Significance: The COVID-19 pandemic is changing the landscape of healthcare delivery in many countries, with a new shift toward remote patient monitoring (RPM).

Aim: The goal of this perspective is to highlight the existing and future role of wearable and RPM optical technologies in an increasingly at-home healthcare and research environment.

Approach: First, the specific changes occurring during the COVID-19 pandemic in healthcare delivery, regulations, and technological innovations related to RPM technologies are reviewed. Then, a review of the current state and potential future impact of optical physiological monitoring in portable and wearable formats is outlined.

Results: New efforts from academia, industry, and regulatory agencies are advancing and encouraging at-home, portable, and wearable physiological monitors as a growing part of healthcare delivery. It is hoped that these shifts will assist with disease diagnosis, treatment, management, recovery, and rehabilitation with minimal in-person contact. Some of these trends are likely to persist for years to come. Optical technologies already account for a large portion of RPM platforms, with a good potential for future growth.

Conclusions: The biomedical optics community has a potentially large role to play in developing, testing, and commercializing new wearable and RPM technologies to meet the changing healthcare and research landscape in the COVID-19 era and beyond.

Significance: The arterial carbon dioxide (CO2) partial pressure PaCO2 is a clinically relevant variable. However, its measurement requires arterial blood sampling or bulky and expensive transcutaneous PtcCO2 meters. While the spectrophotometric determination of hemoglobin species—such as oxy-hemoglobin (O2Hb) and deoxy-hemoglobin (HHb)—allowed for the development of pulse oximetry, the measurement of CO2 blood content with minimal discomfort has not been addressed yet.

Aim: Characterizing human carbamino-hemoglobin (CO2Hb) absorption spectrum, which is missing from the literature. Providing the theoretical background that will allow for transcutaneous, noninvasive PaCO2 measurements.

Approach: A tonometry-based approach was used to obtain gas-equilibrated, lysed, diluted human blood. Equilibration was performed with both CO2, dinitrogen (N2), and ambient air. Spectrophotometric measurements were carried out on the 235- to 1000-nm range. A theoretical background was also derived from that of pulse oximetry.

Results: The absorption spectra of both CO2Hb and HHb were extremely close and comparable with that of state-of-the-art HHb. The above-mentioned theoretical background led to an estimated relative error above 30% on the measured amount of CO2Hb in a subject’s blood. Auxiliary measurements revealed that the use of ethylene diamine tetraacetic acid did not interfere with spectrophotometric measurements, whereas sodium metabisulfite did.

Conclusions: CO2Hb absorption spectrum was measured for the first time. Such spectrum being close to that of HHb, the use of a theoretical background based on pulse oximetry theory for noninvasive PaCO2 measurement seems extremely challenging.

Significance: Raman spectroscopy (RS) applied to surgical guidance is attracting attention among scientists in biomedical optics. Offering a computational platform for studying depth-resolved RS and probing molecular specificity of different tissue layers is of crucial importance to increase the precision of these techniques and facilitate their clinical adoption.

Aim: The aim of this work was to present a rigorous analysis of inelastic scattering depth sampling and elucidate the relationship between sensing depth of the Raman effect and optical properties of the tissue under interrogation.

Approach: A new Monte Carlo (MC) package was developed to simulate absorption, fluorescence, elastic, and inelastic scattering of light in tissue. The validity of the MC algorithm was demonstrated by comparison with experimental Raman spectra in phantoms of known optical properties using nylon and polydimethylsiloxane as Raman-active compounds. A series of MC simulations were performed to study the effects of optical properties on Raman sensing depth for an imaging geometry consistent with single-point detection using a handheld fiber optics probe system.

Results: The MC code was used to estimate the Raman sensing depth of a handheld fiber optics system. For absorption and reduced scattering coefficients of 0.001 and 1  mm^−  1, the sensing depth varied from 105 to 225  μm for a range of Raman probabilities from ^{10  −  6} to ^{10  −  3}. Further, for a realistic Raman probability of ^{10  −  6}, the sensing depth ranged between 10 and 600  μm for the range of absorption coefficients 0.001 to 1.4  mm^−  1 and reduced scattering coefficients of 0.5 to 30  mm^−  1.

Conclusions: A spectroscopic MC light transport simulation platform was developed and validated against experimental measurements in tissue phantoms and used to predict depth sensing in tissue. It is hoped that the current package and reported results provide the research community with an effective simulating tool to improve the development of clinical applications of RS.

Significance: Photoacoustic imaging (PAI) has been greatly developed in a broad range of diagnostic applications. The efficiency of light to sound conversion in PAI is limited by the ubiquitous noise arising from the tissue background, leading to a low signal-to-noise ratio (SNR), and thus a poor quality of images. Frame averaging has been widely used to reduce the noise; however, it compromises the temporal resolution of PAI.

Aim: We propose an approach for photoacoustic (PA) signal denoising based on a combination of low-pass filtering and sparse coding (LPFSC).

Approach: LPFSC method is based on the fact that PA signal can be modeled as the sum of low frequency and sparse components, which allows for the reduction of noise levels using a hybrid alternating direction method of multipliers in an optimization process.

Results: LPFSC method was evaluated using in-silico and experimental phantoms. The results show a 26% improvement in the peak SNR of PA signal compared to the averaging method for in-silico data. On average, LPFSC method offers a 63% improvement in the image contrast-to-noise ratio and a 33% improvement in the structural similarity index compared to the averaging method for objects located at three different depths, ranging from 10 to 20 mm, in a porcine tissue phantom.

Conclusions: The proposed method is an effective tool for PA signal denoising, whereas it ultimately improves the quality of reconstructed images, especially at higher depths, without limiting the image acquisition speed.

Significance: Endoscopes represent electro-optical devices that are used to visualize internal body cavities. The specialized endoscopic procedure of the upper gastrointestinal tract from the esophagus down to the duodenum is called an esophagogastroduodenoscopy.

Aim: We bring our newly developed capsule endoscopy device as a promising alternative diagnostic method for visualization of the upper gastrointestinal tract.

Approach: Capsule endoscopy has become an attractive method that uses a tiny wireless camera to take pictures of the digestive tract. Existing esophageal capsule endoscopy does not allow a retrograde view of the esophagus while retrograde scanning can provide information on the esophageal pathology.

Results: In comparison to the existing esophageal capsule endoscopy, our system is much simpler and cheaper due to the need for fewer electronic devices. Moreover, its use is not limited by the capacity of the batteries used by existing capsule endoscopes. The new esophageal endoscopic system was created by combining the universal serial bus (USB) endoscope module with the thin power wires that are routed through the USB port to the computer.

Conclusions: The endoscope was tested on a volunteer without any side effects such as nausea, belching, and general discomfort. The examination of the patient is performed in a sitting position and the patient discomfort during the examination is minimal so it can be performed without anesthesia.

Significance: Diagnosis of suspicious lung nodules requires precise collection of relevant biopsies for histopathological analysis. Using optical coherence tomography and autofluorescence imaging (OCT-AFI) to improve diagnostic yield in parts of the lung inaccessible to larger imaging methods may allow for reducing complications related to the alternative of computed tomography-guided biopsy.

Aim: Feasibility of OCT-AFI combined with a commercially available lung biopsy needle was demonstrated for visualization of needle puncture sites in airways with diameters as small as 1.9 mm.

Approach: A miniaturized OCT-AFI imaging stylet was developed to be inserted through an 18G biopsy needle. We present design considerations and procedure development for image-guided biopsy. Ex vivo and in vivo porcine studies were performed to demonstrate the feasibility of the procedure and the device.

Results: OCT-AFI scans were obtained ex vivo and in vivo. Discrimination of pullback site is clear.

Conclusions: Use of the device is shown to be feasible in vivo. Images obtained show the stylet is effective at providing structural information at the puncture site that can be used to assess the diagnostic potential of the sample prior to collection.

Significance: For use in medical balloons and related clinical applications, polymers are usually designed for transparency under illumination with white-light sources. However, when illuminated with ultraviolet (UV) or blue light, most of these materials autofluoresce in the visible range, which can be a concern for modalities that rely on tissue autofluorescence for diagnostic or therapeutic purposes.

Aim: A search for published information on spectral properties of polymers that can be used for medical balloon manufacturing revealed a scarcity of published information on this subject. The aim of these studies was to address this gap.

Approach: The autofluorescence properties of polymers used in medical balloon manufacturing were examined for their suitability for hyperspectral imaging and related applications. Excitation-emission matrices of different balloon materials were acquired within the 320- to 620-nm spectral range. In parallel, autofluorescence profiles from the 420- to 620-nm range were extracted from hyperspectral datasets of the same samples illuminated with UV light. The list of tested polymers included polyurethanes, nylon, polyethylene terephthalate (PET), polyether block amide (PEBAX), vulcanized silicone, thermoplastic elastomers with and without talc, and cyclic olefin copolymers, known by their trade name TOPAS.

Results: Each type of polymer exhibited a specific pattern of autofluorescence. Polyurethanes, PET, and thermoplastic elastomers containing talc had the highest autofluorescence values, while sheets made of nylon, PEBAX, and TOPAS exhibited negligible autofluorescence. Hyperspectral imaging was used to illustrate how the choice of specific balloon material can impact the ability of principal component analysis to reveal the ablated cardiac tissue.

Conclusions: The data revealed significant differences between autofluorescence profiles of the polymers and pointed to the most promising balloon materials for clinical implementation of approaches that depend on tissue autofluorescence.

Significance: Researchers have made great progress in single-image super-resolution (SISR) using deep convolutional neural networks. However, in the field of leukocyte imaging, the performance of existing SISR methods is still limited as it fails to thoroughly explore the geometry and structural consistency of leukocytes. The inaccurate super-resolution (SR) results will hinder the pathological study of leukocytes, since the structure and cell lineage determine the types of leukocyte and will significantly affect the subsequent inspection.

Aim: We propose a deep network that takes full use of the geometry prior and structural consistency of the leukocyte images. We establish and annotate a leukocyte dataset, which contains five main types of leukocytes (basophil, eosinophil, monocyte, lymphocyte, and neutrophil), for learning the structure and geometry information.

Approach: Our model is composed of two modules: prior network and SR network. The prior network estimates the parsing map of the low-resolution (LR) image, and then the SR network takes both the estimated parsing map and LR image as input to predict the final high-resolution image.

Result: Experiments show that the geometry prior and structural consistency in use obviously improves the SR performance of leukocyte images, enhancing the peak-signal-to-noise ratio (PSNR) by about 0.4 dB in our benchmark.

Conclusion: As proved by our leukocyte SR benchmark, the proposed method significantly outperforms state-of-the-art SR methods. Our method not only improves the PSNR and structural similarity indices, but also accurately preserves the structural details of leukocytes. The proposed method is believed to have potential use in the wide-field cell prescreening by simply using a low-power objective.

Significance: High-speed 3D imaging methods have been playing crucial roles in many biological discoveries.

Aim: We present a hybrid light-field imaging system and image processing algorithm that can visualize high-speed biological events.

Approach: The hybrid light-field imaging system uses the selective plane optical illumination, which simultaneously records a high-resolution 2D image and a low-resolution 4D light-field image. The high-resolution 4D light-field image is obtained by applying the hybrid algorithm derived from the deconvolution and phase retrieval methods.

Results: High-resolution 3D imaging at a speed of 100-s volumes per second over an imaging field of 250  ×  250  ×  80  μm³ in the x, y, and z axis, respectively, is achieved with a 2.5 times enhancement in lateral resolution over the entire imaging field compared with standard light-field systems. In comparison to the deconvolution algorithm, the hybrid algorithm addresses the artifact issue at the focal plane and reduces the computation time by a factor of 4.

Conclusions: The new hybrid light-field imaging method realizes high-resolution and ultrafast 3D imaging with a compact setup and simple algorithm, which may help discover important applications in biophotonics to visualize high-speed biological events.

Significance: Ultrafast fiber lasers are an attractive alternative to bulk lasers for nonlinear optical microscopy for their compactness and low cost. The high relative intensity noise (RIN) of these lasers poses a challenge for pump-probe measurements such as transient absorption and stimulated Raman scattering, along with modalities that provide label-free contrast from the vibrational and electronic structure of molecules.

Aim: Digital adaptive filtering was applied to determine the applicability for canceling laser RIN in a transient absorption microscope with an ultrafast fiber laser source.

Approach: Digitized signals from the transmitted probe and reference photodetectors were fed to an adaptive filter in MATLAB, running in a noise canceling configuration. This result was then fed to a software lock-in algorithm to demodulate the pump-probe signal. Images were built up one line scan at a time with a 3.5-kHz resonant scanner, with 100  ×   averaging. The imaging target was Bi₄Ge₃O₁₂, which exhibits nondegenerate two-photon absorption at the pump/probe wavelengths used (530-nm pump and 490-nm probe).

Results: Without adaptive noise cancellation, the lock-in output primarily passes the laser RIN within its detection bandwidth, resulting in images that closely follow the linear transmissivity and lack sensitivity to pump-probe time delay. With adaptive noise cancellation in front of the lock-in, the RIN rejection is enough to restore the z-sectioning and sensitivity to pump-probe delay, as expected for transient absorption. Results were limited primarily by noise from the photodetector and analog-to-digital converter.

Conclusions: Digital adaptive noise cancellation, even when limited by electronics noise, can recover pump-probe signals by removal of laser RIN, under conditions where averaging alone fails.

Significance: Axially swept light sheet microscopy is used for deconvolution-free, high-resolution 3D imaging, but usually the axial scan mechanism reduces the top imaging speed. Phased arrays (PAs) for axial scanning enable both high resolution and high speed.

Aim: A high-speed PA with an update rate faster than the camera row read time is used to track the rolling shutter at camera-limited rates.

Approach: The point spread function is evaluated to ensure sub-micron isotropic resolution, and the technique is demonstrated on a live Drosophila embryo.

Results: Isotropic resolution is shown down to 720  ±  55  nm in all three spatial dimensions. With an update rate of 2.85  μs, the PA tracks the camera sensor rolling shutter at camera-limited rates. Features in the Drosophila embryo are resolved clearly compared with the equivalent static light sheet case. The random-access nature of the PA enables a camera sensor readout in the same direction for each frame to maintain even temporal sampling in image sequences with no speed loss.

Conclusions: Use of PAs is compatible with axially swept light sheet microscopy and offers significant improvements in speed.

Significance: Despite recent developments in microscopy, temporal aliasing can arise when imaging dynamic samples. Modern sampling frameworks, such as generalized sampling, mitigate aliasing but require measurement of temporally overlapping and potentially negative-valued inner products. Conventional cameras cannot collect these directly as they operate sequentially and are only sensitive to light intensity.

Aim: We aim to mitigate aliasing in microscopy of dynamic monochrome samples by implementing generalized sampling via the use of a color camera and modulated color illumination.

Approach: We solve the overlap problem by spectrally multiplexing the acquisitions and using (positive) B-spline segments as projection kernels. Reconstruction involves spectral unmixing and inverse filtering. We implemented this method using a color LED illuminator. We evaluated its performance by imaging a rotating grid and its applicability by imaging the beating zebrafish embryo heart in transmission and light-sheet microscopes.

Results: Compared to stroboscopic imaging, our method mitigates aliasing with performance improving as the projection order increases. The approach can be implemented in conventional microscopes but is limited by the number of available LED colors and camera channels.

Conclusions: Generalized sampling can be implemented via color modulation in microscopy to mitigate temporal aliasing. The simple hardware requirements could make it applicable to other optical imaging modalities.

Significance: Mid-infrared (IR) imaging based on the vibrational transition of biomolecules provides good chemical-specific contrast in label-free imaging of biology tissues, making it a popular tool in both biomedical studies and clinical applications. However, the current technology typically requires thin and dried or extremely flat samples, whose complicated processing limits this technology’s broader translation.

Aim: To address this issue, we report mid-IR photoacoustic microscopy (PAM), which can readily work with fresh and thick tissue samples, even when they have rough surfaces.

Approach: We developed a transmission-mode mid-IR PAM system employing an optical parametric oscillation laser operating in the wavelength range from 2.5 to 12  μm. Due to its high sensitivity to optical absorption and the low ultrasonic attenuation of tissue, our PAM achieved greater probing depth than Fourier transform IR spectroscopy, thus enabling imaging fresh and thick tissue samples with rough surfaces.

Results: In our spectroscopy study, the CH₂ symmetric stretching at 2850  cm^−  1 (3508 nm) was found to be an excellent source of endogenous contrast for lipids. At this wavenumber, we demonstrated label-free imaging of the lipid composition in fresh, manually cut, and unprocessed tissue sections of up to 3-mm thickness.

Conclusions: Our technology requires no time-consuming sample preparation procedure and has great potential in both fast clinical histological analysis and fundamental biological studies.