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P3 equations in a slab medium in the steady state and the time domain are proposed in this study. The spatially resolved diffuse reflectance and transmittance of the steady-state P3 equation are presented. Two time-domain equations in a slab medium, the optical parameter method and the double diffusion coefficient method, are established. The Monte Carlo simulation acted as an experimental result for comparison, and the results from the diffusion equation and P3 were compared against the Monte Carlo results. The results showed that the detection distance was less than twice the thickness of the medium, and the P3 equation results were in good agreement with the Monte Carlo simulation results. For the steady state, the P3 equation was more accurate than the diffusion equation when the distance was greater than 0.6 mm and less than 2 mm. However, when the absorption coefficient increased, the P3 steady-state equation was more accurate than the diffusion equation. In the time domain, the optical parameter method was more accurate than the double diffusion coefficient method and the diffusion equation. Therefore, the P3 approximation model can replace the diffusion model, and it can be applied to study tissue optics. [ABSTRACT FROM AUTHOR]

Multiscale visualization of human anatomical structures is revolutionizing clinical diagnosis and treatment. As one of the most promising clinical diagnostic techniques, photoacoustic imaging (PAI), or optoacoustic imaging, bridges the spatial-resolution gap between pure optical and ultrasonic imaging techniques, by the modes of optical illumination and acoustic detection. PAI can non-invasively capture multiple optical contrasts from the endogenous agents such as oxygenated/deoxygenated hemoglobin, lipid and melanin or a variety of exogenous specific biomarkers to reveal anatomy, function, and molecular for biological tissues in vivo, showing significant potential in clinical diagnostics. In 2001, the worldwide first clinical prototype of the photoacoustic system was used to screen breast cancer in vivo, which opened the prelude to photoacoustic clinical diagnostics. Over the past two decades, PAI has achieved monumental discoveries and applications in human imaging. Progress towards preclinical/clinical applications includes breast, skin, lymphatics, bowel, thyroid, ovarian, prostate, and brain imaging, etc., and there is no doubt that PAI is opening new avenues to realize early diagnosis and precise treatment of human diseases. In this review, the breakthrough researches and key applications of photoacoustic human imaging in vivo are emphatically summarized, which demonstrates the technical superiorities and emerging applications of photoacoustic human imaging in clinical diagnostics, providing clinical translational orientations for the photoacoustic community and clinicians. The perspectives on potential improvements of photoacoustic human imaging are finally highlighted. [ABSTRACT FROM AUTHOR]

Significance: Histopathological examination of surgical biopsies, such as in glioma and glioblastoma resection, is hindered in current clinical practice by the long time required for the laboratory analysis and pathological screening, typically taking several days or even weeks to be completed. Aim: We propose here a transportable, high-density, spectral scanning-based hyperspectral imaging (HSI) setup, named HyperProbe1, that can provide in situ, fast biochemical analysis, and mapping of fresh surgical tissue samples, right after excision, and without the need for fixing, staining nor compromising the integrity of the tissue properties. Approach: HyperProbe1 is based on spectral scanning via supercontinuum laser illumination filtered with acousto-optic tunable filters. Such methodology allows the user to select any number and type of wavelength bands in the visible and nearinfrared range between 510 and 900 nm (up to a maximum of 79) and to reconstruct 3D hypercubes composed of high-resolution (4 to 5 µm), widefield images (0.9 × 0.9 mm²) of the surgical samples, where each pixel is associated with a complete spectrum. Results: The HyperProbe1 setup is here presented and characterized. The system is applied to 11 fresh surgical biopsies of glioma from routine patients, including different grades of tumor classification. Quantitative analysis of the composition of the tissue is performed via fast spectral unmixing to reconstruct the mapping of major biomarkers, such as oxy-(HbO2) and deoxyhemoglobin (HHb), as well as cytochrome-c-oxidase (CCO). We also provided a preliminary attempt to infer tumor classification based on differences in composition in the samples, suggesting the possibility of using lipid content and differential CCO concentrations to distinguish between lower and higher-grade gliomas. Conclusions: A proof of concept of the performances of HyperProbe1 for quantitative, biochemical mapping of surgical biopsies is demonstrated, paving the way for improving current post-surgical, histopathological practice via non-destructive, in situ streamlined screening of fresh tissue samples in a matter of minutes after excision. [ABSTRACT FROM AUTHOR]

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As a rapidly growing field, biophotonics demonstrates an increasingly higher demand for interdisciplinary professionals and requires the implementation of a structured approach to educational and outreach activities focused on appropriate curriculum, and teaching and learning for audiences with diverse technical backgrounds and learning styles. Our study shows the main findings upon applying this approach to biophotonics workshops delivered 2 consecutive years while updating and improving learning outcomes, teaching strategies, workshop content based on student and teacher feedback. We provided resources for a variety of lecture‐based, experimental, computer simulation activities. Quality of subject matter, teaching, and overall learning was rated as "Very good" or "Good" by 88%, 76%, and 82% of students in average, respectively. Application of our teaching strategies and materials during short‐ and long‐term workshops/courses could potentially increase the interest in pursuing careers in the biophotonics field and related areas, leading to standardized approaches in designing education and outreach events across centers. [ABSTRACT FROM AUTHOR]

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution. Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz. Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head. Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies. [ABSTRACT FROM AUTHOR]

Abstract The extent of surgical resection is an important prognostic factor in the treatment of patients with glioblastoma. Optical coherence tomography (OCT) imaging is one of the adjunctive methods available to achieve the maximal surgical resection. In this study, the tumor margins were visualized with the OCT image obtained from a murine glioma model. A commercialized human glioblastoma cell line (U-87) was employed to develop the orthotopic murine glioma model. A swept-source OCT (SS-OCT) system of 1300 nm was used for three-dimensional imaging. Based on the OCT intensity signal, which was obtained via accumulation of each A-scan data, an en-face optical attenuation coefficient (OAC) map was drawn. Due to the limited working distance of the focused beam, OAC values decrease with depth, and using the OAC difference in the superficial area was chosen to outline the tumor boundary, presenting a challenge in analyzing the tumor margin along the depth direction. To overcome this and enable three-dimensional tumor margin detection, we converted the en-face OAC map into an en-face difference map with x- and y-directions and computed the normalized absolute difference (NAD) at each depth to construct a volumetric NAD map, which was compared with the corresponding H&E-stained image. The proposed method successfully revealed the tumor margin along the peripheral boundaries as well as the margin depth. We believe this method can serve as a useful adjunct in glioma surgery, with further studies necessary for real-world practical applications.

A novel approach for image formation in optical coherence tomography (OCT) and microscopy is presented. The depth resolution of OCT, including recently developed nanosensitive OCT (nsOCT), is limited by the spectral bandwidth of the light source used for illumination. The proposed approach, synthetic OCT (synOCT), permits label‐free, depth‐resolved quantitative visualization of the subwavelength‐sized structures with nanosensitivity. Using synOCT it is possible to estimate the contribution of axial Fourier components of an object's structure in image formation at each small volume within the image. The size of such areas can be smaller than the resolution limit of the imaging system that provides potential for super‐resolution imaging. Visualization of the subwavelength periodic structures and quantitative visualization of the subwavelength internal structures of highly scattering biological samples, within voxels smaller than resolution limit of the imaging system, are demonstrated. In contrast to nsOCT, the trade‐off between spectral and spatial resolution is removed which results in dramatic improvement of both spectral and spatial resolution in synOCT relative to nsOCT. [ABSTRACT FROM AUTHOR]

Significance: Radiofrequency ablation (RFA) procedures for atrial fibrillation frequently fail to prevent recurrence, partially due to limitations in assessing extent of ablation. Optical spectroscopy shows promise in assessing RFA lesion formation but has not been validated in conditions resembling those in vivo. Aim: Catheter-based near-infrared spectroscopy (NIRS) was applied to porcine hearts to demonstrate that spectrally derived optical indices remain accurate in blood and at oblique incidence angles. Approach: Porcine left atria were ablated and mapped using a custom-fabricated NIRS catheter. Each atrium was mapped first in phosphate-buffered saline (PBS) then in porcine blood. Results: NIRS measurements showed little angle dependence up to 60 deg. A trained random forest model predicted lesions with a sensitivity of 81.7%, a specificity of 86.1%, and a receiver operating characteristic curve area of 0.921. Predicted lesion maps achieved a mean structural similarity index of 0.749 and a mean normalized inner product of 0.867 when comparing maps obtained in PBS and blood. Conclusions: Catheter-based NIRS can precisely detect RFA lesions on left atria submerged in blood. Optical parameters are reliable in blood and without perpendicular contact, confirming their ability to provide useful feedback during in vivo RFA procedures. [ABSTRACT FROM AUTHOR]

A novel approach for image formation in optical coherence tomography (OCT) and microscopy is presented. The depth resolution of OCT, including recently developed nanosensitive OCT (nsOCT), is limited by the spectral bandwidth of the light source used for illumination. The proposed approach, synthetic OCT (synOCT), permits label‐free, depth‐resolved quantitative visualization of the subwavelength‐sized structures with nanosensitivity. Using synOCT it is possible to estimate the contribution of axial Fourier components of an object's structure in image formation at each small volume within the image. The size of such areas can be smaller than the resolution limit of the imaging system that provides potential for super‐resolution imaging. Visualization of the subwavelength periodic structures and quantitative visualization of the subwavelength internal structures of highly scattering biological samples, within voxels smaller than resolution limit of the imaging system, are demonstrated. In contrast to nsOCT, the trade‐off between spectral and spatial resolution is removed which results in dramatic improvement of both spectral and spatial resolution in synOCT relative to nsOCT.

Personalized medicine transforms healthcare by adapting interventions to individuals' unique genetic, molecular, and clinical profiles. To maximize diagnostic and/or therapeutic efficacy, personalized medicine requires advanced imaging devices and sensors for accurate assessment and monitoring of individual patient conditions or responses to therapeutics. In the field of biomedical optics, short-wave infrared (SWIR) techniques offer an array of capabilities that hold promise to significantly enhance diagnostics, imaging, and therapeutic interventions. SWIR techniques provide in vivo information, which was previously inaccessible, by making use of its capacity to penetrate biological tissues with reduced attenuation and enable researchers and clinicians to delve deeper into anatomical structures, physiological processes, and molecular interactions. Combining SWIR techniques with machine learning (ML), which is a powerful tool for analyzing information, holds the potential to provide unprecedented accuracy for disease detection, precision in treatment guidance, and correlations of complex biological features, opening the way for the data-driven personalized medicine field. Despite numerous biomedical demonstrations that utilize cutting-edge SWIR techniques, the clinical potential of this approach has remained significantly underexplored. This paper demonstrates how the synergy between SWIR imaging and ML is reshaping biomedical research and clinical applications. As the paper showcases the growing significance of SWIR imaging techniques that are empowered by ML, it calls for continued collaboration between researchers, engineers, and clinicians to boost the translation of this technology into clinics, ultimately bridging the gap between cutting-edge technology and its potential for personalized medicine. [ABSTRACT FROM AUTHOR]

This document provides brief biographical information about two individuals, Wesley B. Baker and Soren Konecky. Wesley B. Baker is an assistant professor at the University of Pennsylvania and Children's Hospital of Philadelphia, specializing in biomedical optical devices to monitor cerebral health. Soren Konecky is the chief technology officer for Openwater, with expertise in optical imaging and algorithm development. Both individuals have extensive experience in their respective fields and have made significant contributions to research and academia. [Extracted from the article]

Functional near-infrared spectroscopy (fNIRS) promises to be a leading noninvasive neuroimaging method due to its portability and low cost. However, concerns are rising over its inclusivity of all skin tones and hair types (Parker and Ricard, 2022, Webb et al., 2022). Functional NIRS relies on direct contact of lightemitting optodes to the scalp, which can be blocked more by longer, darker, and especially curlier hair. Additionally, NIR light can be attenuated by melanin, which is accounted for in neither fNIRS hardware nor analysis methods. Recent work has shown that overlooking these considerations in other modalities like EEG leads to the disproportionate exclusion of individuals with these phenotypes--especially Black people--in both clinical and research literature (Choy, 2020; Bradford et al., 2022; Louis et al., 2023). In this article, we sought to determine if (Jöbsis, 1977) biomedical optics developers and researchers report fNIRS performance variability between skin tones and hair textures, (2a) fNIRS neuroscience practitioners report phenotypic and demographic details in their articles, and thus, (2b) is a similar pattern of participant exclusion found in EEG also present in the fNIRS literature. We present a literature review of top Biomedical Optics and Human Neuroscience journals, showing that demographic and phenotypic reporting is unpopular in both fNIRS development and neuroscience applications. We conclude with a list of recommendations to the fNIRS community including examples of Black researchers addressing these issues head-on, inclusive best practices for fNIRS researchers, and recommendations to funding and regulatory bodies to achieve an inclusive neuroscience enterprise in fNIRS and beyond. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA) in dermatology usually suffers from low image quality due to the highly scattering property of the skin, the complexity of cutaneous vasculature, and limited acquisition time. Deep‐learning methods have achieved great success in many applications. However, the deep learning approach to improve dermatological OCTA images has not been investigated due to the requirement of high‐performance OCTA systems and difficulty of obtaining high‐quality images as ground truth. This study aims to generate proper datasets and develop a robust deep learning method to enhance the skin OCTA images. A swept‐source skin OCTA system was employed to create low‐quality and high‐quality OCTA images with different scanning protocols. We propose a model named vascular visualization enhancement generative adversarial network and adopt an optimized data augmentation strategy and perceptual content loss function to achieve better image enhancement effect with small amount of training data. We demonstrate the superiority of the proposed method in skin OCTA image enhancement by quantitative and qualitative comparisons. [ABSTRACT FROM AUTHOR]

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation. [ABSTRACT FROM AUTHOR]

BackgroundTotal skin electron therapy (TSET) utilizes high-energy electrons to treat malignancies on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interactions between the high-energy electron beam and tissue.Methods and materialsWith a time-gated intensified camera system, the Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real time. Fifteen patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. Each patient was monitored during TSET via in vivo detectors (IVD) in nine locations. For accurate Cherenkov imaging, a comparison between IVD and Cherenkov profiles was conducted using a polyvinyl chloride board to establish the perspective corrections.Results and discussionWith proper corrections developed in this study including the perspective and inverse square corrections, the Cherenkov imaging provided two-dimensional maps proportional to dose and projected on patient skin. The results of ratio between chest and umbilicus points were in good agreement with in vivo point dose measurements, with a standard deviation of 2.4% compared to OSLD measurements.ConclusionsCherenkov imaging is a viable tool for validating patient-specific dose distributions during TSET.

Functional near-infrared spectroscopy (fNIRS) promises to be a leading non-invasive neuroimaging method due to its portability and low cost. However, concerns are rising over its inclusivity of all skin tones and hair types (Parker and Ricard, 2022, Webb et al., 2022). Functional NIRS relies on direct contact of light-emitting optodes to the scalp, which can be blocked more by longer, darker, and especially curlier hair. Additionally, NIR light can be attenuated by melanin, which is accounted for in neither fNIRS hardware nor analysis methods. Recent work has shown that overlooking these considerations in other modalities like EEG leads to the disproportionate exclusion of individuals with these phenotypes—especially Black people—in both clinical and research literature (Choy, 2020; Bradford et al., 2022; Louis et al., 2023). In this article, we sought to determine if (Jöbsis, 1977) biomedical optics developers and researchers report fNIRS performance variability between skin tones and hair textures, (2a) fNIRS neuroscience practitioners report phenotypic and demographic details in their articles, and thus, (2b) is a similar pattern of participant exclusion found in EEG also present in the fNIRS literature. We present a literature review of top Biomedical Optics and Human Neuroscience journals, showing that demographic and phenotypic reporting is unpopular in both fNIRS development and neuroscience applications. We conclude with a list of recommendations to the fNIRS community including examples of Black researchers addressing these issues head-on, inclusive best practices for fNIRS researchers, and recommendations to funding and regulatory bodies to achieve an inclusive neuroscience enterprise in fNIRS and beyond.

Hyperspectral microscope imaging (HMI) is an emerging modality that integrates spatial information collected by standard laboratory microscopy and the spectral-based contrast obtained by hyperspectral imaging and may be instrumental in establishing novel quantitative diagnostic methodologies, particularly in histopathology. Further expansion of HMI capabilities hinges upon the modularity and versatility of systems and their proper standardization. In this report, we describe the design, calibration, characterization, and validation of the custom-made laboratory HMI system based on a Zeiss Axiotron fully motorized microscope and a custom-developed Czerny-Turner-type monochromator. For these important steps, we rely on a previously designed calibration protocol. Validation of the system demonstrates a performance comparable to classic spectrometry laboratory systems. We further demonstrate validation against a laboratory hyperspectral imaging system for macroscopic samples, enabling future comparison of spectral imaging results across length scales. An example of the utility of our custom-made HMI system on a standard hematoxylin and eosin-stained histology slide is also shown. [ABSTRACT FROM AUTHOR]

Wavefront sensors have now become core components in the fields of metrology of optical systems, biomedical optics, and adaptive optics systems for astronomy. However, none of the designs used or proposed so far achieve simultaneously a high spatial resolution at the pupil of the tested optics and absolute measurement accuracy comparable to those of modern laser-interferometers. This paper presents an improved wavefront sensor concept that reaches both previous goals. This device named Crossed-sine phase sensor (CSPS) is based on a fully transparent gradient phase filter (GPF) placed at an intermediate location between the virtual pupil and image planes of the tested optics. The theoretical principle of the sensor is described in Fourier optics formalism. Numerical simulations confirm that a measurement accuracy of λ/100 RMS is achievable. The CSPS also offers the advantages of being quasi-achromatic and working on spatially or spectrally extended, natural or artificial light sources. • The crossed-sine phase sensor (CSPS) is a wavefront sensor based on a gradient phase filter (GPF). • The CSPS measures first derivatives of the wavefront calculated from intensities of pupil images. • The theoretical principle of the CSPS is described in Fourier optics formalism. • The CSPS achieves simultaneously a high spatial resolution & a measurement accuracy of λ/100 RMS. • The CSPS is quasi-achromatic and can work on extended light sources. [ABSTRACT FROM AUTHOR]

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC  =  0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO2 to surrounding tissue StO2 are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer.

Simple Summary: Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide. The early detection and accurate characterization of colorectal cancer are associated with improved outcomes. With increasing emphasis on early cancer detection and the use of minimally invasive microsurgical techniques, the development of accurate diagnostic technologies to identify tumors and define their boundaries in real time becomes of paramount importance. The current research identifies potential cancer biomarkers and associated light-based instrument specifications to manufacture next-generation medical devices for CRC detection. These specifications have been chosen so that miniaturized instruments can be integrated into colonoscopes. Cancer biomarkers are listed to enable the use of complementary biochemical methods to analyze biological tissues. The impact of using next-generation colonoscopes in reducing cancer deaths can be assessed once medical devices are manufactured. Colorectal cancer (CRC) is the third most common and second most deadly type of cancer worldwide. Early detection not only reduces mortality but also improves patient prognosis by allowing the use of minimally invasive techniques to remove cancer while avoiding major surgery. Expanding the use of microsurgical techniques requires accurate diagnosis and delineation of the tumor margins in order to allow complete excision of cancer. We have used diffuse reflectance spectroscopy (DRS) to identify the main optical CRC biomarkers and to optimize parameters for the integration of such technologies into medical devices. A total number of 2889 diffuse reflectance spectra were collected in ex vivo specimens from 47 patients. Short source-detector distance (SDD) and long-SDD fiber-optic probes were employed to measure tissue layers from 0.5 to 1 mm and from 0.5 to 1.9 mm deep, respectively. The most important biomolecules contributing to differentiating DRS between tissue types were oxy- and deoxy-hemoglobin (Hb and HbO2), followed by water and lipid. Accurate tissue classification and potential DRS device miniaturization using Hb, HbO2, lipid and water data were achieved particularly well within the wavelength ranges 350–590 nm and 600–1230 nm for the short-SDD probe, and 380–400 nm, 420–610 nm, and 650–950 nm for the long-SDD probe. [ABSTRACT FROM AUTHOR]

Optical density based measurements are routinely performed to monitor the growth of microbes. These measurements solely depend upon the number of cells and do not provide any information about the changes in the biochemical milieu or biological status. An objective information about these parameters is essential for evaluation of novel therapies and for maximizing the metabolite production. In the present study, we have applied Raman spectroscopy to monitor growth kinetics of three different pathogenic Gram-negative microbes Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Spectral measurements were performed under 532 nm excitation with 5 seconds of exposure time. Spectral features suggest temporal changes in the "peptide" and "nucleic acid" content of cells under different growth stages. Using principal component analysis (PCA), successful discrimination between growth phases was also achieved. Overall, the findings are supportive of the prospective adoption of Raman based approaches for monitoring microbial growth. Graphical Abstract [ABSTRACT FROM AUTHOR]

Hyperspectral imaging (HSI) is a promising optical modality that is already being used in numerous applications. Further expansion of the capabilities of HSI depends on the modularity and versatility of the systems, which would, inter alia, incorporate profilometry, fluorescence imaging, and Raman spectroscopy while following a rigorous calibration and verification protocols, thus offering new insights into the studied samples as well as verifiable, quantitative measurement results applicable to the development of quantitative metrics. Considering these objectives, we developed a custom-made laboratory HSI system geared toward biomedical applications. In this report, we describe the design, along with calibration, characterization, and verification protocols needed to establish such systems, with the overall goal of standardization. As an additional novelty, our HSI system uses a custom-built broadband LED-based light source for reflectance imaging, which is particularly important for biomedical applications due to the elimination of sample heating. Three examples illustrating the utility and advantages of the integrated system in biomedical applications are shown. Our attempt presents both the development of a custom-based laboratory HSI system with novel LED light source as well as a framework which may improve technological standards in HSI system design. [ABSTRACT FROM AUTHOR]

Frequency-domain photon migration (FDPM) uses modulated laser light to measure the bulk optical properties of turbid media and is increasingly applied for noninvasive functional medical imaging in the near-infrared. Although semiconductor edge-emitting laser diodes have been traditionally used as miniature light sources for this application, we show that vertical-cavity surface-emitting lasers (VCSELs) exhibit output power and modulation performance characteristics suitable for FDPM measurements of tissue optical properties at modulation frequencies exceeding 1 GHz. We also show that an array of multiple VCSEL devices can be coherently modulated at frequencies suitable for FDPM and can improve optical power. In addition, their small size and simple packaging make them an attractive choice as components in wearable sensors and clinical FDPM-based optical spectroscopy systems. We demonstrate the benefits of VCSEL technology by fabricating and testing a unique, compact VCSEL-based optical probe with an integrated avalanche photodiode. We demonstrate sensitivity of the VCSEL-based probe to subcutaneous tissue hemodynamics that was induced during an arterial cuff occlusion of the upper arm in a human subject.

Frequency-domain photon migration (FDPM) uses modulated laser light to measure the bulk optical properties of turbid media and is increasingly applied for noninvasive functional medical imaging in the near-infrared. Although semiconductor edge-emitting laser diodes have been traditionally used as miniature light sources for this application, we show that vertical-cavity surface-emitting lasers (VCSELs) exhibit output power and modulation performance characteristics suitable for FDPM measurements of tissue optical properties at modulation frequencies exceeding 1 GHz. We also show that an array of multiple VCSEL devices can be coherently modulated at frequencies suitable for FDPM and can improve optical power. In addition, their small size and simple packaging make them an attractive choice as components in wearable sensors and clinical FDPM-based optical spectroscopy systems. We demonstrate the benefits of VCSEL technology by fabricating and testing a unique, compact VCSEL-based optical probe with an integrated avalanche photodiode. We demonstrate sensitivity of the VCSEL-based probe to subcutaneous tissue hemodynamics that was induced during an arterial cuff occlusion of the upper arm in a human subject.

Most oral injuries are diagnosed by histopathological analysis of invasive and time-consuming biopsies. This analysis and conventional clinical observation cannot identify biochemically altered tissues predisposed to malignancy if no microstructural changes are detectable. With this in mind, detailed biochemical characterization of normal tissues and their differentiation features on healthy individuals is important in order to recognize biomolecular changes associated with early tissue predisposition to malignant transformation. Raman spectroscopy is a label-free method for characterization of tissue structure and specific composition. In this study, we used Raman spectroscopy to characterize the biochemistry of in vivo oral tissues of healthy individuals. We investigated this biochemistry based on the vibrational modes related to Raman spectra of four oral subsites (buccal, gingiva, lip and tongue) of ten volunteers as well as with principal component (PC) loadings for the difference between the four types of oral subsites. Therefore, we determined the biochemical characteristics of each type of healthy oral subsite and those corresponding to differentiation of the four types of subsites. In addition, we developed a spectral reference of oral healthy tissues of individuals in the Brazilian population for future diagnosis of early pathological conditions using real-time, noninvasive and label-free techniques such as Raman spectroscopy.

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.

Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

Stroke is the second most common cause of death and third most common cause of disability worldwide. Therefore, it is an important disease from a medical standpoint. For this reason, various studies have developed diagnostic and therapeutic techniques for stroke. Among them, developments and applications of optical modalities are being extensively studied. In this article, we explored three important optical modalities for research, diagnostic, and therapeutics for stroke and the brain injuries related to it: (1) photochemical thrombosis to investigate stroke animal models; (2) optical imaging techniques for in vivo preclinical studies on stroke; and (3) optical neurostimulation based therapy for stroke. We believe that an exploration and an analysis of previous studies will help us proceed from research to clinical applications of optical modalities for research, diagnosis, and treatment of stroke. [ABSTRACT FROM AUTHOR]

Collagen is a major structural component of nearly every tissue in the human body, whose hierarchical organization imparts specific mechanical properties and defines overall tissue function. Collagenous soft tissues are dynamic structures that are in a constant state of remodeling but are also prone to damage and pathology. Optical techniques are uniquely suited for imaging collagen in these dynamic situations as they allow for non-invasive monitoring with relatively high spatiotemporal resolution. This review presents an overview of common collagen dynamic processes associated with human health and disease and optical imaging approaches that are uniquely suited for monitoring, sensing, and diagnosing these changes. This review aims to 1) provide researchers with an understanding of the underlying optical properties of collagen that can be leveraged for extracellular matrix visualization and 2) present emerging opportunities for machine learning approaches to drive multiscale and multimodality solutions.

Hyperspectral microscope imaging (HMI) is an emerging modality that integrates spatial information collected by standard laboratory microscopy and the spectral-based contrast obtained by hyperspectral imaging and may be instrumental in establishing novel quantitative diagnostic methodologies, particularly in histopathology. Further expansion of HMI capabilities hinges upon the modularity and versatility of systems and their proper standardization. In this report, we describe the design, calibration, characterization, and validation of the custom-made laboratory HMI system based on a Zeiss Axiotron fully motorized microscope and a custom-developed Czerny-Turner-type monochromator. For these important steps, we rely on a previously designed calibration protocol. Validation of the system demonstrates a performance comparable to classic spectrometry laboratory systems. We further demonstrate validation against a laboratory hyperspectral imaging system for macroscopic samples, enabling future comparison of spectral imaging results across length scales. An example of the utility of our custom-made HMI system on a standard hematoxylin and eosin-stained histology slide is also shown.

This paper discusses and studies the composition and characteristics of biospeckle on the surface of bone tissues. We used a laser speckle device to capture biospeckle patterns from fresh pig bone tissue. Traditional speckle activity metrics were used to measure the speckle activity of ex vivo bone tissue over time. Both Gaussian and Lorentzian correlation functions were used to characterize the ordered and disordered motion of the bone surface, together with volume scattering, to construct the model. Using the established mathematical model of the spatio-temporal evolution of the biospeckle pattern, it is possible to account for the presence of volume scattering from the biospeckle of bones, quantify the ordered or disordered motions in the biological speckle activity at the current time, and assess the ability of laser speckle correlation technique to determine biological activity. [ABSTRACT FROM AUTHOR]

This paper discusses and studies the composition and characteristics of biospeckle on the surface of bone tissues. We used a laser speckle device to capture biospeckle patterns from fresh pig bone tissue. Traditional speckle activity metrics were used to measure the speckle activity of ex vivo bone tissue over time. Both Gaussian and Lorentzian correlation functions were used to characterize the ordered and disordered motion of the bone surface, together with volume scattering, to construct the model. Using the established mathematical model of the spatio-temporal evolution of the biospeckle pattern, it is possible to account for the presence of volume scattering from the biospeckle of bones, quantify the ordered or disordered motions in the biological speckle activity at the current time, and assess the ability of laser speckle correlation technique to determine biological activity.

In optical imaging, optical clearing agents are commonly used to enhance the structural details of a sample. The current study investigates how to use it to improve the data obtained by an optical coherence tomography angiography system. A natural edible oil with no chemical base has been used for optical clearing. In-vivo testing on mice and humans yielded excellent optical clearing. Using computational techniques, the improvement in angiography signal caused by the optical clearing agent is investigated qualitatively and quantitatively. Compared to the control group, applying the edible oil-based optical clearing agent demonstrated improved vessel percentage and refined vascular signal intensity along depth. • In-vivo optical clearing has been performed on mice and human skin. • Optical clearing has been accomplished with edible oil. • The use of optical clearing agent enhanced the OCT Angiography signal and allowed for greater microvasculature visibility. • A quantitative estimation of the improvement in OCT Angiography signal has been made. • In real-time, one can observe the microvasculature changes of the dermal vasculature. [ABSTRACT FROM AUTHOR]

Hyperspectral imaging (HSI) is a promising optical modality that is already being used in numerous applications. Further expansion of the capabilities of HSI depends on the modularity and versatility of the systems, which would, inter alia, incorporate profilometry, fluorescence imaging, and Raman spectroscopy while following a rigorous calibration and verification protocols, thus offering new insights into the studied samples as well as verifiable, quantitative measurement results applicable to the development of quantitative metrics. Considering these objectives, we developed a custom-made laboratory HSI system geared toward biomedical applications. In this report, we describe the design, along with calibration, characterization, and verification protocols needed to establish such systems, with the overall goal of standardization. As an additional novelty, our HSI system uses a custom-built broadband LED-based light source for reflectance imaging, which is particularly important for biomedical applications due to the elimination of sample heating. Three examples illustrating the utility and advantages of the integrated system in biomedical applications are shown. Our attempt presents both the development of a custom-based laboratory HSI system with novel LED light source as well as a framework which may improve technological standards in HSI system design.

Featured Application: Digital histology for tumoral tissues discrimination. Histology is the diagnosis gold standard. Conventional biopsy presents artifacts, delays, or human bias. Digital histology includes automation and improved diagnosis. It digitalizes microscopic images of histological samples and analyzes similar parameters. The present approach proposes the novel use of phase contrast in clinical digital histology to improve diagnosis. The use of label-free fresh tissue slices prevents processing artifacts and reduces processing time. Phase contrast parameters are implemented and calculated: the external scale, the fractal dimension, the anisotropy factor, the scattering coefficient, and the refractive index variance. Images of healthy and tumoral samples of liver, colon, and kidney are employed. A total of 252 images with 10×, 20×, and 40× magnifications are measured. Discrimination significance between healthy and tumoral tissues is assessed statistically with ANOVA (p-value < 0.005). The analysis is made for each tissue type and for different magnifications. It shows a dependence on tissue type and image magnification. The p-value of the most significant parameters is below 10−5. Liver and colon tissues present a great overlap in significant phase contrast parameters. The 10× fractal dimension is significant for all tissue types under analysis. These results are promising for the use of phase contrast in digital histology clinical praxis. [ABSTRACT FROM AUTHOR]

This article is an editorial that discusses recent advances in the field of biomedical optics, specifically focusing on the clinical applications of instrumentation and methods. Biomedical optics is a rapidly growing field that combines biology, optics, and medicine to nondestructively reveal functional, structural, and molecular information. The article highlights six manuscripts that report achievements in the field, including studies on optical coherence tomography (OCT) for imaging tissue, en-bloc hematoxylin-eosin staining for lung cancer diagnosis, and move-contrast X-ray imaging for water transport analysis. The authors emphasize the importance of continued research and development in biomedical optics for future clinical applications. [Extracted from the article]

We report on the experimental determination of the refractive index for eleven freshly-excised human tissue types, acquired from 16 patients. Measurements are based on a prism-coupling refractometer that is pumped by five individual laser sources emitting monochromatic radiation at 450 nm, 532 nm, 633 nm, 964 nm and 1551 nm, respectively. A simple Cauchy model reproduces accurately experimental data and enables the prediction of tissue’s index within the entire visible and near-infrared spectral range, as well the estimation of dispersion-related parameters, such as group velocity dispersion.

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain., Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution., Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz., Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head., Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies., (© 2024 The Authors.)

Stroke is the second most common cause of death and third most common cause of disability worldwide. Therefore, it is an important disease from a medical standpoint. For this reason, various studies have developed diagnostic and therapeutic techniques for stroke. Among them, developments and applications of optical modalities are being extensively studied. In this article, we explored three important optical modalities for research, diagnostic, and therapeutics for stroke and the brain injuries related to it: (1) photochemical thrombosis to investigate stroke animal models; (2) optical imaging techniques for in vivo preclinical studies on stroke; and (3) optical neurostimulation based therapy for stroke. We believe that an exploration and an analysis of previous studies will help us proceed from research to clinical applications of optical modalities for research, diagnosis, and treatment of stroke.