This PDF file contains the front matter associated with SPIE Proceedings Volume 9316, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and Conference Committee listing.

In this presentation, we demonstrate a working prototype of an optical breast imaging system using parallel-paddle architecture with dual-direction scanning, of which the designed module can be incorporated with a mammographic system for the acquisition of optical transmission and reflection information in both directions of up-down and down-up. Additionally, the scanning module enables to move with a designated pitch to accommodate varied breast size for acquiring adequate data to reconstruct the images. Currently, continuous-wave near infrared illumination modules are used for experimentation. The feasibility will be presented by phantom test.

We propose a dense motion analysis method for ultrasound images. A motion analysis is implemented by tracking a lot of lattice points. In this paper, two novel processings are introduced to perform the motion analysis. One is the tracking of lattice points based on an optical flow algorithm in a framework of multiple spring-models. The other is the detection of lattice points based on texture information with confidence value, and its result corrects the tracking errors. We evaluated our method using a sequence of artificial ultrasound images up to 5 minutes. The average and maximum errors of our proposed method have achieved the best performance in the conventional methods.

In vivo fluorescence molecular imaging (FMI) has played an increasingly important role in biomedical research of preclinical area. Fluorescence molecular tomography (FMT) further upgrades the two-dimensional FMI optical information to three-dimensional fluorescent source distribution, which can greatly facilitate applications in related studies. However, FMT presents a challenging inverse problem which is quite ill-posed and ill-conditioned. Continuous efforts to develop more practical and efficient methods for FMT reconstruction are still needed. In this paper, a method based on spectral projected gradient pursuit (SPGP) has been proposed for FMT reconstruction. The proposed method was based on the directional pursuit framework. A mathematical strategy named the nonmonotone line search was associated with the SPGP method, which guaranteed the global convergence. In addition, the Barzilai-Borwein step length was utilized to build the new step length of the SPGP method, which was able to speed up the convergence of this gradient method. To evaluate the performance of the proposed method, several heterogeneous simulation experiments including multisource cases as well as comparative analyses have been conducted. The results demonstrated that, the proposed method was able to achieve satisfactory source localizations with a bias less than 1 mm; the computational efficiency of the method was one order of magnitude faster than the contrast method; and the fluorescence reconstructed by the proposed method had a higher contrast to the background than the contrast method. All the results demonstrated the potential for practical FMT applications with the proposed method.

A hybrid frequency domain (FD)-continuous wave (CW) MRI/NIRS system was validated in a clinical trial involving patients with at least ACR 4 radiologic findings in Xi’an, China. In this study, MRI guided nonlinear iterative reconstruction of near-infrared spectroscopy (NIRS) images with limited phase data is investigated. In addition, a systematic optimization of the system hardware design has been conducted as well. We are able to get less than 3% variation in tumor contrast to the surrounding normal tissue, by reducing the number of FD detectors from 16 to 6, showing the potential of reducing the FD detectors. Furthermore, a lookup table of the scattering properties has been made by averaging four MRI-identified breast density groups. By using this look-up table for the patient with the noisy phase data, similar AUCs and p-values are achieved for differentiating the malignant from benign patients.

Non-contact camera-based imaging photoplethysmography (iPPG) is useful for measuring heart rate in conditions where contact devices are problematic due to issues such as mobility, comfort, and sanitation. Existing iPPG methods analyse the light-tissue interaction of either active or passive (ambient) illumination. Many active iPPG methods assume the incident ambient light is negligible to the active illumination, resulting in high power requirements, while many passive iPPG methods assume near-constant ambient conditions. These assumptions can only be achieved in environments with controlled illumination and thus constrain the use of such devices. To increase the number of possible applications of iPPG devices, we propose a dual-mode active iPPG system that is robust to changes in ambient illumination variations. Our system uses a temporally-coded illumination sequence that is synchronized with the camera to measure both active and ambient illumination interaction for determining heart rate. By subtracting the ambient contribution, the remaining illumination data can be attributed to the controlled illuminant. Our device comprises a camera and an LED illuminant controlled by a microcontroller. The microcontroller drives the temporal code via synchronizing the frame captures and illumination time at the hardware level. By simulating changes in ambient light conditions, experimental results show our device is able to assess heart rate accurately in challenging lighting conditions. By varying the temporal code, we demonstrate the trade-off between camera frame rate and ambient light compensation for optimal blood pulse detection.

Optical imaging techniques are being developed that promise to increase the information content related to specific molecular reporters. Such modalities do not produce contrast in the structural context of the surrounding tissue, making it difficult to reconcile molecular information with morphological context. We report a solution that enables visualization of the tissue morphology on formalin-fixed, paraffin embedded sections prepared for analytical biomarker imaging. Our approach combines modes of transmitted darkfield and fluorescence contrast and computer visualization to produce 2-component image data analogous to the classical hematoxylin and eosin histological stain. An interferometric hyperspectral image capture mode enables measurement of multiplexed biomarkers in annotated anatomic regions. The system enables practical correlative analysis of molecular changes within areas of anatomic pathology.

We present a novel non-contact photoplethysmographic (PPG) imaging system based on high-resolution video recordings of ambient reflectance of human bodies that compensates for body motion and takes advantage of skin erythema fluctuations to improve measurement reliability for the purpose of remote heart rate monitoring. A single measurement location for recording the ambient reflectance is automatically identified on an individual, and the motion for the location is determined over time via measurement location tracking. Based on the determined motion information motion-compensated reflectance measurements at different wavelengths for the measurement location can be acquired, thus providing more reliable measurements for the same location on the human over time. The reflectance measurement is used to determine skin erythema fluctuations over time, resulting in the capture of a PPG signal with a high signal-to-noise ratio. To test the efficacy of the proposed system, a set of experiments involving human motion in a front-facing position were performed under natural ambient light. The experimental results demonstrated that skin erythema fluctuations can achieve noticeably improved average accuracy in heart rate measurement when compared to previously proposed non-contact PPG imaging systems.

Intraoperative feedback on tissue function, such as blood volume and oxygenation would be useful to the surgeon in cases where current clinical practice relies on subjective measures, such as identification of ischaemic bowel or tissue viability during anastomosis formation. Also, tissue surface profiling may be used to detect and identify certain pathologies, as well as diagnosing aspects of tissue health such as gut motility. In this paper a dual modality laparoscopic system is presented that combines multispectral reflectance and 3D surface imaging. White light illumination from a xenon source is detected by a laparoscope-mounted fast filter wheel camera to assemble a multispectral image (MSI) cube. Surface shape is then calculated using a spectrally-encoded structured light (SL) pattern detected by the same camera and triangulated using an active stereo technique. Images of porcine small bowel were acquired during open surgery. Tissue reflectance spectra were acquired and blood volume was calculated at each spatial pixel across the bowel wall and mesentery. SL features were segmented and identified using a ‘normalised cut’ algoritm and the colour vector of each spot. Using the 3D geometry defined by the camera coordinate system the multispectral data could be overlaid onto the surface mesh. Dual MSI and SL imaging has the potential to provide augmented views to the surgeon supplying diagnostic information related to blood supply health and organ function. Future work on this system will include filter optimisation to reduce noise in tissue optical property measurement, and minimise spot identification errors in the SL pattern.

In vivo high-resolution imaging of tumor development is possible through dorsal skinfold chamber implantable on mice model. However, current intravital imaging systems are weakly tolerated along time by mice and do not allow multimodality imaging. Our project aims to develop a new chamber for: 1- long-term micro/macroscopic visualization of tumor (vascular and cellular compartments) and tissue microenvironment; and 2- multimodality imaging (photonic, MRI and sonography). Our new experimental device was patented in March 2014 and was primarily assessed on 75 mouse engrafted with 4T1-Luc tumor cell line, and validated in confocal and multiphoton imaging after staining the mice vasculature using Dextran 155KDa-TRITC or Dextran 2000kDa-FITC. Simultaneously, a universal stage was designed for optimal removal of respiratory and cardiac artifacts during microscopy assays. Experimental results from optical, ultrasound (Bmode and pulse subtraction mode) and MRI imaging (anatomic sequences) showed that our patented design, unlike commercial devices, improves longitudinal monitoring over several weeks (35 days on average against 12 for the commercial chamber) and allows for a better characterization of the early and late tissue alterations due to tumour development. We also demonstrated the compatibility for multimodality imaging and the increase of mice survival was by a factor of 2.9, with our new skinfold chamber. Current developments include: 1- defining new procedures for multi-labelling of cells and tissue (screening of fluorescent molecules and imaging protocols); 2- developing ultrasound and MRI imaging procedures with specific probes; 3- correlating optical/ultrasound/MRI data for a complete mapping of tumour development and microenvironment.

This paper demonstrates the co-registration of ultrasound (US) and frequency domain photoacoustic radar (FD-PAR) images with significant image improvement from applying image normalization, filtering and amplification techniques. Achieving PA imaging functionality on a commercial Ultrasound instrument could accelerate clinical acceptance and use. Experimental results presented demonstrate live animal testing and show enhancements in signal-to-noise ratio (SNR), contrast and spatial resolution. The co-registered image produced from the US and phase PA images, provides more information than both images independently.

While the methods for diagnostic and screening imaging for breast cancer are numerous, each method has its limitations. Multimodality imaging has increasingly been shown to improve the effectiveness of these imaging. Imaging of dense breast tissue has its own set of challenges. Combining MR and gamma for imaging of breast lesions may increase the sensitivity and specificity in theory especially with dense breasts. This experiment was designed as a proof-of-concept for combining MR and gamma images in a pre-clinical setting using an ex vivo bovine tissue model. Keeping the tissue in the same orientation for both imaging modalities was deemed important to increase accuracy. Using the information of the combined images could assist with localization for biopsy.

X-ray luminescence computed tomography (XLCT) was emerged as a new hybrid imaging modality, in which the x-rays are used to excite phosphors emitting optical photons to be measured for imaging. In this paper, we reported a microscopic x-ray luminescence computed tomography (microXLCT) with a spatial resolution up to hundreds of micrometers for deep targets. We use a superfine x-ray pencil beam to scan the phosphor targets. The superfine x-ray pencil beam is generated by a small collimator mounted in front of a powerful x-ray tube (93212, Oxford Instrument). A CT detector is used to image the x-ray beam. We have generated an x-ray beam with a diameter of 192 micrometers with a collimator of 100 micrometers in diameter. The emitted optical photons on the top surface of phantom are reflected by a mirror and acquired by an electron multiplier charge-coupled device (EMCCD) camera (C9100-13, Hamamatsu Photonics). The microXLCT imaging system is built inside an x-ray shielding and light tight cabinet. The EMCCD camera is placed in a lead box. All the imaging components are controlled by a VC++ program. The optical photon propagation is modeled with the diffusion equation solved by the finite element method. We have applied different regularization methods including L² and L¹ in the microXLCT reconstruction algorithms. Numerical simulations and phantom experiments are used to validate the microXLCT imaging system.

Melanin is a pigment that is highly absorptive in the UV and visible electromagnetic spectra. It is responsible for perceived skin tone, and protects against harmful UV effects. Abnormal melanin distribution is often an indicator for melanoma. We propose a novel approach for non-contact melanin distribution via multispectral temporal illumination coding to estimate the two-dimensional melanin distribution based on its absorptive characteristics. In the proposed system, a novel multispectral, cross-polarized, temporally-coded illumination sequence is synchronized with a camera to measure reflectance under both multispectral and ambient illumination. This allows us to eliminate the ambient illumination contribution from the acquired reflectance measurements, and also to determine the melanin distribution in an observed region based on the spectral properties of melanin using the Beer-Lambert law. Using this information, melanin distribution maps can be generated for objective, quantitative assessment of skin type of individuals. We show that the melanin distribution map correctly identifies areas with high melanin densities (e.g., nevi).

Shape-parameterized diffuse optical tomography (DOT), which is based on a priori that assumes the uniform distribution of the optical properties in the each region, shows the effectiveness of complex biological tissue optical heterogeneities reconstruction. The priori tissue optical structure could be acquired with the assistance of anatomical imaging methods such as X-ray computed tomography (XCT) which suffers from low-contrast for soft tissues including different optical characteristic regions. For the mouse model, a feasible strategy of a priori tissue optical structure acquisition is proposed based on a non-rigid image registration algorithm. During registration, a mapping matrix is calculated to elastically align the XCT image of reference mouse to the XCT image of target mouse. Applying the matrix to the reference atlas which is a detailed mesh of organs/tissues in reference mouse, registered atlas can be obtained as the anatomical structure of target mouse. By assigning the literature published optical parameters of each organ to the corresponding anatomical structure, optical structure of the target organism can be obtained as a priori information for DOT reconstruction algorithm. By applying the non-rigid image registration algorithm to a target mouse which is transformed from the reference mouse, the results show that the minimum correlation coefficient can be improved from 0.2781 (before registration) to 0.9032 (after fine registration), and the maximum average Euclid distances can be decreased from 12.80mm (before registration) to 1.02mm (after fine registration), which has verified the effectiveness of the algorithm.

Diffuse optical tomography (DOT) is a biomedical imaging technology for noninvasive visualization of spatial variation about the optical properties of tissue, which can be applied to in vivo small-animal disease model. However, traditional DOT suffers low spatial resolution due to tissue scattering. To overcome this intrinsic shortcoming, multi-modal approaches that incorporate DOT with other imaging techniques have been intensively investigated, where a priori information provided by the other modalities is normally used to reasonably regularize the inverse problem of DOT. Nevertheless, these approaches usually consider the anatomical structure, which is different from the optical structure. Photoacoustic tomography (PAT) is an emerging imaging modality that is particularly useful for visualizing lightabsorbing structures embedded in soft tissue with higher spatial resolution compared with pure optical imaging. Thus, we present a PAT-guided DOT approach, to obtain the location a priori information of optical structure provided by PAT first, and then guide DOT to reconstruct the optical parameters quantitatively. The results of reconstruction of phantom experiments demonstrate that both quantification and spatial resolution of DOT could be highly improved by the regularization of feasible-region information provided by PAT.

Recent development of super-resolution fluorescence imaging technique such as stochastic optical reconstruction microscopy (STORM) and photoactived localization microscope (PALM) has brought us beyond the diffraction limits. It allows numerous opportunities in biology because vast amount of formerly obscured molecular structures, due to lack of spatial resolution, now can be directly observed. A drawback of fluorescence imaging, however, is that it lacks complete structural information. For this reason, we have developed a super-resolution multimodal imaging system based on STORM and full-field optical coherence microscopy (FF-OCM). FF-OCM is a type of interferometry systems based on a broadband light source and a bulk Michelson interferometer, which provides label-free and non-invasive visualization of biological samples. The integration between the two systems is simple because both systems use a wide-field illumination scheme and a conventional microscope. This combined imaging system gives us both functional information at a molecular level (~20nm) and structural information at the sub-cellular level (~1μm). For thick samples such as tissue slices, while FF-OCM is readily capable of imaging the 3D architecture, STORM suffer from aberrations and high background fluorescence that substantially degrade the resolution. In order to correct the aberrations in thick tissues, we employed an adaptive optics system in the detection path of the STORM microscope. We used our multimodal system to obtain images on brain tissue samples with structural and functional information.