SBIR-STTR Award

Critically ill patients commonly arrive at an intensive care unit with anemia. While blood transfusions are the standard of care with the intention to increase or maintain oxygen delivery to tissues, questions have been raised about the benefit of blood transfusions, particularly in non-bleeding patients with moderate anemia. A noninvasive measure of intracellular PO2 is needed to evaluate the effect and efficacy of blood transfusions on tissue and organ oxygen sufficiency. Evidenced by the explosion of new pulse oximetry and near infrared spectroscopy (NIRS) devices on the market, optical spectroscopy is attractive for noninvasive tissue monitoring in many hospital settings. But we are not there yet - no existing clinical device has overcome the critical hurdle of accurately quantifying cellular biomarkers that are sensitive to oxygenation. We propose to develop a novel, noninvasive cell oximeter that will provide real-time measurement of myoglobin saturation from optical reflectance spectra. Intracellular PO2 will be calculated from myoglobin saturation using known myoglobin oxygen dissociation curves. Continuous intracellular PO2 measurement will allow unprecedented assessment of oxygen delivery and consumption. The specific aims of this proposal are to: 1) build a three-distance optical probe; 2) develop and validate measurement of myoglobin saturation in vitro; and 3) assess the benefit of RBC transfusion in an animal model. A new probe will be built to measure spectra from superficial, intermediate, and deep tissue regions from the surface of the rabbit hind limb. In Aim 2, Parallel Factor analysis (PARAFAC) models will be developed and tested with phantoms that model the rabbit hind limb. The phantoms will have known myoglobin and hemoglobin saturations and concentrations so that the accuracy of myoglobin saturation measurement can be objectively evaluated. Finally, in Aim 3, spectra will be acquired from rabbits subjected to hemorrhagic shock. These spectra will be used to calibrate in vivo PARAFAC models. The models will enable myoglobin saturation monitoring in real time from new spectra collected from rabbits with moderate anemia that will receive RBC transfusions. The study will answer two key questions: is tissue hypoxic during moderate anemia and if so, does RBC transfusion remedy the hypoxia? Intracellular PO2 monitoring with our new device will have broad implications in clinical practice and clinical research. We envision that intracellular PO2 monitoring will become a critical component in the care of patients with oxygen insufficiency, including those with sepsis, shock, and cardiac failure. Our long-term goal is to develop the cell oximeter for clinical use in ambulances, emergency departments, intensive care units, and operating rooms.

Public Health Relevance Statement:


Public Health Relevance:
This project will develop an optical medical monitor to assess cellular oxygenation in skeletal muscle. The approach analyzes spectral, or color changes from reflected light through the skin to determine how well oxygen is able to get into muscle cells, and will be used to assess the benefits of blood transfusions. This project will convert successful technology developed at the University of Washington into a clinically useful medical monitoring device. Measurement of muscle cell oximetry may prove very helpful to clinicians caring for anemic patients. (End of Abstract)

Project Terms:
abstracting; Accident and Emergency department; Algorithms; Ambulances; Anemia; Animal Model; base; Biological Markers; Blood; Blood capillaries; Blood Transfusion; capillary; Caring; Cells; Chemical Industry; Clinical; clinical care; clinical practice; Clinical Research; Color; Consumption; Critical Illness; Cytochromes; Decision Making; Devices; Dissociation; Erythrocyte Transfusion; Evaluation; experience; Explosion; Factor Analysis; Food Industry; Goals; Government; Heart failure; Hemoglobin; Hemorrhagic Shock; Hospitals; Hypoxia; In Vitro; in vivo; innovation; Intensive Care Units; Intention; Left; Light; Limb structure; Marketing; Measurement; Measures; Medical; medical specialties; Methods; Modeling; Monitor; monitoring device; Morbidity - disease rate; Mortality Vital Statistics; Muscle; Muscle Cells; Myoglobin; Near-Infrared Spectroscopy; novel; Operating Rooms; Optics; Organ; Oryctolagus cuniculus; Outcome; oxidation; Oxygen; Oxygen saturation measurement; Patient Care; patient oriented; Patients; Peripheral Vascular Diseases; Persons; phantom model; Physiologic pulse; prevent; public health relevance; Pulse Oximetry; Qualifying; Research; Sepsis; Shock; Skeletal muscle structure; Skin; Spectrum Analysis; standard of care; Standardization; Surface; Technology; Testing; Therapeutic; Time; Tissues; Training; Universities; Venous; Washington; Weight; Work

Clinical thresholds for blood transfusions vary by illness and medical specialty, and are largely based on anecdotal experience. Measured hematocrit is the most frequent determinant for clinical decisions to transfuse blood, often resulting in a one-size-fits-all approach. Although lifesaving at times, blood transfusions have also been clearly shown to increase morbidity and mortality. Thus, an objective measure of cellular oxygenation is needed to work toward a patient-centered approach to blood utilization. A noninvasive and continuous measurement of cellular oxygenation, as proposed in this application, will alert clinicians to the presence and degree of cellular hypoxia and help direct patient-specific clinical decisions. By measuring and analyzing full optical spectra in the visible and near-infrared regions at three source-detector separations, Opticyte's CellSat-100 will quantify myoglobin saturation in muscle cells separately from hemoglobin saturation in the vasculature. Since the goal of red blood cell (RBC) transfusion is to improve cellular oxygenation by increasing blood oxygen carrying capacity, decisions about whether a transfusion is needed would optimally be based on knowledge of pre-transfusion cellular oxygenation. If there is no cellular oxygen deficiency, a transfusion may be unnecessary. In our ongoing Phase I STTR project, we have demonstrated the feasibility of measuring cellular oxygen saturation (ScO2) in healthy adults. Our Phase II activities will center on demonstrating proof-of- concept for accurate, real-time measurement of ScO2 in healthy and critically ill adults. We will build a compact prototype device that can be easily used in a clinical setting. With the new prototype, we will perform a pilot study in an ICU of a major regional referral hospital in Seattle. The Specific Aims of this proposal are to: 1) confirm sufficient spectral quality and stability in our next- generation prototype, the CellSat-100; 2) evaluate the accuracy of real-time ScO2 measurements with the CellSat-100 in healthy adults during ischemia, and; 3) test the hypotheses that ScO2 increases following RBC transfusion, and that initial high ScO2 correlates with better patient outcomes in an ICU patient population. The CellSat-100 will provide unprecedented information about cellular oxygenation that has major implications for both research and clinical care. The long-term goal of the company is to market a noninvasive monitor that will provide robust and accurate measurements of ScO2. The device has broad applicability to critical care, and will be useful in ambulances, emergency departments, intensive care units, and operating rooms. The CellSat-100 will allow patient-specific clinical decisions to be made that prevent prolonged tissue hypoxia leading to improve clinical outcomes.

Public Health Relevance Statement:
PROJECT NARRATIVE This project will develop an optical device as a medical monitor to assess cellular oxygenation in skeletal muscle. The approach analyzes spectral, or color changes from reflected light through the skin to determine how well oxygen is able to get into muscle cells, and will be used to assess the benefits of blood transfusions. This project will convert successful technology developed at the University of Washington into a clinically useful medical monitoring device. Measurement of muscle cell oximetry may prove very helpful to clinicians caring for anemic patients.

NIH Spending Category:
Bioengineering; Clinical Research; Emergency Care; Hematology

Project Terms:
Accident and Emergency department; Admission activity; Adult; Ambulances; Animal Experiments; base; Blood; Blood capillaries; Blood Transfusion; Burn Trauma; capillary; Cardiac; Caring; Carrying Capacities; Cell Hypoxia; Cells; Clinical; clinical care; Color; Control Animal; Critical Care; Critical Illness; Data Set; Decision Making; detector; Devices; Erythrocyte Transfusion; Evaluation; experience; Explosion; Goals; Government; Hand; Hematocrit procedure; Hemoglobin; Hospital Referrals; Human; Hypoxia; improved; Intensive Care Units; Ischemia; Knowledge; Left; Length; Light; Marketing; Measurement; Measures; Medical; medical specialties; Modeling; Monitor; monitoring device; Morbidity - disease rate; mortality; Muscle Cells; Myoglobin; Near-Infrared Spectroscopy; next generation; Operating Rooms; optical spectra; Optics; Outcome; Oxygen; Oxygen saturation measurement; patient oriented; patient population; Patient-Focused Outcomes; Patients; Performance; Persons; Phase; Physiologic pulse; Pilot Projects; prevent; Process; prototype; Pulse Oximetry; Recovery; Research; Rest; Skeletal Muscle; Skin; Small Business Technology Transfer Research; Source; Spectrum Analysis; stroke; Technology; temporal measurement; Testing; Therapeutic; Time; tissue phantom; Tissues; Training; Transfusion; Universities; Venous; Washington; Work