Quantitative Laser Doppler Flowmetry

Sammanfattning: Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s.Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate.In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above.Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented.The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations.When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe.The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.