Roman Maniewski

Time-resolved optical imager for assessment of cerebral oxygenation

A time-resolved optical instrument allowing for noninvasive assessment of cerebral oxygenation is presented. The instrument is equipped with picosecond diode lasers, fast photodetectors, and time-correlated single photon counting electronics. This technology enables depth-resolved estimation of changes in absorption and, in consequence, assessment of changes in hemoglobin concentrations in the brain cortex. Changes in oxyhemoglobin (HbO(2)) and deoxyhemoglobin (Hb) can be evaluated selectively in extra- and intracerebral tissue compartments using the moments of distributions of times of flight of photons measured at two wavelengths in the near-infrared region. The combination of the data acquired from multiple sources and detectors located on the surface of the head with the depth-resolved analysis, based on the moments, enables imaging of cortex oxygenation. Results of the tests on physical phantoms as well as in vivo validation of the instrument during the motor stimulation experiment are presented.

Multichannel laser-Doppler probe for blood perfusion measurements with depth discrimination

The laser-Doppler method is frequently used in clinical experiments for blood perfusion measurement. A multichannel laser-Doppler probe was constructed, and calibrated and evaluated using a flow model and real examination of healthy subjects. Results obtained on a three-capillary flow model suggest that the probe can be used to obtain information from superficial and deeper layers of the tissue. The influence of the optical arrangement of the laser-Doppler probe on the parameters of post-occlusive reactive hyperaemia was investigated in a group of 15 healthy subjects. A statistically significant increase of biological zero with distance between emitting and detecting fibres was noted.

Performance assessment of time-domain optical brain imagers, part 2: nEUROPt protocol

The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.

Assessment of inflow and washout of indocyanine green in the adult human brain by monitoring of diffuse reflectance at large source-detector separation.

Recently, it was shown in measurements carried out on humans that time-resolved near-infrared reflectometry and fluorescence spectroscopy may allow for discrimination of information originating directly from the brain avoiding influence of contaminating signals related to the perfusion of extracerebral tissues. We report on continuation of these studies, showing that the near-infrared light can be detected noninvasively on the surface of the tissue at large interoptode distance. A multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The instrument was applied during intravenous injection of indocyanine green and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye in the tissue. Time courses of the statistical moments of distributions of times of flight of photons are presented and compared to the results obtained simultaneously at shorter source-detector separations (3, 4, and 5 cm). We show in a series of experiments carried out on physical phantom and healthy volunteers that the time-resolved data acquisition in combination with very large source-detector separation may allow one to improve depth selectivity of perfusion assessment in the brain.

Optimization of the Monte Carlo code for modeling of photon migration in tissue

The Monte Carlo method is frequently used to simulate light transport in turbid media because of its simplicity and flexibility, allowing to analyze complicated geometrical structures. Monte Carlo simulations are, however, time consuming because of the necessity to track the paths of individual photons. The time consuming computation is mainly associated with the calculation of the logarithmic and trigonometric functions as well as the generation of pseudo-random numbers. In this paper, the Monte Carlo algorithm was developed and optimized, by approximation of the logarithmic and trigonometric functions. The approximations were based on polynomial and rational functions, and the errors of these approximations are less than 1% of the values of the original functions. The proposed algorithm was verified by simulations of the time-resolved reflectance at several source-detector separations. The results of the calculation using the approximated algorithm were compared with those of the Monte Carlo simulations obtained with an exact computation of the logarithm and trigonometric functions as well as with the solution of the diffusion equation. The errors of the moments of the simulated distributions of times of flight of photons (total number of photons, mean time of flight and variance) are less than 2% for a range of optical properties, typical of living tissues. The proposed approximated algorithm allows to speed up the Monte Carlo simulations by a factor of 4. The developed code can be used on parallel machines, allowing for further acceleration.

Decomposition of a laser-Doppler spectrum for estimation of speed distribution of particles moving in an optically turbid medium : Monte Carlo validation study

A method for measurement of distribution of speed of particles moving in an optically turbid medium is presented. The technique is based on decomposition of the laser-Doppler spectrum. The theoretical background is shown together with the results of Monte Carlo simulations, which were performed to validate the proposed method. The laser-Doppler spectra were obtained by Monte Carlo simulations for assumed uniform and Gaussian speed distributions of particles moving in the turbid medium. The Doppler shift probability distributions were calculated by Monte Carlo simulations for several anisotropy factors of the medium, assuming the Hanyey-Greenstein phase function. The results of the spectra decomposition show that the calculated speed distribution of moving particles match well the distribution assumed for Monte Carlo simulations. This result was obtained for the spectra simulated in optical conditions, in which the photon is scattered with the Doppler shift not more than once during its travel between the source and detector. Influence of multiple scattering of the photon is analysed and a perspective of spectrum decomposition under such conditions is considered. Potential applications and limitations of the method are discussed.

Postocclusive Reactive Hyperemia in Healthy Volunteers and Patients With Peripheral Vascular Disease Measured by Three Noninvasive Methods

Postocclusive reactive hyperemia (PORH) was evaluated in three healthy volunteers and in three patients with different etiologies and suffering from peripheral arterial occlusive disease (PAOD). Three noninvasive methods were used: transcutaneous oximetry (TcPO2), near-infrared spectroscopy (NIRS), and laser Doppler flowmetry (LDF). Changes in perfusion and oxygenation of tissue were measured on foot before, during, and after arterial occlusion on thigh. Numerical parameters were derived from measured signals for quantification of the PORH response. Results of all three methods provided distinction between healthy volunteers and patients. The experimental optical techniques of NIRS and LDF demonstrated more clearly than the well-established TcPO2 method the difference between healthy volunteers and patients. The dynamics of the PORH response proved to be a better indicator of peripheral vascular disorder than the amplitude of responses.

Time-resolved detection of fluorescent light during inflow of ICG to the brain?a methodological study

It was reported that time-resolved reflectance measurements carried out during inflow and washout of an optical contrast agent may provide information on the blood supply to the brain cortex of human adults. It was also shown that a measurement of fluorescence excited in the dye circulating in the brain is feasible. Unfortunately, patterns of time-resolved fluorescence signals observed during in vivo measurements are difficult to interpret. The aim of this study was to analyze the influence of several factors on the fluorescence signals measured during in vivo experiments. A laboratory instrument for recording the distributions of arrival of fluorescence photons was constructed and optimized for measurements on humans. Monte Carlo simulations and laboratory measurements on liquid phantoms as well as in vivo measurements on healthy volunteers were carried out. An influence of source-detector separation, position of the source-detector pair on the head, as well as a dose of the injected indocyanine green (ICG) on the fluorescence signals were studied in detail. It was shown that even for a small dose of ICG (0.025 mg kg(-1)) the time-resolved signals can be successfully detected on the surface of the head. Strong influence of the studied factors on the fluorescence signals was observed. It was also noted that the changes in moments of distributions of arrival times of fluorescence photons depend on the anatomical structure of the tissues located between the source and the detector.

Advantages of fluorescence over diffuse reflectance measurements tested in phantom experiments with dynamic inflow of ICG

Time-resolved measurements of diffuse reflectance and fluorescence were carried out using phantom with dynamic inflow of indocyanine green (ICG) in tubes located at different depths. Better sensitivity of fluorescence signals related to the inflow of the dye was observed in comparison to simultaneously acquired diffuse reflectance. Obtained results can be referred to results of in-vivo measurements. We have observed much larger amplitude of changes in relative number of detected photons, mean time of flight and variance of the distributions of times of arrival of fluorescence photons than amplitudes of respective parameters measured from diffuse reflectance distributions of times of flight of photons. The constructed phantom allows us to study influence of concentration of the dye in the tube and the surrounding medium as well as temporal relation between appearance of the boli in deeper and superficial tube. Results of the study were used in optimization of the time-resolved multichannel system for simultaneous monitoring of fluorescence and reflectance.

A calibration standard for laser‐Doppler perfusion measurements

The objective of the present study was the development of a new calibration standard for the laser‐Doppler perfusion monitors. The beat frequency spectrum obtained from a solution of latex spheres undergoing Brownian motion was compared to that obtained from a porous polyethylene material containing the same solution. The mixture of static and dynamic scattering events in the latter case was expected to produce a spectrum similar to that obtained in the real human tissue. The results obtained demonstrate clearly the difference between the signals recorded from the commonly used motility standard which are the result of multiple Doppler shifting and homodyne mixing, and those generated from our enhanced model which predominantly result from single Doppler shifting and heterodyne mixing.