Fabrication of Tuneable Tissue-Mimicking Phantom for Optical Methods.

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.

Functional imaging of the developing brain with wearable high-density diffuse optical tomography: A new benchmark for infant neuroimaging outside the scanner environment.

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.

Distortion corrected tomographic near-eye displays using light field optimization.

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.

Portable, field-based neuroimaging using high-density diffuse optical tomography.

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.

Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study.

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.

In Vivo Evaluation of a Miniaturized Fluorescence Molecular Tomography (FMT) Endoscope for Breast Cancer Detection Using Targeted Nanoprobes.

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.

Optical-Based Analysis of Soft Tissue Structures.

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.

Combined diffuse optical tomography and photoacoustic tomography for enhanced functional imaging of small animals: a methodological study on phantoms.

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.

Large-scale optical diffraction tomography for inspection of optical plastic lenses.

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.

A feasibility study of X-ray phase-contrast mammographic tomography at the Imaging and Medical beamline of the Australian Synchrotron.

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.

109 MHz optical tomography using temporal magnification.

Ultrafast optical tomographic imaging with a 109 MHz A-scan rate is achieved by using temporal magnification. Based on two four-wave mixing (FWM) time lenses with carefully designed group delay dispersion, we construct a temporal imaging system with a magnification factor of 48.3×. The two time-lens scheme not only relaxes the requirement for the pump source but also facilitates the application for tomographic imaging. As a proof-of-concept demonstration, our system achieves an axial resolution of 140 µm in air (∼105 µm in biosample) over a 28 mm depth range with sensitivity up to 55 dB. We then evaluate the imaging performance using a fish-eye lens at a 109 MHz A-scan rate. Utilizing better dispersion-engineered nonlinear media, resolution of less than 5 µm in the biosample with higher sensitivity may be achieved. We believe this scheme will provide a promising solution for video-rate 3D tomographic imaging.

Hyperspectral time-resolved wide-field fluorescence molecular tomography based on structured light and single-pixel detection.

We present a time-resolved fluorescence diffuse optical tomography platform that is based on wide-field structured illumination, single-pixel detection, and hyperspectral acquisition. Two spatial light modulators (digital micro-mirror devices) are employed to generate independently wide-field illumination and detection patterns, coupled with a 16-channel spectrophotometer detection module to capture hyperspectral time-resolved tomographic data sets. The main system characteristics are reported, and we demonstrate the feasibility of acquiring dense 4D tomographic data sets (space, time, spectra) for time domain 3D quantitative multiplexed fluorophore concentration mapping in turbid media.

Implementation of a new scanning method for high-resolution fluorescence tomography using thermo-sensitive fluorescent agents.

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.

Detection of Peripheral Arterial Disease Within the Foot Using Vascular Optical Tomographic Imaging: A Clinical Pilot Study.

OBJECTIVE: Vascular optical tomographic imaging (VOTI) is a novel imaging modality that is capable of detecting hemoglobin concentrations in tissue. VOTI is non-invasive, non-ionizing and does not require contrast injection. This technology was applied to the diagnosis of peripheral arterial disease (PAD) within lower extremities of diabetic patients with calcified arteries. This could be of substantial benefit as these patients suffer from comorbidities such as arterial incompressibility, which complicates diagnosis and monitoring. METHODS: Forty individuals (10 non-diabetic patients with PAD, 10 diabetic patients with PAD, and 20 healthy volunteers) were enrolled in a diagnostic pilot study using the VOTI system. The patients were imaged during at high pressure cuff occlusion. RESULTS: The VOTI system was capable of quantifying the blood volume changes within the foot during the thigh cuff occlusion and outputting diagnostic parameters, such as change in hemoglobin concentration, enabling the assessment of foot perfusion. This study resulted in a statistically significant difference between the healthy cohort and both the non-diabetic and the diabetic PAD cohorts (p = .006, p = .006). Receiver operating characteristic (ROC) curve analysis showed that PAD diagnosis could be made with over 80% sensitivity or specificity depending on the characteristic cutoff point. In addition, VOTI was capable of providing the locations of under-perfused regions within the foot and evaluating the severity of arterial disease, even within diabetic patients with calcified arteries, who are traditionally difficult to diagnose. CONCLUSION: VOTI can effectively diagnose PAD independently of arterial compressibility, making it very useful for assessing vascular disease in diabetic patients.

Fast reconstruction of fluorophore concentration variation based on the derivation of the diffusion equation.

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.

Efficient optical image amplifier using periodically poled lithium niobate.

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.

Demonstration of temperature imaging by H2O absorption spectroscopy using compressed sensing tomography.

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.

Three-dimensional quantitative phase imaging via tomographic deconvolution phase microscopy.

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.

Airborne system for multispectral, multiangle polarimetric imaging.

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%.

3D mouse shape reconstruction based on phase-shifting algorithm for fluorescence molecular tomography imaging system.

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.