Date of Award

January 2011

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

David Silverman

Subject Area(s)

Medicine

Abstract

The purpose of this investigation was to explore the spatial heterogeneity and assess the reliability of LDF in measuring blood flow. Among research techniques used to evaluate vascular blood flow, Laser Doppler flowmetry (LDF) is gaining prominence as a noninvasive measure of blood flow. Monochromatic light is delivered to the tissue under study, where it is frequency-shifted by moving red blood cells in proportion to the concentration of moving RBCs and their velocities. The resulting signal (in volts) provides a measure of RBC "flux" in 1 mm3 of tissue (the approximate volume monitored) per unit time (Johansson et. Al, 1991). Laser Doppler provides a powerful and noninvasive way to measure microvascuar flow.

Several investigators have recommended the use of LDF to monitor changes in perfusion in the perioperative period, specifically as may occur during cardiopulmonary bypass (Podgoreanu et. Al 2002), different disease states and vasoactive interventions (Mowafi, 2005). LDF has demonstrated potential in a wide variety of clinical situations. Primary care physicians may find it useful assessing peripheral vascular disease and treatment response in hypertensive and diabetic patients. In one investigation, LDF evaluation of lower limb blood flow was able to differentiate between healthy subjects and patients with known atherosclerosis (Kvernebo et. al.,, 1988). In 2006, Schonberger et al. used LDF to find a diminished response to vasoactive substances in diabetic subjects compared to healthy subjects, likely a reflection of decreased compliance due to peripheral vascular disease. Surgeons of various specialties may find LDF useful to measure perfusion. In selective devascularization of pig bowel, LDF was used intraoperatively to detect low flow rates that were predictive of subsequent ischemic necrosis (Krohg-Sorensenk et. al., 1992). In graft surgeries, such as flap or coronary bypass, LDF may be able to confirm effective perfusion and predict outcomes.

But LDF has been plagued by spatial heterogeneity which has limited its ability to reliably identify physiologic changes (Wardell et. al., 1994). In a prior study by a Yale medical student, spatial heterogeneity was significant enough to overshadow the vascular effects of experimental factors(Rose et. al., 2005). One problem lies in using a single channel to monitor the flow. The area monitored by one channel is too small to accurately depict flow because its field may not effectively encompass enough microvascular anatomy (Braverman et. al.,, 1992). The variability between arteriolar flow and venular flow is significant enough to confound measurements. Our lab has shown that single channel probe readings are associated with a day-to-day variability averaging 100% with a range of 20% to 300% in patients monitored with and without vasoactive challenges (Nissen et. al.,, 2006). Hence, this lab has experimented with custom designed Perimed (model) probes that have 7 different channels occupying a much larger area. Preliminary evidence indicates that day-to-day variability can be substantially reduced with a multi-channel probe. With a larger area comprised of juxtaposed fields, the probability of encompassing enough anatomy for accuracy is much higher. By averaging a range of data points we can acquire a more realistic picture of flow. In this study, we sought to reproducibly employ LDF by reducing spatial variability with a multi-channel Perimed probe. as a prelude to using this technique to evaluate the course of disease or the effects of medication.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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