Point of care and wearable biophotonics for characterizing tissue composition and metabolism

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications & trials

Abstract

Aberrations in tissue hemodynamics (i.e., blood flow, oxygenation, and oxygen metabolism) and tissue composition are observed in a wide variety of diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. In all such conditions, techniques that can characterize tissue hemodynamics and composition can improve strategies for early diagnosis, screening, and treatment-response monitoring. There are several clinically accepted ways to assess cardiovascular function, specifically pertaining to tissue metabolism and composition . Techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have been used for measuring blood flow through tissue. Additionally, MRI and dual X-ray absorptiometry (DXA) can be used to determine body composition and distinguish between lean and soft tissue. While these techniques can provide comprehensive cardiovascular assessments, they are also time- and resource-intensive and can only be accessed in a hospital setting. As a result, patients typically undergo such assessments only after the onset of severe symptoms. At-home technologies, while more accessible to the general public, are limited to relatively crude cardiovascular assessments such as heart rate, oxygen saturation, and blood pressure. As alterations in vascular health occur gradually over time, there is a need for technologies that can comprehensively assess tissue hemodynamics and composition at the point of care. To characterize tissue hemodynamics or composition in portable form factors, near-infrared spectroscopy (NIRS) techniques have emerged as lower-cost and non-invasive alternatives. Techniques such as diffuse optical spectroscopic imaging (DOSI) or spatial frequency domain imaging (SFDI) can quantify the concentration of hemoglobin, water, and bulk lipids. In addition to the compositional information that can be obtained, continuous measurements with these techniques can also assess tissue hemodynamics in terms of the delivery and consumption of oxygen by observing changes in oxy- and deoxy- hemoglobin concentration. While the techniques employ similar principles to measure similar information, they differ in terms of the field of view and depth of tissue interrogated. Another subset of NIRS techniques can quantify blood flow, which is necessary to more accurately characterize tissue metabolic activity. Technologies such as laser speckle imaging (LSI), laser Doppler flowmetry (LDF), and diffuse correlation spectroscopy (DCS) all measure fluctuations in intensity caused by light scattering events from moving particles such as red blood cells, in order to provide quantitative measure of blood flow. These different optical technologies are promising candidates to provide more comprehensive assessments of tissue metabolism and composition in a range of different measurement configurations. This enables our group to select optical modalities that best suit a given clinical context. We are currently working to translate these biophotonics technologies into a clinical setting and characterize the tissue composition and metabolism in multiple patient cohorts with different disease states. Current studies are being performed in collaboration with various groups in the NIH clinical center to evaluate changes in tissue metabolism and composition in response to different therapeutic interventions. Technology Development A multi-modal diffuse optical spectroscopic imaging (DOSI) system was developed for high-speed monitoring and wide-area mapping of tissue optics properties and hemodynamics. This work expands the capabilities of DOSI to enable acquisition of metabolic, compositional, and pulsatile information at multiple penetration depths in a single hardware platform. A 3D tracking system was also integrated to enable registration of the acquired data to the physical imaging area. One manuscript was published on this work. Ongoing efforts seek to miniaturize the platform, providing more accessibility at the point of care. Development is ongoing to advance a wearable laser speckle imaging (LSI) device capable of directly measuring both vascular blood flow and blood volume changes. This work seeks to improve upon previous iterations of the technology, improving the accuracy of the device over a larger range of flow speeds. Translational Research We have begun conducting human subject research utilizing our suite of optical technologies under the following protocols: NCT04510866 - Evaluation of the Safety,Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects with Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat This study led by Dr. Swee Lay Thein of NHLBI seeks to evaluate the drug Mitapivat for treating sickle cell disease. Optical biomarkers of blood flow and oxygenation will be compared to clinical assessments of cardiovascular function. To date, 9 subjects have been measured across 57 visits. NCT04595773 - COVID-19, Chronic Adaptation and Response to Exercise (COVID-CARE): A Randomized Controlled Trial This study led by Dr. Leighton Chan of the NIHCC will evaluate whether a rehabilitation exercise program can help people recovering from COVID-19. Standard clinical cardiovascular functions tests to evaluate recovery will be compared to optically obtained biomarkers. 9 subjects have currently received optical imaging across 12 visits. NCT03538639 Vascular Disease Discovery Protocol Led by Dr. Manfred Boehm of the NHBLI, this study follows individuals with diseases of the heart and/or blood vessels. Optical signals will be characterized in vascular disease and compared to standard clinical health tests. Optical measurements using our technologies have been made on 2 subjects to date.