Norbert Zolek

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.

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

Wavelength-resolved measurements of fluorescence lifetime of indocyanine green

We study fluorescence lifetime of indocyanine green (ICG) using femtosecond laser and sensitive detection based on time-correlated single-photon counting. A time-resolved multichannel spectral system is constructed and applied for determination of the fluorescence lifetime of the ICG in different solvents. Emission properties of ICG in water, milk, and 1% intralipid solution are investigated. Fluorescence of the fluorophore of different concentrations (in a range of 1.7-160 μM) dissolved in different solutions is excited by femtosecond pulses generated with the use of Ti:Sa laser tuned within the range of 740-790 nm. It is observed that fluorescence lifetime of ICG in water is 0.166 ± 0.02 ns and does not depend on excitation and emission wavelengths. We also show that for the diffusely scattering solvents (milk and intralipid), the lifetime may depend on the dye concentration (especially for large concentrations of ICG). This effect should be taken into account when analyzing changes in the mean time of arrival of fluorescence photons excited in ICG dissolved in such optically turbid media.

Optical system based on time-gated, intensified charge-coupled device camera for brain imaging studies.

An imaging system for brain oxygenation based on a time-gated, intensified charge-coupled device camera was developed. It allows one to image diffusely reflected light from an investigated medium at defined time windows delayed with respect to the laser pulse. Applying a fast optomechanical switch to deliver the light at a wavelength of 780 nm to nine source fibers allowed one to acquire images in times as short as 4 s. Thus, the system can be applied in in vivo studies. The system was validated in phantom experiments, in which absorbing inclusions were localized at different depths and different lateral positions. Then, the decrease in absorption of the brain tissue related to increase in oxygenation was visualized in the motor cortex area during finger tapping by a healthy volunteer.

Laser-Doppler spectrum decomposition applied for the estimation of speed distribution of particles moving in a multiple scattering medium

Recently, a method for the estimation of speed distribution of particles moving in an optically turbid medium has been proposed. The method allows potentially absolute measurement of speed of the particles and can be applied in laser-Doppler perfusion measurements. However, the decomposition technique was limited to short source-detector separations for which the assumption that one photon is Doppler scattered not more than once is fulfilled. In the present paper we show a generalized decomposition technique in which photons can be scattered more than once. We show the theoretical background for decomposition in such a case. We apply a decomposition method for the analysis of laser-Doppler spectra obtained by Monte Carlo simulations. This analysis allows showing noise limits in which the technique can be effectively applied in analysis of measured spectra. We propose an approximated scattering model based on the assumption that for one photon consecutive Doppler scattering events occur on particles moving with the same speed, and we show that this approximation does not influence significantly the uncertainty of the resulting speed distribution. The proposed decomposition procedure is validated in measurements on a physical flow model. The decomposition procedure is also validated by analysis of spectra measured on a physical phantom using laser-Doppler flow meter (Oxford Optronix, UK). A diluted solution of milk was pumped through a tube fixed in an optically turbid material with speed varying from 0 mm s(-1) to 4 mm s(-1). We observed a linear relation between actual speed of milk solution and speed estimated from results of spectra decomposition.

Application of time-gated CCD camera with image intensifier in contactless detection of absorbing inclusions buried in optically turbid medium which mimics local changes in oxygenation of the brain tissue

The near infrared spectroscopy may be implemented using various optoelectronic techniques, however, most of them do not allow to carry out measurements at short source-detector separation. We propose a method, based on time-gated intensified CCD camera, which allows for contactless measurements and can be carried out at short source-detector separation. This technique was tested on a phantom with absorbing inclusions buried in an optically turbid medium which mimics local changes in oxygenation of the brain tissue.

Multiwavelength time-resolved detection of fluorescence during the inflow of indocyanine green into the adult’s brain

Optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for clinical assessment of brain perfusion in adults at the bedside. Methodology of multiwavelength and time-resolved detection of fluorescence light excited in the ICG is presented and advantages of measurements at multiple wavelengths are discussed. Measurements were carried out: 1. on a physical homogeneous phantom to study the concentration dependence of the fluorescence signal, 2. on the phantom to simulate the dynamic inflow of ICG at different depths, and 3. in vivo on surface of the human head. Pattern of inflow and washout of ICG in the head of healthy volunteers after intravenous injection of the dye was observed for the first time with time-resolved instrumentation at multiple emission wavelengths. The multiwavelength detection of fluorescence signal confirms that at longer emission wavelengths, probability of reabsorption of the fluorescence light by the dye itself is reduced. Considering different light penetration depths at different wavelengths, and the pronounced reabsorption at longer wavelengths, the time-resolved multiwavelength technique may be useful in signal decomposition, leading to evaluation of extra- and intracerebral components of the measured signals.

Experimental estimation of the photons visiting probability profiles in time-resolved diffuse reflectance measurement

A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

Performance assessment of time-domain optical brain imagers: a multi-laboratory study

Novel protocols were developed and applied in the European project “nEUROPt” to assess and compare the performance of instruments for time-domain optical brain imaging and of related methods of data analysis. The objective of the first protocol, “Basic Instrumental Performance”, was to record relevant basic instrumental characteristics in a direct way. The present paper focuses on the second novel protocol (“nEUROPt” protocol) that was devoted to the assessment of sensitivity, spatial resolution and quantification of absorption changes within inhomogeneous media. It was implemented with liquid phantoms based on Intralipid and ink, with black inclusions and, alternatively, in two-layered geometry. Small black cylinders of various sizes were used to mimic small localized changes of the absorption coefficient. Their position was varied in depth and lateral direction to address contrast and spatial resolution. Two-layered liquid phantoms were used, in particular, to determine depth selectivity, i.e. the ratio of contrasts due to a deep and a superficial absorption change of the same magnitude. We introduce the tests of the “nEUROPt” protocol and present exemplary results obtained with various instruments. The results are related to measurements with both types of phantoms and to the analysis of measured time-resolved reflectance based on time windows and moments. Results are compared for the different instruments or instrumental configurations as well as for the methods of data analysis. The nEUROPt protocol is also applicable to cw or frequency-domain instruments and could be useful for designing performance tests in future standards in diffuse optical imaging.

Optimization of real-time ultrasound PCIe data streaming and OpenCL processing for SAFT imaging

Our goal is to develop a complete ultrasound platform based on real-time SAFT (Synthetic Aperture Focusing Technique) GPU processing. We are planning to integrate all the ultrasound modules and processing resources (GPU) in a single rack enclosure with the PCIe switch fabric backplane. The first developed module (RX64) provides acquisition and streaming of 64 ultrasound channels. We implemented and benchmarked data streaming from the RX64 to the GPU memory and the SAFT image reconstruction on the GPU. A high system performance was achieved using hardware assisted direct memory transfers and pipelined processing workflow. The complete system throughput, including 128 channel data transfer at 16kS per line and low-resolution 256×256 pixel image SAFT reconstruction on a single Nvidia K5000 GPU, reached 450 fps. The obtained results proved the feasibility of the ultrasound real-time imaging system with GPU SAFT processing.