The determination of photon migration path is important for both near infrared spectroscopy and optical imaging. Time resolved measurement enables one to restrict the volume of tissue sampled since for instance, the early detected photons in a homogeneous medium tend to have migrated along the straightest line between the source and detector. In this study the distribution of time-resolved photon migration paths in a heterogeneous scattering media which includes a non-scattering layer is investigated by Monte Carlo simulation. In a heterogenous concentric circle model, the path distribution of the earliest detected photons lies along the boundary of the non-scattering layer whilst the distribution of photon migration paths for later arriving photons indicates penetration into deeper regions.

We compare two methods to evaluate the time dependence in Monte Carlo simulations of photon migration: sampling of the pulse response in time and evaluation of the transfer function at discrete points in the frequency domain. We show that these two methods differ in accuracy due to quantization and sampling errors, while the statistical error is the same for both methods. From our analysis we also derive alternative techniques to sample the time-domain pulse response with reduced quantization and sampling error.

The scattering of tissue causes the ambiguity of volume of tissue interrogated by near infrared spectroscopy (NIRS) instruments. The sampling volume, which is the volume of tissue interrogated by NIRS instrument with CW light, can be predicted by calculating the distribution of light which arrives the detector. Recently, time-resolved and frequency modulated measurements has been applied to near-infrared spectroscopy instruments. Although the volume of tissue interrogated by the measurements of mean time, phase and so forth may be different from that by CW intensity measurement, there are very few studies on the volume of tissue interrogated by time-resolved and frequency domain measurements. In this study a Monte Carlo algorithm to predict the volume of tissue interrogated by mean time measurements is proposed and is applied to homogeneous and layered models. The volume of tissue interrogated by mean time measurement is significantly different from the sampling volume.

Frequency domain techniques has been increasingly used for near-infrared spectroscopy and theoretical analysis of frequency domain measurement becomes important. Recently a new Monte Carlo algorithm to directly predicts the modulation and phase for frequency domain measurement was proposed. In order to apply this algorithm to heterogeneous scattering medium, a statistically accurate procedure for the photon passing the boundary of different medium is necessary. In this study, frequency domain Monte Carlo algorithm for heterogeneous medium including non scattering clear region is investigated. The modulation and phase shift predicted by frequency domain Monte Carlo is compared with the Fourier transformation of TPSF predicted by time domain Monte Carlo algorithm.

The abilities of the Photon Mean Path (PMP) approach being applied to laser tomography of strongly scattering (biological) objects were under study. The study was aimed to evaluate the computing speed and reconstruction accuracy of the PMP algorithm for the case of a cylindrical scattering body containing absorptive macroinhomogeneity. The simulation of the tomography reconstruction was carried out in two stages. At the first stage the diffusion equation for several locations of the instantaneous point source at the surface of the cylindrical body was solved by the FEM. At the second stage the 2D reconstruction of the absorption in the object was performed with the use of the earlier received equation for the shadow in terms of the integral along the PMP and of the polygonal approximation of the PMP shape. The simple algebraic algorithm was used for the reconstruction. The 1 ms computing time was obtained instead of 1 hour one with multi-iteration algorithms. The most attention was concentrated no the study of the dependence of the reconstruction fidelity on the time-delay of the receiving instant. The additional possibility was shown to improve the spatial resolution by known methods of image restoration.

The aim of the present paper is to deliver a method for exact calculation of the probability of the photon migration in infinite and homogeneous medium scattering photons anisotropically. The phase function is represented as an expansion over spherical harmonics. The migration probability is obtained as an expansion with respect to the number of scatterings, the coefficients being dependent on the ratio distance/time and can be easily calculated from recurrence relations. Up to 30 scatterings are taken into account when computing the migration probabilities, the number of effectively contributing scatterings being essentially dependent on the distance-to-time ratio decreasing when approaching the propagation front. The essential property of the method is its capability to exactly describe migration from the first transmitted photons up to the diffusive ones. The limits of the approximate description of anisotropic scattering as isotropic one with an effective value of the scattering coefficient is analyzed by calculating the best-fit value of the scattering coefficient. The present method is a natural generalization of the earlier suggested theory of photon migration with isotropic scattering.

Results of experimental study of the scattering object shape influence on the photon average trajectories (AT) are presented. The systematic experimental study of the AT inside the scattering bodies of different forms (semi- infinite medium, flat layer, rectangular sector, and cylinder) was carried out. The staking of the AT from a source to detect was carried out with the use of the standard inhomogeneity (SI): a point absolute absorber was embedded inside the object, and the point was searched where the maximal decrease of the detector signal was observed. Also this decreasing was explored as a function of the SI displacement from the AT. As it was predicted in our previous theoretical study, the simple approximation for the AT shape could be done as a three-segment polygonal line that is normal to the body surface at the initial and thermal trajectory points. The approximation error is much less then the width of the area where the presence of the SI is detectable. The obtained results comprise the base for further development of the fast computer algorithms for the real-time multi-aspect 3D optical imaging of strongly scattering objects.

As approach to the examination of the structure of layered tissue can be found in the measurement of the diffuse reflectance of plane diffuse photon-density waves in the near-infrared range. Here, phase resolved reflectance measurements from phantom tissue, at modulation frequencies of up to 2 GHz, are presented and compared to calculations provided by a theoretical model. The examination of the phase shift reveals that the reflectance properties are characterized by photon-density wave interference phenomena. The proposed technique allows the investigation of the structure of tissue down to more than one penetration depth. A medical application may be found in improved examination techniques for deep burns, as the method allows the investigation of the tissue structure without physical contact to the surface.

Monte Carlo (MC) simulations of photon transport in turbid media suffer a severe limitation represented by very high execution times in all practical cases. This problem could be approached with the technique of parallel computing, which, in principle, is very suitable for MC simulations because they consist in the repeated application of the same calculations to unrelated and superposing events. For the first time in the field of the optical and IR photon transport, we developed a MC parallel code running on the parallel processor computer CRAY-T3E (128 DEC Alpha EV5 nodes, 600 Mflops) at CINECA (Bologna, Italy). The comparison of several single processor runs (on Alpha AXP DEC 2100) and N-processor runs (on Cray T3E) for the same tissue models shows that the computation time is reduced by a factor of about 5*N, where N is the number of used processors. This means a computation time reduction by a factor ranging from about 10² (as in our case) up to about 5*10³ (with the most powerful parallel computers) that could make feasible MC simulations till now impracticable.

We constructed a liquid phantom, which mimics the neonatal head for testing near infrared spectrophotometry instruments. It consists of a spherical, 3.5 mm thick layer of silicone rubber simulating skin and bone and acts as container for a liquid solution with Intralipid^TM, 60 micrometers ol/l haemoglobin and yeast. The Intralipid^TM concentration was varied to test the influence of scattering on haemoglobin concentrations and tissue oxygenation determined by the Critikon 2020. The solution was oxygenated using pure oxygen and then deoxygenated by the yeast. For the instruments algorithm, we found with increasing scattering (0.5%, 1%, 1.5% and 2% Intralipid^TM concentration) an increasing offset added to the oxy- (56.7, 90.8, 112.5, 145.2 micrometers ol/l respectively) and deoxyhaemoglobin (25.4, 44.3, 58.5, 65.9 micrometers ol/l) concentration causing a decreasing range (41.3, 31.3, 25.0, 22.2%) of the tissue oxygen saturation reading. However, concentration changes were quantified correctly independently of the scattering level. For an other algorithm based on the analytical solution the offsets were smaller: oxyhaemoglobin 12.2, 34.0, 53.2, 88.8 micrometers ol/l and deoxyhaemoglobin 1.6, 11.2, 22.2, 28.1 micrometers ol/l. The range of the tissue oxygen saturation reading was higher: 71.3, 55.5, 45.7, 39.4%. However, concentration changes were not quantified correctly and depended on scattering. This study demonstrates the need to develop algorithms, which take into consideration the anatomical structures.

A means of determining the concentration of hemoglobin in- vivo using diffuse reflectance is proposed which could be applied to the quantification of laser Doppler flowmetry data. Monte Carlo simulations were used to generate intensity vs. source-detector separation plots for optical fibers of 200 micrometers diameter, with separations up to 6 mm on the skin surface. The plots were then fitted to the equation; I(x) equals a₀.exp(-a₁x + a₂x²) and a polynomial function derived for a₁ that is dependent upon the reduced scattering, microsecond(s) ', and absorption, (mu) a, coefficients. Experimentally two wavelengths with a known difference in the absorption coefficient of hemoglobin, but sharing the same microsecond(s) ', are used to solve simultaneously the derived function for (mu) a, and give the hemoglobin concentration.

We developed a dual-wavelength multichannel system for near infrared tissue oximetry based on the time-correlated single-photon counting (TSCPC) technique. The light sources are two pulsed laser diodes (672 nm and 818 nm, 1 mW average power, 100 ps pulse duration, 80 MHz repetition rate). The time-resolved reflectance photons are detected by a multi- anode photomultiplier and the output signals are redirected by a router to different memory blocks of a TCSPC PC board (25 ps temporal resolution, 1 MHz acquisition frequency). The system accuracy in determining the absorption and reduced scattering coefficients were tested on phantoms. Preliminary in vivo tissue oxygenation measurements were performed on healthy volunteers in different physiological conditions.

Heart-beat-synchronous variations represent a significant noise during functional near-infrared spectroscopy (NIRS) measurements of the brain. ECG-synchronous sampling allows the heart beat correlated pulsatility to be removed from NIRS-signals. During visual stimulation the measured cortical oxy- and deoxy-hemoglobin (oxy-Hb, deoxy-Hb) responses showed a factor > 2 improved signal to noise ratio in comparison to a fixed sampling frequency. The beat- to-beat concentrations of oxi-Hb, deoxi-Hb, the redox status of cytochrome-oxydase (Cyt-Ox) as well as the heart rate variability were analyzed in the frequency domain in order to find a possible correlation between the concentrations and the cardiovascular rhythms. A coherence analysis revealed a close link of these signals in the low frequency band (LF, 0.05 - 0.15 Hz) and the high frequency band (HF, 0.2 - 0.35 Hz). For the different concentration signals a different degree in coherence in the LF- and HF-bands could be observed. Spectral analysis revealed that the cardiovascular rhythms (LF and HF) may represent a noise source in the NIRS-signals which might be removed by special digital filters.

The objective of this study is to evaluate the effect of episodes of apneas and/or mild bradycardia (heart rate decreases of 10 to 20% or more) on cerebral oxyhemoglobin (HbO₂) and reduced hemoglobin (Hb) concentration as measured by Near Infrared Spectrophotometry (NIRS). Measurements were carried out on 7 preterm infants who experienced apneic and bradycardiac events. It is shown how to characterize these events using time-frequency analysis. In addition to NIRS (performed with a NIRO-500 from Hamamatsu, Japan), the heart rate, ECG, peripheral arterial oxygen saturation (measured at the foot) and respiration (abdominal and thoracic pressure, and nasal airflow) were continuously recorded. The impact of apneic events and periodic breathing on these measurements reveals the clinical relevance of NIRS. In particular, we investigate whether these changes in heart rate and respiration also influence HbO₂ and reduced Hb concentration in neonatal brain. These changes are characterized, as well as their relationships with the other simultaneously recorded signals such as peripheral arterial oxygen saturation.

Optical mammography is a new imaging modality currently under development. A contrast agent capable of adding malignancy differentiation signatures is expected to enhance the sensitivity and specificity characteristics of the technique. We report the in vivo characterization of hydrophilic analogs of indocyanine green (ICG) that lead to enhanced tumor absorbance compared to surrounding tissue. The tumor efflux of these dyes was quantitatively studied in tumor-bearing rats by frequency-modulated near-infrared spectroscopy. We demonstrate that the half-lives of hydrophilic cyanine dyes in tumor tissue are considerably enhanced compared to ICG, thus providing a prolonged time window for diagnosis. Moreover, absorption differences between the tumor and normal tissue were observed for 3 hours after injection of the hydrophilic glucamine derivative NIR96010. In conclusion, pharmacokinetic properties as present with NIR96010 may facilitate contrast- agent-aided optical mammography.

Photoacoustics was used to image optically absorbing structures, like hairs and blood vessels in tissue samples. With 532 nm light depths down to 6 - 9 mm were reached. As the samples we used a 10% solution of Intralipid-10% or real tissue (chicken breast), containing capillaries with blood or a variable dilution of Evans blue. Small PVdF piezoelectric hydrophones were used for detection, in scanning mode for imaging purposes. The depth resolution is about 10 micrometers . The lateral resolution is limited by the diameter of the detector (200 micrometers in our case). This study was undertaken to develop Photoacoustic Tomography of tissue for the localization of blood vessels, e.g. for the detection of blood concentrations (angiogenesis) around tumors.

We measured the light scattering properties of muscular tissue using several methods, and compared the obtained results. Calculation of the extinction coefficient by using collimated transmission measurements and applying Beer's law is not appropriate. Probably surface roughness of the sample disables the calculation of the extinction coefficient from such measurements. From angular intensity measurements we found a scattering asymmetry parameter g equals 0.96. In fresh samples the optical diffusion constant D depends on the orientation with respect to the longitudinal direction of the muscular cells. From the D values we calculated s' perpendicular to the longitudinal direction as 0.19 mm^-1 (at 543 nm), 0.39 mm^-1 (at 594 nm) and 0.59 mm^-1 (at 632 nm). The values for D measured from samples that were frozen and thawed did not show dependence on orientation.

Rheumatoid arthritis (RA) is one of the most common diseases of human joints. This progressive disease is characterized by an inflammation process that originates in the inner membrane (synovalis) of the capsule and spreads to other parts of the joint. In early stages the synovalis thickness and the permeability of this membrane changes. This leads to changes in the optical parameters of the synovalis and the synovial fluid (synovia), which occupies the space between the bones. The synovia changes from a clear yellowish fluid to a turbid grayish substance. In this work we present 2 and 3-dimensional reconstruction schemes for optical tomography of the finger joints. Our reconstruction algorithm is based on the diffusion approximation and employs adjoint differentiation techniques for the gradient calculation of the objective function with respect to the spatial distribution of optical properties. In this way, the spatial distribution of optical properties within the joints is reconstructed with high efficiency and precision. Volume information concerning the synovial space and the capsula are provided. Furthermore, it is shown that small changes of the scattering coefficients can be monitored. Therefore, optical tomography has the potential of becoming a useful tool for the early diagnosis and monitoring of disease progression in RA.

Results on the human sclera and skin optical properties controlled by employing administration of various chemical agents are presented. CW transmittance and reflectance measurements as well as intensity correlation experiments were used for tissue structural and optical properties monitoring. As chemical applicators--controllers osmotically active solutions, such as trazograph, glucose, polyethylene glycol, propylene glycol, glycerol, as well as aprotonic solutions like dimethyl sulphoxide were used. The characteristic time response of the human sclera optical clearing lying in the range 3 - 10 min was defined. The diffusion coefficients describing the samples of the human sclera permeability to various solutes were experimentally estimated. Presented results are general and can be applicable for description of many other fibrous tissues.

We investigate a novel approach of the ultrasonic tagging of photons path in scattering media: instead of using a single detector associated with a conventional detection scheme to image biological phantoms, we take advantage of a more efficient scheme using a CCD camera and parallel processing lock-in detection to reveal optical contrasts in real biological tissues.

Secondary haemorrhage is an important cause of brain injury following initial therapy of subdural haematoma (SDH). Early identification and treatment of secondary haemorrhage improves neurologic outcome. Near infrared light at a wavelength of 760 nm shows a high absorption for haemoglobin. The difference in absorbance of light ((Delta) OD) at the wavelength of 760 nm between both hemispheres is measured to detect SDH. We have prospectively studied 20 patients with the CT diagnosis of SDH using near infrared spectroscopy (NIRS). Unilateral subdural haematomas were detected by NIRS in 15 out of 16 patients. Bilateral SDH were detected in 2 out of 3 patients. The median of (Delta) OD was reduced from initially 0.32 (0.05 - 0.85) to 0.1 (0.02 - 0.49) at hospital discharge. The complete resorption of the haematoma has been observed in 12 patients by NIRS. In 7 patients we still obtained pathologic values at discharge. The haematomas were not completely resolved, as proved by the CT scans prior to discharge. Our results showed repeated application of NIRS in patients with SDH help to document the clinical course after surgical treatment. Follow-up NIR evaluation of patients with SDH using NIRS may allow early treatment without time delay and a reduction of secondary brain injury as well as treatment costs.

We present clinical results obtained with a frequency-domain (70 MHz), four-wavelength (690, 750, 788, 856 nm) prototype for optical mammography. The 2D projection images are taken on the slightly compressed breast in craniocaudal and oblique projections, similar to what is done in x-ray mammography. The amplitude and phase images are combined to enhance the contrast and the tumor detectability by reducing the edge effects caused by the breast thickness variations within the scanned area. The analysis of the first set of clinical data (63 patients) has yielded encouraging results. The success rate in the detection of breast cancer was 73%, and specificity was 49%. A comparison of the optical mammograms at the four wavelengths in the range 690 - 856 nm suggests that spectral information may allow for the discrimination of benign and malignant breast lesions, thereby enhancing specificity.

A single photon counting NIR imager designed to work simultaneously with an MRI scanner for concurrent NIR-MR mammography has recently been developed. The combination of imaging modalities aims in effectively investigating the competence of optical imaging as a stand along modality and as an MRI add-on in order to increase the sensitivity and specificity of the mammoraphic examination. In this work we focus on the second aim. We present the methodology developed to employ the MR anatomical information in order to simplify the forward problem and accurately calculate local tissue optical properties, by fitting the NIR data to this model. Derivation of local optical properties due to intrinsic or extrinsic may identify the existence of malignant and benign breast tissue NIR signatures. We have evaluated the performance of the solver with experimental measurements, also presented here, from models with known absorption perturbations. The average quantification error of absolute absorption of local lesions has been found to be less than 10% in simple models and algorithm convergence is always ensured.

Characteristics of images measured by continuous-wave functional near infrared imager was analyzed in this paper by means of Fourier analysis. It is shown that, as an information transfer channel, the imaging system acts as a low pass filter. Low frequency information of the biological system is received by the cw imager. Relationship between scattering coefficient and the transfer function of the sample subsystem is discussed.

The forward model in this work is based on the frequency- dependent diffusion approximation. The diffusion approximation is solved using the Finite Element Method with the Robin Boundary condition. The model is 2D, with a circular domain simulating the cross section of a limb. The meshes are generated with FIDAP, a computational fluid dynamics package. The diffusion matrix is solved using Cholesky decomposition, and results on the boundary for a modulated source include AC and DC data for a given set of optical parameters.

Results obtained with an experimental Optical Tomography system, using a frequency domain technique and a cylindrical geometry are presented. In particular, problems occurring in the reconstruction of Optical Tomography images due to uncertainties in the values for relative refractive index and system calibration factor have been investigated. It is shown that considerable errors can arise in the values for the reconstructed absorption and diffusion images as a result of these uncertainties, and that these uncertainties can give rise to artifacts in the reconstructed images. In addition, the degeneracy between the absorption coefficient, (mu) _a, and the diffusion coefficient, D, is shown for reconstruction from DC data, with the conclusion that for optimal reconstruction DC data cannot be discarded, and therefore an accurate system calibration remains a necessity.

In vivo absorption and scattering spectra of different human tissues were obtained using a system for time-resolved reflectance measurements in the wavelength range from 610 nm to 1010 nm, every 5 nm. The system is based on a dye laser and a Ti:Sapphire laser as light sources and an electronic chain for time-correlated single-photon counting for detection. Measurements were performed on the breast, the arm, the abdomen, and the forehead of healthy volunteers. The scattering spectra decrease upon increasing the wavelength, while the absorption spectra show the spectral features of oxy- and deoxyhemoglobin, water, and lipids.

Photon Migration through diffusive media studied in the frequency-domain is characterized by Diffuse Photon Density Waves (DPDWs). Theoretically, DPDWs propagation is described using the diffraction theory based on the diffusion approximation to the transport equation. Experimentally, 100 MHz modulated DPDWs are generated with our home-made frequency-domain set-up. The actual accuracy of this set-up is 0.3% in amplitude and 0.15 degree(s) in phase. The diffuse media probed are (optical)-breast-like phantoms which contain 5 mm-diameter inhomogeneities with inhomogeneity/background absorption and scattering contrasts of 1.1, 1.5, 2.0 and 4.0 respectively. Experimental results are compared to simulations and time-domain experimental results. Differences between absorption and scattering effects in the frequency-domain are highlighted. Main problems induced by phantom boundaries are presented. Two methods which aim to minimize lateral boundary effects are proposed and tested: the extrapolated lateral-boundary method and the direct polynomial or exponential fitting procedure. With these corrections, we are able to resolve well the two most contrasted inhomogeneities.