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Dual-energy computed tomography (CT) can be used in radiotherapy treatment planning for the calculation of absorbed dose distributions. The aim of this work is to evaluate whether there is room for improvement in the accuracy of the Monoenergetic Plus algorithm by Siemens Healthineers. A Siemens SOMATOM Force scanner was used to scan a cylindrical polymethyl methacrylate phantom with four rod-inserts made of different materials. Images were reconstructed using ADMIRE and processed with Monoenergetic Plus. The resulting CT numbers were compared with tabulated values and values simulated by the proof-of-a-concept algorithm DIRA developed by the authors. Both the Monoenergetic Plus and DIRA algorithms performed well; the accuracy of attenuation coefficients was better than about ±1% at the energy of 70 keV. Compared with DIRA, the worse performance of Monoenergetic Plus was caused by its (i) two-material decomposition to iodine and water and (ii) imperfect suppression of the beam hardening artifact in ADMIRE. Funding: CancerfondenSwedish Cancer Society [CAN 2017/1029, CAN 2018/622]; Swedish state government [LiO-602731]; Swedish county councils, the ALF-agreement [LiO-602731]; Patientsakerhetsforskning Region Ostergotland [LiO-724181]; VetenskapsradetSwedish Research Council [VR-NT 2016-05033]

Significance: High-speed three-dimensional (3D) super-resolution microscopy is a unique tool to investigate various biological phenomena; yet the technology is not broadly adopted due to its high cost and complex system design. Aim: We present a compact, low-cost, and high-speed 3D structured illumination microscopy (SIM) based on a digital micromirror device and binary holography to visualize fast biological events with super-resolution. Approach: The 3D SIM uses a digital micromirror device to generate three laser foci with individually controllable positions, phases, and amplitudes via binary holography at the back aperture of objective lens to form optimal 3D structured patterns. Fifteen raw images are sequentially recorded and processed by the 3D SIM algorithm to reconstruct a super-resolved image. Results: Super-resolution 3D imaging at a speed of 26.7 frames per second is achieved with a lateral and axial resolution of 155 and 487 nm, which corresponds to a 1.65- and 1.63-times resolution enhancement, respectively, comparing with standard deconvolution microscopy. Conclusions: The 3D SIM realizes fast super-resolution imaging with optimal 3D structured illumination, which may find important applications in biophotonics.

This work was supported by the EPSRC (Grant No. EP/K503162/1). Significance : Optical microscopy is characterized by the ability to get high resolution, below 1 μm, high contrast, functional and quantitative images. The use of shaped illumination, such as with lightsheet microscopy, has led to greater three-dimensional isotropic resolution with low phototoxicity. However, in most complex samples and tissues, optical imaging is limited by scattering. Many solutions to this issue have been proposed, from using passive approaches such as Bessel beam illumination to active methods incorporating aberration correction, but making fair comparisons between different approaches has proven to be challenging. Aim : We present a phase-encoded Monte Carlo radiation transfer algorithm (φMC) capable of comparing the merits of different illumination strategies or predicting the performance of an individual approach. Approach : We show that φMC is capable of modeling interference phenomena such as Gaussian or Bessel beams and compare the model with experiment. Results : Using this verified model, we show that, for a sample with homogeneously distributed scatterers, there is no inherent advantage to illuminating a sample with a conical wave (Bessel beam) instead of a spherical wave (Gaussian beam), except for maintaining a greater depth of focus. Conclusion : φMC is adaptable to any illumination geometry, sample property, or beam type (such as fractal or layered scatterer distribution) and as such provides a powerful predictive tool for optical imaging in thick samples. Publisher PDF

Significance: Polyp size is important for selecting the surveillance interval or treatment policy. Nevertheless, it is challenging to accurately estimate the polyp size during endoscopy. An easy and cost-effective function to assist in polyp size estimation is required. Aim: To propose a virtual scale function for endoscopy and evaluate its performance and expected accuracy. Approach: An adaptive virtual scale behavior was demonstrated. The measurement error of the virtual scale along the distance between the tip of the endoscope and the object plane was evaluated using graph paper. The accuracy of polyp size estimation by an expert endoscopist was compared with the accuracy of the biopsy forceps method using phantom images. Results: The measurement errors of the virtual scale were ≤ 0.7 mm when the distance to the graph paper, which faced the tip of the endoscope, varied from 4 to 30 mm. The accuracy with the virtual scale was significantly higher than that obtained with biopsy forceps (5.3 ± 5.5 % versus 11.9 ± 9.4 % , P

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung computed tomography (CT) scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12 month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for three additional follow-up timepoints up to 48 months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection.

Significance: Quantitative stiffness information can be a powerful aid for tumor or fibrosis diagnosis. Currently, very promising elastography approaches developed for non-contact biomedical imaging are based on transient shear-waves imaging. Transient elastography offers quantitative stiffness information by tracking the propagation of a wave front. The most common method used to compute stiffness from the acquired propagation movie is based on shear-wave time-of-flight calculations. Aim: We introduce an approach to transient shear-wave elastography with spatially coherent sources, able to yield full-field quantitative stiffness maps with reduced artifacts compared to typical artifacts observed in time-of-flight. Approach: A noise-correlation algorithm developed for passive elastography is adapted to spatially coherent narrow or any band sources. This noise-correlation-inspired (NCi) method is employed in parallel with a classic time-of-flight approach. Testing is done on simulation images, experimental validation is conducted with a digital holography setup on controlled homogeneous samples, and full-field quantitative stiffness maps are presented for heterogeneous samples and ex-vivo biological tissues. Results: The NCi approach is first validated on simulations images. Stiffness images processed by the NCi approach on simulated inclusions display significantly less artifacts than with a time-of-flight reconstruction. The adaptability of the NCi algorithm to narrow or any band shear-wave sources was tested successfully. Experimental testing on homogeneous samples demonstrates similar values for both the time-of-flight and the NCi approach. Soft inclusions in agarose sample could be resolved using the NCi method and feasibility on ex-vivo biological tissues is presented. Conclusions: The presented NCi approach was successful in computing quantitative full-field stiffness maps with narrow and broadband source signals on simulation and experimental images from a digital holography setup. Results in heterogeneous media show that the NCi approach could provide stiffness maps with less artifacts than with time-of-flight, demonstrating that a NCi algorithm is a promising approach for shear-wave transient elastography with spatially coherent sources.

Significance: Screening and early detection of oral potentially malignant lesions (OPMLs) are of great significance in reducing the mortality rates associated with head and neck malignancies. Intra-oral multispectral optical imaging of tissues in conjunction with cloud-based machine learning (CBML) can be used to detect oral precancers at the point-of-care (POC) and guide the clinician to the most malignant site for biopsy. Aim: Develop a bimodal multispectral imaging system (BMIS) combining tissue autofluorescence and diffuse reflectance (DR) for mapping changes in oxygenated hemoglobin (HbO2) absorption in the oral mucosa, quantifying tissue abnormalities, and guiding biopsies. Approach: The hand-held widefield BMIS consisting of LEDs emitting at 405, 545, 575, and 610 nm, 5MPx monochrome camera, and proprietary Windows-based software was developed for image capture, processing, and analytics. The DR image ratio (R610/R545) was compared with pathologic classification to develop a CBML algorithm for real-time assessment of tissue status at the POC. Results: Sensitivity of 97.5% and specificity of 92.5% were achieved for discrimination of OPML from patient normal in 40 sites, whereas 82% sensitivity and 96.6% specificity were obtained for discrimination of abnormal (OPML + SCC) in 89 sites. Site-specific algorithms derived for buccal mucosa (27 sites) showed improved sensitivity and specificity of 96.3% for discrimination of OPML from normal. Conclusions: Assessment of oral cancer risk is possible by mapping of HbO2 absorption in tissues, and the BMIS system developed appears to be suitable for biopsy guidance and early detection of oral cancers.

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations. In this paper, we investigate the feasibility of atlas construction and spatial normalisation in paediatric radiotherapy. We used planning computed tomography (CT) scans from twenty paediatric patients historically treated with craniospinal irradiation to generate a template CT that is suitable for spatial normalisation. This childhood cancer population representative template was constructed using groupwise image registration. An independent set of 53 subjects from a variety of childhood malignancies was then used to assess the quality of the propagation of new subjects to this common reference space using deformable image registration (i.e. spatial normalisation). The method was evaluated in terms of overall image similarity metrics, contour similarity and preservation of dose-volume properties. After spatial normalisation, we report a dice similarity coefficient of 0.95 ± 0.05, 0.85 ± 0.04, 0.96 ± 0.01, 0.91 ± 0.03, 0.83 ± 0.06 and 0.65 ± 0.16 for brain and spinal canal, ocular globes, lungs, liver, kidneys and bladder. We then demonstrated the potential advantages of an atlas-based approach to study the risk of second malignant neoplasms after radiotherapy. Our findings indicate satisfactory mapping between a heterogeneous group of patients and the template CT. The poorest performance was for organs in the abdominal and pelvic region, likely due to respiratory and physiological motion and to the highly deformable nature of abdominal organs. More specialised algorithms should be explored in the future to improve mapping in these regions. This study is the first step toward voxel-based analysis in radiation-induced toxicities following paediatric radiotherapy.

Significance: Digital holographic microscopy is widely used to get the quantitative phase information of transparent cells. Aim: However, the sample phase is superimposed with aberrations. To quantify the phase information, aberrations need to be fully compensated. Approach: We propose a technique to obtain aberration-free phase imaging, using the derivative-based principal component analysis (dPCA). Results: With dPCA, almost all aberrations can be extracted and compensated without requirements on background segmentation, making it efficient and convenient. Conclusions: It solves the problem that the conventional principal component analysis (PCA) algorithm cannot compensate the common but intricate higher order cross-term aberrations, such as astigmatism and coma. Moreover, the dPCA strategy proposed here is not only suitable for aberration compensation but also applicable for other cases where there exist cross-terms that cannot be analyzed with the PCA algorithm.

For the validation of optical diagnostic technologies, experimental results need to be benchmarked against the gold standard. Currently, the gold standard for tissue characterization is assessment of hematoxylin and eosin (H&E)-stained sections by a pathologist. When processing tissue into H&E sections, the shape of the tissue deforms with respect to the initial shape when it was optically measured. We demonstrate the importance of accounting for these tissue deformations when correlating optical measurement with routinely acquired histopathology. We propose a method to register the tissue in the H&E sections to the optical measurements, which corrects for these tissue deformations. We compare the registered H&E sections to H&E sections that were registered with an algorithm that does not account for tissue deformations by evaluating both the shape and the composition of the tissue and using microcomputer tomography data as an independent measure. The proposed method, which did account for tissue deformations, was more accurate than the method that did not account for tissue deformations. These results emphasize the need for a registration method that accounts for tissue deformations, such as the method presented in this study, which can aid in validating optical techniques for clinical use. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

Significance: Non-contact, camera-based heart rate variability estimation is desirable in numerous applications, including medical, automotive, and entertainment. Unfortunately, camera-based HRV accuracy and reliability suffer due to two challenges: (a) darker skin tones result in lower SNR and (b) relative motion induces measurement artifacts. Aim: We propose an algorithm HRVCam that provides sufficient robustness to low SNR and motion-induced artifacts commonly present in imaging photoplethysmography (iPPG) signals. Approach: HRVCam computes camera-based HRV from the instantaneous frequency of the iPPG signal. HRVCam uses automatic adaptive bandwidth filtering along with discrete energy separation to estimate the instantaneous frequency. The parameters of HRVCam use the observed characteristics of HRV and iPPG signals. Results: We capture a new dataset containing 16 participants with diverse skin tones. We demonstrate that HRVCam reduces the error in camera-based HRV metrics significantly (more than 50% reduction) for videos with dark skin and face motion. Conclusion: HRVCam can be used on top of iPPG estimation algorithms to provide robust HRV measurements making camera-based HRV practical.

Significance: The potential of fluorescence lifetime imaging microscopy (FLIM) is recently being recognized, especially in biological studies. However, FLIM does not directly measure the lifetimes, rather it records the fluorescence decay traces. The lifetimes and/or abundances have to be estimated from these traces during the phase of data processing. To precisely estimate these parameters is challenging and requires a well-designed computer program. Conventionally employed methods, which are based on curve fitting, are computationally expensive and limited in performance especially for highly noisy FLIM data. The graphical analysis, while free of fit, requires calibration samples for a quantitative analysis. Aim: We propose to extract the lifetimes and abundances directly from the decay traces through machine learning (ML). Approach: The ML-based approach was verified with simulated testing data in which the lifetimes and abundances were known exactly. Thereafter, we compared its performance with the commercial software SPCImage based on datasets measured from biological samples on a time-correlated single photon counting system. We reconstructed the decay traces using the lifetime and abundance values estimated by ML and SPCImage methods and utilized the root-mean-squared-error (RMSE) as marker. Results: The RMSE, which represents the difference between the reconstructed and measured decay traces, was observed to be lower for ML than for SPCImage. In addition, we could demonstrate with a three-component analysis the high potential and flexibility of the ML method to deal with more than two lifetime components. Conclusions: The ML-based approach shows great performance in FLIM data analysis.

Automatic segmentation of bones in computed tomography (CT) images is used for instance in beam hardening correction algorithms where it improves the accuracy of resulting CT numbers. Of special interest are pelvic bones, which—because of their strong attenuation—affect the accuracy of brachytherapy in this region. This work evaluated the performance of the JJ2016 algorithm with the performance of MK2014v2 and JS2018 algorithms; all these algorithms were developed by authors. Visual comparison, and, in the latter case, also Dice similarity coefficients derived from the ground truth were used. It was found that the 3D-based JJ2016 performed better than the 2D-based MK2014v2, mainly because of the more accurate hole filling that benefitted from information in adjacent slices. The neural network-based JS2018 outperformed both traditional algorithms. It was, however, limited to the resolution of 1283 owing to the limited amount of memory in the graphical processing unit (GPU). Funding: VetenskapsradetSwedish Research Council [VR-NT 2016-05033]

Photoacoustic tomography (PAT) is an imaging technique that enables us to visualize vasculature networks at high resolution at depths much greater than optical microscopy.1,2 PAT can also resolve tissue chromophores such as oxyhemoglobin and deoxyhemoglobin, which allows estimation of tissue oxygentation levels.1,3 Accurate estimation of tissue oxygentation is very important in the fields of neuroimaging, cancer diagnostics, and critical care medicine.4,5 PAT involves collection of broadband acoustic waves generated by thermoelastic expansion of tissue upon absorption of light (illuminated at near-infrared wavelengths).6,7 PAT image reconstruction involves recovery of the acoustic source distribution from the detected broadband acoustic waves, which can be performed using analytical or model-based methods.8 Analytical methods are computationally less expensive compared to model-based image reconstruction.8,9 In contrary, model-based schemes are known to generate accurate images compared to analytical schemes, specifically in scenarios where irregular acquisition geometry is involved or limited data is acquired.9,10 Even with the model-based schemes, PAT inversion becomes difficult when the number of ultrasound detector positions is limited, and the situation gets aggravated due to the presence of noise in the data. More recently deep learning-based image postprocessing schemes have been developed for artifact removal and for limited data situations in PAT/microscopy;11–13 however, these schemes were trained on simulated data and generating large experimental data is very difficult. Segmentation approaches were proposed to delineate skin lining in mesoscopic photoacoustic images.14 Active contours-based image segmentation was used to obtain the PAT region of interest (ROI), the obtained ROI was then used to perform fluence correction to make PAT more quantitative.15,16 Different computational techniques have been reported in the literature to obtain vascular network in photoacoustic imaging. Vesselness filter has been proposed to enable accurate recovery of vasculature in PAT;17–19 however, questions have been raised on the accuracy of using the vesselness filter (due to generation of artificial vasculature).20 Probabilistic approach involving different steps such as smoothing and filtering the data, clustering, vessel-segmentation using clusters, and morphological filling was developed for segmenting vessels in photoacoustic images.21 More recently convolution neural network-based approaches were also developed for jointly performing the image reconstruction and segmentation.22 Further, deep learning-based approach was proposed for segmenting animal boundary using multi-modal photoacoustic and ultrasound data.23 Further, deep learning-based method has also been developed for animal brain imaging.24 Notably segmenting vasculature is very important in the context of diagnosis and surgical guidance, specifically for cardiovascular diseases.25,26 In this work, we developed a binary tomography approach wherein we assume the reconstruction distribution contains only two unknowns namely the background and the absorbers. The major contributions of this work include: (a) application of binary tomographic methods for photoacoustic tomographic imaging involving spherical wave propagation as opposed to straight line approximation applied in x-ray computed tomography; (b) showing the utility of binary tomographic methods for improving photoacoustic tomographic imaging of vasculature; and (c) establishing the binary tomographic method superiority in photoacoustic tomographic imaging for providing approximate priors to improve model-based image reconstruction. Binary tomography problem is solved based on a dual optimization approach with an auxiliary variable posed as a constrained optimization problem. We compared the binary tomography algorithm against standard backprojection approach and model-based reconstruction schemes such as Tikhonov regularization and sparsity-based regularization.27 The performance of these different algorithms was validated with in-silico data, physical phantom, and in-vivo brain vasculature imaging data.

Traditional filtered back projection (FBP) reconstruction methods have served the computed tomography (CT) community wellfor over 40 years. With the increased use of CT during the last decades, efforts to minimise patient exposure, while maintainingsufficient or improved image quality, have led to the development of model-based iterative reconstruction (MBIR) algorithms fromseveral vendors. The usefulness of the advanced modeled iterative reconstruction (ADMIRE) (Siemens Healthineers) MBIR inabdominal CT is reviewed and its noise suppression and/or dose reduction possibilities explored. Quantitative and qualitativemethods with phantom and human subjects were used. Assessment of the quality of phantom images will not always correlatepositively with those of patient images, particularly at the higher strength of the ADMIRE algorithm. With few exceptions,ADMIRE Strength 3 typically allows for substantial noise reduction compared to FBP and hence to significant (≈30%) patientdose reductions. The size of the dose reductions depends on the diagnostic task. Funding: ALF-grant from Region Ostergotland [LiO-602731, LIO-697941]; FoU-grant from Region Ostergotland [LIO-724631, LIO-620341]; RFoU-grant from Region Ostergotland; Medical Faculty at Linkoping University

Significance: Melanoma is a deadly cancer that physicians struggle to diagnose early because they lack the knowledge to differentiate benign from malignant lesions. Deep machine learning approaches to image analysis offer promise but lack the transparency to be widely adopted as stand-alone diagnostics. Aim: We aimed to create a transparent machine learning technology (i.e., not deep learning) to discriminate melanomas from nevi in dermoscopy images and an interface for sensory cue integration. Approach: Imaging biomarker cues (IBCs) fed ensemble machine learning classifier (Eclass) training while raw images fed deep learning classifier training. We compared the areas under the diagnostic receiver operator curves. Results: Our interpretable machine learning algorithm outperformed the leading deep-learning approach 75% of the time. The user interface displayed only the diagnostic imaging biomarkers as IBCs. Conclusions: From a translational perspective, Eclass is better than convolutional machine learning diagnosis in that physicians can embrace it faster than black box outputs. Imaging biomarkers cues may be used during sensory cue integration in clinical screening. Our method may be applied to other image-based diagnostic analyses, including pathology and radiology.

Significance: Practical implementation of acousto-optic imaging (AOI) encounters difficulties that prevent it from rapid adoption in clinical use. In many practical medical applications, the region of interest may be accessed only from one side, and using a water tank for coupling is not feasible. The solution might be to use reflection-mode imaging with an electronically scanned ultrasound (US) focus. Such an approach, however, entails considerable challenges. Aim: The possibilities of detecting and localizing light-absorbing inclusions inside turbid media by combining reflection-mode AOI conducted using a one-dimensional US array with electronic scanning of the US focus are investigated experimentally and signal processing algorithms that could be used for this purpose are introduced. Approach: We determine the speckle contrast decrease due to the acousto-optic effect as a function of the US focal point coordinates. Different signal postprocessing techniques are investigated. Results: A significant decrease in the determined speckle contrast difference values is observed due to the presence of light-absorbing inclusions. However, local minima occur in the plots only under specific conditions. Subtracting individual distributions and determining symmetry deviations allow for localizing the inclusions. Conclusions: Detection and localization of optically distinct regions are possible using the introduced approach. Signal postprocessing is required in a general case.

Significance: We introduce an application of machine learning trained on optical phase features of epithelial and mesenchymal cells to grade cancer cells’ morphologies, relevant to evaluation of cancer phenotype in screening assays and clinical biopsies. Aim: Our objective was to determine quantitative epithelial and mesenchymal qualities of breast cancer cells through an unbiased, generalizable, and linear score covering the range of observed morphologies. Approach: Digital holographic microscopy was used to generate phase height maps of noncancerous epithelial (Gie-No3B11) and fibroblast (human gingival) cell lines, as well as MDA-MB-231 and MCF-7 breast cancer cell lines. Several machine learning algorithms were evaluated as binary classifiers of the noncancerous cells that graded the cancer cells by transfer learning. Results: Epithelial and mesenchymal cells were classified with 96% to 100% accuracy. Breast cancer cells had scores in between the noncancer scores, indicating both epithelial and mesenchymal morphological qualities. The MCF-7 cells skewed toward epithelial scores, while MDA-MB-231 cells skewed toward mesenchymal scores. Linear support vector machines (SVMs) produced the most distinct score distributions for each cell line. Conclusions: The proposed epithelial–mesenchymal score, derived from linear SVM learning, is a sensitive and quantitative approach for detecting epithelial and mesenchymal characteristics of unknown cells based on well-characterized cell lines. We establish a framework for rapid and accurate morphological evaluation of single cells and subtle phenotypic shifts in imaged cell populations.

Significance: Machine learning is increasingly being applied to the classification of microscopic data. In order to detect some complex and dynamic cellular processes, time-resolved live-cell imaging might be necessary. Incorporating the temporal information into the classification process may allow for a better and more specific classification. Aim: We propose a methodology for cell classification based on the time-lapse quantitative phase images (QPIs) gained by digital holographic microscopy (DHM) with the goal of increasing performance of classification of dynamic cellular processes. Approach: The methodology was demonstrated by studying epithelial-mesenchymal transition (EMT) which entails major and distinct time-dependent morphological changes. The time-lapse QPIs of EMT were obtained over a 48-h period and specific novel features representing the dynamic cell behavior were extracted. The two distinct end-state phenotypes were classified by several supervised machine learning algorithms and the results were compared with the classification performed on single-time-point images. Results: In comparison to the single-time-point approach, our data suggest the incorporation of temporal information into the classification of cell phenotypes during EMT improves performance by nearly 9% in terms of accuracy, and further indicate the potential of DHM to monitor cellular morphological changes. Conclusions: Proposed approach based on the time-lapse images gained by DHM could improve the monitoring of live cell behavior in an automated fashion and could be further developed into a tool for high-throughput automated analysis of unique cell behavior. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

When analyzing multidiameter single-fiber reflectance (MDSFR) spectra, the inhomogeneous distribution of melanin pigments in skin tissue is usually not accounted for. Especially in heavily pigmented skins, this can result in bad fits and biased estimation of tissue optical properties. A model is introduced to account for the inhomogeneous distribution of melanin pigments in skin tissue. In vivo visible MDSFR measurements were performed on heavily pigmented skin of type IV to VI. Skin tissue optical properties and related physiological properties were extracted from the measured spectra using the introduced model. The absorption of melanin pigments described by the introduced model demonstrates a good correlation with the co-localized measurement of the well-known melanin index. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

The mesh-based Monte Carlo (MMC) algorithm is increasingly used as the gold-standard for developing new biophotonics modeling techniques in 3-D complex tissues, including both diffusion-based and various Monte Carlo (MC)-based methods. Compared to multilayered and voxel-based MCs, MMC can utilize tetrahedral meshes to gain improved anatomical accuracy but also results in higher computational and memory demands. Previous attempts of accelerating MMC using graphics processing units (GPUs) have yielded limited performance improvement and are not publicly available. We report a highly efficient MMC—MMCL—using the OpenCL heterogeneous computing framework and demonstrate a speedup ratio up to 420× compared to state-of-the-art single-threaded CPU simulations. The MMCL simulator supports almost all advanced features found in our widely disseminated MMC software, such as support for a dozen of complex source forms, wide-field detectors, boundary reflection, photon replay, and storing a rich set of detected photon information. Furthermore, this tool supports a wide range of GPUs/CPUs across vendors and is freely available with full source codes and benchmark suites at http://mcx.space/#mmc.

As photoacoustic imaging (PAI) technology matures, computational modeling will increasingly represent a critical tool for facilitating clinical translation through predictive simulation of real-world performance under a wide range of device and biological conditions. While modeling currently offers a rapid, inexpensive tool for device development and prediction of fundamental image quality metrics (e.g., spatial resolution and contrast ratio), rigorous verification and validation will be required of models used to provide regulatory-grade data that effectively complements and/or replaces in vivo testing. To address methods for establishing model credibility, we developed an integrated computational model of PAI by coupling a previously developed three-dimensional Monte Carlo model of tissue light transport with a two-dimensional (2D) acoustic wave propagation model implemented in the well-known k-Wave toolbox. We then evaluated ability of the model to predict basic image quality metrics by applying standardized verification and validation principles for computational models. The model was verified against published simulation data and validated against phantom experiments using a custom PAI system. Furthermore, we used the model to conduct a parametric study of optical and acoustic design parameters. Results suggest that computationally economical 2D acoustic models can adequately predict spatial resolution, but metrics such as signal-to-noise ratio and penetration depth were difficult to replicate due to challenges in modeling strong clutter observed in experimental images. Parametric studies provided quantitative insight into complex relationships between transducer characteristics and image quality as well as optimal selection of optical beam geometry to ensure adequate image uniformity. Multidomain PAI simulation tools provide high-quality tools to aid device development and prediction of real-world performance, but further work is needed to improve model fidelity, especially in reproducing image noise and clutter.

We report a small exploratory study of a methodology for real-time imaging of chemical and physical changes in spinal cords in the immediate aftermath of a localized contusive injury. One hundred separate experiments involving scanning NIR images, one-dimensional, two-dimensional (2-D), and point measurements, obtained in vivo, within a 3×7 mm field, on spinal cords surgically exposed between T9 and T10 revealed differences between injured and healthy cords. The collected raw data, i.e., elastic and inelastic emission from the laser probed tissues, combined via the PV[O]H algorithm, allow construction of five images over the first 5 h post injury. Within the larger study, a total of 13 rats were studied using 2-D images, i.e., injured and control. A single 830-nm laser (100-μm diameter round spot) was spatially line-scanned across the cord to reveal photobleaching effects and surface profiles possibly locating a near surface longitudinal artery/vein. In separate experiments, the laser was scanned in two dimensions across the exposed cord surface relative to the injury in a specific pattern to avoid uneven photobleaching of the imaged tissue. The 2-D scanning produced elastic and inelastic emission that allowed construction of PV[O]H images that had good fidelity with the visually observed surfaces and separate line scans and suggested differences between the volume fractions of fluid and turbidity of injured and healthy cord tissue.

Since it was first demonstrated more than a decade ago, the single-pixel camera concept has been used in numerous applications in which it is necessary or advantageous to reduce the channel count, cost, or data volume. Here, three-dimensional (3-D), compressed-sensing photoacoustic tomography (PAT) is demonstrated experimentally using a single-pixel camera. A large area collimated laser beam is reflected from a planar Fabry–Pérot ultrasound sensor onto a digital micromirror device, which patterns the light using a scrambled Hadamard basis before it is collected into a single photodetector. In this way, inner products of the Hadamard patterns and the distribution of thickness changes of the FP sensor—induced by the photoacoustic waves—are recorded. The initial distribution of acoustic pressure giving rise to those photoacoustic waves is recovered directly from the measured signals using an accelerated proximal gradient-type algorithm to solve a model-based minimization with total variation regularization. Using this approach, it is shown that 3-D PAT of imaging phantoms can be obtained with compression rates as low as 10%. Compressed sensing approaches to photoacoustic imaging, such as this, have the potential to reduce the data acquisition time as well as the volume of data it is necessary to acquire, both of which are becoming increasingly important in the drive for faster imaging systems giving higher resolution images with larger fields of view.

Single-shot, two-frame, π-shifted spatially multiplexed interference microscopy (π-SMIM) is presented as an improvement to previous SMIM implementations, introducing a versatile, robust, fast, and accurate method for cumbersome, noisy, and low-contrast phase object analysis. The proposed π-SMIM equips a commercially available nonholographic microscope with a high-speed (video frame rate) enhanced quantitative phase imaging (QPI) capability by properly placing a beam-splitter in the microscope embodiment to simultaneously (in a single shot) record two holograms mutually phase shifted by π radians at the expense of reducing the field of view. Upon subsequent subtractive superimposition of holograms, a π-hologram is generated with reduced background and improved modulation of interference fringes. These features determine superior phase retrieval quality, obtained by employing the Hilbert spiral transform on the π -hologram, as compared with a single low-quality (low signal-to-noise ratio) hologram analysis. In addition, π-SMIM enables accurate in-vivo analysis of high dynamic range phase objects, otherwise measurable only in static regime using time-consuming phase-shifting. The technique has been validated utilizing a 20 × / 0.46 NA objective in a regular Olympus BX-60 upright microscope for QPI of different lines of prostate cancer cells and flowing microbeads.

Label-free mass spectrometry (MS) has developed into an important tool applied in various fields of biological and life sciences. Several software exist to process the raw MS data into quantified protein abundances, including open source and commercial solutions. Each software includes a set of unique algorithms for different tasks of the MS data processing workflow. While many of these algorithms have been compared separately, a thorough and systematic evaluation of their overall performance is missing. Moreover, systematic information is lacking about the amount of missing values produced by the different proteomics software and the capabilities of different data imputation methods to account for them. In this study, we evaluated the performance of five popular quantitative label-free proteomics software workflows using four different spike-in data sets. Our extensive testing included the number of proteins quantified and the number of missing values produced by each workflow, the accuracy of detecting differential expression and logarithmic fold change and the effect of different imputation and filtering methods on the differential expression results. We found that the Progenesis software performed consistently well in the differential expression analysis and produced few missing values. The missing values produced by the other software decreased their performance, but this difference could be mitigated using proper data filtering or imputation methods. Among the imputation methods, we found that the local least squares (lls) regression imputation consistently increased the performance of the software in the differential expression analysis, and a combination of both data filtering and local least squares imputation increased performance the most in the tested data sets.

To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data.