Date of Award

6-2026

Degree Name

MS in Biomedical Engineering

Department/Program

Biomedical Engineering

College

College of Engineering

Advisor

Trevor Cardinal

Advisor Department

Biomedical and General Engineering

Advisor College

College of Engineering

Abstract

Peripheral Artery Disease (PAD), caused by plaque buildup and narrowing of the arteries, reduces blood flow to the extremities. Promoting collateral arteriogenesis can help redirect blood flow. However, simple growth of collaterals may not be enough to reverse PAD. Instead, the ability for the collaterals to vasodilate and control blood flow is important, meaning assessing collateral function is important for the arteriogenesis assesment. Although microscopy techniques can measure vasodilation, contrast limitations in larger vessels such as collaterals make blood flow measurements difficult. Techniques such as ultrasound or magnetic resonance imaging (MRI) can measure blood flow but have limitations with cost or diameter resolution. The use of lasers to measure blood flow helps resolve these issues. Therefore, the studies in this thesis aimed to adapt two methods of measuring blood flow with lasers within the confines of the lab: Laser Doppler Flowmetry (LDF) using probes to measure frequency change of light and transillumination Laser Speckle Contrast Imaging (LSCI) using changes in laser speckle contrast. In the first study, transcutaneous LDF was used, but yielded inconsistent results that required protocol changes. The ability of the LDF to measure blood flow changes in exposed tissue were evaluated using acute and chronic mouse ischemia models caused by femoral artery ligation (FAL). The acute studies demonstrated that the LDF system could measure changes in left:right perfusion ratios of the saphenous artery and vein pre- (1.010 ± 0.024 and 1.125 ± 0.072, respectively) and post-ligation (0.157 ± 0.016 and 0.287 ± 0.003, respectively). The higher muscle perfusion ratio post-ligation (1.337 ± 0.071) vs. pre-ligation (1.125 ± 0.046) was likely in error based on studies showing reduction in muscle perfusion post-ligation and reveals a limitation of single point measurements. The acute studies also demonstrated that the LDF was not sterile, meaning serial measurements for the same mouse are not possible. The chronic studies showed that there was no difference between day 0 pre ligation (1.010 ± 0.024 and 1.125 ± 0.072, respectively) and day 7 post ligation (1.058 ± 0.029 and 0.972 ± 0.024, respectively) for the saphenous artery and vein. This creates an issue wherein the LDF measurements of saphenous vessel perfusion cannot be used to identify treatments that restore blood flow. Instead, increases in vessel flow can be used to assess treatments. The nearby skeletal muscle can help show the possibility of higher flow, as muscle perfusion day 7 post-ligation (1.458 ± 0.119) was higher than pre-ligation (1.125 ± 0.046) LSCI makes up for the sterility, single point measurement, and saphenous recovery issues of the LDF with its wide field of view, lack of contact with the tissue surface, and direct measurements of the collaterals. Initial tests of the transillumination LSCI system were performed with in vitro tissue phantoms to reduce costs before in vivo mice tests. The inconsistent results (linear and no relationship) of the tissue phantom revealed that alterations in the LSCI system were necessary. Further investigation into LDF measurement areas, and protocol adjustments to the LSCI system are needed to confirm if these two systems can reliably measure blood flow changes in the context of hindlimb ischemia

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