Detour to success: photoswitching via indirect excitation.

Photoswitchable molecules that undergo nanoscopic changes upon photoisomerisation can be harnessed to control macroscopic properties such as colour, solubility, shape, and motion of the systems they are incorporated into. These molecules find applications in various fields of chemistry, physics, biology, and materials science. Until recently, research efforts have focused on the design of efficient photoswitches responsive to low-energy (red or near-infrared) irradiation, which however may compromise other molecular properties such as thermal stability and robustness. Indirect isomerisation methods enable photoisomerisation with low-energy photons without altering the photoswitch core, and also open up new avenues in controlling the thermal switching mechanism. In this perspective, we present the state of the art of five indirect excitation methods: two-photon excitation, triplet sensitisation, photon upconversion, photoinduced electron transfer, and indirect thermal methods. Each impacts our understanding of the fundamental physicochemical properties of photochemical switches, and offers unique application prospects in biomedical technologies and beyond.

mHealth learning strategies to support behaviour change in individuals using wheelchairs and/or scooters: a systematic review.

PURPOSE: The purpose of this systematic review of the literature is to build understanding of the key elements and recommendations for the design of mHealth technology for individuals using wheelchairs and/or scooters and identify key features associated with the use of mHealth to support healthy behaviour changes for this population. MATERIALS AND METHODS: Eight major electronic databases were systematically searched to identify mobile health (mHealth) interventions, which targeted adult WC/S users. Independent reviewers used Endnote and Covidence to manage articles meeting review criteria and to exclude duplicates. A quality assessment was conducted on each included article. RESULTS: Nine articles describing studies with diverse study designs met criteria to be included in this review. Several interactive application intervention features, such as participant collaboration and goal setting, and key technical features to support mHealth app development and utilisation were identified. Results found intuitive and simple designs of mHealth apps, with the ability to customise to support learning styles and preferences, support usability and acceptability by participants. CONCLUSIONS: More research is needed to evaluate best practices to support initial training of end-users, mHealth apps' ability to support long-term behaviour change and maintenance, and the understanding of active ingredients in complex interventions that include mHealth apps. Both interactive mHealth application intervention and technical features support healthy behaviour change among individuals using wheelchairs and scooters.

Utilizing evidence to develop mHealth applications (apps) support best practices, participant satisfaction, and usability.mHealth apps are feasible to support health behavior change for wheelchair and/or scooter users, with considerations for customization to support diverse learning preferences and needs.Active learning strategies (e.g., goal setting, self-assessment, collaborative learning), within or in conjunction with the app, support behavior change.

Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in lethal prostate cancer.

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSIs) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. EXPERIMENTAL DESIGN: We applied targeted cell-free DNA sequencing to 126 mCRPC patients from three academic cancer centers, and separately performed genome-wide cell-free DNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome-positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 mCRPC patients, respectively, to develop and validate a stem-like signature, which we inferred from cell-free DNA. RESULTS: Targeted cell-free DNA sequencing detected AR/enhancer alterations prior to first-line ARSIs which correlated with significantly worse PFS (p = 0.01; HR = 2.12) and OS (p = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (p < 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cell-free DNA revealed enrichment for stemness-associated transcription factors in lethal mCRPC patients. The resulting stemness signature was then validated in a completely held-out cohort of 80 mCRPC patients profiled by tumor RNA sequencing. CONCLUSIONS: We analyzed a total of 220 mCRPC patients, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness.

Atropisomerism Observed in Galactose-Based Monosaccharide Inhibitors of Galectin-3 Comprising 2-Methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione.

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (compound 20) and 4-phenyl-4H-1,2,4-triazole (compound 15). Notably, hindered rotation caused by steric interaction between the 3-thione and ortho-trifluoromethyl group of compounds 20, 21 induced formation of thermodynamically stable atropisomers. Distinct X-ray cocrystal structures of 20 and 21 were obtained, which clearly demonstrated that the configuration of 21 proscribes a key halogen bonding σ-hole interaction of 3-chloro with carbonyl oxygen of Gly182, thereby leading to significant loss in potency. Ultimately, 20 and 15 were evaluated in mouse pharmacokinetic studies, and both compounds exhibited oral exposures suitable for further in vivo assessment.

A Mathematical Model of Diel Activity and Long Time Survival in Phototrophic Mixed-Species Subaerial Biofilms.

Subaerial biofilms (SAB) are intricate microbial communities living on terrestrial surfaces, of interest in a variety of contexts including cultural heritage preservation, microbial ecology, biogeochemical cycling, and biotechnology. Here we propose a mathematical model aimed at better understanding the interplay between cyanobacteria and heterotrophic bacteria, common microbial SAB constituents, and their mutual dependence on local environmental conditions. SABs are modeled as thin mixed biofilm-liquid water layers sitting on stone. A system of ordinary differential equations regulates the dynamics of key SAB components: cyanobacteria, heterotrophs, polysaccharides and decayed biomass, as well as cellular levels of organic carbon, nitrogen and energy. These components are interconnected through a network of energetically dominant metabolic pathways, modeled with limitation terms reflecting the impact of biotic and abiotic factors. Daily cylces of temperature, humidity, and light intensity are considered as input model variables that regulate microbial activity by influencing water availability and metabolic kinetics. Relevant physico-chemical processes, including pH regulation, further contribute to a description of the SAB ecology. Numerical simulations explore the dynamics of SABs in a real-world context, revealing distinct daily activity periods shaped by water activity and light availability, as well as longer time scale survivability conditions. Results also suggest that heterotrophs could play a substantial role in decomposing non-volatile carbon compounds and regulating pH, thus influencing the overall composition and stability of the biofilm.

Borrelia burgdorferi BB0346 is an Essential, Structurally Variant LolA Homolog that is Primarily Required for Homeostatic Localization of Periplasmic Lipoproteins.

In diderm bacteria, the Lol pathway canonically mediates the periplasmic transport of lipoproteins from the inner membrane (IM) to the outer membrane (OM) and therefore plays an essential role in bacterial envelope homeostasis. After extrusion of modified lipoproteins from the IM via the LolCDE complex, the periplasmic chaperone LolA carries lipoproteins through the periplasm and transfers them to the OM lipoprotein insertase LolB, itself a lipoprotein with a LolA-like fold. Yet, LolB homologs appear restricted to γ-proteobacteria and are missing from spirochetes like the tick-borne Lyme disease pathogen Borrelia burgdorferi, suggesting a different hand-off mechanism at the OM. Here, we solved the crystal structure of the B. burgdorferi LolA homolog BB0346 (LolABb) at 1.9 Å resolution. We identified multiple structural deviations in comparative analyses to other solved LolA structures, particularly a unique LolB-like protruding loop domain. LolABb failed to complement an Escherichia coli lolA knockout, even after codon optimization, signal I peptide adaptation, and a C-terminal chimerization which had allowed for complementation with an α-proteobacterial LolA. Analysis of a conditional B. burgdorferi lolA knockout strain indicated that LolABb was essential for growth. Intriguingly, protein localization assays indicated that initial depletion of LolABb led to an emerging mislocalization of both IM and periplasmic OM lipoproteins, but not surface lipoproteins. Together, these findings further support the presence of two separate primary secretion pathways for periplasmic and surface OM lipoproteins in B. burgdorferi and suggest that the distinct structural features of LolABb allow it to function in a unique LolB-deficient lipoprotein sorting system.

Exploring the Ligand Binding and Conformational Dynamics of the Substrate-Binding Domain 1 of the ABC Transporter GlnPQ.

The adenosine triphosphate (ATP)-binding cassette (ABC) importer GlnPQ from Lactococcus lactis has two sequential covalently linked substrate-binding domains (SBDs), which capture the substrates and deliver them to the translocon. The two SBDs differ in their ligand specificities, binding affinities and the distance to the transmembrane domain; interestingly, both SBDs can bind their ligands simultaneously without affecting each other. In this work, we studied the binding of ligands to both SBDs using X-ray crystallography and molecular dynamics simulations. We report three high-resolution structures of SBD1, namely, the wild-type SBD1 with bound asparagine or arginine, and E184D SBD1 with glutamine bound. Molecular dynamics (MD) simulations provide a detailed insight into the dynamics associated with open-closed transitions of the SBDs.

Neurologic Symptoms After 177Lu-Prostate-Specific-Membrane Antigen-617 Therapy: A Single-Center Experience.

Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.

Structural and physical-chemical properties of milk fat globules fractionated by a series of silicon carbide membranes.

Driven by the acknowledged health and functional properties of milk fat globules (MFGs), there is a growing interest to develop gentle methodologies for separation of fat from milk. In this study, separation of fat from raw milk and fractionation in streams containing MFGs of different size was achieved using a series of two silicon carbide ceramic membranes. A first step consisting of a 1.4 µm membrane aimed to concentrate the bulk of the fat, i.e. the larger MFGs (D[4,3] âˆ¼ 4 µm) followed by a 0.5 µm fractionation aimed to concentrate the residual milk fat in the permeate, i.e. fraction with the smaller MFGs (D[4,3] âˆ¼ 1.8-2.4 µm. The fat separation performance showed a yield of 92 % for the 1.4 µm membrane and 97 % for the 0.5 µm membrane. Both fat enriched retentates showed, by the confocal laser scanning microscopy, intact MFGs with limited damage in the MFG membrane. The fatty acid profile analysis and SAXS showed minor differences in fat acid composition and the crystallization behavior was related to differences in the fat content. The 0.5 µm permeate containing the smallest MFGs however showed larger aggregates and a trinomial particle size distribution, due to probably pore pressure induced coalescences. The series of silicon carbide membranes showed potential to concentrate some of MFGM proteins such as Periodic Schiff base 3/4 and cluster of differentiation 36 especially in the 0.5 µm retentates. A shift in casein to whey protein ratio from 80:20 (milk) to 50:50 was obtained in the final 0.5 µm permeate, which opens new opportunities for product development.

A Mechanism-Based Reaction-Diffusion Model for Accelerated Discovery of Thermoset Resins Frontally Polymerized by Olefin Metathesis.

Frontal ring-opening metathesis polymerization (FROMP) involves a self-perpetuating exothermic reaction, which enables the rapid and energy-efficient manufacturing of thermoset polymers and composites. Current state-of-the-art reaction-diffusion FROMP models rely on a phenomenological description of the olefin metathesis kinetics, limiting their ability to model the governing thermo-chemical FROMP processes. Furthermore, the existing models are unable to predict the variations in FROMP kinetics with changes in the resin composition and as a result are of limited utility toward accelerated discovery of new resin formulations. In this work, we formulate a chemically meaningful model grounded in the established mechanism of ring-opening metathesis polymerization (ROMP). Our study aims to validate the hypothesis that the ROMP mechanism, applicable to monomer-initiator solutions below 100 °C, remains valid under the nonideal conditions encountered in FROMP, including ambient to >200 °C temperatures, sharp temperature gradients, and neat monomer environments. Through extensive simulations, we demonstrate that our mechanism-based model accurately predicts the FROMP behavior across various resin compositions, including polymerization front velocities and thermal characteristics (e.g., Tmax). Additionally, we introduce a semi-inverse workflow that predicts FROMP behavior from a single experimental data point. Notably, the physiochemical parameters utilized in our model can be obtained through DFT calculations and minimal experiments, highlighting the model's potential for rapid screening of new FROMP chemistries in pursuit of thermoset polymers with superior thermo-chemo-mechanical properties.

In vivo terahertz sensing of psoriasis and eczema patients.

In this study we present the first in vivo clinical study of patients with eczema and psoriasis using terahertz (THz) sensing. Eczema and psoriasis patients were measured using a handheld THz scanner, both before and after the application of moisturiser. We show that THz sensing can distinguish between dry and healthy skin in different regions of the body. Furthermore, the impact of applying moisturiser on the skin can also be observed and potentially evaluated using THz light.

Cyclopropanation with Non-Stabilized Carbenes via Ketyl Radicals.

A radical mechanism enables simple and robust access to nonstabilized, alkyl iron carbenes for novel (2 + 1) cycloadditions. This Fe-catalyzed strategy employs simple, aliphatic aldehydes as carbene precursors in a practical, efficient, and stereoselective cyclopropanation. This air- and water-tolerant method permits convenient generation of iron carbenes and coupling to an exceptionally wide range of sterically and electronically diverse alkenes (nucleophilic, electrophilic, and neutral). A transient ketyl radical intermediate is key to accessing and harnessing this rare, alkyl iron carbene reactivity. Mechanistic experiments confirm the (a) intermediacy of ketyl radicals, (b) iron carbene formation by radical capture, and (c) nonconcerted nature of the (2 + 1) cycloaddition.

Force Field X: A computational microscope to study genetic variation and organic crystals using theory and experiment.

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.

Validation of a commercially available CAD-system for lung nodule detection and characterization using CT-scans.

OBJECTIVES: This study aims to externally validate a commercially available Computer-Aided Detection (CAD)-system for the automatic detection and characterization of solid, part-solid, and ground-glass lung nodules (LN) on CT scans. METHODS: This retrospective study encompasses 263 chest CT scans performed between January 2020 and December 2021 at a Dutch university hospital. All scans were read by a radiologist (R1) and compared with the initial radiology report. Conflicting scans were assessed by an adjudicating radiologist (R2). All scans were also processed by CAD. The standalone performance of CAD in terms of sensitivity and false-positive (FP)-rate for detection was calculated together with the sensitivity for characterization, including texture, calcification, speculation, and location. The R1's detection sensitivity was also assessed. RESULTS: A total of 183 true nodules were identified in 121 nodule-containing scans (142 non-nodule-containing scans), of which R1 identified 165/183 (90.2%). CAD detected 149 nodules, of which 12 were not identified by R1, achieving a sensitivity of 149/183 (81.4%) with an FP-rate of 49/121 (0.405). CAD's detection sensitivity for solid, part-solid, and ground-glass LNs was 82/94 (87.2%), 42/47 (89.4%), and 25/42 (59.5%), respectively. The classification accuracy for solid, part-solid, and ground-glass LNs was 81/82 (98.8%), 16/42 (38.1%), and 18/25 (72.0%), respectively. Additionally, CAD demonstrated overall classification accuracies of 137/149 (91.9%), 123/149 (82.6%), and 141/149 (94.6%) for calcification, spiculation, and location, respectively. CONCLUSIONS: Although the overall detection rate of this system slightly lags behind that of a radiologist, CAD is capable of detecting different LNs and thereby has the potential to enhance a reader's detection rate. While promising characterization performances are obtained, the tool's performance in terms of texture classification remains a subject of concern. CLINICAL RELEVANCE STATEMENT: Numerous lung nodule computer-aided detection-systems are commercially available, with some of them solely being externally validated based on their detection performance on solid nodules. We encourage researchers to assess performances by incorporating all relevant characteristics, including part-solid and ground-glass nodules. KEY POINTS: Few computer-aided detection (CAD) systems are externally validated for automatic detection and characterization of lung nodules. A detection sensitivity of 81.4% and an overall texture classification sensitivity of 77.2% were measured utilizing CAD. CAD has the potential to increase single reader detection rate, however, improvement in texture classification is required.

Consequential insights for advancing informal STEM learning and outcomes for students from historically marginalized communities.

Consequential STEM experiences in informal settings can address issues of equity by fully engaging historically marginalized high school students in complex socio-scientific issues. However, inclusive and effective programs are in high demand, and there is little research on what specific aspects, context, and timeframes are most important when scaling these experiences. Using a mixed method approach, this study demonstrates that students make significant gains, in the short and long term, through in-person and remote informal programs ranging between 22-h and 320-h. Progress across STEM learning constructs is attributed to authentic research experiences, students' connections to STEM professionals, direct hands-on participation in projects, and group work. Relative to formal education settings, research-based informal STEM programs can be implemented with minimal resources, can maintain effectiveness while scaling, and work towards addressing the societal challenge of improving STEM learning and outcomes for high school students from historically marginalized communities.

Interobserver Agreement and Performance of Concurrent AI Assistance for Radiographic Evaluation of Knee Osteoarthritis.

Background Due to conflicting findings in the literature, there are concerns about a lack of objectivity in grading knee osteoarthritis (KOA) on radiographs. Purpose To examine how artificial intelligence (AI) assistance affects the performance and interobserver agreement of radiologists and orthopedists of various experience levels when evaluating KOA on radiographs according to the established Kellgren-Lawrence (KL) grading system. Materials and Methods In this retrospective observer performance study, consecutive standing knee radiographs from patients with suspected KOA were collected from three participating European centers between April 2019 and May 2022. Each center recruited four readers across radiology and orthopedic surgery at in-training and board-certified experience levels. KL grading (KL-0 = no KOA, KL-4 = severe KOA) on the frontal view was assessed by readers with and without assistance from a commercial AI tool. The majority vote of three musculoskeletal radiology consultants established the reference standard. The ordinal receiver operating characteristic method was used to estimate grading performance. Light kappa was used to estimate interrater agreement, and bootstrapped t statistics were used to compare groups. Results Seventy-five studies were included from each center, totaling 225 studies (mean patient age, 55 years ± 15 [SD]; 113 female patients). The KL grades were KL-0, 24.0% (n = 54); KL-1, 28.0% (n = 63); KL-2, 21.8% (n = 49); KL-3, 18.7% (n = 42); and KL-4, 7.6% (n = 17). Eleven readers completed their readings. Three of the six junior readers showed higher KL grading performance with versus without AI assistance (area under the receiver operating characteristic curve, 0.81 ± 0.017 [SEM] vs 0.88 ± 0.011 [P < .001]; 0.76 ± 0.018 vs 0.86 ± 0.013 [P < .001]; and 0.89 ± 0.011 vs 0.91 ± 0.009 [P = .008]). Interobserver agreement for KL grading among all readers was higher with versus without AI assistance (κ = 0.77 ± 0.018 [SEM] vs 0.85 ± 0.013; P < .001). Board-certified radiologists achieved almost perfect agreement for KL grading when assisted by AI (κ = 0.90 ± 0.01), which was higher than that achieved by the reference readers independently (κ = 0.84 ± 0.017; P = .01). Conclusion AI assistance increased junior readers' radiographic KOA grading performance and increased interobserver agreement for osteoarthritis grading across all readers and experience levels. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Performance of ChatGPT-4 and Bard chatbots in responding to common patient questions on prostate cancer 177Lu-PSMA-617 therapy.

Background: Many patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information. Purpose: To evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel 177Lu-PSMA-617 therapy for prostate cancer. Materials and methods: Two experts listed the 12 most commonly asked questions by patients on 177Lu-PSMA-617 therapy. These twelve questions were prompted to OpenAI ChatGPT-4 and Google Bard. AI-generated responses were distributed using an online survey platform (Qualtrics) and blindly rated by eight experts. The performances of the AI chatbots were evaluated and compared across three domains: accuracy, conciseness, and readability. Additionally, potential safety concerns associated with AI-generated answers were also examined. The Mann-Whitney U and chi-square tests were utilized to compare the performances of AI chatbots. Results: Eight experts participated in the survey, evaluating 12 AI-generated responses across the three domains of accuracy, conciseness, and readability, resulting in 96 assessments (12 responses x 8 experts) for each domain per chatbot. ChatGPT-4 provided more accurate answers than Bard (2.95 ± 0.671 vs 2.73 ± 0.732, p=0.027). Bard's responses had better readability than ChatGPT-4 (2.79 ± 0.408 vs 2.94 ± 0.243, p=0.003). Both ChatGPT-4 and Bard achieved comparable conciseness scores (3.14 ± 0.659 vs 3.11 ± 0.679, p=0.798). Experts categorized the AI-generated responses as incorrect or partially correct at a rate of 16.6% for ChatGPT-4 and 29.1% for Bard. Bard's answers contained significantly more misleading information than those of ChatGPT-4 (p = 0.039). Conclusion: AI chatbots have gained significant attention, and their performance is continuously improving. Nonetheless, these technologies still need further improvements to be considered reliable and credible sources for patients seeking medical information on 177Lu-PSMA-617 therapy.

A transgenic mouse model of Down syndrome acute lymphoblastic leukemia identifies targetable vulnerabilities.

Not available.

Optimization of handheld spectrally encoded coherence tomography and reflectometry for point-of-care ophthalmic diagnostic imaging.

Significance: Handheld optical coherence tomography (HH-OCT) systems enable point-of-care ophthalmic imaging in bedridden, uncooperative, and pediatric patients. Handheld spectrally encoded coherence tomography and reflectometry (HH-SECTR) combines OCT and spectrally encoded reflectometry (SER) to address critical clinical challenges in HH-OCT imaging with real-time en face retinal aiming for OCT volume alignment and volumetric correction of motion artifacts that occur during HH-OCT imaging. Aim: We aim to enable robust clinical translation of HH-SECTR and improve clinical ergonomics during point-of-care OCT imaging for ophthalmic diagnostics. Approach: HH-SECTR is redesigned with (1) optimized SER optical imaging for en face retinal aiming and retinal tracking for motion correction, (2) a modular aluminum form factor for sustained alignment and probe stability for longitudinal clinical studies, and (3) one-handed photographer-ergonomic motorized focus adjustment. Results: We demonstrate an HH-SECTR imaging probe with micron-scale optical-optomechanical stability and use it for in vivo human retinal imaging and volumetric motion correction. Conclusions: This research will benefit the clinical translation of HH-SECTR for point-of-care ophthalmic diagnostics.