Noninvasive Functional Biomarker for Early Detection and Continuous Monitoring of Microvascular Dysfunction

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Some people with a bacterial infection must be admitted to a hospital Critical Care Unit (CCU) because the infection caused an excessive inflammatory response, which resulted in organ failure. Doctors define this as sepsis. There is no cure other than administration of antibiotics and supportive therapies. Once a patient is diagnosed with sepsis, mortality rates are from 25 to 40%. Clinical evidence shows that early detection and aggressive treatment to maintain tissue oxygenation, reduces mortality significantly; however, there is no tool or blood test to diagnose the onset of sepsis other than evidence of organ failure and by then many organs have experienced severe injury. For those who survive, none fully recover and during the first year mortality rates remains high. Using animal models of sepsis our research shows that organ failure is due to injury to small blood vessels (microvasculature) that plugs 50% of capillaries so they no longer deliver oxygen (O2). This impairs the ability of the microvasculature to regulate O2 supply to meet O2 needs of the tissue. This microvascular injury is responsible for organ failure. Recently we discovered unique patterns of microvascular blood flow and oxygen levels that distinguish between a healthy and damaged microvasculature. We developed a simple non-invasive optical method to track this microvascular signature. Our goal is to detect the onset of micovascular injury before patients develop organ failure and to monitor whether treatment is restoring microvascular function. We have assembled a new team of researchers to develop the technology. Prototype devices will be made in our Facility for Advanced Biomedical Device Design and Fabrication, optimized in our Facility for Optics and Flow Simulation and validated in septic animals, healthy volunteers and finally on patients in CCUs. Early detection has the potential to save lives, reduce health care costs and place Canada as a global leader in the treatment of sepsis.