This PDF file contains the front matter associated with SPIE Proceedings Volume 10874 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

In this paper, we show that interfering multiple photon density waves created by intensity-modulated sources in frequency domain diffuse optical spectroscopy (fd-DOS) can be used to recover the optical properties of homogenous and heterogeneous tissues. While fd-DOS can recover the optical properties of homogenous tissue using a single source-detector pair, heterogeneous or layered tissues such as breast, brain, and skin require additional source-detector pairs with multiple separations. Through modelling, we show that the varying illumination patterns created by the interference of two intensity modulated sources can be used to recover the optical properties of two-layer tissue using only a single detector and two phased sources. Two-dimensional fd-DOS models of the conventional multi-distance and proposed multi-phase approaches were compared for homogenous and two-layered tissues. In a homogenous tissue with absorption and reduced scattering coefficients representative of human breast, the simulation results showed that both multi-distance and multi-phase approaches are capable of recovering the absorption and reduced scattering coefficients of the tissue. However, the multi-phase approach has less precision than the conventional multidistance approach. In the two-layer model, the multi-phase approach was capable of recovering the optical properties of both layers, while the multi-distance approach could not.

This paper describes RTBioT, one of the first Internet of Things (IoT) healthcare platforms based on spatially resolved near infrared (NIR) spectroscopy to support non-invasively quantify chromophores in biological tissue. Bluetooth Low Energy (BLE) is used as the primary communication protocol, an IR-enhanced Si PIN photodiode is for a light-receiving element, and a compact fiber-stub type beam combiner is employed as a multiple wavelengths light-emitting source. Most of all, a lock-in amplifier is to retrieve the low noise signal from photodiode which enables accurate measurement of small modulated signals in the presence of noise interference orders of magnitude greater than the signal amplitude by using phase-sensitive detection technique (PSD). The sampling rate of the RTBioT is up to 33Hz, so that it can directly measure mayer wave oscillation, respiration, and cardiac cycle from the raw data. However, it is necessary to approach to the statistical analysis to quantify the concentration of tissue chromophores. First, we determine the optical absorption and scattering properties in the tissue from the locked-in received signal by using the algorithm composed of least square method and diffusion equation. Then, inverse-matrix equation with absorption, reduced scattering and extinction coefficients is solved by the algorithm with respect to chromophores. We conducted an experiment through phantoms simulating human tissue and human subjects to demonstrate its feasibility for the IoT healthcare platform. The experimental results show that it is possible to monitor the biological signals and the concentrations of chromophores in a human subject in near real time fashion.

Frequency domain diffuse optical spectroscopy (fd-DOS) uses modulated laser light to image tissue and extract quantitative chromophore information. Currently no fd-DOS systems are completely handheld and only one is capable of displaying chromophore data in real time, which could allow for real-time studies of tissue hemodynamics, spatial chromophore (e.g. water, lipid, and hemoglobin) concentrations, greater ease of use by clinicians, and more generally, a simple platform for quantitative tissue spectroscopy. We present progress towards a handheld, real time fd-DOS system based upon an all-digital FPGA coupled hardware approach that includes data collection and processing and can attain imaging speeds of >30Hz. Quantitative optical scattering and absorption measurements are found to be within 10% agreement as compared to a reference system. We conclude that high speed quantitative tissue chromophore assessments are possible with this system-on-a-chip fd-DOS approach, which will enable real time handheld monitoring of rapid physiological changes.

We present a new full-custom instrument for time-domain diffuse optical spectroscopy developed within Horizon 2020 LUCA (Laser and Ultrasound Co-Analyzer for thyroid nodules) project. It features eight different picosecond diode lasers (in the 635 - 1050 nm range), two 1.3 × 1.3 mm² active-area SiPMs (Silicon PhotoMultipliers) working in single-photon mode and two 10 ps resolution time-to-digital converters. A custom FPGA-based control board manages the instrument and communicates with an external computer via USB connection. The instrument proved state-of-the-art performance: an instrument response function narrower than 160 ps (fullwidth at half-maximum), a long-term measurement stability better than 1%, and an output average optical power higher than 1 mW at 40 MHz. The instrument has been validated with phantom measurements.

The use of bioresorbable fibers represents an innovative way to build optical implantable devices and to look inside the body. Recently, a new kind of bioresorbable fibers, based on calcium-phosphate glasses, has been introduced by some of us. They show a good biocompatibility and improved attenuation loss coefficient with respect to other bioresorbable fibers. In this work, we used those fibers to explore their suitability in diffuse optics. Indeed, the time-domain technique is a non-invasive methodology which allows to have an absolute estimate of the absorption and reduced scattering spectra of the diffusive medium. It allows to bring information about concentration of chemical components (water, oxyand deoxy-hemoglobin), thus conveying information about the functional status and/or the scattering properties (changes in tissue microstructure, edema). Such information can then be related to the tissue regeneration, healing process, or to a harmful evolution. This makes the time domain optical spectroscopy coupled to bioresorbable fibers a good candidate for future medical devices. Here we demonstrate the suitability of these fibers for diffuse optics by means of standardized tests and then we use them for a proof-of-principle measurement on ex-vivo chicken breast, obtaining results comparable with standard fibers. Thanks to the encouraging results, we are working on a system based on a single fiber (serving as both injection and collection fiber) to go closer to a single interstitial fiber which can lessen the effect of the implant.

Time-domain (TD) near-infrared spectroscopy (NIRS) is an effective method of quantifying optical and biological properties, such as the mean optical path length, absorption coefficient, reduced scattering coefficient, and oxyhemoglobin and deoxy-hemoglobin concentrations of biological tissues. In addition to these parameters, water and lipid contents are important biological parameters expected to be useful information in clinical application. For our previous TD-NIRS systems, we used three wavelengths (760, 800, and 830 nm) that are sensitive to oxy- and deoxy-hemoglobin. To quantitatively measure water and lipid contents of biological tissues, we developed a new TD-NIRS system with three additional wavelengths (908, 936, and 976 nm) that are sensitive to water and lipids. The new six-wavelength TDNIRS system comprises six-wavelength pulsed light sources, two types of photomultiplier tubes (GaAs and InGaAs PMTs), a time-correlated single-photon counting unit, and optical fiber bundles. In this pilot study, we present the measurement results of oxy- and deoxy-hemoglobin concentrations, tissue oxygen saturation, and water and lipid contents at the calf, forearm, and abdomen of five healthy adult volunteers in a resting state using the six-wavelength TD-NIRS system. We thus confirmed that the fat thickness measured by ultrasonography and the water content measured by the six-wavelength TD-NIRS system were negatively correlated, whereas the fat thickness and lipid content were positively correlated. We expect that the six-wavelength TD-NIRS system will be used in clinical studies as a point-of-care testing device for the bedside monitoring of human subjects.

With the rapid development of spatial light modulators, structured light strategies have been readily implemented for efficient diffuse optical tomography (DOT) and fluorescent molecular tomography (FMT) applications. Compared to traditional pencil-beam sources, wide-field illumination enables larger imaging field-of-view (FOV), higher signal-to-noise ratios (SNR), and faster data acquisition speed, making it attractive for small-animal whole-body imaging. As the gold-standard for simulating photon propagations inside complex biological tissues, the Monte Carlo (MC) method is one of the most accurate approaches for imaging general media. Recently, thanks to parallel hardware such as graphics processing units (GPUs), MC simulations can be computed with high efficiency even with personal computers. While we have added support for wide-field illumination patterns in our widely distributed MC platform (http://mcx.space), the computation for multiple patterns is currently performed sequentially. To further accelerate forward modeling of large number of wide-field patterns, we propose a new method, referred to as “photon sharing”, to simultaneously simulate multiple structure-light sources. We demonstrate a 5- to 10-fold reduction of the MC simulation time. This technique is particularly valuable in DOT or FMT applications using structured light illumination and/or single-pixel-camera based systems. The proposed algorithm has been implemented in our open-source MC simulation platforms, supporting both CPUs and GPUs.

Diffuse Optical Tomography (DOT) provides quantitative information about optical absorption and total hemoglobin concentration of breast tumors which is directly related to tumor angiogenesis. However, measurements errors caused by tissue heterogeneity may introduce artifacts in reconstructed absorption and total hemoglobin maps and therefore cause errors in quantitative characterization of lesions. With ultrasound-guided DOT, these artifacts can be recognized if they are isolated and located at edges of the absorption maps. However, effectively recognize image artifacts and automatically remove them is a challenge because artifacts can be merged partially with lesions maps. A new two-step algorithm is proposed to iteratively identify and remove measurement outliers based on assignment of local outlier factors and hence to reduce image artifacts and produce more consistent absorption maps among different wavelengths. In first step, perturbation measurements were ranked based on data density and the local outlier factor which is the probability of each measurement being an outlier. In second step, outliers are iteratively removed until normalized pattern correlation of different wavelength absorption maps is beyond a specified threshold. The proposed algorithm is evaluated on 20 clinical cases and it has demonstrated its capability to automatically reconstruct more consistent images for different wavelengths. The improvement on characterizing benign breast lesions is more dramatic because outliers can cause the reconstructed benign lesions with higher optical absorption and therefore high hemoglobin contrast.

Peripheral artery disease (PAD) affects approximately 12 million people in the US. The disease is caused by an accumulation of plaque in arteries, which leads to stenosis and reduction in blood flow. In advanced cases, surgery or endovascular interventions are required to re-establish blood flow to the extremities. In over 40% of these cases a second intervention is required within 12 months. Therefore, accurate monitoring the blood flow in the feet of these patients is crucial. In this study, dynamic vascular optical spectroscopy was used to assess perfusion in 4 different angiosomes of 25 patients who underwent a surgical intervention. Imaging was performed just before the intervention, 4 hours later and 1 month later. Each optical spectroscopy session consisted in inflating a thigh pressure cuff to 60 mmHg, maintaining the pressure for 60 seconds and releasing it, then repeating the procedure while inflating the cuff to 100 mmHg. Totalhemoglobin [THb] time traces for each angiosome were calculated. We found a strong correlation between the dynamic shapes of the THb-signals obtained before the intervention, 3 hours after the intervention and 1 month later and the longterm outcome of the procedure.

It is estimated that in the USA 1.5 million people suffer from systemic lupus erythematosus (SLE). This autoimmune disease often involves joints, and more than 90% of those affected will experience joint pain, stiffness and swelling at some time during the course of their illness. It is currently difficult to both diagnose and estimate the severity of lupus, because signs and symptoms vary considerably from person to person and there is no single diagnostic test for it. We explored the clinical utility of frequency-domain optical tomography (FDOT) to distinguish finger joints affected by SLE from healthy ones of volunteers. The proximal interphalangeal joints (PIP) of the 2nd to the 5th digit from both hands of 10 SLE patients and 4 healthy volunteers were examined. This resulted in a total of 80 joints affected by SLE and 32 healthy joints. The FDOT system was operated at a frequency of 600MHz. The laser diode employed produced a 1-mm beam at 670nm light, which was guided to 11 positions on the top of the PIP joints. At every location, using an exposure time of 80 ms for 16 phase steps, transmission images were acquired using an ICCD camera. First results of the analysis of the amplitude and phase shift of the images acquired show a sensitivity of 100% and a specificity of 80% to distinguish between joints of healthy volunteers and SLE patients.

The large liver transplant waitlists and increasing of marginal donor organs call for a rapid, non-destructive method of evaluating organ quality for transplantation. We demonstrate a diffuse optical non-destructive organ risk (DONOR) indexing method for identifying significant liver pathology, in particular unacceptable fibrosis and necrosis. Measurements were acquired from 27 human livers not meeting the clinical criteria for transplantation (OUHSC IRB #8155). A portable lab-on-a-crate diffuse optical spectroscopy (DOS) device with a hands-free probe of 3mm source-detector separation was used for measurements on liver surface and cross-section. The DOS measurements were obtained from a total of five sites, including the right anterior, right posterior, and left anterior liver surfaces and the right and left cut sections, and corresponding tissue sections were obtained for formalin-fixed paraffin embedded (FFPE) H&E controls of 8 types of liver pathology. Due to the difficulty of obtaining a control liver, a clinically inconspicuous and histologically unremarkable liver number 24 was used as the baseline for DONOR index processing. For the measurements at the cross-sectional parenchyma of the right lobe alone, a single threshold of the DONOR index at 1.5 identified all six livers with fibrosis stage ≥2 and one liver with necrosis=5, in the presence of mixed pathologies. A prime pattern of altering the DOS profile by the fibrosis alone is identified. The surface measurements differ from the parenchyma measurements at various levels, due to the shielding effect of the thin collagen-rich capsule. DONOR indexing of liver pathology is promising, but requiring unsheilding the capsular effect.

Regulation of renal hemodynamics and oxygenation is complex and its detailed understanding is crucial to improve therapeutic procedures for kidney diseases like acute kidney injury. For the challenging task of monitoring renal hemodynamics and oxygenation in rats, we designed a continuous wave (cw) multispectral near-infrared spectroscopy setup. A fiber probe with a source fiber and eight detection fibers is placed on the ventral surface of the exposed rat kidney in vivo, and an additional source fiber is positioned on the dorsal surface. Nine wavelengths from 658 nm to 1060 nm are used to have sufficient redundancy for reliable quantification of hemoglobin concentration, oxygen saturation of hemoglobin, and tissue water content. To investigate both, the surface layer and deeper tissues, the setup alternates between reflection and transmission at a rate of 10 Hz. Our system relies on spatially resolved reflection and transmission, and multispectral analysis to differentiate absorption from scattering. Monte-Carlo Simulations for a layered tissue structure are used as a model for quantitative characterization of the renal cortex and medulla. Renal parameters are monitored during baseline conditions and during dedicated pathophysiologically relevant interventions including arterial occlusion and changes of inspiratory gas mixture. Together with invasive probes, which monitor arterial blood pressure, renal perfusion and tissue oxygenation, a detailed picture of renal hemodynamics and oxygenation in several pathophysiological conditions is acquired. This detailed information can serve as a quantitative reference to other methods such as MRI.

A recent clinical study involved multi-spatial frequency (0.00, 0.15, 0.61, 1.37 mm^-1 ), multi-spectral (490, 550, 600, 700 nm) structured light imaging (SLI) of freshly excised, bread-loafed breast conserving surgery tumor specimens. The specimens contained regions of interest (ROIs) of confirmed and homogeneous histological categories of breast tumor tissue determined by expert histopathological analysis. ROIs were sampled into ~4x4mm sub-images before conversion into Gabor filter bank feature vectors. Feature vectors were used in binary, benign-malignant classification scenarios using a support vector machine classifier and 8-fold cross validation. Classification was performed first on feature vectors containing only planar (0.00 mm^-1 ) 490 nm monochromatic SLI data. For comparison, a second set of feature vectors from the same sub-images contained the same planar 490 nm illumination data concatenated with high spatial frequency (1.37 mm^-1 ) 490 nm monochromatic SLI data. The classification performance of each filter bank was determined for both sets of feature vectors based on receiver operating characteristic (ROC) area under the curve (AUC) values. Gabor filtering and subsequent classification revealed that surface tissue textures exhibited strong rotational dependence and that high spatial frequency surface tissue features were more diagnostic than low spatial frequency surface tissue features. A Gabor filter bank that included 4 relatively high spatial frequencies (0.70-1.98 mm^-1 ) and 8 rotation angles (0-157.5°, equally spaced) achieved ROC AUC values <0.9 for 9 of 12 binary tissue subtype classifications.

Reflectance-based, handheld diffuse optical tomography (DOT) uses multi-spectral frequency-domain (FD) and/or continuous-wave (CW) discrete wavelength sources. During DOT reconstruction, spectral constraints are commonly applied assuming a limited number of chromophores in the tissue in order to more accurately recover chromophore concentrations and scattering parameters. However, there are cases where spectral recovery cannot be applied, such as for the quantification of unknown tissue absorbers, where the chromophore extinction spectra are not known a priori. Therefore, we have worked toward a hyperspectral, hybrid FD and CW-DOT approach that can accurately recover tissue absorption and scattering spectra without needing a spectral constraint. Our approach increases the number of recoverable chromophores continuously across a 650 - 1050 nm spectrum. We have implemented and evaluated this technique in a prototype handheld probe for reflectance-mode breast imaging. Currently, no handheld portable DOT probe has this broadband hyperspectral capability. We simulated the accuracy of optical property recovery, showing that hybrid DOT successfully recovers the absorption spectra with average of 10% error across 650 − 1000 nm spectrum. We have also validated this technique by successfully imaging an inhomogeneous physical phantom with optical properties mimicking breast tissue. The methodology for the probe design along with the results of simulations and phantom studies are presented.

Neoadjuvant radiotherapy, as part of the conventional treatment of rectal cancer, can induce fibrotic tissue formation around the tumor. This complicates the exact determination of the tumor borders during surgery, which might increase the chance of positive resection margins. In a previous ex vivo study, we distinguished tumor tissue from healthy rectal wall and fat with an accuracy of 0.95, using diffuse reflectance spectroscopy (DRS). Since this study did not include fibrosis, the aim of the current ex vivo study was to examine whether differentiation of tumor and fibrosis with DRS is possible. DRS measurements from freshly resected specimen of 16 patients were obtained. In eight patients fibrosis was measured, in the other eight patients tumor was measured. The measurements were performed using a DRS probe with a source-detector distance of 2 mm. The spectra were obtained in the wavelength range of 450-1600 nm. Classification of the measurements was done using a support vector machine (SVM) and a set of features extracted from the spectra. The SVM was evaluated using an eight-fold cross-validation, which was repeated ten times. For all repetitions, the area under the ROC curve was greater than 0.85 (mean = 0.87, STD = 0.02). The mean sensitivity and specificity were 0.85 (STD = 0.03) and 0.88 (STD = 0.01) respectively. It can be concluded that tumor tissue can be distinguished from fibrosis based on spectral features from DRS measurements. The next step will be to conduct an in vivo study, to verify these results during surgery.

Spatial frequency domain imaging (SFDI) is a non-invasive technique that can quantify tissue chromophore concentrations. SFDI has been implemented previously using visible and near-infrared wavelengths to provide information on oxy- and deoxy-hemoglobin concentrations for applications including assessment of burn wounds, pressure ulcers, and tumor resections. Further tissue characterization can potentially be achieved using short-wave infrared (SWIR) wavelengths (approx. 1,000 – 1,700 nm) due to the distinctive absorption bands of water, lipid, and collagen in this spectral range. Quantification of these tissue components may have clinical significance in relation to such topics as inflammation, obesity, and wound healing. Previous work on extending SFDI into the SWIR region combined VIS/NIR-SFDI with planar imaging at SWIR wavelengths1 . There is currently no literature that directly performs SFDI in the SWIR range for the absolute quantification of water content. In this study, we used laser sources centered at 980 nm and 1,550 nm to directly perform SFDI at these SWIR wavelengths to capture differences in hydration in a biomedically significant context.

Oxygen plays a role in many aspects of tumor biology such as metastasis, drug resistance, and angiogenesis. Chaotic vasculature and cell signaling can lead to segments of the tumor that are oxygen-rich while neighboring regions can be severely hypoxic. Previous work has shown that this spatial variation is a dynamic process, but the precise spatio-temporal evolution is poorly understood. Spatial Frequency Domain Imaging (SFDI) is an emerging technique for measuring wide-field maps of absolute concentrations of tissue chromophores. Here we present an SFDI device capable of acquiring hyperspectral (~10 wavelengths) SFDI images at relatively high speeds (0.1 Hz). A Quartz Tungsten Halogen lamp source is used as the input to a Czerny-Turner monochromator. Instead of an exit slit, a digital micromirror device (DMD) is used to select any wavelength within the range of the DMD. The monochromatic beam is directed onto a second DMD which spatially modulates the light incident on the sample. This system is highly flexible and allows for rapid selection and projection of any wavelength from 500-1800 nm. We verified the accuracy and precision of the instrument on a series of tissue mimicking optical phantoms, and collected what we believe to be the first wide-field, time-resolved measurement of the spatio-temporal dynamics of a xenograft breast tumor in a mouse model in vivo. These measurements will further our understanding of tumor oxygen dynamics for use in developing more effective drug treatment schedules, and discovery of novel drug targets.

Revascularization is required to deliver the factors necessary for bone injury healing to the injury site. Therefore, vascularization is usually monitored to assess the bone healing outcome in preclinical settings. Previously, blood flow changes measured by diffuse correlation tomography have shown the potential to predict the healing outcome of the mouse femoral graft in vivo. To obtain more comprehensive hemodynamic information in addition to blood flow, we adapted spatial frequency domain imaging (SFDI) method to quantify the total hemoglobin concentration and oxygen saturation in the mouse bone graft model. An in-house SFDI system was built based on a Texas Instrument digital micromirror device (DMD) and a near-infrared camera. The system was tested using a simplified tissue phantom mimicking the mouse hindlimb with a femoral allograft (avascular) implanted. A single time-point measurement for mouse hindlimbs with and without allograft was performed. The SFDI results were compared with traditional contrast agent-mediated micro-CT for validation. Longitudinal measurements are being performed before and weekly after the allograft surgery. The SFDI-derived properties will be related to the biomechanical outcomes of the healed bones. Preliminary results of tissue phantom experiments showed the capability of SFDI for mapping the absorption and scattering properties of the graft mimicking tube at a 2 mm depth. Since the mouse femur is usually ~1-2 mm under the skin surface, the SFDI technique has the potential for monitoring the vascularization in healing bone grafts.

A multi-spectral, portable, hand-held LED based spatial frequency domain imaging system was used for ex vivo imaging pretreatment and post treatment human colon and rectal tissues. Freshly excised human colon and rectal tissue samples were imaged with the hand-held SFDI probe with 9 wavelengths extending from visible to NIR (660-950 nm). Important tumor biomarkers such as hemoglobin, scatter amplitude, scatter spectral slope, water and lipid content were quantitatively extracted from the SFDI absorption and scattering images. Significant differences were observed between the absorption as well as scattering distribution of normal, tumor and polyp tissue as well as between pretreated and post-treated tumors.

During neoadjuvant chemotherapy for breast cancer, little information is available on the response or non-response of the tumor to the treatment. Pathologic complete response is correlated with survival, but patients and clinicians both must wait until after the patient undergoes surgery and the resected tissue is analyzed in order to assign pathologic response. Because structural imaging modalities and clinical palpation are poor predictors of pathologic response, there is need for an inexpensive imaging method which is sensitive to the changing physiology of the tumor. Such a method should be noninvasive, to permit frequent monitoring during therapy. Near-infrared optical imaging has already shown promise for monitoring neoadjuvant chemotherapy, with measurement of hemodynamics providing additional information over baseline chromophore concentrations. These contrasts rely on the highly vascularized nature of most breast tumors, as well as the abnormal vasculature, which can produce a different response to perturbations than healthy tissue. Here we describe the development of a new held-held spatial-frequency domain imaging (SFDI) device, to be used for measuring the response of breast tissue to local compression. Device design is described, as well as validation on optical phantoms, and in vivo. Compression studies were performed in soft optical phantoms containing stiff, tumor-mimicking inclusions, which indicate the potential for compression to be used to bring stiff lesions within a depth which can be measured with SFDI. Additionally, the hemodynamic response of pressure cuff venous occlusion is described, measured on the forearm, and this response is contrasted with the hemodynamic response to local tissue compression.

A new reconstruction algorithm for fluorescence optical tomography of biological tissues is proposed. The radiative transport equation in the frequency domain is used to model light propagation. The adjoint method studied in this work provides an efficient way for solving the inverse problem. The methodology is applied to a 2D tissue-like phantom subjected to a collimated laser beam. Indocyanine Green is used as fluorophore. Reconstructed images of the spatial fluorophore absorption distribution is assessed taking into account the residual fluorescence in the medium. We show that illuminating the tissue surface from a collimated centered direction near the inclusion gaves a better reconstruction quality. Two closely positioned inclusions can be accurately localized and quantified. However, the algorithm fails to reconstruct smaller or deeper inclusions due to light attenuation in the medium. Reconstructions with noisy data are also achieved with a reasonable accuracy.

Imaging with a single pixel confers many advantages for biological imaging, particularly in the case of tissues, where optical scattering obscured image signals for conventional imaging techniques. While laser scanning confocal and multiphoton imaging are powerful techniques that are routinely deployed for biological imaging, the signals must be acquired by scanning the focal spot sequentially through the entire region of interest. In recent years, we have introduced a new single pixel imaging method that speeds up imaging in tissues by spreading the conventional excitation spot to a spatial-temporally modulated line focus. In our method, the illumination beam is modulated with a spatial frequency that sweeps linearly in time, and is thus called spatial frequency projection imaging (SPIFI). SPIFI used with a nonlinear optical response also results in super-resolution imaging. The challenge with SPIFI is that it is a one-dimensional imaging method, and consequentially, the spatial resolution enhancements afforded by nonlinear SPIFI imaging similarly only appear along the modulated spatial coordinate. Here, we introduce a new form of tomographic imaging that homogenized SPIFI imaging resolution along both coordinates of the object that is imaged. The method is a conjugate domain form of computed tomography (CT), that forms spatial frequency projections, parameterized by rotation angle, rather than spatial projections that are used in conventional CT. We develop theory and experimentally demonstrate Fourier coherent tomographic imaging of objects both with bright field (intensity transmission) and fluorescent emission modes. We demonstrate isotropic improvement in spatial resolution with this technique.

High scattering in biological tissues severely degrades the spatial resolution of optical fluorescence imaging in thick tissue. As one of the most sensitive in vivo molecular imaging modalities, Fluorescence Tomography plays an essential role in preclinical studies. To overcome the limitations of FT, we introduced a novel method termed, temperature modulated fluorescence tomography (TMFT). TMFT is based on two key elements: 1) temperature sensitive fluorescent agent (ThermoDots) and 2) high intensity focused ultrasound (HIFU). TMFT localizes the position of the fluorescent ThermoDots by scanning a HIFU beam across the tissue while monitoring the variation in the measured fluorescence signals. Actually, a binary mask is built by monitoring the sudden jumps in the fluorescence signal corresponding to the HIFU scan over a position containing ThermoDots. This binary map is used as functional a priori during the FT image reconstruction process. TMFT not only allowed us to resolve ThermoDots with high spatial resolution (~1.3 mm), deep in tissue (~ 60 mm) but with high quantitative accuracy as well (< 3% error). In this paper, we present the latest prototype of TMFT. Here, the fluorescence signals are acquired using a CCD camera, which increases the sensitivity of the system compared to the previous fiber-based system.

Fluorescence diffuse optical tomography (f-DOT) is an imaging technique that can quantify the spatial distribution of fluorescent tracers in small animals and human soft tissues. Efficacy of f-DOT imaging can be improved by tagging a functional group to the dye. A novel estrogen receptor (ER) specific near-infrared (NIR) fluorescent dye conjugate was synthesized which can be effectively used for detecting breast cancer tissues at an early stage. Our novel dye, Near Infrared Dye Conjugate-2 (NIRDC-2), is a conjugate of 17β-estradiol with an analogue of Indocyanine Green dye, bis1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. Our present study focuses on imaging cylindrical silicone phantoms using Frequency Domain f-DOT system. Background absorption and scattering coefficients were 0.01mm^-1 and 1mm^-1 respectively. 10μM concentration of NIRDC-2 and Indocyanine Green (ICG) were administered separately into a cylindrical hole (target) of size 8mm diameter in the phantom. In-silico studies were performed to analyze the properties of dyes using experimental data. Absorption coefficient of 0.0002 mm^-1 was recovered for the background. Fluorophore absorption coefficient at the target recovered were 0.000173 mm^-1 and 0.000408 mm^-1 for ICG and NIRDC-2 respectively. In comparison with ICG, our novel dye had a two fold higher target to background contrast. Recovered target position was accurate but size altered. In concurrence with the recovered fluorescent property and the cell lines studies carried out earlier, binding properties of NIRDC-2 makes it a potential probe for the early tumor detection using f-DOT system.

Fluorescence diffuse optical tomography has traditionally employed near infrared (NIR) light (700 nm - 850 nm), owing to the lower absorption, and consequently, deeper penetration through thick biological tissue in these wavelengths. However, tissue scattering is a major impediment that has limited spatial resolution. We demonstrate that tomography using light in the short-wave infrared (SWIR) spectrum (>1000 nm), characterized by lower tissue scattering, can provide a several-fold improvement in spatial resolution compared to that using NIR light. We also show that the use of SWIR light for both excitation and detection provides the improved spatial resolution enhancement compared to using SWIR detection alone. Using Monte Carlo simulations and phantom experiments, we characterize the tomographic spatial resolution performance across both the NIR and SWIR spectral regions. We also validate the application of SWIR tomography in complex shaped, heterogeneous biological tissue using mouse cadavers with embedded fluorescent inclusions in the brain. These results suggest that SWIR tomography will offer a powerful new approach for non-invasive, depth resolved, 3D tomographic imaging in whole animals.

As the role of immuno-oncological therapeutics expands, the capacity to noninvasively quantify molecular targets and drug-target engagement is increasingly critical to drug development efforts and treatment monitoring. Previously, we showed that MRI-coupled dual-agent fluorescence tomography (FMT) is capable of estimating the concentration of epidermal growth factor receptor (EGFR) in orthotopic glioma models noninvasively. This approach uses the dynamic information of two fluorescent agents (a targeted agent and untargeted isotype) to estimate tumor receptor concentration in vivo. This approach generally relies on the two tracers having similar kinetics in normal tissues, which may not always be the case. Herein, we describe an additional channel added to the MRI-FMT system which measures the uptake of both agents in the normal muscle, data which can be used to compensate for differing kinetic behavior.

Tissue optical properties attenuate a substantial percentage of the optical light being detected during real-time Cherenkov acquisition, which distortsthe signal linearity previously observed with absorbed dose in homogeneous media. This hinders progression toward establishing quantitative dosimetry using Cherenkov imaging in vivo. By spectrally weighting effective attenuation (μ_eff) maps generated by multi-wavelength Spatial Frequency Domain Imaging (SFDI), it became possible to more successfully correct clinical Cherenkov images for areolar attenuation (6% difference, as compared to the treatment plan) compared to selecting one wavelength channel in a previous study (41% difference). Additionally, using a reflected light-based patient positioning system, we were able to characterize and correct for gross tissue optical properties in patient images, namely for large-scale surface and subsurface attenuation. While the use of wide-field SFDI enabled pixel-bypixel corrections, the benefit of using an integrated, light-based system for reflectance-based corrections negates the use of an external imaging system, which substantially smooths workflow.

Numerous methods consider the temporal field autocorrelation function in order to study the dynamical properties of a medium, e.g. diffuse correlation tomography (DCT) [1] and speckle contrast optical tomography (SCOT) [5]. In this paper, we calculate the field correlation function in the transport regime as the solution to the correlation transport equation (CTE) introduced in [1]. We show how perturbation theory can be applied to the CTE in order to calculate the sensitivity kernel relating the variation of the local Brownian motion of particles to the typical data. The Green’s function of the standard radiative transport equation (RTE) can be used to construct the sensitivity kernel in the first Born approximation where the correlation time is considered to be the small parameter. We stress that the sensitivity kernel is defined for every point within the scattering medium. The sensitivity kernel is then the Jacobian matrix required in DCT or SCOT in order to perform the image reconstruction [5]. Eventually, we demonstrate how the use of the CTE, instead of the correlation diffusion approximation, is increasing the resolution of reconstructed images of dynamical parts of a scattering medium.

Diffuse correlation spectroscopy (DCS) is an optical method for non-invasive measurements of blood flow in deep tissue microvasculature, such as the brain, without the need for tracers or ionizing radiation. The technique relies on determining temporal autocorrelations of light intensity fluctuations which arise due to time changing speckle patterns of moving scatterers when illuminated by a long coherence length laser. Measurements of blood flow using DCS have extensively been validated and have found some clinical translation already. High temporal resolution by fast sampling of the autocorrelation curves has recently been achieved by software based correlators. Here we demonstrate a new software correlator approach which uses components that are an order of magnitude cheaper than current approaches. We will present on the instrument design, as well as measurements of pulsatile blood flow on healthy volunteers. We will show blood flow measurements with a signal bandwidth of 50Hz and present on signal to noise ratios (SNR) of extracted pulse waveforms as a function of sampling rate. We will show how using an EKG based timing of the signal for averaging increases the fidelity of extracting the blood flow waveform even in low SNR environments. We will further present results of the pulsatile waveforms and the latency of the dicrotic notch as affected by posture changes in healthy volunteers.

We used coherent hemodynamics spectroscopy (CHS) and near-infrared spectroscopy (NIRS) for dynamic measurements of absolute cerebral blood flow (CBF) in one healthy subject over the prefrontal cortex. Temporal transients in mean arterial pressure (MAP) and CBF were induced by rapid deflation of pneumatic thigh cuffs following a sustained 2-minute occlusion at a super-systolic pressure. We studied the sensitivity of relative and absolute measurements of CBF with NIRS-CHS (CBF_NIRS-CHS) to the physiological parameters in the CHS model. The temporal dynamics of CBF_NIRS-CHS were compared with co-localized NIRS measurements of hemoglobin difference ([HbD] = [HbO₂]−[Hb]), and with diffuse correlation spectroscopy (DCS) measurements of relative CBF. We demonstrated that NIRS-CHS provides quantitative measurements of absolute baseline CBF, and corrects [HbD] estimations of CBF dynamics for blood volume contributions and for blood transit times in the microvasculature resulting in a better agreement with CBF dynamics measured by DCS.

Guiding treatment in traumatic brain injury based on managing and optimizing cerebral perfusion pressure, which is the difference between mean arterial blood pressure and intracranial pressure (ICP), has been demonstrated to improve patient outcome. However, this requires ICP to be measured, which currently is only possible by placing pressure probes inside the brain. The feasibility of optical systems to measure ICP non-invasively has shown preliminary promising evidence of feasibility. To pursue the goal of non-invasive ICP acquisition further, an understanding of the influence of different pressure changes on the brain and their hemodynamic response is necessary. To investigate the frequency content of hemodynamic reactions to pressure changes in both ICP as well as arterial blood pressure (ABP), we induced changes of both pressures in non-human primates. We then demonstrate that ABP and ICP changes both influence cerebral blood flow and hemoglobin concentrations, measured with diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS), respectively. We found that the magnitude of induced oscillations is dependent on the frequency of the oscillation. Our data suggests, changes in ABP and ICP influence the hemodynamics differently, which we can use as a basis for non-invasive ICP measurements.

As with the functional magnetic imaging community, multiple challenges exist in standardization of data format and processing pipelines. NeuroDOT is a MATLAB-based toolbox in the style of a conventional MATLAB toolbox. Its functionality is distributed among several pipelines, with extensive functions for data quality analysis and visualization. To aid in end-user support at multiple levels of familiarity and expertise, beyond the basic functionality, NeuroDOT contains data samples, support files, help sections, appendices, and tutorials. Specifically, a set of anonymized and published data samples have been chosen to reflect common experimental paradigms in neuroimaging (e.g., retinotopy and language based tasks), and are provided in both raw and pre-processed versions to aid in troubleshooting and training for the new user. The extensive support files contain geometric information for some of our diffuse optical tomography caps, sensitivity matrices, spectroscopy matrices, and standard atlases. Together with the documentation, these files provide a blueprint for users to create counterparts for their own systems. The toolbox currently supports a wide variety of standard data file formats. Help sections for each function are searchable from the MATLAB command line, with a Help Viewer version as well, each written and formatted in the style of their native MATLAB counterparts for familiarity and ease of use. Several appendices detail data structures, pipelines and their construction, and select visualizations of our pipelines’ results for multiple data samples. Multiple tutorials provide guidance to process data through a given pipeline to help the user harness the power and flexibility of NeuroDOT.

For functional neuroimaging, existing small-animal diffuse optical tomography (DOT) systems either do not provide adequate temporal sampling rates, have sparse spatial sampling, or have limited three-dimensional fields of view. To achieve adequate frame rates (1-10 Hz), we have constructed a system using sCMOS detection-based DOT, with asymmetric measurements, with many (>10,000) detectors and fewer (<100) structured illumination patterns (using digital micromirror devices: DMDs). The system employs multiple views, involving multiple cameras and illuminators, to provide a three-dimensional field of view. To coregister the measurements with the mouse head anatomy, we developed a surface profiling method in which point illumination patterns are scanned over the mouse head and combined with calibration data to create three-dimensional point clouds and meshes representing the head. We applied this method to a 3D-printed figurine, and the resulting mesh had surface vertices whose positions deviated 0.4 ± 0.2 mm (mean ± SD) from the original "ground truth" mesh that had been employed to 3D-print the figurine. To evaluate the imaging system's resolution, field of view, and sensitivity versus depth, we placed simulated activations at different depths within a tissue model of a real mouse head imaged with our surface profiling method. Results indicate that this imaging system is sensitive to absorption changes at depths of >3 mm. In addition, a partial (one-camera, one-illuminator) version of the system successfully imaged neural activations evoked by forepaw stimulation of a live mouse.

Functional near infrared spectroscopy (fNIRS) can separately measure spatially differentiated brain functions by appropriately positioning irradiation and detection probes on the scalp, where brain region that could be assessed is limited to the adjacent region directly below the probe pair. A key challenge is determining the appropriate probe position for measuring the function of target brain region. Here, we propose an fNIRS probe positioning system using augmented reality technology. From a subject’s anatomical 3D magnetic resonance images, geometry of the head tissues including the appropriate position directly above the targeted brain region was obtained. The system captured an image of the subject’s head and several facial landmarks were extracted. Subsequently, the anatomical geometry was fitted into the captured image of the head to align with the landmark positions. Finally, the target probe positions were indicated icons on the captured head images. These were processed in real-time, while following the motion of the subject’s head. Therefore, the appropriate probe position was spatially determined by taking a video of the subject's head from various directions. The system was implemented on a generic tablet computer. Positioning accuracy of system in a mannequin head with a shape and color similar to that of a human face was assessed. Errors from the appropriate position were less than 10 mm, which is adequate for appropriate probe positioning in hemodynamic response measurement from the target gyrus, since brain gyri in human adults are approximately 10 mm in width.

Oscillations in the tissue concentrations of deoxyHemoglobin ([Hb]) and OxyHemoglobin ([HbO]) can be measured in the human brain using Near InfraRed Spectroscopy (NIRS). These oscillations may be driven by temporal dynamics of Arterial Blood Pressure (ABP). Coherent Hemodynamics Spectroscopy (CHS) is a technique that measures oscillations of [Hb] and [HbO] that are coherent with ABP. These oscillations, at a frequency of 0.1 Hz in this work, can then be interpreted with CHS to get physiologically relevant parameters to monitor cerebral AutoRegulation (AR) and microvascular integrity. Systemic oscillations in ABP can be induced with cyclic inflation and deflation of pneumatic thigh cuffs or by paced breathing. ABP oscillations may also occur spontaneously during resting conditions. Here, these three types of ABP oscillations (induced with thigh cuffs, induced with paced breathing, and spontaneously occurring) are considered, and the phase between coherent [Hb] and [HbO] oscillations is interpreted in terms of AR. In two healthy human subjects, it was found that paced breathing may be subjective, either improving or impairing AR depending on the individual paced breathing amplitude. Cuff cyclic inflations and spontaneous hemodynamics resulted in no significant difference in the relative phase of cerebral [Hb] and [HbO] oscillations at 0.1 Hz. These initial results suggest that spontaneous hemodynamics may be used for CHS in place of induced ABP oscillations, with the advantage of not relying on subject’s actions (like paced breathing) or special equipment (like pneumatic thigh cuffs).

Typical treatment for locally advanced breast cancer includes pre-surgical chemotherapy treatment to enable breast conserving surgery. Some patients, however, do not respond to chemotherapy, and endure months of treatment and unpleasant side-effects with no benefit. Near infrared spectroscopy is emerging as a promising candidate to differentiate patients responding to treatment from non-responders. Frequency-domain diffuse optical spectroscopy (FD-DOS) is capable of measuring concentrations of oxy-, and deoxyhemoglobin, lipid, and water in biological tissue. Changes in these concentrations over the course of chemotherapy can help predict a patient’s chemotherapy response. Most FD-DOS systems either use manually positioned, handheld probes, or complex arrays of source and detector fibers to acquire data from many tissue locations, allowing for the generation of 2D or 3D maps of tissue. Here, we present a new method to rapidly acquire a wide range of source-detector separations via high-speed mechanical scanning of a single source-detector pair. The scanning pattern chosen allows for the generation of axial line images of chromophore concentrations while the probe is stationary. Linear translation of the probe results in B-mode images that are capable of measuring the size and location of an absorbing inhomogeneity such as a tumor. Recently developed high speed acquisition electronics allow DOS data to be collected at nearly 100 Hz resulting in an a-line rate of 2-4 Hz. By utilizing a Deep Neural Network to estimate chromophore concentrations from the raw data, clinically relevant, depth resolved diffuse optical images of human tissue can be presented in real-time.

The aim of this study was to investigate the optical chemotherapy changes induced by neoadjuvant chemotherapy (NAC) in PgR-positive and PgR-negative breast cancer subtypes using a diffuse optical tomographic breast imaging system (DOTBIS). ctTHb reduction in the tumor volume was greater for patients with PgR-negative, a statistically significant difference of 48.91μM, p = .022, which suggest that PgR-negative tumors are generally less resistant to NAC. These observations indicate that PgR negativity may be combined to optically derived biomarkers for predicting pCR during neoadjuvant chemotherapy.

Time domain Diffuse Optical Tomography (TD-DOT) non-invasively probes the optical proprieties of biological tissue. These can be related to changes in tissue composition, thus making TD-DOT potentially valuable for cancer imaging. In particular, an application of interest is therapy monitoring for breast cancer. Thus, we developed a software tool for multiwavelength TD-DOT in reflectance geometry. While the use of multiple wavelengths probes the main components of the breast, the chosen geometry offers the advantage of linking the photon flight time to the investigated depth. We validated the tool on silicon phantoms embedding an absorbing inclusion to simulate a malignant lesion in breast tissue. Also, we exploited the a priori information on position and geometry of the inclusion by using a morphological prior constraint. The results show a good localization of the depth of inclusion but a reduced quantification. When the morphological constraint is used, though, the localization improves dramatically, also reducing surface artifacts and improving quantification as well. Still, there is room for improvement in the quantification of the “lesion” properties.

The current standard of care for treating rheumatoid arthritis (RA) involves early use of disease modifying antirheumatic drugs (DMARDs). Nevertheless, 30% of RA patients still fail their first DMARD and it takes 3–6 months to detect treatment failure with current monitoring methods; this places patients at a higher risk of irreversible joint damage. We previously developed a dynamic contrast-enhanced time-resolved near-infrared spectroscopy technique (DCE TR-NIRS) for quantifying joint blood flow (BF). We now aim to investigate whether joint BF, as measured with DCE TR-NIRS, can be used to monitor disease activity and treatment response in a rat model of RA. Arthritis was induced in 4 adult male Lewis rats using the well-established adjuvant-induced arthritis model. Baseline measurements were acquired prior to adjuvant injection on day 0. Arthritis progressed until day 20 (“Pre-treatment” phase), after which rats received DMARD treatment (Enbrel®: 0.5 ml/kg; intramuscular injection) once every 5 days (“Treatment” phase). Starting on day 0, ankle joint BF was measured every 5 days until the end of the study on day 40. Mean rat ankle joint BF (mL/min/100g) increased from 7.94±3.71 at baseline to 15.77±4.58 during the Pre-treatment phase. Following treatment, mean joint BF decreased to 12.15±1.82 mL/min/100g. This is an ongoing study and the preliminary results shown here suggest that joint BF measured with DCE TR-NIRS is sensitive to RA disease activity and could detect response to treatment.

Near-infrared spectroscopy (NIRS) has received extensive attention in the field of brain functional investigation because of its noninvasiveness, safety and environmental adaptation. Nevertheless, this modality still demands an enhancement in the measurement reliability and the channel availability for broader applications and quantitative accomplishment. In this study we have developed a three-wavelength, 240-channel continuous-wave NIRS-DOT system of lock-in photoncounting mode. The system combines high-superiority of the lock-in detection in noise suppression and parallelism capability with ultra-high sensitivity of the photon-counting technology, and provides 20 source-fiber optodes connecting to their respective three-wavelength laser diode sets and 12 detection-fiber optodes connecting to their respective photoncounting photomultiplier-tubes. The light intensity can be automatically adjusted according to the custom configurations for an optimal operation. The system has been validated using a series of static and dynamic phantom experiments, demonstrating appealing performances in stability, linearity, anti-noise, inter-channel crosstalk and temporal resolution.

Spatial frequency domain (SFD) imaging offers a wide-field modality to effectively characterize the optical properties (absorption and scattering coefficients), and furthermore to calculate the chromophore concentrations from multiwavelength measurements, in biological tissues. Previous SFD imaging systems mostly capture the two-dimensional reflected light using an expensive charge-coupled device camera that requires switching between the multi-wavelength collections. With recent proliferation in low-cost and technology we present herein a highly-sensitive novel single-pixel SFD imaging system for simultaneous and acquisition of multi-wavelength images. In the approach, three LED-sources at 455-nm, 530-nm and 660-nm wavelengths are temporally modulated at different frequencies, and all focused to the first digital micromirror device (DMD) to generate a wide-field sinusoidal illumination on tissues. The reflected signal is spatially integrated by the second DMD that is coded according to the transform matrix, and fed into a lock-in photoncounting module and temporally demodulated to extract the signals at each wavelength. The SFD images at each wavelength are recovered by single-pixel imaging algorithm, respectively, and then used to calculate the modulation transfer function for extraction of the optical properties. The proposed system is experimentally validated on phantoms, demonstrating the system stability, measurement linearity, negligible inter-wavelength crosstalk, and recovery effectiveness.

Diffuse optical tomography (DOT) is a novel functional imaging technique that has the vital clinical application. Aiming at the problems in DOT technology, we developed a three-wavelength continuous wave DOT system with high sensitivity and temporal resolution by adopting photo-multiple tube and photon counting detection, as well as lock-in technique. To assess the performance of the system, we conducted a series of cylindrical phantom experiments with optical properties that closely match those of human tissue, and obtained the reconstruction images by combining with our developed imaging scheme. The experimental results show that the position and size of the reconstructed targets are accurate, demonstrating the feasibility of the system. Additionally, the sensitivity, quantitativeness and spatial resolution of the imaging system were assessed by varying the target-to-background contrasting absorption contrast and target size. These preliminary results indicate that the system is scientifically capable of subcentimeter resolution imaging of low-contrast the lesion from the normal background.

In optical tomography, the reconstructions have only been limited to the absorption μ_a and scattering μ_s coefficients of biological tissues due to theoretical and computational limitations. In this study, The authors propose an efficient method to reconstruct, in 3D geometries, the anisotropy factor g of the Henyey-Greenstein phase function as a new optical contrast for cancer diagnosis. The light propagation in biological tissues is accurately modeled by the Radiative Transfer Equation (RTE) in the frequency domain. The adjoint method is used to efficiently compute the gradient of the objective function. A parallel implementation is carried out to reduce the computational times. The results show the robustness of the algorithm to reconstruct the g-factor for different contrast levels and for different initial guesses. The crosstalk problem between μ_s and g has been achieved with a reasonable quality which makes the new algorithm a candidate of choice to image this factor as new intrinsic contrast for optical imaging.

We advance our previous research on spread spectrum spectroscopy by adding spectroscopic functionality using a custom-made optical transceiver. The new transceiver module features a 680nm communications-grade verticalcavity surface-emitting laser (VCSEL) and matches the performance of commercial 10Gb/s optical transceivers, which allow for a sub-ns instrument response. The optical power of the VCSEL can be software-adjusted up to 2mW with ∼40μA driving current resolution. This module, combined with a commercially available Gigabit optical transceiver at 850nm, allows us to derive information about the optical properties of tissue-equivalent phantoms and the concentration of various haemodynamic parameters in in vivo measurements.

We present here a new dynamic fluorescence tomographic model that makes use of spatial-temporal constraints in order to reconstruction both fluorescent biomarkers and anatomical structure simultaneously within reasonable accuracy. A discrete cosine transformation (DCT) is used to compress images in the spatial and temporal domains. The appropriate set of dominant DCT components is found from analyzing mouse internal structure and measurements of dynamic time traces of fluorescent signals. These sought characteristic functions are used later as spatial-temporal constraints in the reconstruction, which can aid to bring internal structure of major organs as well as fluorescent biomarkers into the reconstruction image. We use radiative transfer equation (RTE) as a light propagation model that provides more accurate predictions of light distribution in small geometries and high absorbing media. In addition, the reconstructed tomographic images are processed with principal components analysis (PCA) in order to differential between various regions with different functional kinetic behaviors. The performance of this new method is tested using a dynamic data of fluorescent signals resulting from changes in tumor vasculature in response to anti-angiogenesis, and the preliminary results have been presented to show the potential of the proposed dynamic fluorescence tomographic model.

Optical tomography imaging (OTI) of joints is challenging since light is highly scattered by tissue, leading to poor spatial resolution. Image quality can be improved by early-photons imaging; however, the image reconstruction will require more advanced forward models than the classic methods based on the diffusion approximation. We aim to use Monte-Carlo simulations as forward model for early-photons OTI. To test the feasibility, DICOM images of the hand of an adult male, obtained from an MRI, were imported into 3DSlicer where the bones and soft tissue were segmented. The MATLAB-based toolbox Iso2Mesh was used to generate a 3D volumetric mesh of the segmented image. Typical optical properties (i.e., absorption coefficient, scattering coefficient, anisotropic index, and refractive index) of bone and soft tissue were assigned to each node of the 3D mesh and light propagation was simulated using the Mesh-based MonteCarlo (MMC) toolbox. Our results show that our approach can reliable model propagation of early-photons in the highly heterogeneous human wrist.

Bioluminescence tomography (BLT) is a promising optical imaging tool broadly used in preclinical research to observe and quantify the distribution of bioluminescent markers in small animal models. However, due to the highly scattering property of the biological tissues and the limited surface measurements, fast and precise reconstruction in BLT remains a challenging problem. Permissible source region is a cost-effective strategy to partially solve the problem. In this paper, we present a matched filtering based strategy to extract the permissible region (PSR) adaptively for bioluminescence tomography. First, a digital matched filter is formulated according to the forward weight matrix, then the surface measurements are filtered and the permissible source region is extracted according to the first several biggest outputs of the matched filter larger than a threshold value, and finally the bioluminescent source in the permissible source region is recovered. Numerical simulation experiments are performed to evaluate the performance of the proposed method. The results show that the number of unknowns can be significantly reduced even using a small threshold value and the BLT reconstruction quality can be improved with appropriate PSR.

We have compared different methods for analyzing dynamic changes of oxy- and deoxyhemoglobin concentrations oscillations, measured by near infrared spectroscopy (NIRS), during cyclic pneumatic thigh cuff occlusion and release at the frequency of 0.1 Hz. This protocol is usually adopted in coherence hemodynamics spectroscopy (CHS) to induce controlled arterial blood pressure perturbations which drive hemodynamic changes in the brain. It is a general problem of NIRS to differentiate hemodynamic signals originated in the brain from those in the extracerebral tissue layer. The purpose of this study is to gain some understanding about the spatial origin of the oscillating optical signals according to these five different methods of data analysis during the thigh cuff occlusion and release protocol. The results obtained on six human subjects show that similar qualitative behavior of oxy- and deoxyhemoglobin dynamic changes are found by using: (1) modified Beer-Lambert law at far source detector separations (d > 25 mm); (2) DC intensity slope method at d > 25 mm; (3) multi-distance method at d >25 mm; (4) Two-layer modified Beer-Lambert law (using d > 25 mm) when we consider dynamic changes in the second (deeper) layer. At short source-detector separations (d < 15 mm), the hemoglobin concentration changes obtained with the modified Beer-Lambert law are consistent with those obtained for the first (superficial) layer with the two-layer modified Beer-Lambert law. For more quantitative assessment of cerebral dynamic changes, we argue that DC slope or two-layer modified Beer-Lambert law should provide better estimates. We support this claim by comparing the sensitivity to layered absorption perturbations obtained by using the modified BeerLambert law and the DC slope methods.

Current wearable optical technologies generally utilize superficial tissue continuous-wave measurements for biological metrics such as heart rate monitoring. There has been limited prior work in wearables that extract quantitative information including tissue optical properties and hemoglobin concentrations. These parameters may assist in tracking physiological status for cardio-pulmonary conditions and cancer. Next-generation optical wearables must meet substantial technical requirements, including small footprint, high sensitivity, and thermal stability. Here we investigate the use of a new multi-wavelength optical laser and compact avalanche photodiode for use in a miniaturized diffuse optical frequency-domain optode (miniOptode). These components represent the most compact fiberless optode for frequency-domain measurements to date. The miniOptode had high SNR (53.5dB at 50 MHz), and achieved high accuracy and precision in optical property extractions (accuracy: μ_a 0.0018 mm^-1 and μ_s′ 0.0547 mm^-1; precision: μ_a 0.00008mm^-1 and μ_s′ 0.0015 mm^-1). It provided high SNR for test measurements taken on nine different anatomic locations and was capable of tracking hemodynamics during a cuff occlusion test. Active thermoelectric cooling was required for thermal stability during longer tissue measurements. This work demonstrates that frequency domain diffuse optical measurements can be achieved in a highly portable format, providing new opportunities for long-term monitoring with quantitative oximetry.

A semi-empirical model initiated in 2009 has facilitated clinical investigations of steady-state single-fiber reflectance spectroscopy (SfRS). We demonstrate an integration model for steady-state SfRS. Our model treats the single-fiber diffuse reflectance as the integration of a lever-set spatially resolved diffuse reflectance associated with a light incidence at the center of the fiber over the entire fiber facet. The integration over the collection area with a diameter ݀d_fib reproduces the steady-state features of SfRS over the dimensionless reduced scattering μ_sd_fib= [10^-2, 10³], absorption coefficient μ_a=[0.001, 1.0] mm^-1 and an anisotropy factor ݃g= 0.9 for the Henyey-Greenstein scattering phase function.

Functional Diffuse Optical Tomography (fDOT) has the potential to provide the functional status of tissue by mapping 3D distribution of chromophores concentration in deep tissue non-inversely. Region-of-Interest (ROI) DOT, we presented earlier, uses optical patch using only a few NIR light sources and detectors arranged in a circular pattern for the depth-sensitive 3D DOT imaging of the tissue at a high-speed. However, ROI DOT system is not portable enough to carry with and to operate in an unconstrained setting. In this work, we have developed a handheld ROI fDOT system that allows functional imaging of tissue wirelessly. We have proposed a new embedded system architecture based on the Internet-of-things (IoT) concept. Our low-level embedded system and analog circuit design, and embedded computing algorithm also capable of source modulation, lock-in detection, onboard calibration and basic signal processing for the continuous wave (cw) DOT measurement at a high speed while reducing the overall form factor of the system. The optical probe has two sets of source and detector, each contains four triple-wavelengths NIR LEDs and four silicon-photodiode detectors arranged at two different source-detector separations. The handheld system sends measured data to a server wirelessly in real-time. The server performs high-speed GPU-based ROI 3D fDOT image reconstruction and displays result at 3 frames-per-second. The image reconstruction algorithm solves the diffusion equation using the finite element method and utilizes two depth sensitive measurement sets. The experimental results of regional tissue imaging on eight participants have proven the working of the system.