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Diffuse Correlation Spectroscopy (DCS) is an increasingly popular non-invasive optical technique to clinically measure deep tissue blood flow, albeit at slow measurement rates of 0.5-1 Hz. We recently reported the development of a new ‘fast’ DCS instrument that continuously measures blood flow at 50-100 Hz (simultaneously from 8 channels), using conventional DCS sources/detectors, and optimized software computations. A particularly interesting result was our ability to optically record pulsatile micro-vascular blood flow waveforms, and therein readily identify high frequency features such as the dicrotic notch. Here, we showcase the utility and potential of high-speed measurements of blood flow (and arterial blood pressure) in a few clinical applications. First, we employ the fast-DCS instrumentation to measure cerebral autoregulation (CVAR) dynamics. Cerebral autoregulation refers to the mechanism by which cerebral blood flow (CBF) is maintained during fluctuations in blood pressure; CVAR is impaired in the injured brain. We derive an index of autoregulation by measuring the rates of decrease (and recovery) of blood flow and blood pressure following a sudden, induced change in systemic blood pressure (e.g., bilateral thigh cuff deflation). Our pilot experiments in healthy volunteers show that DCS measured rates of micro-vascular regulation are comparable to conventional large vessel regulatory metrics ( e.g., measured with transcranial Doppler ultrasound). Second, we utilized pulsatile blood flow oscillations in cerebral arteries to estimate the critical closing pressure (CrCP), i.e., the arterial blood pressure at which CBF approaches zero. Pilot experiments in healthy subjects show good agreement between CrCP measured with DCS and transcranial Doppler ultrasound.

Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor vasculature and stimulates the body’s anti-tumor immune response. Although light fluence rate and photosensitizer concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration (FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper, we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT. A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32% higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).

Indocyanine Green (ICG) is currently the only FDA-approved contrast agent suitable for imaging tumor vascularity and performing permeability measurements. However, it is non-specific; clearance (wash-out) by the liver is very rapid, and tumor to normal tissue contrast is not optimal for medical imaging applications. Therefore, new ICG derivatives are being developed with improved affinity tumor cell affinity, and prolonged circulation times. 1 Furthermore, several new contrast agents (molecular beacons) with specific tumor targeting have been reported. Tumor cells over-express certain receptors which results in an increased uptake of ligands specific to those receptors. Chemical conjugation of molecular beacons to such ligands allows for accumulation of the agents specifically at tumor cites. For example, Weissleder et al . 2 have developed protease-activated molecular beacons that achieved a 12-fold tumor to normal tissue contrast. New molecular beacons might have direct impact on therapy monitoring: with higher sensitivity and specificity, one can noninvasively monitor and therapeutically intervene tumors in their early stages, which should lead to better survival rates.

We have developed a novel method for combining non-concurrent MR and DOT data, which integrates advanced multimodal registration and segmentation algorithms within a well-defined workflow. The method requires little user interaction, is computationally efficient for practical applications, and enables joint MR/DOT analysis. The method presents additional advantages: More flexibility than integrated MR/DOT imaging systems, The ability to independently develop a standalone DOT system without the stringent limitations imposed by the MRI device environment, Enhancement of sensitivity and specificity for breast tumor detection, Combined analysis of structural and functional data, Enhancement of DOT data reconstruction through the use of MR-derived a priori structural information. We have conducted an initial patient study which asks an important question: how can functional information on a tumor obtained from DOT data be combined with the anatomy of that tumor derived from MRI data? The study confirms that tumor areas in the patient breasts exhibit significantly higher total hemoglobin concentration (THC) than their surroundings. The results show significance in intra-patient THC variations, and justify the use of our normalized difference measure defined as the distance from the average THC inside the breast, to the average THC inside the tumor volume in terms of the THC standard deviation inside the breast. This method contributes to the long-term goal of enabling standardized direct comparison of MRI and DOT and facilitating validation of DOT imaging methods in clinical studies.

We have developed a software platform for multimodal integration and visualization of diffuse optical tomography and magnetic resonance imaging. Novel registration and segmentation algorithms have been integrated into the platform. The multimodal registration technique enables the alignment of non-concurrently acquired MR and DOT breast data. The non-rigid registration algorithm uses two-dimensional signatures (2D digitally reconstructed radiographs) of the reference and moving volumes in order to register them. Multiple two-dimensional signatures can robustly represent the volume depending on the way signatures are generated. An easy way to conceptualize the idea is to understand the motion of an object by tracking three perpendicular shadows of the object. The breast MR image segmentation technique enables a priori structural information derived from MRI to be incorporated into the reconstruction of DOT data. The segmentation algorithm is based on "Random walkers". Both registration and segmentation algorithms were tested and have shown promising results. The average Target Registration Error (TRE) for phantom models simulating the large breast compression differences was always below 5%. Tests on patient datasets also showed satisfying visual results. Several tests were also conducted for segmentation assessment and results have shown high quality MR breast image segmentation.

Gadolinium (Gd) pharmacokinetics are useful in diagnosis of breast cancer with MRI; previous work has suggested that the pharmacokinetics of indocyanine green (ICG) may prove to be similarly useful in optical mammography. Here, we describe a fast optical imaging device to acquire images of ICG kinetics simultaneously with Gd kinetics and coregister the images. This direct comparison between the widely accepted Gd diagnostic techniques and optical methods is essential for clinical acceptance of optical techniques by the radiological community.

We have developed a software platform for multimodal integration and visualization of diffuse optical tomography (DOT) and magnetic resonance imaging (MRI) of breast cancer. The image visualization platform allows multimodality 3D image visualization and manipulation of datasets, such as a variety of 3D rendering technique, and the ability to simultaneously control multiple fields of view. This platform enables quantitative and qualitative analysis of structural and functional diagnostic data, using both conventional & molecular imaging. The functional parameters, together with morphological parameters from MR can be suitably combined and correlated to the absolute diagnosis from histopathology. Fusion of the multimodal datasets will eventually lead to a significant improvement in the sensitivity and specificity of breast cancer detection. Fusion may also allow a priori structural information derived from MRI to be incorporated into the reconstruction of diffuse optical tomography images. We will present the early results of image visualization and registration on multimodal breast cancer data, DOT and MRI.

A study using pregnant sheep was designed to simulate fetal hypoxia in order to investigate the ability of near-infrared spectroscopy (NIRS) to detect and quantify fetal hypoxia in utero . The near-infrared spectroscopic probe consisted of two detectors and six source positions. It was placed on the maternal ewe abdomen above the fetal head. The light sources were modulated at 70 MHz and frequency-encoded so that simultaneous measurements at 675, 786, 830 nm for each source position were possible. After the baseline measurements, fetal hypoxia was induced by blocking the aorta of pregnant ewe and thus compromising the blood supply to the uterus. Blood gas samples were concurrently drawn from the fetal brachial artery and jugular veins. Analysis of the diffuse optical data used a two-layer model to separate the maternal layer from the fetal head. The analysis also employed a priori spectral information about tissue chromophores. This approach provided good quantification of blood oxygenation changes, which correlated well with the blood gas analyses. By contrast the homogeneous model underestimated oxygenation changes during hypoxia.

In this work, we analyze the image reconstruction problem within the first order Rytov approximation and optimize the image reconstruction by looking at the singular value spectrum of the "weight matrix". We show that the optimal data is from the tail of the temporal intensity autocorrelation curve by investigating the condition number. Furthermore, by doing a standard L-curve analysis, we find the optimal regularization constant (Tikhonov regularization). Images from simulated data are shown to illustrate the advantage of the optimization process.

A hybrid instrument combining near infrared and diffuse correlation spectroscopies was used to measure muscle oxygenation and blood flow dynamics during cuff occlusion and ischemia. Measurements were done on six healthy subjects on their arm and leg flexor muscles. Hemodynamic response was characterized for blood oxygen saturation, total hemoglobin concenration and relative blood flow speed. The characterization allowed us to define the normal response range as well as showing the feasibility of using a hybrid instrument for dynamic measurements.

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a patient with peripheral vascular disease (PVD) were found.

Photodynamic therapy (PDT) employs a combination of photosensitizing chemical, light, and oxygen Knowledge of tissue optical properties, including absorption (μa) and reduce scattering coefficients (μs’), makes possible to derive blood oxygen saturation, light penetration depth, and drug concentration, which are important to ensure PDT treatment efficacy at the specific wavelengths. We have developed an absorption spectroscopy system to measure μa and μs’ in the spectral range 600-800nm using a contact linear probe with a source fiber and multiple source-detector separation distances less than 1 cm. The μa and μs’ were recovered based on diffusion approximations of the photon transport equation. We measured tissue optical properties among various organs of patients with intraperitoneal malignancies for an on-going Phase II PDT protocol. The results from 12 patients showed various effective penetration depth from site to site and from organ to organ. The percentage oxygen saturation (%StO2) are similar before and after PDT. Before PDT, meff (mean (standard deviation) (number of patients)) in cm-1 at 630nm are 2.4 (0.2) (12) in small bowel, 2.2(0.4) (9) in large bowel, 4.2(2.7) (7) in tumor, 3.3 (0.3) (10) in peritoneum, 2.7 (0.3) (11) in skin, and 10.1 (0.6) (10) in liver. %StO2 is 60-80% for most organs but 30-40% for tumor.

Changes in blood flow and oxygenation during and after PDT provide information about tumor vessel and cellular damage. The characterization of these changes may improve our understanding of PDT mechanisms and help predict treatment efficacy. We have designed a hybrid system that can non-invasively measure in vivo hemodynamic changes and provide independent information about tumor oxygenation and blood flow. Diffuse correlation spectroscopy (DCS) monitors blood flow by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave (DPDW) spectroscopy measures tissue absorption and scattering. When mounted on a camera, our unique probe allows non-contact measurements that avoid compressing the tumor and altering blood flow. An optical filter mounted in front of the camera lens cut off light below 650nm, which allowed monitoring of blood flow during PDT. The utility of the hybrid system was demonstrated by monitoring the hemodynamic changes during and after PDT in mice bearing the experimental radiation-induced fibrosarcoma (RIF). For the first time, we non-invasively and continually monitored the in vivo flow changes during PDT. Relative oxygen consumption was calculated using flow values measured by DCS and oxygenation measured by a broadband absorption spectrometer. During PDT an initial rapid increase in blood flow was found, followed by a decrease and slow recovery. After PDT, substantial and continued reductions in blood saturation, blood flow and oxygen consumption were found after 3 hours, suggesting that permanent damage to tumor cells and blood vessels had occurred. The comparison of flow values after PDT as measured by DCS and by Power Doppler ultrasound (CWFA) demonstrated that both techniques non-invasively detected similar global changes in tumor blood flow or perfusion after PDT.

Diffuse Optical Tomography (DOT) is a typical inverse problem that aims to retrieve internal chromophore distributions noninvasively. Algebraic Reconstructions Techniques (ART) are one of the popular image reconstruction techniques used in DOT. We investigate in this report the influence of the order in which data are accessed in ART. Simulations mimicking breast tissues in transmission geometry with contrast agent tumor enhancement were used to evaluate the image quality of the diverse projection access investigated. We show that by selecting proper projection access order, the convergence speed can be significantly improved when ART is used to perform DOT. Moreover, low- contrast detection is improved.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The properties of the field re-emitted by an absorbing- fluorescent object embedded in a highly scattering media excited by a dual-interfering sources system are investigated. The geometry considered is transmission geometry with a breast like phantom. This study is based on simulations performed in the frequency domain with a finite difference method to solve the diffusion equation. The fluorescent detected field possessed the features of the interfering excitation pattern. This specific pattern allows to accurately localization of the inhomogeneity.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Modeling of skin burns has been realized in this study. Autocorrelation functions of intensity fluctuations of scattered light were measured for two-layered turbid media. The first layer served as a model of motionless scatterers whereas the second one simulated dynamic light scattering. This medium was used as a model of skin burns. A theory related quasi-elastic light scattering measurements to cutaneous blood flow was used. The dependencies of statistical properties of Doppler signal on the properties of skin burns as well as on the velocity of cutaneous blood flow has ben investigated. Predictions were verified by measurements both of dynamic and stationary light scattering in model media. Experimental results might be used as a basis for blood micro circulation diagnostics as well as for precise measurements of a depth of burned skin.

The preliminary results of an ongoing Phase II trial of Photofrin-mediated intraperitoneal PDT (IP PDT) are presented. The clinical endpoints of this trial are to determine the response rates of patients with carcinomatosis and sarcomatosis to IP PDT and to document the toxicities of IP PDT in a defined patient population. Photofrin, 2.5 mg/kg, was administered intravenously 48 hours prior to debulking surgery and light delivery, 57 patients with ovarian cancer, gastrointestinal cancers, and sarcomas were enrolled. 44 patients received Photofrin and received light treatment. 39 patients are valuable for response. 8 of 39 patients had a complete radiographic response to IP PDT 3 months after treatment. 3 patients are alive without evidence of disease 6, 6 and 9 months after treatment. 1 patient is alive and has no evidence of intra-abdominal disease but has developed lung metastases. Toxicities include post-operative fluid shifts, hypotension, hydronephrosis, pleural effusions, enteric fistula, transient liver function test elevation, thrombocytopenia, and wound dehiscence. Toxicity is related to pre-operative tumor bulk and to the extensiveness of surgery required. IP PDT is feasible and leads to an initial clinical response rate of 25 percent in patients with incurable peritoneal carcinomatosis and sarcomatosis.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

An angular spectrum algorithm is presented for fast, near-field diffraction tomographic imaging with diffuse photon density waves in highly scattering media. A general relation in K-space is derived that connects the spatial variations of the optical properties of heterogeneities to the spatial spectra of the measured scattered diffuse photon density waves. The theory is verified with experimental results. We further describe an approach to reconstruct the absorption and scattering simultaneously. We also present how to incorporate boundary conditions into this angular spectrum algorithm for a turbid medium of finite size, in particular, the slab medium.

By extending the technique of dynamic light scattering from single light scattering to high order multiple scattering, we are able to measure the dynamics of a turbid medium averaged over some deep scattering volume. One biological application is to measure blood flow in deep tissues like the brain. Furthermore, by moving the light source and detector positions to cover an extended area, we are able to reconstruct images of the dynamics.

We introduce a novel imaging technique that combines the complementary features of ultrasound and near infrared diffusive light imaging. It may have potential for improved breast cancer detection and specificity. The combined technology is achieved experimentally by mounting an ultrasound array together with multiple laser diode sources and multiple optical detectors on a hand held scan probe. We demonstrate the technique in tissue phantoms wherein both acoustic and optical sensors image the volume underneath the probe. Co-registration of acoustic and optical images is achieved with an accuracy of 0.42 cm (std 0.28cm) which is the image pixel size of our prototype.

In this work we reconstruct and compare NIR images of the intrinsic and extrinsic distribution of the absorption coefficient in the breast. The NIR protocol followed involves optical imaging before and after the administration of the NIR contrast agent Infracyanine 25 or Cardiogreen¨ and runs in parallel with the MRI examination protocol, while the patient is located in the magnet. For imaging purposes we employ a time-resolved imager using two wavelengths at 780 and 830 nm. The tomographic needs are served with a perturbation analysis that solves the heterogeneous diffusion equation and creates the forward model. Inversion is performed using the algebraic reconstruction technique (ART). Coregistration with Gd-DTPA enhanced MR images allows for direct and unequivocal comparison between optical and MR images. We focus on the comparison between the use of intrinsic or extrinsic contrast to differentiate breast tissue types. The distribution of the NIR contrast agent yields very good coregistration with the MR contrast enhanced images and that it allows accurate quantification. Our results greatly exemplify the need for NIR contrast agents in optical mammography. Conversely imaging of the intrinsic coefficient is associated with more experimental uncertainties leading to less quantification accuracy.

We present a preliminary assessment of the feasibility of using a frequency domain spectrometer for measuring fetal cerebral blood oxygenation in-utero at 750 and 780 nm of modulation at 70 MHz. The amplitude and phase of the diffuse photon density wave which propagates through the tissue is detected by a photomultiplier tube. The absorption coefficient ?a and the reduced scattering coefficient ?'s are calculated based on the analytic solution of the photon diffusion equation for a semi-infinite geometry. The accuracy of the instrument and the algorithm in measuring ?a is tested by an experiment performed on a homogeneous ink/intralipid tissue phantom. Also the sensitivity of the system to the change of blood volume and oxgenation is evaluated through a homogeneous blood/intralipid tissue phantom experiment. Clinical data was recorded during the elective Cesarean section of human subjects. The measurements were made on maternal abdomen in the post-epidural stage and on the fontanel region of neonate before (pre-cord) and after (post-cord) the umbilical cord was detached. The source detector separation used were 7 and 3(or 4) cm respectively. The deoxygenated and oxygenated hemoglobin concentration, blood volume and saturation were calculated based on ?a of 2 wavelength. The averaged optical properties and blood parameters for each stage are presented. The post-epidural blood saturation value correlates well with the pre-cord saturation value. A larger number of human subjects are being evaluated to provide statistically significant results.

Time-resolved spectroscopy of tissue is considered to be a powerful tool in the NIR that can readily measure absorption and scattering properties of diffuse media. This can be done employing curve-shape fitting of the experimental measurements to the diffusion equation. Several experimental factors however can significantly affect the accuracy of the method and should be taken under consideration when quantitative measurements are desired. In this work we examine the influence of laser time drift and jitter, limited excitation of waveguide modes in multimode collection fibers and the finite width of the impulse response. The percent error in absorption coefficient calculation grows with an average rate of 5% error per 20 ps of time-uncertainty while the percent error in determining the reduced scattering coefficient increases with a rate of 10% per 20 ps of time uncertainty. Deconvolution is found necessary to compensate for photon dispersion higher than 50 ps. Furthermore the quantification accuracy is shown to be dependent on the medium optical properties in a non-linear fashion due to intrinsic time-characteristics of the diffusion process.

Features of the speckle patterns formation due to the laser light propagation in multiple scattering systems which influence on the accuracy of measurement of the scattering system dynamic parameters by means of statistical analysis of the time-averaged spatial speckle intensity fluctuations have been studied experimentally. Two different experimental techniques have been used: photon correlation spectroscopy and contrast analysis for time-averaged speckle patterns similar to LASCA method. Results of in-vivo experiments as well as experiments with model scattering media (water solution of Intralipid) are presented. Recommendations about the choose of appropriate data processing algorithms as well as about calibration technique for time-averaged speckle technique are discussed.

The refractive index matching of components of highly scattering tissue has a strong influence on its transmittance and reflectance what can be considered as a new tool for imaging within relatively thick tissues. We present experimental data on various solutions, gels and oils influence on optical properties of in vivo human eye and in vivo human skin. The dynamics of tissue optical properties depending on matter diffusion rate within tissue is studied. The possible application of refractive index matching effect for diffusing-photon imaging is discussed.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Concurrently the measurement of autocorrelation function of the light backscattering from the forearm and phase and amplitude changes of the phase modulated photon diffusion wave has been acquired in the arm cuff experiment. Dynamical performances with the varying blood pressure are presented and analyzed.

We have non-invasively measured in vivo blood flow changes using photon correlation spectroscopy with a simple correlation diffusion model to study and quantify blood flow in the human arm during cuff ischemia. The method utilizes the Doppler broadening of light that arises in a multiply scattering dynamic media, and is also responsive to changes in absorption and scattering coefficients. Our measurements clearly show blood flow changes with cuff pressures, including the hyperemic overshoot after cuff release, that qualitatively agree with the physiological behavior of the cardiovascular system. In this paper, we present our method, results and discuss the clinical relevance of our findings.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We present a new data reduction algorithm to quantify absorption and reduced scattering coefficients of living tissues. The method requires source-detector separations larger than 2 cm and provides a simple, economic way to characterize tissue optical properties in the range of 600-900 nm and blood oxygenation. The results show that blood oxygenation in tissue can be quantified simply and accurately with this method for diffusing steady-state light, provided a suitable base-line calibration is available.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In this work we compare the Born and Rytov approximations for frequency-domain diffusing wave tomography.We confirm that the Rytov approximation gives a more accuate reconstruction of the absorptive properties. Inaddition, the natural separation of amplitude and phase within the Rytov approximation presents the possibility for image reconstruction algorithms which use either the phase shift or the amplitude decay of the diffusive waves. We demonstrate this effect, and apply these algorithms to simultaneously reconstruct the scattering andabsorption properties of heterogeneous turbid media. 1 Introduction Near infrared diffusing light probes offer new possibilties for medical applications such as the non-invasive mea-surement of tissue oxygenation' in homogeneous tissues. Direct imaging of the optical properties of heterogeneoustissue is an important potential improvement to these schemes that has only recently been considered.2'3In this study we employ amplitude modulated (frequency-domain) sources of photons which are injected intoa scattering medium to generate diffuse photon density waves4 (DPDW's). The diffusive waves are composed ofrandomly walking photons, that collectively produce an exponentially damped spherical wave of photon densitypropagating outward from the source with well defined amplitude and phase at each position in the medium. Inour work, measurements of the phase and amplitude of DPDW's are used to derive images of objects embeddedwithin tissue phantoms.The equations used for frequency-domain diffusing-wave tomographic imaging are approximations to the het-erogeneous light diffusion equation. In the Born approximation, the amplitude of the perturbation is assumed tobe small, and in the Rytov approximation, the perturbation is assumed to be slowly varying.5 We have previouslyiresentecl experinnta.l images of absorbing or scattering heterogeneities using the Born approximation.6 In thiswork we demonstrate the relative advantages of working in the Rytov approximation for frequency-domain mea-surements and image reconstruction. We then use the Rytov approximation to create maps of both the absorptionand scattering properties of a turbid sample. Finally, we demonstrate that we are able to use the amplitude and

The diffusion approximation to the photon transport equation is the simplest model for photon migration. The applicability of the diffusion approximation, however, is limited. For example, it is strictly valid only when the absorption coefficient is small compared to the scattering coefficient and the source modulation frequency is small compared to the scattering rate. In this contribution we establish the theoretical range of validity of the diffusion approximation, review a frequency-dependent solution of the transport equation within the P3 approximation, and establish the significance of the P3 solution using Monte Carlo computer simulations. We find that the P3 approximation, in most cases, permits a more accurate determination of the optical properties of highly absorbing media as well as from data obtained at modulation frequencies greater than 3 GHz. Interestingly, for highly anisotropic scattering (g equals 0.9), we find that diffusion theory and the P3 approximation predict approximately the same values for the reduced scattering coefficient.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Time resolved IR spectroscopy is used to monitor the stretch mode of CO on Cu(111) following femtosecond visible excitation. A time dependent shift in the stretch mode complex frequency is observed and is attributed to low frequency adsorbate-like modes becoming excited via coupling to substrate electrons and phonons. At low levels of excitation it is found that the frustrated translation is coupling to the bulk electron reservoir with a rate (gamma) eequals167(24) GHz, and to the bulk phonon reservoir with a rate (gamma) Lequals145(56) GHz. At higher excitation levels deviations from the model are observed.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We describe the use of diffuse light in homogeneous media to determine the dynamic properties of small scattering particles. A novel interferometric technique is used to measure average displacements of freely diffusing particles over times of just 20 nsec. Another experiment on an industrially significant dispersion provides insight into the process of gel formation.

We perform experiments which confirm the existence of diffuse photon density waves in homogeneous diffusive media and show that these waves obey some simple principles of optics. In particular, experiments are done to show that Snell's law holds for waves moving across a boundary between media of different diffusional indices of refraction. Other experiments are performed which investigate the scattering of these waves from spherical objects, and simple models are presented to explain these results. Finally we demonstrate that it is possible to excite a fluorescent object with a diffuse photon density wave, creating a transduced diffuse photon density wave with a different wavelength. In summary we discuss the implications of these results for medical imaging.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Two methods for experimentation with ultrashort mid-infrared light pulses are presented. The techniques utilize high repetition rate sources, and are therefore suitable for use with lock-in modulation detection.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

International audience; Current methodologies for obtaining depth-sensitive contrast information from an optically diffusive medium involve complex hardware and software implementations. In turn, such methods typically lead to long acquisition and long reconstruction times, rendering them impractical for real-time use. In this work, we report preliminary proof-of-concept for a hardware-only method capable of providing depth sensitive contrast information without requiring post acquisition image reconstruction and with rapid acquisition. This method, termed Masked Detection of Structured Illumination (MDSI), relies on physically masking, in the detection arm, the point spread function from a collimated beam illuminating a diffusive medium, to isolate the contribution of the photon path lengths of interest. By continuously scanning and integrating the obtained images, MDSI allows, for the first time, optical depth sectioning of a diffusive medium without any processing.