Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy.

BACKGROUND: Breast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment. METHODS: A total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created. RESULTS: We observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The "Tumor volume" model and the "Vascularization index" model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively). CONCLUSIONS: Diffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Quantification of bowel ischaemia using real-time multispectral Single Snapshot Imaging of Optical Properties (SSOP).

BACKGROUND: Single snapshot imaging of optical properties (SSOP) is a relatively new non-invasive, real-time, contrast-free optical imaging technology, which allows for the real-time quantitative assessment of physiological properties, including tissue oxygenation (StO2). This study evaluates the accuracy of multispectral SSOP in quantifying bowel ischaemia in a preclinical experimental model. METHODS: In six pigs, an ischaemic bowel segment was created by dividing the arcade branches. Five regions of interest (ROIs) were identified on the bowel loop, as follows: ROI 1: central ischaemic; ROI 2: left marginal; ROI 3: left vascularised; ROI 4: right marginal; and ROI 5: right vascularised. The Trident imaging system, specifically developed for real-time tissue oxygenation imaging using SSOP, was used to image before (T0) and after ischaemia induction. Capillary and systemic lactates were measured at each time point (T0, T15, T30, T45, T60), as well as StO2 values acquired by means of SSOP (SSOP-StO2). RESULTS: The mean value of SSOP-StO2 in ROI 1 was 30.08 ± 6.963 and was significantly lower when compared to marginal ROIs (ROI 2 + ROI 4: 45.67 ± 10.02 p = < 0.0001), and to vascularised ROIs (ROI 3 + ROI 5: 48.08 ± 7.083 p = < 0.0001). SSOP-StO2 was significantly correlated with normalised lactates r = - 0.5892 p < 0.0001 and with histology r =- 0.6251 p = 0.0002. CONCLUSION: Multispectral SSOP allows for a contrast-free accurate assessment of small bowel perfusion identifying physiological tissue oxygenation as confirmed with perfusion biomarkers.

Sensor-to-Image Based Neural Networks: A Reliable Reconstruction Method for Diffuse Optical Imaging of High-Scattering Media.

Imaging tasks today are being increasingly shifted toward deep learning-based solutions. Biomedical imaging problems are no exception toward this tendency. It is appealing to consider deep learning as an alternative to such a complex imaging task. Although research of deep learning-based solutions continues to thrive, challenges still remain that limits the availability of these solutions in clinical practice. Diffuse optical tomography is a particularly challenging field since the problem is both ill-posed and ill-conditioned. To get a reconstructed image, various regularization-based models and procedures have been developed in the last three decades. In this study, a sensor-to-image based neural network for diffuse optical imaging has been developed as an alternative to the existing Tikhonov regularization (TR) method. It also provides a different structure compared to previous neural network approaches. We focus on realizing a complete image reconstruction function approximation (from sensor to image) by combining multiple deep learning architectures known in imaging fields that gives more capability to learn than the fully connected neural networks (FCNN) and/or convolutional neural networks (CNN) architectures. We use the idea of transformation from sensor- to image-domain similarly with AUTOMAP, and use the concept of an encoder, which is to learn a compressed representation of the inputs. Further, a U-net with skip connections to extract features and obtain the contrast image, is proposed and implemented. We designed a branching-like structure of the network that fully supports the ring-scanning measurement system, which means it can deal with various types of experimental data. The output images are obtained by multiplying the contrast images with the background coefficients. Our network is capable of producing attainable performance in both simulation and experiment cases, and is proven to be reliable to reconstruct non-synthesized data. Its apparent superior performance was compared with the results of the TR method and FCNN models. The proposed and implemented model is feasible to localize the inclusions with various conditions. The strategy created in this paper can be a promising alternative solution for clinical breast tumor imaging applications.

A New Method Based on Graphics Processing Units for Fast Near-Infrared Optical Tomography.

The accuracy of images obtained by Diffuse Optical Tomography (DOT) could be substantially increased by the newly developed time resolved (TR) cameras. These devices result in unprecedented data volumes, which present a challenge to conventional image reconstruction techniques. In addition, many clinical applications require taking photons in air regions like the trachea into account, where the diffusion model fails. Image reconstruction techniques based on photon tracking are mandatory in those cases but have not been implemented so far due to computing demands. We aimed at designing an inversion algorithm which could be implemented on commercial graphics processing units (GPUs) by making use of information obtained with other imaging modalities. The method requires a segmented volume and an approximately uniform value for the reduced scattering coefficient in the volume under study. The complex photon path is reduced to a small number of partial path lengths within each segment resulting in drastically reduced memory usage and computation time. Our approach takes advantage of wavelength normalized data which renders it robust against instrumental biases and skin irregularities which is critical for realistic clinical applications. The accuracy of this method has been assessed with both simulated and experimental inhomogeneous phantoms showing good agreement with target values. The simulation study analyzed a phantom containing a tumor next to an air region. For the experimental test, a segmented cuboid phantom was illuminated by a supercontinuum laser and data were gathered by a state of the art TR camera. Reconstructions were obtained on a GPU-installed computer in less than 2 h. To our knowledge, it is the first time Monte Carlo methods have been successfully used for DOT based on TR cameras. This opens the door to applications such as accurate measurements of oxygenation in neck tumors where the presence of air regions is a problem for conventional approaches.

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges.

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system.

Spatial Distribution of Changes in Oxidised Cytochrome C Oxidase During Visual Stimulation Using Broadband Near Infrared Spectroscopy Imaging.

Functional hyperaemia, characterised as an increase in concentration of oxyhaemoglobin [HbO2] and a decrease in concentration of deoxyhaemoglobin [HHb] in response to neuronal activity, can be precisely mapped using diffuse optical spectroscopy. However, such techniques do not directly measure changes in metabolic activity during neuronal activation. Changes in the redox state of cerebral oxidised cytochrome c oxidase Δ[oxCCO] measured by broadband spectroscopy may be a more specific marker of neuronal metabolic activity. This study aims to investigate the spatial distribution of Δ[oxCCO] responses during the activation of the visual cortex in the healthy adult human brain, and reconstruct images of these changes.Multi-channel broadband NIRS measurements were collected from the left visual cortex of four healthy volunteers using an in-house broadband spectrometer during an inverting checkerboard visual stimulation paradigm. Δ[HbO2], Δ[HHb] and Δ[oxCCO] were calculated by fitting the broadband spectra between 780 and 900 nm using the UCLn algorithm. Centre of gravity analysis was applied to the concentration data to determine the centres of activation for [HbO2], [HHb] and [oxCCO].All four subjects showed similar changes in [oxCCO] in the presence of a typical visual-evoked haemodynamic response in channels overlying the visual cortex. Image reconstruction of the optical data showed a clear and spatially localized activation for all three chromophores. Centre of gravity analysis showed different localisation of the changes in each of the three chromophores across the visual cortex with the x-y coordinates of the mean centres of gravity (across 4 subjects) of HbO2, HHb and oxCCO at (63.1 mm; 24.8 mm), (56.2 mm; 21.0 mm) and (63.7 mm; 23.8 mm), respectively.The spatial distribution of Δ[oxCCO] response appears distinct from the haemodynamic response in the human visual cortex. Image reconstruction of Δ[oxCCO] shows considerable promise as a technique to visualise regional variation in [oxCCO] in a range of scenarios.

A 4D neonatal head model for diffuse optical imaging of pre-term to term infants.

Diffuse optical tomography is most accurate when an individual's MRI data can be used as a spatial prior for image reconstruction and for visualization of the resulting images of changes in oxy- and deoxy-hemoglobin concentration. As this necessitates an MRI scan to be performed for each study, which undermines many of the advantages of diffuse optical methods, the use of registered atlases to model the individual's anatomy is becoming commonplace. Infant studies require carefully age-matched atlases because of the rapid growth and maturation of the infant brain. In this paper, we present a 4D neonatal head model which, for each week from 29 to 44 weeks post-menstrual age, includes: 1) a multi-layered tissue mask which identifies extra-cerebral layers, cerebrospinal fluid, gray matter, white matter, cerebellum and brainstem, 2) a high-density tetrahedral head mesh, 3) surface meshes for the scalp, gray-matter and white matter layers and 4) cranial landmarks and 10-5 locations on the scalp surface. This package, freely available online at www.ucl.ac.uk/medphys/research/4dneonatalmodel can be applied by users of near-infrared spectroscopy and diffuse optical tomography to optimize probe locations, optimize image reconstruction, register data to cortical locations and ultimately improve the accuracy and interpretation of diffuse optical techniques in newborn populations.

Atlas-based head modeling and spatial normalization for high-density diffuse optical tomography: in vivo validation against fMRI.

Diffuse optical imaging (DOI) is increasingly becoming a valuable neuroimaging tool when fMRI is precluded. Recent developments in high-density diffuse optical tomography (HD-DOT) overcome previous limitations of sparse DOI systems, providing improved image quality and brain specificity. These improvements in instrumentation prompt the need for advancements in both i) realistic forward light modeling for accurate HD-DOT image reconstruction, and ii) spatial normalization for voxel-wise comparisons across subjects. Individualized forward light models derived from subject-specific anatomical images provide the optimal inverse solutions, but such modeling may not be feasible in all situations. In the absence of subject-specific anatomical images, atlas-based head models registered to the subject's head using cranial fiducials provide an alternative solution. In addition, a standard atlas is attractive because it defines a common coordinate space in which to compare results across subjects. The question therefore arises as to whether atlas-based forward light modeling ensures adequate HD-DOT image quality at the individual and group level. Herein, we demonstrate the feasibility of using atlas-based forward light modeling and spatial normalization methods. Both techniques are validated using subject-matched HD-DOT and fMRI data sets for visual evoked responses measured in five healthy adult subjects. HD-DOT reconstructions obtained with the registered atlas anatomy (i.e. atlas DOT) had an average localization error of 2.7mm relative to reconstructions obtained with the subject-specific anatomical images (i.e. subject-MRI DOT), and 6.6mm relative to fMRI data. At the group level, the localization error of atlas DOT reconstruction was 4.2mm relative to subject-MRI DOT reconstruction, and 6.1mm relative to fMRI. These results show that atlas-based image reconstruction provides a viable approach to individual head modeling for HD-DOT when anatomical imaging is not available.

Label-free assessment of the transformation zone using multispectral diffuse optical imaging toward early detection of cervical cancer.

The assessment of the transformation zone is a critical step toward diagnosis of cervical cancer. This work involves the development of a portable, label-free transvaginal multispectral diffuse optical imaging (MDOI) imaging probe to estimate the transformation zone. The images were acquired from N = 5 (N = 1 normal, N = 2 premalignant, and N = 2 malignant) patients. Key parameters such as spectral contrast ratio (ρ) at 545 and 450 nm were higher in premalignant (0.29, 0.25 for 450 nm and 0.30, 0.17 for 545 nm) as compared to the normal patients (0.13 and 0.14 for 450 and 545 nm, respectively). The threshold for the spectral intensity ratio R610/R450 and R610/R545 can also be used as a marker to correlate with the new and original squamous columnar junction (SCJ), respectively. The pilot study highlights the use of new markers such as spectral contrast ratio (ρ) and spectral intensity ratio (R610/R450 and R610/R545) images.

Using spectral derivatives to remove the influence of hair on optical images of the static absorbing properties of tissue-like turbid media.

Significance: Although measurements of near-infrared light diffusely reflected from the head and other biological tissues are commonly used to generate images revealing changes in the concentrations of oxy- and deoxy-hemoglobin, static imaging of absolute concentrations has been inhibited by the unknown and variable coupling between the optical probe and the skin, to which hair is often a significant contributor. Measurements of spectral derivatives provide a means of overcoming this shortcoming. Aim: The aim is to demonstrate experimentally that measurements of the derivative of the attenuation of the detected signal with respect to wavelength can be used to achieve images that are immune to the spatial variation of hair on the surface. The objective is to generate topographic images representative of static absorbing properties rather than retrieving absolute optical coefficients, which requires a tomographic approach. Approach: The surface of a tissue-equivalent phantom, containing targets with different concentrations of absorbing dye, was coated with a layer of dark hair. The phantom was then imaged using a broadband source and spectrometer, and prior knowledge of the absorbing characteristics of the dye and of melanin was used to acquire separate images of each. Results: The targets within the phantom are revealed with remarkable clarity, although a nonlinear relationship between the target contrast and absorption was observed. This nonlinear behavior was confirmed and explained using a Monte Carlo model of light propagation in a slab of similar absorbing properties. Conclusions: A spectral derivative approach could be an effective tool for in vivo topographic imaging of the static optical properties of the brain and other tissues, avoiding the deleterious effects of hair.

Alzheimer's disease progression detection based on optical fluence rate measurements using alternative laser wavelengths.

Alzheimer's disease (AD) levels have increased globally, which is considered the sixth reason for deaths. So, a requirement exists for economic and quantitative methods to follow up the gradual progression of AD. The current study presents a simulation for a non-irradiated, safe, wearable, and noninvasive mobile approach for detecting the progression of Alzheimer's brain atrophy using the optical diffusion technique and for investigating the difference between the normal and the diseased brain. The virtual study was accomplished using COMSOL Multiphysics. The simulated head is implemented as the following: scalp, skull, cerebrospinal fluid, gray matter, and white matter. The optical properties of the heterogeneous tissue are observed using the fluence rate after irradiating the head with different wavelengths (630, 700, 810, 915, and 1000 nm) of lasers. Two assessment techniques were applied to evaluate the brain atrophy measurements; the first technique was an array of photodetectors, which were lined at the head posterior, while a matrix of photodetectors was applied over the head surface in the second technique. The results show that the surface photodetectors approach differentiates the normal from AD brains without measuring the brain atrophy percentages by applying 630 nm. The array of photodetectors distinguishes normal from AD brains without detecting the brain atrophy percentages when the wavelengths 630, 700, and 810 nm were applied. The line detector at 1000 nm evaluates the brain atrophy percentages with AD. The future explores applying those techniques in vivo and analyzing the information by the spectrometer for extensively safer early detection of neural disorders.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: theoretical development and in silico validation.

Objective.Effective early treatment-within 3-5 months of disease onset-significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 1 in 3 patients experiences treatment failure which takes 3-6 months to detect with current monitoring techniques. The aim of this work is to develop a method for extracting quantitative features from data obtained with time-domain diffuse optical imaging (TD-DOI), and demonstrate their sensitivity to RA disease activity.Approach.80 virtual phantoms of the proximal interphalangeal joint-obtained from a realistic tissue distribution derived from magnetic resonance imaging-were created to simulate RA-induced alterations in 5 physiological parameters. TD-DOI images were generated using Monte Carlo simulations, and Poisson noise was added to each image. Subsequently, each image was convolved with an instrument response function (IRF) to mimic experimental measurements. Various spatiotemporal features were extracted from the images (i.e. statistical moments, temporal Fourier components), corrected for IRF effects, and correlated with the disease index (DI) of each phantom.Main results.Spatiotemporal Fourier components of TD-DOI images were highly correlated with DI despite the confounding effects of noise and the IRF. Moreover, lower temporal frequency components (⩽0.4 GHz) demonstrated greater sensitivity to small changes in disease activity than previously published spatial features extracted from the same images.Significance.Spatiotemporal components of TD-DOI images may be more sensitive to small changes in RA disease activity than previously reported DOI features. TD-DOI may enable earlier detection of RA treatment failure, which would reduce the time needed to identify treatment failure and improve patient prognosis.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: experimental validation in tissue-mimicking finger phantoms.

Objective.Effective treatment within 3-5 months of disease onset significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 30% of RA patients fail their first treatment, and it takes 3-6 months to identify failure with current monitoring techniques. Time-domain diffuse optical imaging (TD-DOI) may be more sensitive to RA disease activity and could be used to detect treatment failure. In this report, we present the development of a TD-DOI hand imaging system and validate its ability to measure simulated changes in RA disease activity using tissue-mimicking finger phantoms.Approach.A TD-DOI system was built, based on a single-pixel camera architecture, and used to image solid phantoms which mimicked a proximal interphalangeal finger joint. For reference,in silicoimages of virtual models of the solid phantoms were also generated using Monte Carlo simulations. Spatiotemporal Fourier components were extracted from both simulated and experimental images, and their ability to distinguish between phantoms representing different RA disease activity was quantified.Main results.Many spatiotemporal Fourier components extracted from TD-DOI images could clearly distinguish between phantoms representing different states of RA disease activity.Significance.A TD-DOI system was built and validated using finger-mimicking solid phantoms. The findings suggest that the system could be used to monitor RA disease activity. This single-pixel TD-DOI system could be used to acquire longitudinal measures of RA disease activity to detect early treatment failure.

Shortwave infrared diffuse optical wearable probe for quantification of water and lipid content in emulsion phantoms using deep learning.

Significance: The shortwave infrared (SWIR, ∼900 to 2000 nm) holds promise for label-free measurements of water and lipid content in thick tissue, owed to the chromophore-specific absorption features and low scattering in this range. In vivo water and lipid estimations have potential applications including the monitoring of hydration, volume status, edema, body composition, weight loss, and cancer. To the best of our knowledge, there are currently no point-of-care or wearable devices available that exploit the SWIR wavelength range, limiting clinical and at-home translation of this technology. Aim: To design and fabricate a diffuse optical wearable SWIR probe for water and lipid quantification in tissue. Approach: Simulations were first performed to confirm the theoretical advantage of SWIR wavelengths over near infrared (NIR). The probe was then fabricated, consisting of light emitting diodes at three wavelengths (980, 1200, 1300 nm) and four source-detector (S-D) separations (7, 10, 13, 16 mm). In vitro validation was then performed on emulsion phantoms containing varying concentrations of water, lipid, and deuterium oxide (D2O). A deep neural network was developed as the inverse model for quantity estimation. Results: Simulations indicated that SWIR wavelengths could reduce theoretical water and lipid extraction errors from ∼6% to ∼1% when compared to NIR wavelengths. The SWIR probe had good signal-to-noise ratio (>32 dB up to 10 mm S-D) and low drift (<1.1% up to 10 mm S-D). Quantification error in emulsion phantoms was 2.1±1.1% for water and -1.2±1.5% for lipid. Water estimation during a D2O dilution experiment had an error of 3.1±3.7%. Conclusions: This diffuse optical SWIR probe was able to quantify water and lipid contents in vitro with good accuracy, opening the door to human investigations.

Dual-slope imaging of cerebral hemodynamics with frequency-domain near-infrared spectroscopy.

Significance: This work targets the contamination of optical signals by superficial hemodynamics, which is one of the chief hurdles in non-invasive optical measurements of the human brain. Aim: To identify optimal source-detector distances for dual-slope (DS) measurements in frequency-domain (FD) near-infrared spectroscopy (NIRS) and demonstrate preferential sensitivity of DS imaging to deeper tissue (brain) versus superficial tissue (scalp). Approach: Theoretical studies (in-silico) based on diffusion theory in two-layered and in homogeneous scattering media. In-vivo demonstrations of DS imaging of the human brain during visual stimulation and during systemic blood pressure oscillations. Results: The mean distance (between the two source-detector distances needed for DS) is the key factor for depth sensitivity. In-vivo imaging of the human occipital lobe with FD NIRS and a mean distance of 31 mm indicated: (1) greater hemodynamic response to visual stimulation from FD phase versus intensity, and from DS versus single-distance (SD); (2) hemodynamics from FD phase and DS mainly driven by blood flow, and hemodynamics from SD intensity mainly driven by blood volume. Conclusions: DS imaging with FD NIRS may suppress confounding contributions from superficial hemodynamics without relying on data at short source-detector distances. This capability can have significant implications for non-invasive optical measurements of the human brain.

Gen-2 hand-held optical imager towards cancer imaging: reflectance and transillumination phantom studies.

Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1-5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies.

Anthropomorphic Polydimethylsiloxane silicone-based phantom for Diffuse Optical Imaging.

This work presents a method for constructing phantoms suitable for diffuse optical mammography. They are based on Polydimethylsiloxane silicones, with the characteristic of being anthropomorphic, and having similar mechanical and optical properties as a real breast. These phantoms are useful for testing the performance of diffuse optical imaging devices in the near infrared, both in transmittance and reflectance geometries, since they can be constructed containing inclusions, to simulate breast tumors. An alternative component to be used as scattering agent, that is easier to handle than traditional scattering agents, is also studied. The optical properties of the phantoms were tested varying the concentration of scattering and absorbing agents, while their mechanical properties were modified by adding a silicone fluid to the basic mixture. Finally, the phantoms were tested by Diffuse Optical Imaging experiments, and these images were compared to the ones obtained by conventional ultrasound techniques. Results show that the constructed anthropomorphic phantoms properly reproduce the optical and mechanical characteristics of human breasts, and are suitable to be used in Diffuse Optical Imaging.

Quantitative molecular bioluminescence tomography.

SIGNIFICANCE: Bioluminescence imaging and tomography (BLT) are used to study biologically relevant activity, typically within a mouse model. A major limitation is that the underlying optical properties of the volume are unknown, leading to the use of a "best" estimate approach often compromising quantitative accuracy. AIM: An optimization algorithm is presented that localizes the spatial distribution of bioluminescence by simultaneously recovering the optical properties and location of bioluminescence source from the same set of surface measurements. APPROACH: Measured data, using implanted self-illuminating sources as well as an orthotopic glioblastoma mouse model, are employed to recover three-dimensional spatial distribution of the bioluminescence source using a multi-parameter optimization algorithm. RESULTS: The proposed algorithm is able to recover the size and location of the bioluminescence source while accounting for tissue attenuation. Localization accuracies of <1 mm are obtained in all cases, which is similar if not better than current "gold standard" methods that predict optical properties using a different imaging modality. CONCLUSIONS: Application of this approach, using in-vivo experimental data has shown that quantitative BLT is possible without the need for any prior knowledge about optical parameters, paving the way toward quantitative molecular imaging of exogenous and indigenous biological tumor functionality.

In Vivo Validation of Diffuse Optical Imaging with a Dual-Direction Measuring Module of Parallel-Plate Architecture for Breast Tumor Detection.

We demonstrate a working prototype of an optical breast imaging system involving parallel-plate architecture and a dual-direction scanning scheme designed in combination with a mammography machine; this system was validated in a pilot study to demonstrate its application in imaging healthy and malignant breasts in a clinical environment. The components and modules of the self-developed imaging system are demonstrated and explained, including its measuring architecture, scanning mechanism, and system calibration, and the reconstruction algorithm is presented. Additionally, the evaluation of feature indices that succinctly demonstrate the corresponding transmission measurements may provide insight into the existence of malignant tissue. Moreover, five cases are presented including one subject without disease (a control measure), one benign case, one suspected case, one invasive ductal carcinoma, and one positive case without follow-up treatment. A region-of-interest analysis demonstrated significant differences in absorption between healthy and malignant breasts, revealing the average contrast between the abnormalities and background tissue to exceed 1.4. Except for ringing artifacts, the average scattering property of the structure densities was 0.65-0.85 mm-1.

High optode-density wearable diffuse optical probe for monitoring paced breathing hemodynamics in breast tissue.

SIGNIFICANCE: Diffuse optical imaging (DOI) provides in vivo quantification of tissue chromophores such as oxy- and deoxyhemoglobin (HbO2 and HHb, respectively). These parameters have been shown to be useful for predicting neoadjuvant treatment response in breast cancer patients. However, most DOI devices designed for the breast are nonportable, making frequent longitudinal monitoring during treatment a challenge. Furthermore, hemodynamics related to the respiratory cycle are currently unexplored in the breast and may have prognostic value. AIM: To design, fabricate, and validate a high optode-density wearable continuous wave diffuse optical probe for the monitoring of breathing hemodynamics in breast tissue. APPROACH: The probe has a rigid-flex design with 16 dual-wavelength sources and 16 detectors. Performance was characterized on tissue-simulating phantoms, and validation was performed through flow phantom and cuff occlusion measurements. The breasts of N = 4 healthy volunteers were measured while performing a breathing protocol. RESULTS: The probe has 512 unique source-detector (S-D) pairs that span S-D separations of 10 to 54 mm. It exhibited good performance characteristics: µa drift of 0.34%/h, µa precision of 0.063%, and mean SNR ≥ 24 dB up to 41 mm S-D separation. Absorption contrast was detected in flow phantoms at depths exceeding 28 mm. A cuff occlusion measurement confirmed the ability of the probe to track expected hemodynamics in vivo. Breast measurements on healthy volunteers during paced breathing revealed median signal-to-motion artifact ratios ranging from 8.1 to 8.7 dB. Median ΔHbO2 and ΔHHb amplitudes ranged from 0.39 to 0.67 µM and 0.08 to 0.12 µM, respectively. Median oxygen saturations at the respiratory rate ranged from 82% to 87%. CONCLUSIONS: A wearable diffuse optical probe has been designed and fabricated for the measurement of breast tissue hemodynamics. This device is capable of quantifying breathing-related hemodynamics in healthy breast tissue.