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OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics. To overcome these barriers, we introduce a cross correlation method to more accurately recover blood flow information using InGaAs/InP SPADs. METHODS: Two InGaAs/InP SPAD detectors were used for during in vitro and in vivo DCS measurements. Cross correlation of the photon streams from each detector was performed to calculate the correlation function. Detector operating parameters were varied to determine parameters which maximized measurement SNR. State-space modeling was performed to determine the detector characteristics at each operating point. RESULTS: Evaluation of detector characteristics was performed across the range of operating conditions. Modeling the effects of the detector noise on the correlation function provided a method to correct the distortion of the correlation curve, yielding accurate recovery of flow information as confirmed by a reference detector. CONCLUSION: Through a combination of cross-correlation of the signals from two detectors, model-based characterization of detector response, and optimization of detector operating parameters, the method allows for the accurate estimation of the true blood flow index. Significance: This work presents a method by which DCS can be performed at longer NIR wavelengths with existing detector technology, taking advantage of the increased SNR.

Capacitive proximity sensing is widespread in our everyday life, but no sensor for biomedical optics takes advantage of this technology to monitor the probe attachment to the subject’s skin. In particular, when using optical monitoring devices, the capability to quantitatively measure the probe contact can significantly improve data quality and ensure the subject’s safety. We present a custom novel optical probe based on a flexible printed circuit board which integrates a capacitive contact sensor, 3D-printed optic fiber holders and an accelerometer sensor. The device can be effectively adopted during continuous monitoring optical measurements to detect contact quality, motion artifacts, probe detachment and ensure optimal signal quality.

We introduce a portable system for clinical studies based on time-domain diffuse correlation spectroscopy (DCS). After evaluating different lasers and detectors, the final system is based on a pulsed laser with about 550 ps pulsewidth, a coherence length of 38 mm, and two types of single-photon avalanche diodes (SPAD). The higher efficiency of the red-enhanced SPAD maximizes detection of the collected light, increasing the signal-to-noise ratio, while the better timing response of the CMOS SPAD optimizes the selection of late photons and increases spatial resolution. We discuss component selection and performance, and we present a full characterization of the system, measurement stability, a phantom-based validation study, and preliminary in vivo results collected from the forearms and the foreheads of four healthy subjects. With this system, we are able to resolve blood flow changes 1 cm below the skin surface with improved depth sensitivity and spatial resolution with respect to continuous wave DCS.

Significance: Intracranial pressure (ICP), variability in perfusion, and resulting ischemia are leading causes of secondary brain injury in patients treated in the neurointensive care unit. Continuous, accurate monitoring of cerebral blood flow (CBF) and ICP guide intervention and ultimately reduce morbidity and mortality. Currently, only invasive tools are used to monitor patients at high risk for intracranial hypertension. Aim: Diffuse correlation spectroscopy (DCS), a noninvasive near-infrared optical technique, is emerging as a possible method for continuous monitoring of CBF and critical closing pressure (CrCP or zero-flow pressure), a parameter directly related to ICP. Approach: We optimized DCS hardware and algorithms for the quantification of CrCP. Toward its clinical translation, we validated the DCS estimates of cerebral blood flow index (CBFi) and CrCP in ischemic stroke patients with respect to simultaneously acquired transcranial Doppler ultrasound (TCD) cerebral blood flow velocity (CBFV) and CrCP. Results: We found CrCP derived from DCS and TCD were highly linearly correlated (ipsilateral R2 = 0.77, p = 9 × 10 − 7; contralateral R2 = 0.83, p = 7 × 10 − 8). We found weaker correlations between CBFi and CBFV (ipsilateral R2 = 0.25, p = 0.03; contralateral R2 = 0.48, p = 1 × 10 − 3) probably due to the different vasculature measured. Conclusion: Our results suggest DCS is a valid alternative to TCD for continuous monitoring of CrCP.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. Recent advances in the field have seen the introduction of iDWS/iDCS, which have allowed for the use of conventional photodetectors to replace the single photon counting detectors required to measure the traditional, homodyne DCS signal. Here we detail a high framerate, highly parallel iDCS system at 1064 nm which allows for improved signal to noise ratio at extended source detector separations.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. DCS cerebral blood flow measurements in clinical applications have shown promise, but measurements contain contamination of the signal from changes in superficial blood flow. Recent studies have shown that moving to wavelengths beyond the water absorption peak at 970 nm when making DCS measurements improves SNR and reduced influence of superficial flow. Here, we present a DCS system operating at 1064 nm utilizing two InGaAs SPADs to calculate the cross correlation to address detector non-idealities.

Significance: The use of diffuse correlation spectroscopy (DCS) has shown efficacy in research studies as a technique capable of noninvasively monitoring blood flow in tissue with applications in neuromonitoring, exercise science, and breast cancer management. The ability of DCS to resolve blood flow in these tissues is related to the optical sensitivity and signal-to-noise ratio (SNR) of the measurements, which in some cases, particularly adult cerebral blood flow measurements, is inadequate in a significant portion of the population. Improvements to DCS sensitivity and SNR could allow for greater clinical translation of this technique. Aim: Interferometric diffuse correlation spectroscopy (iDCS) was characterized and compared to traditional homodyne DCS to determine possible benefits of utilizing heterodyne detection. Approach: An iDCS system was constructed by modifying a homodyne DCS system with fused fiber couplers to create a Mach–Zehnder interferometer. Comparisons between homodyne and heterodyne detection were performed using an intralipid phantom characterized at two extended source–detector separations (2.4, 3.6 cm), different photon count rates, and a range of reference arm power levels. Characterization of the iDCS signal mixing was compared to theory. Precision of the estimation of the diffusion coefficient and SNR of the autocorrelation curve were compared between different measurement conditions that mimicked what would be seen in vivo. Results: The mixture of signals present in the heterodyne autocorrelation function was found to agree with the derived theory and resulted in accurate measurement of the diffusion coefficient of the phantom. Improvement of the SNR of the autocorrelation curve up to ∼2× and up to 80% reduction in the variability of the diffusion coefficient fit were observed for all measurement cases as a function of increased reference arm power. Conclusions: iDCS has the potential to improve characterization of blood flow in tissue at extended source–detector separations, enhancing depth sensitivity and SNR.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. DCS has been shown to be an effective monitor of cerebral blood flow in many neuro-monitoring applications, though still suffers from depth sensitivity issues. Recent studies have shown that moving to 1064 nm when making DCS measurements improves SNR and sensitivity to depth, but detector challenges have slowed the change to that wavelength. Here, we present on a multipixel, interferometric DCS (iDCS) system that improves measurement capabilities at this wavelength.

Our team has recently shown the SNR and depth-sensitivity advantages of using 1064 nm light for diffuse correlation spectroscopy as well as the challenges of commercially available single-photon detectors at this wavelength. We will review two strategies for custom readout integrated circuit designs that simultaneously target lower pixel dead times and lower afterpulsing probabilities. Both designs use macropixels comprising many detectors, each having a programmable hold-off time. We will compare simulated autocorrelations for our detector models and compare predicted performance against commercial InGaAs/InP detectors.

Cerebral blood flow monitoring is crucial during hypothermic circulatory arrest for aortic arch surgery. This study uses diffuse optics to demonstrate simultaneous monitoring of cerebral blood flow and blood oxygen saturation during surgery.

In-vivo, optical measurements of cerebral blood flow are confounded by superficial blood flow. Here, we present acousto-optic modulated diffuse correlation spectroscopy (AOM-DCS) for blood flow monitoring, showing good agreement between theoretical predictions and experimental results.

Diffuse correlation spectroscopy (DCS) is an emerging technique that allows for estimation of the motion of particles. By monitoring the time course of the speckle intensity fluctuations, the motion of the scattering particles, usually red blood cells in the microvasculature of biological tissues, can be quantified. Though these measurements are traditionally taken at near infrared wavelengths, where the attenuation of light by tissue chromophores, primarily hemoglobin, is reduced, the multiply scattered field is still heavily attenuated and expensive photon counting detectors are required to measure the signal intensity. By decreasing the cost of these systems, they may be more applicable in measuring patient hemodynamics at the bedside. Other groups have explored the use of heterodyne techniques [1,2] to amplify the intensity of the scattered field for detection with less expensive detectors, showing the potential for lowering the cost of DCS systems. Here we detail the performance characteristics of a single mode fiber (SMF) interferometer as well as follow through to investigate the theoretical relationship between the measured correlation function and the underlying dynamics. DCS measurements in the traditional homodyne configuration made with photon counting detectors are compared with those made with the interferometer with the photon counting detectors to explore experimental parameters that optimize the SNR of the blood flow index. The feasibility of utilizing fast photodiodes in the detection of the amplified field is also explored. Through the use of amplified optical signals, the detection of the DCS signal using less expensive detectors is shown to be possible. References: 1. Nakaji, H. US Application. No. 15/424581 (2017). 2. Zhou, W., Kholiqov, O., Chong, S. P. & Srinivasan, V. J. Highly parallel, interferometric diffusing wave spectroscopy for monitoring cerebral blood flow dynamics. Optica 5, 518 (2018).

Diffuse correlation spectroscopy (DCS) is an emerging technology that allows for the quantitative estimation of blood flow in tissue. By monitoring the autocorrelation of the time course of light speckle intensity, information about the motion of scattering particles, mostly red blood cells in the microvasculature of biological tissues, can be determined. The speckle fluctuations are due to motion of scatters along the entire path length of the photon from the source to the detector, which makes the determination of the location of the motion a difficult task. Multi-distance and tomographic methods have been employed to measure decorrelation times at different source detector separations, which helps to separate superficial blood flow from blood flow deeper in the tissue. DCS in the time-domain (TD-DCS) is being evaluated as a method to increase depth sensitivity by considering only the late arriving photons. Depth resolved quantification of blood flow is especially important when blood flow measurements of the brain are desired, as the superficial blood flow of the scalp is a known contaminant to the cortical signal. Recent demonstrations by other groups have shown the utility of ultrasound tagging of light to be an effective method to discriminate flow at different depths.1 Here we utilize ultrasound pulses to modulate the motion of particles at specific depths, which is dependent upon the time-of-flight of the ultrasound pulse. By analyzing the autocorrelation of the speckle intensity at different delay periods after the pulse, quantitative, depth specific information about the flow can be determined. References: 1. Tsalach, A. et al. Depth selective acousto-optic flow measurement. Biomed. Opt. Express 6, 4871–86 (2015).

Diffuse correlation spectroscopy (DCS) is a technique that has traditionally required low noise, single photo counting detectors. By utilizing an interferometric approach, we show that these hardware conditions can be relaxed.

Diffuse correlation spectroscopy (DCS) is an optical technique that non-invasively quantifies an index of blood flow (BF(i)) by measuring the temporal autocorrelation function of the intensity fluctuations of light diffusely remitted from the tissue. Traditional DCS measurements use continuous wave (CW) lasers with coherence lengths longer than the photon path lengths in the sample to ensure that the diffusely remitted light is coherent and generates a speckle pattern. Recently, we proposed time domain DCS (TD-DCS) to allow measurements of the speckle fluctuations for specific path lengths of light through the tissue, which has the distinct advantage of permitting an analysis of selected long path lengths of light to improve the depth sensitivity of the measurement. However, compared to CW-DCS, factors including the instrument response function (IRF), the detection gate width, and the finite coherence length need to be considered in the model analysis of the experimental data. Here we present a TD-DCS model describing how the intensity autocorrelation functions measured for different path lengths of light depend on the coherence length, pulse width of the laser, detection gate width, IRF, BF(i)s and optical properties of the scattering sample. Predictions of the model are compared with experimental results using a homogeneous liquid phantom sample that mimics human tissue optical properties. The BF(i)s obtained from the TDDCS model for different path lengths of light agree with the BF(i) obtained from CW-DCS measurements, while the standard simplified model underestimates the BF(i) by a factor of ~2. This Letter establishes the theoretical foundation of the TD-DCS technique and provides guidance for future BF(i) measurements in tissue.

Time-Domain Diffuse Correlation Spectroscopy (TD-DCS) is a novel approach that aims at merging Diffuse Correlation Spectroscopy (DCS) with time-domain near-infrared spectroscopy (TD-NIRS) in a single modality [1]. The idea is to excite the tissue with a long-coherence, pulsed laser and acquire the temporal point spread function (TPSF) through the measurement of the photons time-of-flight (ToF). The optical properties of the tissue are recovered by TD-NIRS analysis, while DCS processes the temporal speckle fluctuations due to the moving scatterers in tissue (blood cells) to measure an index of microvascular blood flow (BFi) [2]. Furthermore, the time-domain information allows us discriminate between short and long photon paths to perform NIRS and DCS processing only on photons that have travelled deep into the tissue, increasing the sensitivity to the brain. This discrimination allows us to shorten the source-detector separation, increasing the signal-to-noise ratio, and making the optical sensor more compact.

DCS monitoring of cerebral blood flow in adult subjects requires accounting for extracerebral contributions to the signal. We explore the impact of the choice of model on using the recently proposed pressure modulation method for calibrating the extracerebral contribution.

This paper presents a multidistance and multiwavelength diffuse correlation spectroscopy (DCS) approach and its implementation to simultaneously measure the optical proprieties of deep tissue as well as the blood flow. The system consists of three long coherence length lasers at different wavelengths in the near-infrared, eight single-photon detectors, and a correlator board. With this approach, we collect both light intensity and DCS data at multiple distances and multiple wavelengths, which provide unique information to fit for all the parameters of interest: scattering, blood flow, and hemoglobin concentration. We present the characterization of the system and its validation with phantom measurements.

We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 microM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured in the brain after the piglet had been sacrificed.

Frequency domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) use near-infrared light to quantify static and dynamic properties of brain tissue. We present a novel FDNIRS-DCS system and characterize its performance.

We suggest that Diffuse Correlation Spectroscopy (DCS) measurements of tissue blood flow primarily probe relative red blood cell (RBC) motion, due to the occurrence of multiple sequential scattering events within blood vessels. The magnitude of RBC shear-induced diffusion is known to correlate with flow velocity, explaining previous reports of linear scaling of the DCS "blood flow index" with tissue perfusion despite the observed diffusion-like auto-correlation decay. Further, by modeling RBC mean square displacement using a formulation that captures the transition from ballistic to diffusive motion, we improve the fit to experimental data and recover effective diffusion coefficients and velocity de-correlation time scales in the range expected from previous blood rheology studies.

NIRS is safe, non-invasive and offers the possibility to record local hemodynamic parameters at the bedside, avoiding the transportation of neonates and critically ill patients. In this work, we evaluate the accuracy of the frequency-domain multi-distance (FD-MD) method to retrieve brain optical properties from neonate to adult. Realistic measurements are simulated using a 3D Monte Carlo modeling of light propagation. Height different ages were investigated: a term newborn of 38 weeks gestational age, two infants of 6 and 12 months of age, a toddler of 2 year (yr.) old, two children of 5 and 10 years of age, a teenager of 14 yr. old, and an adult. Measurements are generated at multiple distances on the right parietal area of head models and fitted to a homogeneous FD-MD model to estimate the brain optical properties. In the newborn, infants, toddler and 5 yr. old child models, the error was dominated by the head curvature, while the superficial layer in the 10 yr. old child, teenager and adult heads. The influence of the CSF is also evaluated. In this case, absorption coefficients suffer from an additional error. In all cases, measurements at 5 mm provided worse estimation because of the diffusion approximation.

The absorption and scattering coefficient of a macroscopically homogeneous strongly scattering medium (lipid emulsion) containing Methylene Blue is quantitatively measured in the spectral range from 620 to 700 nm. We conduct the measurements in the frequency domain by using a light-emitting diode (LED) whose intensity is modulated at a frequency of 60 MHz. We derive an analytical expression for the absorption and scattering coefficients that is based on a two-distance measurement technique. A comparison with other measurement protocols such as measurement at two modulation frequencies shows that the two-distance method gives a better determination of the scattering and absorption coefficients. This study highlights the efficiency and ease of use of the LED technique, which lends itself to in vivo spectroscopy of biological tissues.

Simultaneous measurements with microelectrodes and frequency domain optical coherence tomography were done on rats to investigate neurovascular coupling. Neuronal and vascular responses to parametric forepaw stimulation were found to be in agreement under different anesthetics.

A standard corona preionized XeCl laser prototype has been excited by a very simple L-C circuit consisting of a large storage capacitance charged at relatively low voltage (12 kV) and discharged via a switch on the electrodes, tightly coupled with the peaking capacitors. The resulting overvoltage following the switch closure behaves as an effective and automatic prepulse, providing a homogeneous discharge lasting up to 400 ns. Energy output levels of the order of 150 mJ at 1.4% overall efficiency have been achieved.

We present a method for the noninvasive determination of the size, position, and optical properties ~absorption and reduced scattering coefficients! of tumors in the human breast. The tumor is first detected by frequency-domain optical mammography. It is then sized, located, and optically characterized by use of diffusion theory as a model for the propagation of near-infrared light in breast tissue. Our method assumes that the tumor is a spherical inhomogeneity embedded in an otherwise homogeneous tissue. We report the results obtained on a 55-year-old patient with a papillary cancer in the right breast. We found that the tumor absorbs and scatters near-infrared light more strongly than the surrounding healthy tissue. Our method has yielded a tumor diameter of 2.1 6 0.2 cm, which is comparable with the actual size of 1.6 cm, determined after surgery. From the tumor absorption coefficients at two wavelengths ~690 and 825 nm!, we calculated the total hemoglobin concentration ~40 6 10 mM! and saturation ~71 6 9%! of the tumor. These results can provide the clinical examiner with more detailed information about breast lesions detected by frequency-domain optical mammography, thereby enhancing its potential for specificity. © 1998 Optical Society of America OCIS codes: 170.3830, 300.0300, 300.1030, 290.0290.

Using Monte-Carlo simulations in realistic head models segmented from MRI scans, we determine the accuracy of the multi-distance frequency-domain method to recover the brain absorption coefficient from premature infants to adults.

We describe a diffuse optical tomography system that combines frequency encoding with time-division multiplexing to enable overlapping measurements of brain activation. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.

Diffuse optical imaging is an effective technique for noninvasive functional brain imaging. However, the measurements respond to systemic hemodynamic fluctuations caused by the cardiac cycle, respiration, and blood pressure, which may obscure or overwhelm the desired stimulus-evoked response. Previous work on this problem employed temporal filtering, estimation of systemic effects from background pixels, or modeling of interference signals with predefined basis functions, with some success. However, weak signals are still lost in the interference, and other complementary methods are desirable. We use the spatial behavior of measured baseline signals to identify the interference subspaces. We then project signals components in this subspace out of the stimulation data. In doing so, we assume that systemic interference components will be more global spatially, with higher energy, than the stimulus-evoked signals of interest. Thus, the eigenvectors corresponding to the largest eigenvalues of an appropriate correlation matrix form the basis for an interference subspace. By projecting the data onto the orthogonal nullspace of these eigenvectors, we can obtain more localized response, as reflected in improved contrast-to-noise ratio and correlation coefficient maps.

Time domain (TD) diffuse optical measurement systems are being applied to neuroimaging, where they can detect hemodynamics changes associated with cerebral activity. We show that TD systems can provide better depth sensitivity than the more traditional continuous wave (CW) systems by gating late photons, which carry information about deep layers of the brain, and rejecting early light, which is sensitive to the superficial physiological signal clutter. We use an analytical model to estimate the contrast due to an activated region of the brain, the instrumental noise of the systems, and the background signal resulting from superficial physiological signal clutter. We study the contrast-to-noise ratio and the contrast-to-background ratio as a function of the activation depth and of the source-detector separation. We then present experimental results obtained with a time-gated instrument on the motor cortex during finger-tapping exercises. Both the model and the experimental results show a similar contrast-to-noise ratio for CW and TD, but that estimation of the contrast is experimentally limited by background fluctuations and that a better contrast-to-background ratio is obtained in the TD case. Finally, we use the time-gated measurements to resolve in depth the brain activation during the motor stimulus.

We use a time-domain system based on a pulsed laser and an intensified CCD camera to detect cerebral hemodynamics. We show experimentally and theoretically an improvement in the depth sensitivity over continuous wave systems.

We use a spatial subspace approach to identify and reduce the interference signals in diffuse optical functinal imaging and obtain a more localized response and improved maps of correlation coefficients.

This talk addresses diffuse optical imaging and what it can tell us about the healthy brain. Comparisons with fMRI, EEG, and MEG measurements will be presented, and the macroscopic origin of optical signals will be discussed.

We present measurements of the heartbeat obtained on human foreheads, using frequency domain and time domain systems. Preliminary results indicate that we are able to measure signals of the heartbeat originated from intracranial layers (brain).

We have measured relative diffuse reflectance images on tissue-like liquid phantoms using a laser diode (784 nm, 40 mW) as a broad-beam source and a CCD camera detector. We have found that, to a good approximation, the result that the reflectance R only depends on the ratio of the absorption and reduced scattering coefficients of the medium (μa/μs') can be extended to geometrical configurations that are more general than those considered by theoretical studies. In fact, over the range 0.0028

We describe an instrument for frequency-domain light mammography (LIMA), and we present clinical results obtained on patients affected by breast cancer. This instrument uses two laser diodes emitting at 690 and 825 nm. Their intensities are modulated at a frequency of 110 MHz. The amplitude and the phase of the intensity wave are the measured quantities. The breast is slightly compressed between two glass plates and the optical signal is detected in transmission, i.e. on the opposite side of the illuminated spot of the breast. The acquisition time for a full breast image is about 3 minutes. Edge effects (that are mainly due to the breast thickness variability within the scanned area) are corrected by an algorithm of data analysis which enhances the contrast of the optical mammograms. In the clinical applications, we successfully detected 27 out of 37 malignant tumors (73%). This result shows the practical feasibility and the significant potential of frequency-domain optical mammography.

The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.

Received February 16, 1999 We present a frequency-domain optical method for real-time noninvasive measurement of absolute tissue and arterial saturation. This method is based on quantitative measurement of the tissue absorption spectrum (for tissue saturation) and of the amplitude of the arterial-pulsation-induced absorption oscillations (for arterial saturation) at eight wavelengths in the range 633 ‐ 841 nm. We report results obtained from readings taken from the forehead of a healthy volunteer, showing baseline saturation values of 74.7 6 0.2% (tissue) and 96.9 6 0.5% (arterial). These values dropped to minimum values of 71.6 6 0.2% and 90.0 6 0.2%, respectively, after 1 min of reduced inspired oxygen concentration [10% (by volume) O2 from a baseline value of 21% O2]. © 1999 Optical Society of America OCIS codes: 000.1430, 170.3890, 170.5280, 170.6510, 170.5270.

We propose photon-density-wave fluctuation correlation spectroscopy as a method to study the dynamics of tissue optical properties. Phantom measurements have shown that our frequency-domain instrument is appropriate to explore intensity, modulation and phase fluctuations in the frequency band from 0 to 125 Hz. Preliminary in vivo studies have revealed a rich optical dynamics in human tissues.

We have performed non-invasive, real-time optical mapping of the piglet brain during a subcortical injection of autologous blood. The time resolution of the optical maps is 192 ms, thus allowing us to generate a real-time video of the growing subcortical hematoma. The increased absorption at the site of blood injection is accompanied by a decreased absorption at the contralateral brain side. This contralateral decrease in the optical absorption and the corresponding time traces of the cerebral hemoglobin parameters are consistent with a reduced cerebral blood flow caused by the increased intracranial pressure. © 1999 Optical Society of America.

We measured the effective absorption and reduced scattering coefficients on the surface of two-layered turbid media using a frequency-domain multi-distance method. We measured the amplitude and the phase of the modulated intensity at source-detector distances ranging from 1.5 to 3.0 cm. We considered several combinations of one layer (L) (thickness: 0.1-1.6 cm) placed on top of one block (B) (thickness ~ 5 cm). We found that for layers less than about 0. 40 cm thick the frequency-domain multi-distance method yields the optical properties of the underlying block. We also found that for layers more than 1.3 cm thick the frequency-domain multi-distance method yields a reduced scattering coefficient which reproduces that of the superficial layer. For a layer thickness in the range of 1.31.6 cm, the effective absorption coefficient approaches the layer absorption coefficient but does not match it to within experimental errors.

We have performed frequency-domain optical measurements on the surface of two- and three-layered turbid media (in vitro) and on infant heads (in vivo). For the in vitro experiment we measured a number of combinations of one layer (thickness in the range 0.1-1.6 cm) on top of one semi-infinite block, with or without a clear layer (thickness of 0.1 cm) sandwiched in between. For the in vivo experiment, we did measurements on 20 preterm infants at the Meyer Children's Hospital in Florence, Italy. In the two-layered samples, we measured the effective absorption and reduced scattering coefficients with a multi-distance method based on data taken at source-detector distances in the range 1.5-4.5 cm. We found that the effective optical coefficients reproduce those of the underlying block if the superficial layer is less than about 0.4 cm thick, whereas they are representative of the superficial layer if it is more than about 1.3 cm thick. Larger source detector separations reduce the effect of the superficial layer on the recovery of the effective optical coefficients. Measurements in the presence of the clear layer gave results that did not reproduce, even qualitatively, the in vivo measurements on infant heads.

We present a re-engineered frequency-domain tissue oximeter operating in the near-infrared spectral region. This instrument is based on the multi-distance measurement protocol, which we have implemented in our original design by multiplexing multiple light sources. The new instrument uses intensity modulated (110 MHz) laser diodes emitting at 750 and 840 nm. The laser diodes are coupled to glass optical fibers (600 micrometer core diameter). The average light intensity delivered to the tissue is about 3 mW. The multiplexing electronics are based on solid state switches that allow for acquisition times per point as short as tens of milliseconds. Our tests on phantoms and in vivo with the new oximeter have shown significant improvement in terms of stability, reliability, and reproducibility with respect to the original prototype. Furthermore, by using optical fibers we achieve a high versatility in the design of the measuring probe, permitting custom design for various tissue contours and different measurements. To verify the improved performance of the new oximeter, we have performed an in vivo test consisting of monitoring the hemoglobin saturation (Y) and concentration (THC) on the calf of 18 healthy volunteers during walking and running routines.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We have investigated the accuracy of the frequency-domain, diffusion equation Green's function in modeling optical signals in turbid media. Our optical measurements were conducted in strongly scattering media having absorption coefficients in the range 0.035 - 0.14 cm-1 and reduced scattering coefficients in the range 5 - 22 cm-1. The optical signal was both delivered to and collected from the sample by means of optical fibers. We have verified that the r-independent factor in the Green's function does not agree with the experimental data. This discrepancy shows that the photons launched in the medium by an optical fiber cannot be modeled by a point source located at a fixed position. These results have no influence on multi-distance measurement protocols (which only employ the r-dependent part of the solution), while they must be considered when calibration measurements on a known sample are performed.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We present a novel approach to optical mammography and initial clinical results. We have designed and developed a frequency-domain (110-MHz) optical scanner that performs a transillumination raster scan of the female breast in approximately 3 min. The probing light is a dual-wavelength (690 and 810 nm, 10-mW average power), 2-mm-diameter laser beam, and the detection optical fiber is 5 mm in diameter. The ac amplitude and phase data are processed with use of an algorithm that performs edge effect corrections, thereby enhancing image contrast. This contrast enhancement results in a greater tumor detectability compared with simple light intensity images. The optical mammograms are displayed on a computer screen in real time. We present x-ray and optical mammograms from two patients with breast tumors. Our initial clinical results show that the frequency-domain scanner, even at the present stage of development, has the potential to be a useful tool in mammography.

Fluorescence spectroscopy provides potential contrast enhancement for near-infrared tissue imaging and physiologically correlated spectroscopy. We present a fluorescence photon migration model and test its quantitative predictive capabilities with a frequency-domain measurement that involves a homogeneous multiple-scattering tissue phantom (with optical properties similar to those of tissue in the near infrared) that contains a fluorophore (rhodamine B). After demonstrating the validity of the model, we explore its ability to recover the fluorophore’s spectral properties from within the multiple-scattering medium. The absolute quantum yield and the lifetime of the fluorophore are measured to within a few percent of the values measured independently in the absence of scattering. Both measurements are accomplished without the use of reference fluorophores. In addition, the model accurately predicts the fluorescence emission spectrum in the scattering medium. Implications of these absolute measurements of lifetime, quantum yield, concentration, and emission spectrum from within multiple-scattering media are discussed.

We have investigated the problem of edge effects in laser-beam transillumination scanning of the human breast. Edge effects arise from tissue thickness variability along the scanned area, and from lateral photon losses through the sides of the breast. Edge effects can be effectively corrected in frequency-domain measurements by employing a two-step procedure: (1) use of the phase infor-mation to calculate an effective tissue thickness for each pixel location; (2) application of the knowledge of tissue thickness to calculate an edge-corrected optical image from the ac signal image. The measurements were conducted with a light mammography apparatus (LIMA) designed for feasibility tests in the clinical environment. Operating in the frequency-domain (110 MHz), this instrument performs a transillumination optical scan at two wavelengths (685 and 825 nm). We applied the proposed two-step procedure to data from breast phantoms and from human breasts. The processed images provide higher contrast and detectability in optical mammography with respect to raw data breast images. © 1996 American Association of Physicists in Medicine.

A possible approach to optical mammography consists of a planar tandem scan of a light source and an optical detector in a transmission geometry. The main difficulty with interpreting the data collected in this sampling geometry arises from edge effects, which are due to variable breast thickness within the scanned region and to photon losses through the sides of the breast. We have developed an algorithm for frequency-domain data analysis that corrects for edge effects, thus providing significantly enhanced image contrast with respect to raw data images. The application of our algorithm to data collected in vivo strongly improves the detectability of optical inhomogeneities in the breast.

Our research is aimed at the development of a frequency-domain instrument for conducting non-invasive, real-time, near-infrared optical tomography of tissue in vivo. Our goal is to reconstruct aspatial map of the optical properties of a strongly scattering medium in a semi-infinite-geometry sampling configuration. Specifically, we focus our attention on the absorption coefficient (pta) and the reduced scattering coefficient (j) of the medium. We have developed a frequency-domain measurement protocol (which we call pre-calibrated), which permits one to recover the values of and _tsI of a uniform tissue-like phantom from a measurement at a single source-detector separation and asingle modulation frequency. It requires a preliminary reference measurement on a calibration sample of known optical properties before the measurement on the investigated sample. This approach is in principle rigorous only in macroscopically homogenous media. We have verified that the equations valid for uniform media can still be applied to yield qualitative information on the optical nature of the

Near-IR optical tomography is thwarted by the highly scattering nature of light propagation in tissue. We propose a weighted back-projection method to produce a spatial map of an optical parameter which characterized the investigated medium. We have studied the problem of the choice of the back-projection weight function for the absorption coefficient ((mu) a) and for the reduced scattering coefficient ((mu) s') of tissuelike phantoms. Working in frequency-domain optical imaging, we have initially approached the problem of quantifying the effect caused by a small absorbing defect embedded in the medium on the measured DC intensity, AC amplitude, and phase. The collection of DC, AC, and phase changes during a 1 mm step raster scan of the absorbing defect provides information on the photon path distributions and, in general, on the probed spatial region when DC, AC, and phase are, respectively, the measured parameters. We report experimentally determined weight functions for (mu) a and (mu) s'. They indicate that absorption and scattering maps can significantly differ in terms of resolution.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.