Wolfson Family Laboratory for Clinical and Biomedical Optics Research Overview

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Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations, blood flow, and oxygen metabolism are desired. Measurements are made by placing near-infrared light sources and detectors on the tissue of interest. The sources shine light on the skin (~650-950 nm wavelength), and the detectors measure the intensities of re-emerging diffuse light exiting the tissue.

Diffuse optical spectroscopy (DOS) techniques use multispectral diffuse light to measure the concentrations of oxy- and deoxy-hemoglobin, water, and other light-absorbing tissue chromophores. The diffuse correlation spectroscopy (DCS) technique derives blood flow from speckle intensity fluctuations in the diffuse light induced by red blood cell motion.

Useful review articles:

The Wolfson family laboratory complements the work of other outstanding principal investigators in diffuse optics at CHOP, including Brian White, MD, PhD, Tiffany Ko, PhD, Rodrigo Menezes Forti, PhD, and Jennifer Lynch, MD, PhD. In addition, the laboratory collaborates broadly with clinicians to develop new clinical indications and diagnostics.

Some current research activities include:

The lab aims to optimize light detection schemes and other instrument hardware to increase signal-to-noise, measurement speed, and tissue depth sensitivity. Design work is also needed to improve the durability and clinical usability of optical devices, which will significantly impact the success of current and future clinical trials by enabling optical devices to be used reliably by clinical staff. Improved analysis algorithms for filtering motion artifacts, contamination from superficial tissues, and other artifacts in cerebral signals is another area of focus.

Elevated intracranial pressure (ICP) is a major cause of disability and death in numerous patient populations, including individuals with traumatic brain injury (TBI), hydrocephalus, and stroke. High pressure on the brain results in structural deformation and reduced delivery of oxygen. Timely treatment of dangerous ICP elevations is vital to prevent brain injury, but detection and treatment is challenging without knowledge of the patient's ICP.

A clinician at the bedside, or a medic in the field, does not typically know the patient's ICP because highly invasive devices are currently the only way to measure ICP—a bolt is inserted into the skull, and a sensor is pushed into the brain. Due to their complexities, these devices are typically not placed, or placed well after the initial injury, and many patients experience irreversible injury as a result of undetected, prolonged exposure to elevated ICP.

We are working on an optical method based on diffuse correlation spectroscopy (DCS) to non-invasively diagnose elevated ICP. The method exploits the ability of DCS to non-invasively measure pulsatile heart-beat fluctuations in microvascular cerebral blood flow. Using an electrical circuit analogy to model blood flow (current) through the cerebral microvasculature (resistor), ICP is calculated from the heart-rate pulsatility of cerebral blood flow and arterial blood pressure. Clinical and piglet model studies are underway in pediatric hydrocephalus and TBI to validate the optical diagnostic. Optical ICP is also being explored as a diagnostic of shunt failure in patients with hydrocephalus.

Much future work is needed to improve this diagnostic, such as boosting signal-to-noise of the blood flow pulsatility measurements, improving modeling of the flow through the whole arterial vascular tree, and leveraging multiple features in the blood flow and blood pressure waveforms to improve diagnostic accuracy.

Arterial stiffness is a major cause of a host of cardiovascular complications. Decreased vascular compliance, also called stiffening, affects the aorta and proximal elastic arteries and, to a lesser degree, cerebral and peripheral arteries. Stiffening leads to increases in pulse wave velocity through the arteries and increases in pulsatile pressure in the microcirculation. The latter, which can damage small blood vessels, is thought to be a major cause of small vessel disease, a disorder of the brain's small perforating arterioles and capillaries that cause brain lesions which are observable on brain imaging scans. Small vessel disease increases the risk of developing stroke and dementia.

An active area of interest is the development of biomarkers of cerebral arterial stiffness based on high-speed optical measurements of the morphology of pulsatile blood flow waveforms during the cardiac cycle.

Diffuse optics methods measure tissue properties relevant to critical care, including elevated intracranial pressure sensing. Other optical diagnostics under development include cerebral ischemia (i.e., not enough flow to the brain), hyperemia (i.e., too much flow to the brain), and adverse hypermetabolic conditions that increase risk of injury in critically ill patients (e.g., seizure, cortical spreading depression).

The team will work with animal models of critical care and patient populations with invasive neuromonitoring to develop and validate these diagnostics. Optics also has potential to measure cerebral tissue water volume fraction, which can be used as a biomarker of vasogenic edema (i.e., excess fluid accumulation resulting from blood-brain barrier disruptions) and lymphatic failure (i.e., the lymphatic system manages fluid levels in the body). Both avenues of investigations are clinically important future research directions.

Important work is needed on developing improved data-fitting approaches (e.g., based on Monte Carlo and finite element modeling of light transport) to account for the effects of tissue heterogeneity on diffuse optical cortical signals and improve diagnostic accuracy.

Similarly, there is substantial scope to improve the quantitative accuracy of diffuse correlation spectroscopy via a detailed understanding of the relation between diffuse correlation spectroscopy signals and vascular flow mechanics.

Finally, there are exciting opportunities to leverage multimodal hemodynamic data for developing advanced predictive models of brain injuries.