Göran Salerud

A mathematical analysis on the biological zero problem in laser Doppler flowmetry

The biological zero (BZ) problem is a critical issue inherent in laser Doppler flowmetry (LDF). It causes confusion when measuring low tissue blood flows. Many experimental studies have been done on the question of whether the BZ flux should be subtracted from the normally measured flux in various situations. However this problem can only be solved after a proper mathematical analysis. Only then can one clearly define and formulate what flux is truly meaningful in blood perfusion measurement and what movement generates the BZ flux and how can one correctly remove it. Following this motivation, the movement of moving blood cells (MBCs) is decomposed into a net translation and a random wandering based on in vivo observations. This important step leads to a clear definition of the BZ and net perfusion flux and reveals that subtraction of BZ flux from the normal flux will certainly cause an underestimation of the net flux. Using this decomposition, the relationship between the net, BZ and normal flux is established which leads to the correct formula to recover the net flux from the BZ and normal fluxes. This recovered net flux is shown to be bounded by the normal flux and the normal flux minus the BZ flux. Numerical studies, preliminary phantom model and clinical evaluations manifest that the new approach is more accurate and reasonable at measuring low net fluxes. In contrast, subtracting BZ flux causes a systematic underestimation of perfusion and is apparently inappropriate even from a methodological point of view. In addition to the novel BZ solution, a general density function of the speed of MBCs is given which is more faithful than the Maxwell density used in R. Bonner and R. Nossals paper (Appl. Opt., vol. 20, 1981). This general density function offers new possibilities for further theoretical developments in LDF.

Blood interference in fiber-optical based fluorescence guided resection of glioma using 5-aminolevulinic acid

Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.

Spatial frequency domain imaging using a snap-shot filter mosaic camera with multi-wavelength sensitive pixels

Spatial frequency domain imaging (SFDI) utilizes a digital light processing (DLP) projector for illuminating turbid media with sinusoidal patterns. The tissue absorption (μa) and reduced scattering coefficient (μ,s) are calculated by analyzing the modulation transfer function for at least two spatial frequencies. We evaluated different illumination strategies with a red, green and blue light emitting diodes (LED) in the DLP, while imaging with a filter mosaic camera, XiSpec, with 16 different multi-wavelength sensitive pixels in the 470-630 nm wavelength range. Data were compared to SFDI by a multispectral camera setup (MSI) consisting of four cameras with bandpass filters centered at 475, 560, 580 and 650 nm. A pointwise system for comprehensive microcirculation analysis was used (EPOS) for comparison. A 5-min arterial occlusion and release protocol on the forearm of a Caucasian male with fair skin was analyzed by fitting the absorption spectra of the chromophores HbO2, Hb and melanin to the estimatedμa. The tissue fractions of red blood cells (fRBC), melanin (/mel) and the Hb oxygenation (S02 ) were calculated at baseline, end of occlusion, early after release and late after release. EPOS results showed a decrease in S02 during the occlusion and hyperemia during release (S02 = 40%, 5%, 80% and 51%). The fRBC showed an increase during occlusion and release phases. The best MSI resemblance to the EPOS was for green LED illumination (S02 = 53%, 9%, 82%, 65%). Several illumination and analysis strategies using the XiSpec gave un-physiological results (e.g. negative S02 ). XiSpec with green LED illumination gave the expected change in /RBC , while the dynamics in S02 were less than those for EPOS. These results may be explained by the calculation of modulation using an illumination and detector setup with a broad spectral transmission bandwidth, with considerable variation in μa of included chromophores. Approaches for either reducing the effective bandwidth of the XiSpec filters or by including their characteristic in a light transport model for SFDI modulation, are proposed.

Acute skin trauma induces hyperemia, but superficial papillary nutritive perfusion remains unchanged

Superficial skin papillary capillaries with blood supply from a superficial vascular plexus and regulated by local metabolic needs supply oxygen and nutrients for epithelial cell proliferation. A deep vascular plexus regulated by autonomous nerves serves body thermoregulation. In healthy volunteers, we assessed circulatory effects of a standardized skin trauma by CAVM, DRS, and LDPM to assess the measuring depth of the three techniques and to describe the acute trauma effects on nutritive and thermoregulatory perfusion.