Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Diop, Mamadou

Abstract

Sepsis, an exaggerated immune response leading to multi-organ dysfunction, is responsible for 20% of global deaths, disproportionately affecting vulnerable and low-resource populations. Since early intervention is associated with increased survival, there is a need for accessible diagnostic technology. Microcirculatory impairment, manifesting as increased amplitude of vasomotion (i.e., low-frequency oscillations in microhemodynamics), occurs prior to systemic hypotension and organ injury. Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are non-invasive optical tools capable of continuously quantifying microvascular hemoglobin content, oxygenation, and perfusion at the bedside. The objective of this thesis was to monitor the skeletal muscle and brain using NIRS and DCS in a rat model of early sepsis. The results revealed that while the brain is partly protected, perfusion to the skeletal muscle drops and the amplitude of vasomotion increases. Importantly, this thesis demonstrated the feasibility of NIRS and DCS for detecting early sepsis-related changes in microcirculatory regulation.

Summary for Lay Audience

Sepsis is a life-threatening overreaction to infection, which causes 20% of deaths worldwide. Early recognition and intervention are crucial for patient outcomes; however, there are limited tools sensitive to the onset of sepsis and progression to organ injury. Since this condition predominantly affects vulnerable and low-resource populations, there is a global need for accessible tools to guide timely intervention. Importantly, such tools should be based on frugal technology capable of continuous, non-invasive monitoring in both remote settings and at the bedside in the clinic. Microcirculatory impairment, manifesting as reduced blood flow and imbalance between oxygen supply and demand, are thought to drive early sepsis-related tissue injury and organ dysfunction. Near-infrared spectroscopy (NIRS) is a promising, relatively low-cost tool for point-of-care microcirculation monitoring. This technology takes advantage of the unique absorption properties of hemoglobin, a protein in red blood cells (RBC) responsible for oxygen transport, to quantify its concentration. Furthermore, by monitoring the oxygenation state of the hemoglobin in tissue, NIRS can provide insight into the oxygen supply-consumption balance. Like NIRS, diffuse correlation spectroscopy (DCS) is another non-invasive, bedside tool for continuous assessment of the microcirculation. By monitoring the dynamics of RBC, DCS can directly quantify changes in blood flow. The purpose of this thesis was to evaluate markers of microvascular health detectable with NIRS and DCS at the onset of sepsis. We used an animal model to mimic the early stages of sepsis, collecting NIRS and DCS data from the brain and skeletal muscle. We found that before changes in tissue oxygenation, the skeletal muscle blood flow drops significantly, while brain oxygenation and blood flow is intact. We also showed that the skeletal muscle demonstrates exaggerated vasomotion, which is slow and rhythmic contraction-relaxation of the arterioles, and this phenotype can be detected as rhythmic fluctuations in microvascular markers detectable with both NIRS and DCS. Importantly, the findings of this thesis show that while the microcirculation in the brain is partly protected in the early stages of sepsis, microcirculatory impairment can be detected with NIRS and DCS in the skeletal muscle, potentially providing an accessible solution for triaging septic patients.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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