This editorial offers some ways to think about how best to position a research group for funding, by examining the parallels between what is needed for translational grants versus industry start-ups.

Solid-organ transplant is one of the most complex areas of modern medicine involving surgery. There are challenging opportunities in solid-organ transplant, specifically regarding the deficiencies in pathology workflow or gaps in pathology support, which may await alleviations or even de novo solutions, by means of point-of-care, or point-of-procedure optical biomarkers. Focusing the discussions of pathology workflow on donor liver assessment, we analyze the undermet need for intraoperative, real-time, and nondestructive assessment of the donor injuries (such as fibrosis, steatosis, and necrosis) that are the most significant predictors of post-transplant viability. We also identify an unmet need for real-time and nondestructive characterization of ischemia or irreversible injuries to the donor liver, earlier than appearing on morphological histology examined with light microscopy. Point-of-procedure laparoscopic optical biomarkers of liver injuries and tissue ischemia may also facilitate post-transplant management that is currently difficult for or devoid of pathological consultation due to lack of tools. The potential and pitfalls of point-of-procedure optical biomarkers for liver assessment are exemplified in breadth for steatosis. The more general and overarching challenges of point-of-procedure optical biomarkers for liver transplant pathology, including the shielding effect of the liver capsule that was quantitated only recently, are projected. The technological and presentational benchmarks that a candidate technology of point-of-procedure optical biomarkers for transplant pathology must demonstrate to motivate clinical translation are also foreseen.

We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for simulation, visualization, and analysis of light propagation in heterogeneous turbid media including tissue. It provides the highest computational performance and richest set of input, output, and analysis facilities of any open-source tetrahedral-mesh MC light simulator. It also provides a robust framework for statistical verification. A scripting interface makes set-up of simulation runs simple, including parameter sweeps, while simultaneously providing customization options. Data formats shared with class-leading visualization tools, VTK and Paraview, facilitate interactive generation of publication-quality fluence and irradiance maps. The simulator can read and write file formats supported by other similar simulators, such as TIM-OS, MMC, COMSOL (finite-element simulations), and MCML to support comparison. Where simulator features permit, FullMonte can take a single test case, run it in multiple software packages, and load the results together for comparison. Example meshes, optical properties, set-up scripts, and output files are provided for user convenience. We demonstrate its use in several test cases, including photodynamic therapy of the brain, bioluminescence imaging (BLI) in a mouse phantom, and a comparison against MCML for layered geometries. Application domains that can benefit from use of FullMonte include photodynamic, photothermal, and photobiomodulation therapies, BLI, diffuse optical tomography, MC software development, and biophotonics education. Since MC results may be used for preclinical or even clinical experiments, a robust and rigorous verification process is essential. Being a stochastic numerical method, MC simulation has unique challenges associated with verification of output results since observed differences may be due simply to output variance or actual differences in expected output. We describe and have implemented a rigorous and statistically justified framework for comparing between simulators of the same class and for performing regression testing.

Fluorescence molecular tomography (FMT) has been widely used in preclinical tumor imaging, which enables three-dimensional imaging of the distribution of fluorescent probes in small animal bodies via image reconstruction method. However, the reconstruction results are usually unsatisfactory in the term of robustness and efficiency because of the ill-posed and ill-conditioned of FMT problem. In this study, an FMT reconstruction method based on primal accelerated proximal gradient (PAPG) descent and L1-norm regularized projection (L1RP) is proposed. The proposed method utilizes the current and previous iterations to obtain a search point at each iteration. To achieve fast convergence, the PAPG method is applied to efficiently solve the search point, and then L1RP is performed to obtain the robust and accurate reconstruction. To verify the performance of the proposed method, simulation experiments are conducted. The comparative results revealed that it held advantages of robustness, accuracy, and efficiency in FMT reconstructions. Furthermore, a phantom experiment and an in vivo mouse experiment were also performed, which proved the potential and feasibility of the proposed method for practical applications.

Constructing models of cells’ realistic internal and external morphology is vital for correlation between light scattering and morphology of the scattering structure. The image stack obtained from fluorescent confocal microscopy is at present used to construct the cell’s three-dimensional (3-D) morphology. However, due to the poor labeling quality and unavoidable optical noise present in the image stacks, 3-D morphologies are difficult to construct and are an impediment to the statistical analyses of cell structures. We propose a method called the “area and shape constraint method (ASCM)” for constructing 3-D morphology. Blurred 3-D morphologies constructed by common methods from image stacks considered as defective and which are commonly discarded are well restored by the ASCM. Seventy-four clinical blood samples and a series of standard fluorescent spheres are selected to evaluate the validity and precision of our proposed ASCM. Both the qualitative and quantitative results obtained by ASCM indicate the good performance of the method in constructing the cell’s 3-D morphology.

Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation. An automated elastic scattering spectroscopy (ESS) scanning device was constructed to take measurements from the entire cut surface of the excised sentinel node and to produce ESS images for cancer diagnosis. Here, we report on a partially supervised image classification scheme employing a Bayesian multivariate, finite mixture model with a Markov random field (MRF) spatial prior. A reduced dimensional space was applied to represent the scanning data of the node by a statistical image, in which normal, metastatic, and nonnodal-tissue pixels are identified. Our results show that our model enables rapid imaging of lymph nodes. It can be used to recognize nonnodal areas automatically at the same time as diagnosing sentinel node metastases with sensitivity and specificity of 85% and 94%, respectively. ESS images can help surgeons by providing a reliable and rapid intraoperative determination of sentinel nodal metastases in breast cancer.

Diffuse reflectance spectroscopy (DRS) is a probe-based spectral biopsy technique used in cancer studies to quantify tissue reduced scattering (μs′) and absorption (μa) coefficients and vary in source–detector separation (SDS) to fine-tune sampling depth. In subcutaneous murine tumor allografts or xenografts, a key design requirement is ensuring that the source light interrogates past the skin layer into the tumor without significantly sacrificing signal-to-noise ratio (target of ≥15  dB). To resolve this requirement, a DRS probe was designed with four SDSs (0.75, 2.00, 3.00, and 4.00 mm) to interrogate increasing tissue volumes between 450 and 900 nm. The goal was to quantify percent errors in extracting μa and μs′, and to quantify sampling depth into subcutaneous Balb/c-CT26 colon tumor allografts. Using an optical phantom-based experimental method, lookup-tables were constructed relating μa,μs′, diffuse reflectance, and sampling depth. Percent errors were <10  %   and 5% for extracting μa and μs′, respectively, for all SDSs. Sampling depth reached up to 1.6 mm at the first Q-band of hemoglobin at 542 nm, the key spectral region for quantifying tissue oxyhemoglobin concentration. This work shows that the DRS probe can accurately extract optical properties and the resultant physiological parameters such as total hemoglobin concentration and tissue oxygen saturation, from sufficient depth within subcutaneous Balb/c-CT26 colon tumor allografts. Methods described here can be generalized for other murine tumor models. Future work will explore the feasibility of the DRS in quantifying volumetric tumor perfusion in response to anticancer therapies.

Photothermal therapy with various nanoparticles, as photothermal transducers, is a widely researched technique. A continuous wave (CW) laser is employed during this procedure. The therapeutic setup is slightly modified to measure the optical absorption cross-section of the graphene oxide (GO), by mitigating the effects of heat diffusion and light scattering. With an 808-nm CW laser setup modulated by a waveform modulation setup, the effect of nanoparticle size and composition of GO in water on optical absorption cross section is characterized.

Diagnostic accuracy of needle-based optical coherence tomography (OCT) for prostate cancer detection by visual and quantitative analysis is defined. 106 three-dimensional (3-D)-OCT data sets were acquired in 20 prostates after radical prostatectomy and precisely matched with pathology. OCT images were grouped per histological category. Two reviewers performed blind assessments of the OCT images. Sensitivity and specificity for malignancy detection were calculated. Quantitative analyses by automated optical attenuation coefficient calculation were performed. OCT can reliably differentiate between fat, cystic, and regular atrophy and benign glands. The overall sensitivity and specificity for malignancy detection was 79% and 88% for reviewer 1 and 88% and 81% for reviewer 2. Quantitative analysis for differentiation between stroma and malignancy showed a significant difference (4.6  mm^−  1 versus 5.0  mm^−  1 Mann–Whitney U-test p  &lt;  0.0001). A Kruskal–Wallis test showed a significant difference in median attenuation coefficient between stroma, inflammation, Gleason 3, and Gleason 4 (4.6, 4.1, 5.9, and 5.0  mm^−  1, respectively). However, attenuation coefficient varied per patient and a related-samples Wilcoxon signed-rank test showed no significant difference per patient (p  =  0.17). This study confirmed the one to one correlation of histopathology and OCT. Precise matching showed that most histological tissues categories in the prostate could be distinguished by their unique pattern in OCT images. In addition, the optical attenuation coefficient can play a role in the differentiation between stroma and malignancy; however, a per patient analysis of the optical attenuation coefficient did not show a significant difference.

Three-dimensional (3-D) large-scale imaging of microvascular networks is of interest in various areas of biology and medicine related to structural, functional, developmental, and pathological issues. Light-sheet fluorescence microscopy (LSFM) techniques are rapidly spreading and are now on the way to offer operational solutions for large-scale tissue imaging. This contribution describes how reliable vessel segmentation can be handled from LSFM data in very large tissue volumes using a suitable image analysis workflow. Since capillaries are tubular objects of a few microns scale radius, they represent challenging structures to reliably reconstruct without distortion and artifacts. We provide a systematic analysis of multiview deconvolution image processing workflow to control and evaluate the accuracy of the reconstructed vascular network using various low to high level, metrics. We show that even if low-level structural metrics are sensitive to isotropic imaging enhancement provided by a larger number of views, functional high-level metrics, including perfusion permeability, are less sensitive. Hence, combining deconvolution and registration onto a few number of views appears sufficient for a reliable quantitative 3-D vessel segmentation for their possible use for perfusion modeling.

Retinal blood vessel oxygenation is considered to be an important marker for numerous eye diseases. Oxygenation is typically assessed by imaging the retinal vessels at different wavelengths using multispectral imaging techniques, where the choice of wavelengths will affect the achievable measurement accuracy. Here, we present a detailed analysis of the error propagation of measurement noise in retinal oximetry, to identify optimal wavelengths that will yield the lowest uncertainty in saturation estimation for a given measurement noise level. In our analysis, we also investigate the effect of hemoglobin packing in discrete blood vessels (pigment packaging), which may result in a nonnegligible bias in saturation estimation if unaccounted for under specific geometrical conditions, such as subdiffuse sampling of smaller blood vessels located deeper within the retina. Our analyses show that using 470, 506, and 592 nm, a fairly accurate estimation of the whole oxygen saturation regime [0 1] can be realized, even in the presence of the pigment packing effect. To validate the analysis, we developed a scanning laser ophthalmoscope to produce high contrast images with a maximum pixel rate of 60 kHz and a maximum 30-deg imaging field of view. Confocal reflectance measurements were then conducted on a tissue-mimicking scattering phantom with optical properties similar to retinal tissue including narrow channels filled with absorbing dyes to mimic blood vessels. By imaging at three optimal wavelengths, the saturation of the dye combination was calculated. The experimental values show good agreement with our theoretical derivations.

In optical coherence tomography (OCT) systems, to precisely obtain the scattering properties of samples is an essential issue in diagnostic applications. Especially with a higher density turbid medium, the light interferes among the adjacent scatters. Combining an OCT experiment with the finite-difference time-domain simulation method, the multiple scattering effect is shown to affect the scattering properties of medium depending on the interparticle spacing. The far-field scattering phase function of scatters with various diameters was simulated to further analyze the corresponding anisotropy factors, which can be introduced into the extended Huygens-Fresnel theory to find the scattering coefficient of measured samples.

Polarization-sensitive optical coherence tomography (PS-OCT) enables noninvasive, high-resolution imaging of tissue polarization properties. In the anterior segments of human eyes, PS-OCT allows the visualization of birefringent and depolarizing structures. We present the use of PS-OCT for imaging the murine anterior eye. Using a spectral domain PS-OCT setup operating in the 840-nm regime, we performed in vivo volumetric imaging in anesthetized C57BL/6 mice. The polarization properties of murine anterior eye structures largely replicated those known from human PS-OCT imagery, suggesting that the mouse eye may also serve as a model system under polarization contrast. However, dissimilarities were found in the depolarizing structure of the iris which, as we confirmed in postmortem histological sections, were caused by anatomical differences between both species. In addition to the imaging of tissues in the anterior chamber and the iridocorneal angle, we demonstrate longitudinal PS-OCT imaging of the murine anterior segment during mydriasis as well as birefringence imaging of corneal pathology in an aged mouse.