21 is to perform proof-of-principle studies to demonstrate our ability to measure ICP using DCS.
Our specific aims are: 1) Develop a DCS device able to measure an index of pCBF; 2) In a small number of rats and neuro-ICU patients test the hypothesis that the DCS pCBFi measure can be used to estimate ICP, CPP and CVR. This initial feasibility study will provide motivation for larger studies. This method has the potential to overcome the limitations of present non-invasive and non-viable alternative ICP monitoring methods.

Public Health Relevance

To manage severe brain injury continuous intracranial pressure (ICP) monitoring using an intracranial catheter is recommended. We propose a novel non-invasive optical method, diffuse correlation spectroscopy, to measure pulsatile cerebral blood flow, and from that to estimate intracranial pressure. This method will avoid complications arising from insertion of invasive catheters, and has the potential to overcome the current limitations of non-invasive and non-viable alternative ICP monitoring methods developed to date.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Biomedical Imaging Technology Study Section (BMIT)
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Koenig, James I
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Massachusetts General Hospital
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Selb, Juliette; Wu, Kuan-Cheng; Sutin, Jason et al. (2018) Prolonged monitoring of cerebral blood flow and autoregulation with diffuse correlation spectroscopy in neurocritical care patients. Neurophotonics 5:045005
Tamborini, Davide; Farzam, Parisa; Zimmermann, Bernhard et al. (2018) Development and characterization of a multidistance and multiwavelength diffuse correlation spectroscopy system. Neurophotonics 5:011015
Roberts, Susan B; Franceschini, Maria Angela; Krauss, Amy et al. (2017) A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in Childhood. Curr Dev Nutr 1:
Boas, David A; Sakadži?, Sava; Selb, Juliette et al. (2016) Establishing the diffuse correlation spectroscopy signal relationship with blood flow. Neurophotonics 3:031412