Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation

Sammanfattning: The microcirculation, involving the smallest vessels in the body, is where the oxygen transport to all tissue occurs. Evaluating microcirculatory parameters is, therefore, important and involves the quantification of oxygen content of red blood cells (RBCs), the amount of RBCs and their speed.Diffuse reflectance spectroscopy (DRS) can be used to estimate blood oxygen saturation and fraction of RBCs in tissue since oxygenated and deoxygenated blood have different light absorption characteristics. By illuminating the skin with white light and detecting the spectrum of the backscattered light, tissue absorption and scattering can be assessed. Laser Doppler flowmetry (LDF) is a technique to measure blood flow in tissue. When laser light encounter moving objects in tissue, i.e. RBCs, the light is Doppler shifted, which can be detected and used to calculate tissue perfusion (the fraction of moving RBCs times their speed). With a small distance between light source and detector, both techniques measure superficially where most vessels are microcirculatory vessels. Photon transport in tissue can be simulated with Monte Carlo techniques and the simulations form the basis of modeled DRS and LDF spectra. The estimated microcirculatory parameters are given by the model that best describe measured DRS and LDF data.This thesis describes the development and the evaluation of an optical method to simultaneously measure oxygen saturation, RBC tissue fraction and speed resolved perfusion in absolute units by integrating DRS and LDF. By combining DRS and LDF into one system with a common tissue model, the two modalities can benefit from each other’s strengths. Different calibration methods and model assumptions for the system were evaluated in optical phantoms and in skin measurements. A simple calibration method with two detector distances for DRS was found adequate to accurately estimate absorption and scattering in optical phantoms. It was also necessary to model blood located in vessels, rather than homogeneously distributed in the skin, to obtain accurate parameter estimates. The system was evaluated in healthy subjects during standard provocations, where the parameters were in agreement with other studies and followed an expected pattern during the provocations. In patients with diabetes type 2, tissue fraction of RBCs and nutritive blood flow were reduced in baseline compared to healthy controls. These differences were not related to prevalence of microalbuminuria, a marker sign of microvascular complications in the kidneys.A combined system with DRS and LDF enables a more comprehensive assessment of the microcirculation by measuring oxygen saturation, RBC tissue fraction and speed resolved perfusion simultaneously and in absolute units. This system has clinical potential to assist in the evaluation of the microcirculation both in healthy and diseased individuals.