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The development of non-destructive, tomographic imaging systems is a current topic of research in biomedical technologies. One of these technologies is Scanning Laser Optical Tomography (SLOT), which features a highly modular setup with various contrast mechanisms. Extending this technology with new acquisition mechanisms allows us to investigate untreated and non-stained biological samples, leaving their natural biological physiology intact. To enhance the development of SLOT, we aimed to extend the density of information with a significant increase of acquisition channels. This should allow us to investigate samples with unknown emission spectra and even allow for label-fee cell identification. We developed and integrated a hyperspectral module into an existing SLOT system. The adaptations allow for the acquisition of three-dimensional datasets containing a highly increased information density. For validation, artificial test objects were made from fluorescent acrylic and acquired with the new hyperspectral setup. In addition, measurements were made on two different human cell spheroids with an unknown spectra, to test the possibilities of label-free cell identification. The validation measurements of the artificial test target show the expected results. Furthermore, the measurements of the biological cell spheroids show small variations in their tomographic spectrum that allow for label-free cell type differentiation. The results of the biological sample demonstrate the potential of label-free cell identification of the newly developed setup., (© 2024. The Author(s).)

Purpose: Employing a Fresnel lens and a point-like light source to create a convergent light beam for the camera effectively minimizes stray light and enhances image quality in optical computed tomography (OCT), benefiting 3D dosimetry applications. This study outlines the development of an economical cone-beam optical computed scanner for 3D dosimetry., Methods: Optical performance was assessed by calculating modulation transfer function (MTF) with pattern charts. Stray light was evaluated by imaging a cylinder flask and a square grid with 5 mm diameter holes to determine the stray-to-primary ratio. Reconstruction quality was determined using SIRT-TV and compared with spectrophotometry attenuation coefficients, with the best regularization parameter (λ = 0.01) chosen based on contrast-to-noise ratio (CNR). Dosimetry performance was assessed by determining percentage dose depth (PDD) for a 6MV beam with a 5 × 5 cm 2 field using FXO-f gel dosimeter, compared with ionization chamber data., Results: MTF evaluation yielded ≥ 50 % agreement with pattern charts. Stray-to-primary ratio was less than 0.1 or 10 % of the total signal. Reconstruction showed low noise and artifacts, with optimal CNR at λ = 0.01. Attenuation coefficients from optical CT aligned with spectrometer measurements within 1.2 %. PDD calculated with FXO-f gel dosimeter closely matched ionization chamber data (<1.2 % difference), achieving a dose resolution of 0.1 Gy., Conclusion: The built and optimization the de optical-CT based on a convergent beam is read to perform the 3D quality assurance in clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Significance: Frequency-domain diffuse optical tomography (FD-DOT) could enhance clinical breast tumor characterization. However, conventional diffuse optical tomography (DOT) image reconstruction algorithms require case-by-case expert tuning and are too computationally intensive to provide feedback during a scan. Deep learning (DL) algorithms front-load computational and tuning costs, enabling high-speed, high-fidelity FD-DOT., Aim: We aim to demonstrate a simultaneous reconstruction of three-dimensional absorption and reduced scattering coefficients using DL-FD-DOT, with a view toward real-time imaging with a handheld probe., Approach: A DL model was trained to solve the DOT inverse problem using a realistically simulated FD-DOT dataset emulating a handheld probe for human breast imaging and tested using both synthetic and experimental data., Results: Over a test set of 300 simulated tissue phantoms for absorption and scattering reconstructions, the DL-DOT model reduced the root mean square error by 12 % ± 40 % and 23 % ± 40 % , increased the spatial similarity by 17 % ± 17 % and 9 % ± 15 % , increased the anomaly contrast accuracy by 9 % ± 9 % ( μ a ), and reduced the crosstalk by 5 % ± 18 % and 7 % ± 11 % , respectively, compared with model-based tomography. The average reconstruction time was reduced from 3.8 min to 0.02 s for a single reconstruction. The model was successfully verified using two tumor-emulating optical phantoms., Conclusions: There is clinical potential for real-time functional imaging of human breast tissue using DL and FD-DOT., (© 2024 The Authors.)

Background: Tissue mimicking optical phantoms are commonly used to calibrate or validate the performance of near-infrared spectroscopy or tomography. Human tissue is not only irregular in shape, but also exhibits dynamic behaviour, which can cause changes in optical properties. However, existing phantoms lack complex structures and/or continuously varying optical properties., Aim: The project aimed to design, fabricate and characterise a novel phantom system for testing near-infrared imaging devices., Material and Methods: We designed a dynamic tissue-mimicking phantom platform which features arbitrary internal shapes and variable optical properties. The solid part of phantom was made of silicone material with absorbing and scattering properties similar to the brain. We printed a semi-ellipsoidal sphere (a major axis = 20 mm and a minor axis = the third axis = 12 mm) using a water-soluble material polyvinyl alcohol (PVA). The shape was placed at the depth of 5 mm in the silicone bulk. The desired internal hollow structure was formed after curing and submerging the phantom in water. The liquid part contained dyes and Intralipid. The optical properties within the internal shape were adjusted by injecting the liquid solutions of varying dye concentrations with a syringe pump at a constant rate. The phantom was measured by a frequency domain near-infrared spectroscopy (FD NIRS) and imaged by a time domain near-infrared optical tomography (TD NIROT)., Results and Discussion: A dynamic phantom system with a complex internal structure and varying optical properties was created. Changes in light intensity were detected by the FD NIRS. The internal structure of this phantom was accurately recovered by NIROT image reconstruction., Conclusion: We successfully developed a novel phantom system with an internal complex shape and continuously adjustable optical properties. This phantom was accurately imaged using NIROT, and the changing light intensity was detected by NIRS. It is a valuable tool for validating optical technologies., (© 2024. Oxygen Transport to Tissue International.)

Several multifocal displays have been proposed to provide accurate accommodation cues. However, multifocal displays have an undesirable feature, which is especially emphasized in near-eye displays configuration, that the field of views (FOVs) of the virtual planes change over depth. We demonstrate that this change in FOV causes image distortions, which reduces overall image quality, and depth perception error due to the variation of image sizes according to depths. Here, we introduce a light field optimization technique to compensate for magnification variations among the focal planes. Our approach alleviates image distortions, especially noticeable in the contents with large depth discontinuity, and reconstructs the image size to precise depths, while maintaining a specific tolerance length for the target eye relief. To verify the feasibility of the algorithm, we employ this optimization method for the tomographic near-eye display system to acquire the optimal image and backlight sequences for a volumetric scene. In general, we confirm that the structural similarity index measure of reconstructed images against ground truth increases by 20% when the eye relief is 15 mm, and the accommodation cue is appropriately stimulated at the target depth with our proposed method.

Studies of cortical function in the awake infant are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become increasingly common in developmental neuroscience, but has significant limitations including resolution, spatial specificity and ergonomics. In adults, high-density arrays of near-infrared sources and detectors have recently been shown to yield dramatic improvements in spatial resolution and specificity when compared to typical fNIRS approaches. However, most existing fNIRS devices only permit the acquisition of ~20-100 sparsely distributed fNIRS channels, and increasing the number of optodes presents significant mechanical challenges, particularly for infant applications. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first study of the infant brain using wearable HD-DOT. Using a well-established social stimulus paradigm, and combining this new imaging technology with advances in cap design and spatial registration, we show that it is now possible to obtain high-quality, functional images of the infant brain with minimal constraints on either the environment or on the infant participants. Our results are consistent with prior low-density fNIRS measures based on similar paradigms, but demonstrate superior spatial localization, improved depth specificity, higher SNR and a dramatic improvement in the consistency of the responses across participants. Our data retention rates also demonstrate that this new generation of wearable technology is well tolerated by the infant population., Competing Interests: Declaration of Competing Interest This paper involves the application of a prototype technology developed by UCL spin-out company Gowerlabs Ltd. In addition to the Gowerlabs-affiliated authors, RJC holds a financial interest in Gowerlabs Ltd., (Copyright © 2020. Published by Elsevier Inc.)

In this study, in vivo animal experiments with 12 nude mice bearing breast-cancer-patient-tissue-derived xenograft (PDX) tumors were performed aiming to verify the imaging capability of a novel miniaturized fluorescence molecular tomography (FMT) endoscope, in combination with targeted nanoparticle-near-infrared (NIR) dye conjugates. Tumor-bearing mice were divided into two groups by systematic injection with urokinase plasminogen activator receptor-targeted ( n = 7) and nontargeted ( n = 5) imaging nanoprobes as a contrast agent, respectively. Each mouse was imaged at 6, 24, and 48 h following the injection of nanoprobes using the FMT endoscope. The results show that systemic delivery of targeted nanoprobes produced a 4-fold enhancement in fluorescence signals from tumors, compared with tumors that received nontargeted nanoprobes. This study indicates that our miniaturized FMT endoscope, coupled with the targeted nanoparticle-NIR dye conjugates as a contrast agent, has high sensitivity and specificity, and thus great potential to be used for image-guided detection and removal of a primary tumor and local metastatic tumors during surgery.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed., Competing Interests: The authors declare no conflict of interest.

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is beginning to approach the data quality of fMRI for superficial cortical regions. In this work, we developed a customized HD-DOT system for use in malnutrition studies in Cali, Colombia. Our results evaluate the performance of the HD-DOT instrument for assessing brain function in a cohort of malnourished children. In addition to demonstrating portability and wearability, we show the HD-DOT instrument's sensitivity to distributed brain responses using a sensory processing task and measurements of homotopic functional connectivity. Task-evoked responses to the passive word listening task produce activations localized to bilateral superior temporal gyrus, replicating previously published work using this paradigm. Evaluating this localization performance across sparse and dense reconstruction schemes indicates that greater localization consistency is associated with a dense array of overlapping optical measurements. These results provide a foundation for additional avenues of investigation, including identifying and characterizing a child's individual malnutrition burden and eventually contributing to intervention development., Competing Interests: Declaration of competing interest The authors declare no conflicting interests, financial or otherwise., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: The objective of the study was to assess a new technology, the tear film imager (TFI), which can dynamically image the muco-aqueous and lipid layers., Methods: Prospective pilot case series of individuals with and without dry eye (DE). Two sequential images were obtained with the TFI. Measurements were assessed for reproducibility and compared with clinically derived DE metrics. Individuals were grouped into DE categories based on signs of DE., Results: 49 patients participated in the study with a mean age of 58.8 years (SD 15.9) and a female majority (69%). Reproducibility of the muco-aqueous layer thickness (MALT) was excellent (r=0.88). MALT measurements significantly correlated with the Schirmer score (r=0.31). Lipid break up time (LBUT) as measured by the TFI significantly correlated with the clinical measure of tear break up time (TBUT) (r=0.73). MALT and LBUT were significantly thinner and shorter, respectively, in the DE groups (mild-moderate and severe) compared with the control group. When comparing TFI parameters to clinically assessed signs, sensitivity of the device was 87% and specificity was 88%., Conclusion: The TFI is the first machine capable of reproducibly measuring muco-aqueous thickness in human subjects which correlates with Schirmer score. In parallel, it assesses other important aspects of tear film function which correlate with clinician assessed DE metrics., Competing Interests: Competing interests: FS, NG, YC, RG, YA, SE and AH: equity and consulting to AdOM, Advance Optical Technologies Ltd. AO: consulting to AdOM, Advance Optical Technologies Ltd. AH: consulting to Shire, CIPLA and BioLight Life Sciences Investments Ltd. RG and AH: Equity of Nano Retina Ltd., AH: Equity of Oxymap Ltd., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Within image-guided surgery, 'hybrid' guidance technologies have been used to integrate the complementary features of radioactive guidance and fluorescence guidance. Here, we explore how the generation of a novel freehand fluorescence (fhFluo) imaging approach complements freehand SPECT (fhSPECT) in a hybrid setup. Near-infrared optical tracking was used to register the position and the orientation of a hybrid opto-nuclear detection probe while recording its readings. Dedicated look-up table models were used for 3D reconstruction. In phantom and excised tissue settings (i.e., flat-surface human skin explants), fhSPECT and fhFluo were investigated for image resolution and in-tissue signal penetration. Finally, the combined potential of these freehand technologies was evaluated on prostate and lymph node specimens of prostate cancer patients receiving prostatectomy and sentinel lymph node dissection (tracers: indocyanine green (ICG) + 99m Tc-nanocolloid or ICG- 99m Tc-nanocolloid). After hardware and software integration, the hybrid setup created 3D nuclear and fluorescence tomography scans. The imaging resolution of fhFluo (1 mm) was superior to that of fhSPECT (6 mm). Fluorescence modalities were confined to a maximum depth of 0.5 cm, while nuclear modalities were usable at all evaluated depths (<2 cm). Both fhSPECT and fhFluo enabled augmented- and virtual-reality navigation toward segmented image hotspots, including relative hotspot quantification with an accuracy of 3.9% and 4.1%. Imaging in surgical specimens confirmed these trends (fhSPECT: in-depth detectability, low resolution, and fhFluo: superior resolution, superficial detectability). Overall, when radioactive and fluorescent tracer signatures are used, fhFluo has complementary value to fhSPECT. Combined the freehand technologies render a unique hybrid imaging and navigation modality.

This review describes the unique opportunities and challenges for noninvasive optical mapping of human brain function. Diffuse optical methods offer safe, portable, and radiation free alternatives to traditional technologies like positron emission tomography or functional magnetic resonance imaging (fMRI). Recent developments in high-density diffuse optical tomography (HD-DOT) have demonstrated capabilities for mapping human cortical brain function over an extended field of view with image quality approaching that of fMRI. In this review, we cover fundamental principles of the diffusion of near infrared light in biological tissue. We discuss the challenges involved in the HD-DOT system design and implementation that must be overcome to acquire the signal-to-noise necessary to measure and locate brain function at the depth of the cortex. We discuss strategies for validation of the sensitivity, specificity, and reliability of HD-DOT acquired maps of cortical brain function. We then provide a brief overview of some clinical applications of HD-DOT. Though diffuse optical measurements of neurophysiology have existed for several decades, tremendous opportunity remains to advance optical imaging of brain function to address a crucial niche in basic and clinical neuroscience: that of bedside and minimally constrained high fidelity imaging of brain function.

Volumetric optical microscopy approaches that enable acquisition of three-dimensional (3D) information from a biological sample are attractive for numerous non-invasive imaging applications. The unprecedented structural details that these techniques provide have helped in our understanding of different aspects of architecture of cells, tissues, and organ systems as they occur in their natural states. Nonetheless, the instrumentation for most of these techniques is sophisticated, bulky, and costly, and is less affordable to most laboratory settings. Several miniature imagers based on webcams or low-cost sensors featuring easy assembly have been reported, for in situ imaging of biological structures at low costs. However, they have not been able to achieve the ability of 3D imaging throughout the entire volumes for spatiotemporal analyses of the structural changes in these specimens. Here we present a miniaturized optical tomography (mini-Opto) platform for low-cost, volumetric characterization of engineered living systems through hardware optimizations as well as applications of an optimized algebraic algorithm for image reconstruction.

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system's ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.

In vivo imaging of tissue/vasculature oxygen saturation levels is of prime interest in many clinical applications. To this end, the feasibility of combining two distinct and complementary imaging modalities is investigated: optoacoustics (OA) and near-infrared optical tomography (NIROT), both operating noninvasively in reflection mode. Experiments were conducted on two optically heterogeneous phantoms mimicking tissue before and after the occurrence of a perturbation. OA imaging was used to resolve submillimetric vessel-like optical absorbers at depths up to 25 mm, but with a spectral distortion in the OA signals. NIROT measurements were utilized to image perturbations in the background and to estimate the light fluence inside the phantoms at the wavelength pair (760 nm, 830 nm). This enabled the spectral correction of the vessel-like absorbers' OA signals: the error in the ratio of the absorption coefficient at 830 nm to that at 760 nm was reduced from 60%-150% to 10%-20%. The results suggest that oxygen saturation (SO 2 ) levels in arteries can be determined with <10% error and furthermore, that relative changes in vessels' SO 2 can be monitored with even better accuracy. The outcome relies on a proper identification of the OA signals emanating from the studied vessels., (© 2018 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Near-infrared diffuse optical tomography (DOT) has demonstrated a great potential as an adjunct modality for differentiation of malignant and benign breast lesions and for monitoring treatment response in patients with locally advanced breast cancers. The path toward commercialization of DOT techniques depends upon the improvement of robustness and user-friendliness of this technique in hardware and software. In this study, we introduce our recently developed ultrasound-guided DOT system, which has been improved in system compactness, robustness, and user-friendliness by custom-designed electronics, automated data preprocessing, and implementation of a new two-step reconstruction algorithm. The system performance has been tested with several sets of solid and blood phantoms and the results show accuracy in reconstructed absorption coefficients as well as blood oxygen saturation. A clinical example of a breast cancer patient, who was undergoing neoadjuvant chemotherapy, is given to demonstrate the system performance.

Purpose: The precise dosimetric and geometric characteristics of small animal irradiators are essential to achieving reproducible dose delivery, especially in cases where image-guidance is utilized. Currently, radiochromic film is the established measurement tool used to evaluate beam characteristics for these systems. However, only 2D information can be acquired with film. This study characterized both the dosimetric and geometric properties of the small animal research radiation platform (SARRP, Xstrahl) for commissioning purposes using a 3D radiochromic dosimetry system with a submillimeter resolution optical computed tomography (OCT) scanner., Methods: Like a modern clinical linear accelerator, the SARRP features both a beam delivery system and a cone beam computed tomography (CBCT) imaging system. Dosimetric and geometric characteristics of the SARRP were studied using EBT3 radiochromic film and 3D PRESAGE dosimeters. Dosimetric measurements included percent depth dose (PDD) curves and beam profiles. For geometric evaluation, the isocenter sizes of the treatment stage and gantry rotations as well as their coincidence were measured using star shot patterns. A commercial Epson Expression 11000XL flatbed scanner was used for readout of irradiated EBT3 films at 300 dpi resolution. Each irradiated PRESAGE dosimeter was scanned using a submillimeter resolution single laser beam OCT scanner. Acquired data were reconstructed with a resolution of 0.3 mm/pixel., Results: PDD data measured from films and 3D dosimeters agree to within ±3% for depths up to 5 cm, for both 3 × 3 and 10 × 10 mm 2 fixed collimation. Profiles were analyzed at 10, 20, and 30 mm depth for 3 × 3 mm 2 and 10 × 10 mm 2 fields. The FWHM measurements for both dosimeters agreed to within 0.01 mm, and the penumbras agreed to within 0.1 mm for 3 × 3 mm 2 and 0.5 mm for 10 × 10 mm 2 . Gantry and treatment stage isocenter sizes were determined to be 0.21 and 0.43 mm using EBT3 film, and 1.72 and 0.75 mm using PRESAGE dosimeters. Absolute isocenter shifts, evaluated with 3D phantoms, were 0.80 mm for the gantry rotation isocenter (treatment isocenter) with respect to the laser-defined setup isocenter, and 0.71 mm for the gantry rotation isocenter relative to treatment stage rotation isocenter (CBCT isocenter). The difference between CBCT isocenter and laser-defined setup isocenter was 0.68 mm., Conclusions: This study demonstrated that 3D PRESAGE dosimeters can be used for verification of precise targeting for the SARRP. This 3D dosimetry system can be utilized to obtain information on both geometric and dosimetric properties, as well as acquire beam data parameters for the purpose of commissioning image-guided small animal irradiator systems., (© 2018 American Association of Physicists in Medicine.)

We present a multimodal approach for measuring the three-dimensional (3D) refractive index (RI) and fluorescence distributions of live cells by combining optical diffraction tomography (ODT) and 3D structured illumination microscopy (SIM). A digital micromirror device is utilized to generate structured illumination patterns for both ODT and SIM, which enables fast and stable measurements. To verify its feasibility and applicability, the proposed method is used to measure the 3D RI distribution and 3D fluorescence image of various samples, including a cluster of fluorescent beads, and the time-lapse 3D RI dynamics of fluorescent beads inside a HeLa cell, from which the trajectory of the beads in the HeLa cell is analyzed using spatiotemporal correlations.

Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitative absorption-based imaging in true 3D that allows objects of interest to be viewed and measured from any orientation. However, x-ray CT has not been useful at the level of single cells because there is insufficient contrast to form an image. Recently, optical CT has been developed successfully for fixed cells, but this technology called Cell-CT is incompatible with live-cell imaging due to the use of stains, such as hematoxylin, that are not compatible with cell viability. We present a novel development of optical CT for quantitative, multispectral functional 4D (three spatial + one spectral dimension) imaging of living single cells. The method applied to immune system cells offers truly isotropic 3D spatial resolution and enables time-resolved imaging studies of cells suspended in aqueous medium. Using live-cell optical CT, we found a heterogeneous response to mitochondrial fission inhibition in mouse macrophages and differential basal remodeling of small (0.1 to 1 fl) and large (1 to 20 fl) nuclear and mitochondrial structures on a 20- to 30-s time scale in human myelogenous leukemia cells. Because of its robust 3D measurement capabilities, live-cell optical CT represents a powerful new tool in the biomedical research field.

Optoacoustic tomography (OT) is now widely used in preclinical imaging; however, the precision (repeatability and reproducibility) of OT has yet to be determined. Methods: We used a commercial small-animal OT system. Measurements in stable phantoms were used to independently assess the impact of system variables on precision (using coefficient of variation, COV), including acquisition wavelength, rotational position, and frame averaging. Variables due to animal handling and physiology, such as anatomic placement and anesthesia conditions, were then assessed in healthy nude mice using the left kidney and spleen as reference organs. Temporal variation was assessed by repeated measurements over hours and days both in phantoms and in vivo. Sensitivity to small-molecule dyes was determined in phantoms and in vivo; precision was assessed in vivo using IRDye800CW. Results: OT COV in a stable phantom was less than 2.8% across all wavelengths over 30 d. The factors with the greatest impact on signal repeatability in phantoms were rotational position and user experience, both of which still resulted in a COV of less than 4% at 700 nm. Anatomic region-of-interest size showed the highest variation, at 12% and 18% COV in the kidney and spleen, respectively; however, functional SO 2 measurements based on a standard operating procedure showed an exceptional reproducibility of less than 4% COV. COV for repeated injections of IRDye800CW was 6.6%. Sources of variability for in vivo data included respiration rate, degree of user experience, and animal placement. Conclusion: Data acquired with our small-animal OT system were highly repeatable and reproducible across subjects and over time. Therefore, longitudinal OT studies may be performed with high confidence when our standard operating procedure is followed., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

The purpose of this study was to assess the potential of U.S. Food and Drug Administration-cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery., Methods: Consenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed preoperatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio characterized fluorescence contrast., Results: In the preoperative clinic, the open-field device demonstrated potential to guide preoperative mapping of tumor borders, optimize the day of surgery, and identify occult lesions. Intraoperatively, the device demonstrated robust potential to guide surgical resections, as all peak tumor-to-background ratios were greater than 2 (range, 2.2-14.1). Postresection wound bed fluorescence was significantly less than preresection tumor fluorescence (P < 0.001). The repurposed device also successfully identified positive margins., Conclusion: The open-field imaging device was successfully repurposed to distinguish cancer from normal tissue in the preoperative clinic and throughout surgical resection. This study illuminated the potential for existing open-field optical imaging devices with overlapping excitation and emission spectra to be used for fluorescence-guided surgery., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Hybrid imaging methods combining diffuse optical tomography (DOT) and other anatomical or nonoptical functional modalities have been widely investigated to improve imaging performance degraded by the strong optical scattering of biological tissues, through constraining the reconstruction process by prior structures. However, these modalities with different contrast mechanisms may be ineffective in revealing early-staged lesions with high optical contrast but no morphological changes. Photoacoustic tomography (PAT) is particularly useful for visualizing light-absorbing structures embedded in soft tissues with high spatial resolution. Although it is still challenging for PAT to quantitatively disclose the absorption distribution, the modality does provide reliable and specific a priori information differentiating light-absorbing structures of soft tissues and might be more appropriate to guide DOT in lesion diagnosis, as compared with other anatomical or nonoptical functional modalities. In this study, a PAT-guided DOT approach is introduced with both soft- and hard-prior regularizations. The methodology is experimentally validated on small-animal-sized phantoms using a computed-tomography-analogous (CT-analogous) PAT/DOT dual-modality system, focusing on future whole-body applications. The results show that the proposed scheme is capable of effectively improving the quantitative accuracy and spatial resolution of DOT reconstruction.

Objective: Photoacoustic (PA) imaging emerges as a unique tool to study biological samples based on optical absorption contrast. In PA imaging, piezoelectric transducers are commonly used to detect laser-induced ultrasonic waves. However, they typically lack adequate broadband sensitivity at ultrasonic frequency higher than 100 MHz, whereas their bulky size and optically opaque nature cause technical difficulties in integrating PA imaging with conventional optical imaging modalities. To overcome these limitations, optical methods of ultrasound detection were developed and shown their unique applications in PA imaging., Methods: We provide an overview of recent technological advances in optical methods of ultrasound detection and their applications in PA imaging. A general theoretical framework describing sensitivity, bandwidth, and angular responses of optical ultrasound detection is also introduced., Results: Optical methods of ultrasound detection can provide improved detection angle and sensitivity over significantly extended bandwidth. In addition, its versatile variants also offer additional advantages, such as device miniaturization, optical transparency, mechanical flexibility, minimal electrical/mechanical crosstalk, and potential noncontact PA imaging., Conclusion: The optical ultrasound detection methods discussed in this review and their future evolution may play an important role in PA imaging for biomedical study and clinical diagnosis.

Cerenkov luminescence imaging can image radiopharmaceuticals using a high-sensitivity charge-coupled device camera. However, Cerenkov luminescence emitted from the radiopharmaceuticals is weak and has low penetration depth in biologic tissues, which severely limits the sensitivity and accuracy of Cerenkov luminescence imaging. This study presents 3-dimensional (3D) radiopharmaceutical-excited fluorescence tomography (REFT) using europium oxide (EO) nanoparticles, which enhances the Cerenkov luminescence signal intensity, improves the penetration depth, and obtains more accurate 3D distribution of radiopharmaceuticals., Methods: The enhanced optical signals of various radiopharmaceuticals (including Na 131 I, 18 F-FDG, 68 GaCl 3 , Na 99m TcO 4 ) by EO nanoparticles were detected in vitro. The location and 3D distribution of the radiopharmaceuticals of REFT were then reconstructed and compared with those of Cerenkov luminescence tomography through the experiments with the phantom, artificial source-implanted mouse models, and mice bearing hepatocellular carcinomas., Results: The mixture of 68 GaCl 3 and EO nanoparticles possessed the strongest optical signals compared with the other mixtures. The in vitro phantom and implanted mouse studies showed that REFT revealed more accurate 3D distribution of 68 GaCl 3 REFT can detect more tumors than small-animal PET in hepatocellular carcinoma-bearing mice and achieved more accurate 3D distribution information than Cerenkov luminescence tomography., Conclusion: REFT with EO nanoparticles significantly improves accuracy of localization of radiopharmaceuticals and can precisely localize the tumor in vivo., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Silicon photomultipliers (SiPMs) have been very recently introduced as the most promising detectors in the field of diffuse optics, in particular due to the inherent low cost and large active area. We also demonstrate the suitability of SiPMs for time-domain diffuse optical tomography (DOT). The study is based on both simulations and experimental measurements. Results clearly show excellent performances in terms of spatial localization of an absorbing perturbation, thus opening the way to the use of SiPMs for DOT, with the possibility to conceive a new generation of low-cost and reliable multichannel tomographic systems.

We recently developed an algorithm for multiplexed fluorescence tomographic imaging of at least four fluorophores concurrently in the red and near-infrared wavelength region by jointly using spectral and temporal data. We report the design of a fluorescence tomography instrument that acquires spectral and temporal data, and validate its use in tissue-mimicking phantoms with four embedded fluorescent targets with highly overlapped spectral signatures. Critically, this requires measurement or computation of extended fluorophore signature libraries, which capture the variability in the measured signal due to the unknown position of the targets in the media. We demonstrate that we can demix and tomographically image all four fluorophores with zero image cross-talk, and 1 mm or better spatial resolution.

Diffuse optical tomography is an imaging technique, based on evaluation of how light propagates within the human head to obtain the functional information about the brain. Precision in reconstructing such an optical properties map is highly affected by the accuracy of the light propagation model implemented, which needs to take into account the presence of clear and scattering tissues. We present a numerical solver based on the radiosity-diffusion model, integrating the anatomical information provided by a structural MRI. The solver is designed to run on parallel heterogeneous platforms based on multiple GPUs and CPUs. We demonstrate how the solver provides a 7 times speed-up over an isotropic-scattered parallel Monte Carlo engine based on a radiative transport equation for a domain composed of 2 million voxels, along with a significant improvement in accuracy. The speed-up greatly increases for larger domains, allowing us to compute the light distribution of a full human head ( ≈ 3 million voxels) in 116 s for the platform used.

Ambulatory diffuse optical tomography (aDOT) is based on near-infrared spectroscopy (NIRS) and enables three-dimensional imaging of regional hemodynamics and oxygen consumption during a person’s normal activities. Although NIRS has been previously used for muscle assessment, it has been notably limited in terms of the number of channels measured, the extent to which subjects can be ambulatory, and/or the ability to simultaneously acquire synchronized auxiliary data such as electromyography (EMG) or electrocardiography (ECG). We describe the development of a prototype aDOT system, called NINscan-M, capable of ambulatory tomographic imaging as well as simultaneous auxiliary multimodal physiological monitoring. Powered by four AA size batteries and weighing 577 g, the NINscan-M prototype can synchronously record 64-channel NIRS imaging data, eight channels of EMG, ECG, or other analog signals, plus force, acceleration, rotation, and temperature for 24+ h at up to 250 Hz. We describe the system’s design, characterization, and performance characteristics. We also describe examples of isometric, cycle ergometer, and free-running ambulatory exercise to demonstrate tomographic imaging at 25 Hz. NINscan-M represents a multiuse tool for muscle physiology studies as well as clinical muscle assessment.

Purpose: The practical use of the PRESAGE® solid plastic dosimeter is limited by the inconvenience of immersing it in high-viscosity oils to achieve refractive index matching for optical computed tomography (CT) scanning. The oils are slow to mix and difficult to clean from surfaces, and the dosimeter rotation can generate dynamic Schlieren inhomogeneity patterns in the reference liquid, limiting the rotational and overall scan speed. Therefore, it would be beneficial if lower-viscosity, water-based solutions with slightly unmatched refractive index could be used instead. The purpose of this work is to demonstrate the feasibility of allowing mismatched conditions when using a scanning laser system with a large acceptance angle detector. A fiducial-based ray path measurement technique is combined with an iterative CT reconstruction algorithm to reconstruct images., Methods: A water based surrounding liquid with a low viscosity was selected for imaging PRESAGE® solid dosimeters. Liquid selection was optimized to achieve as high a refractive index as possible while avoiding rotation-induced Schlieren effects. This led to a refractive index mismatch of 6% between liquid and dosimeters. Optical CT scans were performed with a fan-beam scanning-laser optical CT system with a large area detector to capture most of the refracted rays. A fiducial marker placed on the wall of a cylindrical sample occludes a given light ray twice. With knowledge of the rotation angle and the radius of the cylindrical object, the actual internal path of each ray through the dosimeter can be calculated. Scans were performed with 1024 projections of 512 data samples each, and rays were rebinned to form 512 parallel-beam projections. Reconstructions were performed on a 512 × 512 grid using 100 iterations of the SIRT iterative CT algorithm. Proof of concept was demonstrated with a uniformly attenuating solution phantom. PRESAGE® dosimeters (11 cm diameter) were irradiated with Cobalt-60 irradiator to achieve either a uniform dose or a 2-level "step-dose" pattern., Results: With 6% refractive index mismatching, a circular field of view of 85% of the diameter of a cylindrical sample can be reconstructed accurately. Reconstructed images of the test solution phantom were uniform (within 3%) inside this radius. However, the dose responses of the PRESAGE® samples were not spatially uniform, with variations of at least 5% in sensitivity. The variation appears as a "cupping" artifact with less sensitivity in the middle than at the periphery of the PRESAGE® cylinder. Polarization effects were also detected for these samples., Conclusions: The fiducial-based ray path measurement scheme, coupled with an iterative reconstruction algorithm, enabled optical CT scanning of PRESAGE® dosimeters immersed in mismatched refractive index solutions. However, improvements to PRESAGE® dose response uniformity are required.

Fibrous structures are an integral and dynamic feature of soft biological tissues that are directly related to the tissues' condition and function. A greater understanding of mechanical tissue behavior can be gained through quantitative analyses of structure alone, as well as its integration into computational models of soft tissue function. Histology and other nonoptical techniques have traditionally dominated the field of tissue imaging, but they are limited by their invasiveness, inability to provide resolution on the micrometer scale, and dynamic information. Recent advances in optical modalities can provide higher resolution, less invasive imaging capabilities, and more quantitative measurements. Here we describe contemporary optical imaging techniques with respect to their suitability in the imaging of tissue structure, with a focus on characterization and implementation into subsequent modeling efforts. We outline the applications and limitations of each modality and discuss the overall shortcomings and future directions for optical imaging of soft tissue structure.

Purpose: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry., Methods: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source-detector pairs (10(6)). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements., Results: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI., Conclusions: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high-resolution CCD detection in the frequency-domain was demonstrated.

Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT’s basic principles, major implementations, imaging contrasts, and recent applications.

Myoglobin is an essential oxygen-binding hemoprotein in skeletal and cardiac muscles that buffers intracellular oxygen (O2) concentration in response to hypoxia or elevated muscle activities. We present a method that uses photoacoustic computed tomography to measure the distribution of myoglobin in tissue and the oxygen saturation of myoglobin (sO2-Mb ). From photoacoustic measurements of mice in different oxygenation states, we performed calibration-free quantification of the sO2-Mb change in the backbone muscle in vivo.

Purpose: To overcome the limitation of CT/cone-beam CT (CBCT) in guiding radiation for soft tissue targets, the authors developed a spectrally resolved bioluminescence tomography (BLT) system for the small animal radiation research platform. The authors systematically assessed the performance of the BLT system in terms of target localization and the ability to resolve two neighboring sources in simulations, tissue-mimicking phantom, and in vivo environments., Methods: Multispectral measurements acquired in a single projection were used for the BLT reconstruction. The incomplete variables truncated conjugate gradient algorithm with an iterative permissible region shrinking strategy was employed as the optimization scheme to reconstruct source distributions. Simulation studies were conducted for single spherical sources with sizes from 0.5 to 3 mm radius at depth of 3-12 mm. The same configuration was also applied for the double source simulation with source separations varying from 3 to 9 mm. Experiments were performed in a standalone BLT/CBCT system. Two self-illuminated sources with 3 and 4.7 mm separations placed inside a tissue-mimicking phantom were chosen as the test cases. Live mice implanted with single-source at 6 and 9 mm depth, two sources at 3 and 5 mm separation at depth of 5 mm, or three sources in the abdomen were also used to illustrate the localization capability of the BLT system for multiple targets in vivo., Results: For simulation study, approximate 1 mm accuracy can be achieved at localizing center of mass (CoM) for single-source and grouped CoM for double source cases. For the case of 1.5 mm radius source, a common tumor size used in preclinical study, their simulation shows that for all the source separations considered, except for the 3 mm separation at 9 and 12 mm depth, the two neighboring sources can be resolved at depths from 3 to 12 mm. Phantom experiments illustrated that 2D bioluminescence imaging failed to distinguish two sources, but BLT can provide 3D source localization with approximately 1 mm accuracy. The in vivo results are encouraging that 1 and 1.7 mm accuracy can be attained for the single-source case at 6 and 9 mm depth, respectively. For the 2 sources in vivo study, both sources can be distinguished at 3 and 5 mm separations, and approximately 1 mm localization accuracy can also be achieved., Conclusions: This study demonstrated that their multispectral BLT/CBCT system could be potentially applied to localize and resolve multiple sources at wide range of source sizes, depths, and separations. The average accuracy of localizing CoM for single-source and grouped CoM for double sources is approximately 1 mm except deep-seated target. The information provided in this study can be instructive to devise treatment margins for BLT-guided irradiation. These results also suggest that the 3D BLT system could guide radiation for the situation with multiple targets, such as metastatic tumor models.

We present a generalized strategy for direct reconstruction in pharmacokinetic diffuse fluorescence tomography (DFT) with CT-analogous scanning mode, which can accomplish one-step reconstruction of the indocyanine-green pharmacokinetic-rate images within in vivo small animals by incorporating the compartmental kinetic model into an adaptive extended Kalman filtering scheme and using an instantaneous sampling dataset. This scheme, compared with the established indirect and direct methods, eliminates the interim error of the DFT inversion and relaxes the expensive requirement of the instrument for obtaining highly time-resolved date-sets of complete 360 deg projections. The scheme is validated by two-dimensional simulations for the two-compartment model and pilot phantom experiments for the one-compartment model, suggesting that the proposed method can estimate the compartmental concentrations and the pharmacokinetic-rates simultaneously with a fair quantitative and localization accuracy, and is well suitable for cost-effective and dense-sampling instrumentation based on the highly-sensitive photon counting technique.

Herein is presented an optical diffraction tomography (ODT) technique for measuring 3-D refractive index (RI) maps of optical plastic lenses. A Mach-Zehnder interferometer was used to measure multiple complex optical fields of a plastic lens immersed in RI-matching oil at various rotational orientations. From this, ODT was used to reconstruct a 3-D RI distribution of the plastic lens with unprecedented RI sensitivity (Δn=4.21×10(-5) and high resolution (12.8 μm). As a demonstration, 3-D RI distributions of a 2 mm-diameter borosilicate sphere and a 5 mm-diameter plastic lens were reconstructed. Defects in the lens, generated by pulsed laser ablation, were also detected using the present method.

We present a continuous-wave instrument for non-invasive diffuse optical imaging of the breast in a parallel-plate transmission geometry. The instrument measures continuous spectra in the wavelength range 650-1000 nm, with an intensity noise level <1.5% and a spatial sampling rate of 5 points/cm in the x- and y-directions. We collect the optical transmission at four locations, one collinear and three offset with respect to the illumination optical fiber, to recover the depth of optical inhomogeneities in the tissue. We imaged a tissue-like, breast shaped, silicone phantom (6 cm thick) with two embedded absorbing structures: a black circle (1.7 cm in diameter) and a black stripe (3 mm wide), designed to mimic a tumor and a blood vessel, respectively. The use of a spatially multiplexed detection scheme allows for the generation of on-axis and off-axis projection images simultaneously, as opposed to requiring multiple scans, thus decreasing scan-time and motion artifacts. This technique localizes detected inhomogeneities in 3D and accurately assigns their depth to within 1 mm in the ideal conditions of otherwise homogeneous tissue-like phantoms. We also measured induced hemodynamic changes in the breast of a healthy human subject at a selected location (no scanning). We applied a cyclic, arterial blood pressure perturbation by alternating inflation (to a pressure of 200 mmHg) and deflation of a pneumatic cuff around the subject's thigh at a frequency of 0.05 Hz, and measured oscillations with amplitudes up to 1 μM and 0.2 μM in the tissue concentrations of oxyhemoglobin and deoxyhemoglobin, respectively. These hemodynamic oscillations provide information about the vascular structure and functional integrity in tissue, and may be used to assess healthy or abnormal perfusion in a clinical setting.

Diffuse fluorescence tomography (DFT) has been developed to image the spatial distribution of fluorescence-tagged tracers in living tissue. This capability facilitates the recovery of any number of functional parameters, including enzymatic activity, receptor density, blood flow, and gene expression. However, deploying DFT effectively is complex and often requires years of know-how, especially for newer mutlimodal systems that combine DFT with conventional imaging systems. In this chapter, we step through the process of using MRI-DFT imaging of a receptor-targeted tracer in small animals.

In this study, the effect of the geometrical configuration of retroreflective markers on the maximum tracking uncertainty of target points during a medical navigation is analyzed. Methods that help users select and set up an optimal configuration for minimizing the navigation uncertainty are proposed. The methods are evaluated by simulating surgical navigation environment using an optical tracking system. The result shows that the maximum uncertainty of tracking the target points lying outside the marker region is a function of the configuration of some of the associated markers and the precision of the optical tracking system used. We also show that the use of flexible rigid bodies minimizes target tracking uncertainty by enabling a customized reconfiguration of markers for optimal pose with respect to individual surgical target position during preoperative planning phase.

In vivo fluorescence imaging in the second near-infrared window (NIR-II window, 1000-1700 nm) is a powerful imaging technique that emerged in recent years. This imaging tool allows for noninvasive, deep-tissue visualization and interrogation of anatomical features and functions with improved imaging resolution and contrast at greater tissue penetration depths than traditional fluorescence imaging. Here, we present the detailed protocol for conducting NIR-II fluorescence imaging in live animals, including the procedures for preparation of biocompatible and NIR-II fluorescent carbon nanotube solution, live animal administration and NIR-II fluorescence image acquisition.

This work introduces a fast, low-cost, robust method based on fringe pattern and phase shifting to obtain three-dimensional (3D) mouse surface geometry for fluorescence molecular tomography (FMT) imaging. We used two pico projector/webcam pairs to project and capture fringe patterns from different views. We first calibrated the pico projectors and the webcams to obtain their system parameters. Each pico projector/webcam pair had its own coordinate system. We used a cylindrical calibration bar to calculate the transformation matrix between these two coordinate systems. After that, the pico projectors projected nine fringe patterns with a phase-shifting step of 2π/9 onto the surface of a mouse-shaped phantom. The deformed fringe patterns were captured by the corresponding webcam respectively, and then were used to construct two phase maps, which were further converted to two 3D surfaces composed of scattered points. The two 3D point clouds were further merged into one with the transformation matrix. The surface extraction process took less than 30 seconds. Finally, we applied the Digiwarp method to warp a standard Digimouse into the measured surface. The proposed method can reconstruct the surface of a mouse-sized object with an accuracy of 0.5 mm, which we believe is sufficient to obtain a finite element mesh for FMT imaging. We performed an FMT experiment using a mouse-shaped phantom with one embedded fluorescence capillary target. With the warped finite element mesh, we successfully reconstructed the target, which validated our surface extraction approach.

Purpose: The present work evaluates an iterative reconstruction approach, namely, the ordered subsets convex (OSC) algorithm with regularization via total variation (TV) minimization in the field of cone-beam optical computed tomography (optical CT). One of the uses of optical CT is gel-based 3D dosimetry for radiation therapy, where it is employed to map dose distributions in radiosensitive gels. Model-based iterative reconstruction may improve optical CT image quality and contribute to a wider use of optical CT in clinical gel dosimetry., Methods: This algorithm was evaluated using experimental data acquired by a cone-beam optical CT system, as well as complementary numerical simulations. A fast GPU implementation of OSC-TV was used to achieve reconstruction times comparable to those of conventional filtered backprojection. Images obtained via OSC-TV were compared with the corresponding filtered backprojections. Spatial resolution and uniformity phantoms were scanned and respective reconstructions were subject to evaluation of the modulation transfer function, image uniformity, and accuracy. The artifacts due to refraction and total signal loss from opaque objects were also studied., Results: The cone-beam optical CT data reconstructions showed that OSC-TV outperforms filtered backprojection in terms of image quality, thanks to a model-based simulation of the photon attenuation process. It was shown to significantly improve the image spatial resolution and reduce image noise. The accuracy of the estimation of linear attenuation coefficients remained similar to that obtained via filtered backprojection. Certain image artifacts due to opaque objects were reduced. Nevertheless, the common artifact due to the gel container walls could not be eliminated., Conclusions: The use of iterative reconstruction improves cone-beam optical CT image quality in many ways. The comparisons between OSC-TV and filtered backprojection presented in this paper demonstrate that OSC-TV can potentially improve the rendering of spatial features and reduce cone-beam optical CT artifacts.

In this paper, we describe the design, fabrication, calibration, and deployment of an airborne multispectral polarimetric imager. The motivation for the development of this instrument was to explore its ability to provide information about water constituents, such as particle size and type. The instrument is based on four 16 MP cameras and uses wire grid polarizers (aligned at 0°, 45°, 90°, and 135°) to provide the separation of the polarization states. A five-position filter wheel provides for four narrow-band spectral filters (435, 550, 625, and 750 nm) and one blocked position for dark-level measurements. When flown, the instrument is mounted on a programmable stage that provides control of the view angles. View angles that range to ±65° from the nadir have been used. Data processing provides a measure of the polarimetric signature as a function of both the view zenith and view azimuth angles. As a validation of our initial results, we compare our measurements, over water, with the output of a Monte Carlo code, both of which show neutral points off the principle plane. The locations of the calculated and measured neutral points are compared. The random error level in the measured degree of linear polarization (8% at 435) is shown to be better than 0.25%.

An efficient optical image amplification scheme has been proposed and demonstrated using the quasi-phase-matched optical parametric amplifier. Pumped with the 152 μJ per pulse pump laser at 532 nm, the input weak infrared image at 1064 nm with 3.5 pJ energy is amplified with a 55 dB optical gain using only a 3 mm long MgO-doped periodically poled lithium niobate (MgO:PPLN) crystal. A spatial resolution of 17 lines/mm on the surface of the PPLN crystal is obtained. Further numerical simulation indicates that our scheme enables efficient image enhancement with a long pulsed pumping source, such as nanosecond lasers.

The information of fluorophore concentration variation (FCV) has the potential for drug development and tumor studies, but the reconstruction of FCV is time-consuming in dynamic fluorescence molecular tomography (DFMT). In this paper, a time-efficient reconstruction method for FCV is presented. The system equation of this method is derived from the derivation of the diffusion equation, and its size does not change with the number of frames. The computational time can be significantly reduced by using this method because the images of different frames are reconstructed separately. Simulations and phantom experiments are performed to validate the performance of the proposed method. The results show that compared with the previous method, the proposed method can obtain better results and consumes less computational time with the same number of iterations. In addition, the time consumption in a single iteration of the proposed method increases much slower with the number of frames.

Results are presented of a recent experiment at the Imaging and Medical beamline of the Australian Synchrotron intended to contribute to the implementation of low-dose high-sensitivity three-dimensional mammographic phase-contrast imaging, initially at synchrotrons and subsequently in hospitals and medical imaging clinics. The effect of such imaging parameters as X-ray energy, source size, detector resolution, sample-to-detector distance, scanning and data processing strategies in the case of propagation-based phase-contrast computed tomography (CT) have been tested, quantified, evaluated and optimized using a plastic phantom simulating relevant breast-tissue characteristics. Analysis of the data collected using a Hamamatsu CMOS Flat Panel Sensor, with a pixel size of 100 µm, revealed the presence of propagation-based phase contrast and demonstrated significant improvement of the quality of phase-contrast CT imaging compared with conventional (absorption-based) CT, at medically acceptable radiation doses.

Background and Purpose: The Oculus Pentacam® is one of the most commonly used devices in ophthalmology for assessment of the anterior eye segment. The purpose of this study was to determine the reproducibility of the corneal power as measured by the Pentacam® in a normal population., Methods: We enrolled 25 eyes of 25 subjects aged between 13 and 68 (46.7 ± 21.7) years, within a spherical equivalent from - 4 D to + 4 D and refractive cylinder up to 5 D and without notable pathologies or history of surgery. A sequence of 5 measurements was performed using the Pentacam®, the Zeiss IOLMaster® as well as an autorefractometer after (re-)positioning the patient's head and the measurement device. From the Pentacam® we collected power data for the corneal front and back surfaces, apical corneal thickness at apex and internal anterior chamber depth. From the IOLMaster®, we extracted corneal power data, and from the autorefractometer we obtained refractive power data of both cardinal meridians. For statistical analysis, we used Cronbach's α as a measure of reproducibility and Spearman's rank correlation test for correlation of data., Results: Pentacam® yields highly reproducible power data for both corneal surfaces, with Cronbach's α of greater than 0.97 for primary parameters (e.g. radii of curvature) and 0.9 for secondary parameters (e.g. vector components of astigmatism). Central corneal thickness and eccentricities of both surfaces as well as anterior chamber depth yielded highly reproducible values, with α of ≥ 0.97. Corneal power derived from IOLMaster® and objective refraction extracted from the autorefractometer yielded α values of around 0.9. Mean corneal power of Pentacam® and IOLMaster® correlated well, but there was no correlation to spherical equivalent. Astigmatism values from Pentacam® and IOLMaster® correlated well with each other and with refractive cylinder., Conclusion: Our results indicate that measurements of anterior segment using the Pentacam® yield highly reproducible results in a normal population without major pathologies of the anterior eye segment., (Georg Thieme Verlag KG Stuttgart · New York.)

This paper introduces temperature imaging by total-variation-based compressed sensing (CS) tomography of H2O vapor absorption spectroscopy. A controlled laboratory setup is used to generate a constant two-dimensional temperature distribution in air (a roughly Gaussian temperature profile with a central temperature of 677 K). A wavelength-tunable laser beam is directed through the known distribution; the beam is translated and rotated using motorized stages to acquire complete absorption spectra in the 1330-1365 nm range at each of 64 beam locations and 60 view angles. Temperature reconstructions are compared to independent thermocouple measurements. Although the distribution studied is approximately axisymmetric, axisymmetry is not assumed and simulations show similar performance for arbitrary temperature distributions. We study the measurement error as a function of number of beams and view angles used in reconstruction to gauge the potential for application of CS in practical test articles where optical access is limited.

The field of three-dimensional quantitative phase imaging (3D QPI) is expanding rapidly with applications in biological, medical, and industrial research, development, diagnostics, and metrology. Much of this research has centered on developing optical diffraction tomography (ODT) for biomedical applications. In addition to technical difficulties associated with coherent noise, ODT is not congruous with optical microscopy utilizing partially coherent light, which is used in most biomedical laboratories. Thus, ODT solutions have, for the most part, been limited to customized optomechanical systems which would be relatively expensive to implement on a wide scale. In the present work, a new phase reconstruction method, called tomographic deconvolution phase microscopy (TDPM), is described which makes use of commercial microscopy hardware in realizing 3D QPI. TDPM is analogous to methods used in deconvolution microscopy which improve spatial resolution and 3D-localization accuracy of fluorescence micrographs by combining multiple through-focal scans which are deconvolved by the system point spread function. TDPM is based on the 3D weak object transfer function theory which is shown here to be capable of imaging "nonweak" phase objects with large phase excursions. TDPM requires no phase unwrapping and recovers the entire object spectrum via object rotation, mitigating the need to fill in the "missing cone" of spatial frequencies algorithmically as in limited-angle ODT. In the present work, TDPM is demonstrated using optical fibers, including single-mode, polarization-maintaining, and photonic-crystal fibers as well as an azimuthally varying CO2-laser-induced long-period fiber grating period as test phase objects.

Conventional fluorescence tomography provides images of the distribution of fluorescent agents within highly scattering media, but suffers from poor spatial resolution. Previously, we introduced a new method termed "temperature-modulated fluorescence tomography" (TM-FT) that generates fluorescence images with high spatial resolution. TM-FT first uses focused ultrasound to locate the distribution of temperature-sensitive fluorescence probes. Afterward, this a priori information is utilized to improve the performance of the inverse solver for conventional fluorescence tomography and reveal quantitatively accurate fluorophore concentration maps. However, the disadvantage of this novel method is the long data acquisition time as the ultrasound beam was scanned in a step-and-shoot mode. In this Letter, we present a new, fast scanning method that reduces the imaging time 40 fold. By continuously scanning the ultrasound beam over a 50 mm by 25 mm field-of-view, high-resolution fluorescence images are obtained in less than 29 min, which is critical for in vivo small animal imaging.