Optical in situ deciphering of the surface reconstruction-assistant multielectron transfer event of single Co3O4 nanoparticles.

Surface reconstruction determines the fate of catalytic sites on the near-surface during the oxygen evolution reaction. However, deciphering the conversion mechanism of various intermediate-states during surface reconstruction remains a challenge. Herein, we employed an optical imaging technique to draw the landscape of dynamic surface reconstruction on individual Co3O4 nanoparticles. By regulating the surface states of Co3O4 nanoparticles, we explored dynamic growth of the CoOx(OH)y sublayer on single Co3O4 nanoparticles and directly identified the conversion between two dynamics. Rich oxygen vacancies induced more active sites on the surface and prolonged surface reconstruction, which enhanced electrochemical redox and oxygen evolution. These results were further verified by in situ electrochemical extinction spectroscopy of single Co3O4 nanoparticles. We elucidate the heterogeneous evolution of surface reconstruction on individual Co3O4 nanoparticles and present a unique perspective to understand the fate of catalytic species on the nanosurface, which is of enduring significance for investigating the heterogeneity of multielectron-transfer events.

Evaluation of ophthalmic vascular and neuroretinal alterations in fibromyalgia syndrome: a cross-sectional comparative study.

INTRODUCTION: Fibromyalgia syndrome (FMS) is a prevalent rheumatic disorder, and its pathogenesis includes genetic, neuroendocrine, and autonomic abnormalities, which may impact ocular structures. The aim was to conduct a comparative analysis of the ophthalmic vasculature and the retinal nerve fiber layer (RNFL) thickness between FMS and control groups using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: This cross-sectional comparative study included 43 FMS patients and 40 healthy controls recruited from a tertiary education and research hospital between January 2024 and May 2024. All patients satisfied the 2016 American College of Rheumatology criteria for FMS and consented. OCT and OCTA were used to assess the RNFL thickness and the retinal microvasculature structure. The Fibromyalgia Impact Questionnaire (FIQ) was performed to evaluate disease severity. RESULTS: The study found significantly higher total retinal parafoveal thickness and foveal density in FMS patients (p = 0.017 and p = 0.044, respectively). Nevertheless, there were no significant differences among the groups concerning total retinal foveal thickness, foveal avascular zone characteristics, superficial and deep capillary plexus densities, choriocapillaris flow area, and outer retinal flow area values (p > 0.05). The RNFL thickness in all quadrants did not reveal significant differences between the groups (p > 0.05). Furthermore, there was no significant correlation between FIQ scores and OCTA parameters or RNFL thickness values (p > 0.05). CONCLUSION: The study revealed slight differences in retinal parafoveal thickness and foveal density in FMS patients, but no substantial vascular or neurodegenerative alterations were observed compared to healthy controls. These data indicate that FMS may not substantially affect ocular structures, contrary to earlier hypotheses.

Advanced optical imaging techniques for bladder cancer detection and diagnosis: a systematic review.

OBJECTIVES: To systematically assess the current available literature concerning advanced optical imaging methods for the detection and diagnosis of bladder cancer (BCa), focusing particularly on the sensitivity and specificity of these techniques. METHODS: First a scoping search was performed to identify all available optical techniques for BCa detection and diagnosis. The optical imaging techniques used for detecting BCa are: the Storz professional image enhancement system (IMAGE1 S), narrow-band imaging (NBI), photoacoustic imaging (PAI), autofluorescence imaging (AFI), photodynamic diagnosis (PDD), and scanning fibre endoscopy (SFE). The staging and grading techniques for BCa are: optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), Raman spectroscopy, endocytoscopy, and non-linear optical microscopy (NLO). Then a systematic literature search was conducted using MEDLINE, EMBASE and Web of Science from inception to 21 November 2023. Articles were screened and selected by two independent reviewers. Inclusion criteria were: reporting on both the sensitivity and specificity of a particular technique and comparison to histopathology, and in the case of a detection technique comparison to white light cystoscopy (WLC). RESULTS: Out of 6707 articles, 189 underwent full-text review, resulting in 52 inclusions. No articles met criteria for IMAGE1 S, PAI, SFE, Raman spectroscopy, and endocytoscopy. All detection techniques showed higher sensitivity than WLC, with NBI leading (87.8-100%). Overall, detection technique specificity was comparable to WLC, with PDD being most specific (23.3-100%). CLE and OCT varied in sensitivity and specificity, with OCT showing higher specificity for BCa diagnosis, notably for carcinoma in situ (97-99%) compared to CLE (62.5-81.3%). NLO demonstrated high sensitivity and specificity (90-97% and 77-100%, respectively) based on limited data from two small ex vivo studies. CONCLUSIONS: Optical techniques with the most potential are PDD for detecting and OCT for staging and grading BCa. Further research is crucial to validate their integration into routine practice and explore the value of other imaging techniques.

Evaluation of cerebral microcirculation in a mouse model of systemic inflammation.

Significance: Perturbations in the microcirculatory system have been observed in neurological conditions, such as Alzheimer's disease or systemic inflammation. However, changes occurring at the level of the capillary are difficult to translate to biomarkers that could be measured macroscopically. Aim: We aim to evaluate whether transit time changes reflect capillary stalling and to what degree. Approach: We employ a combined spectral optical coherence tomography (OCT) and fluorescence optical imaging (FOI) system to investigate the relation between capillary stalling and transit time in a mouse model of systemic inflammation induced by intraperitoneal injection of lipopolysaccharide. Angiograms are obtained using OCT, and fluorescence signal images are acquired by the FOI system upon intravenous injection of fluorescein isothiocyanate via a catheter inserted into the tail vein. Results: Our findings reveal that lipopolysaccharide (LPS) administration significantly increases both the percentage and duration of capillary stalling compared to mice receiving a 0.9% saline injection. Moreover, LPS-induced mice exhibit significantly prolonged arteriovenous transit time compared to control mice. Conclusions: These observations suggest that capillary stalling, induced by inflammation, modulates cerebral mean transit time, a measure that has translational potential.

Label-free assessment of the transformation zone using multispectral diffuse optical imaging toward early detection of cervical cancer.

The assessment of the transformation zone is a critical step toward diagnosis of cervical cancer. This work involves the development of a portable, label-free transvaginal multispectral diffuse optical imaging (MDOI) imaging probe to estimate the transformation zone. The images were acquired from N = 5 (N = 1 normal, N = 2 premalignant, and N = 2 malignant) patients. Key parameters such as spectral contrast ratio (ρ) at 545 and 450 nm were higher in premalignant (0.29, 0.25 for 450 nm and 0.30, 0.17 for 545 nm) as compared to the normal patients (0.13 and 0.14 for 450 and 545 nm, respectively). The threshold for the spectral intensity ratio R610/R450 and R610/R545 can also be used as a marker to correlate with the new and original squamous columnar junction (SCJ), respectively. The pilot study highlights the use of new markers such as spectral contrast ratio (ρ) and spectral intensity ratio (R610/R450 and R610/R545) images.

Topical Diclofenac Reduces Joint Synovitis in Hand Osteoarthritis: A Pilot Investigation Using Fluorescent Optical Imaging.

Purpose: Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality. Patients and Methods: Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied. Results: The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15. Conclusion: This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images.

Simultaneous Optical Imaging of Action Potentials and Calcium Transients in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiovascular diseases have emerged as one of the leading causes of human mortality, but the discovery of new drugs has been hindered by the absence of suitable in vitro platforms. In recent decades, continuously refined protocols for differentiating human induced pluripotent stem cells (hiPSCs) into hiPSC-derived cardiomyocytes (hiPSC-CMs) have significantly advanced disease modeling and drug screening; however, this has led to an increasing need to monitor the function of hiPSC-CMs. The precise regulation of action potentials (APs) and intracellular calcium (Ca2+) transients is critical for proper excitation-contraction coupling and cardiomyocyte function. These important parameters are usually adversely affected in cardiovascular diseases or under cardiotoxic conditions and can be measured using optical imaging-based techniques. However, this procedure is complex and technologically challenging. We have adapted the IonOptix system to simultaneously measure APs and Ca2+ transients in hiPSC-CMs loaded with the fluorescent dyes FluoVolt and Rhod 2, respectively. This system serves as a powerful high-throughput platform to facilitate the discovery of new compounds to treat cardiovascular diseases with the cellular phenotypes of abnormal APs and Ca2+ handling. Here, we present a comprehensive protocol for hiPSC-CM preparation, device setup, optical imaging, and data analysis. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Maintenance and seeding of hiPSC-CMs Basic Protocol 2: Simultaneous detection of action potentials and Ca2+ transients in hiPSC-CMs.

Microscopic photoplethysmography-based evaluation of cardiotoxicity in whitefish larvae induced by acute exposure to cadmium and phenol.

Toxic environmental pollutants pose a health risk for both humans and animals. Accumulation of industrial contaminants in freshwater fish may become a significant threat to biodiversity. Comprehensive monitoring of the impact of environmental stressors on fish functional systems is important and use of non-invasive tools that can detect the presence of these toxicants in vivo is desirable. The blood circulatory system, by virtue of its sensitivity to the external stimuli, could be an informative indicator of chemical exposure. In this study, microscopic photoplethysmography-based approach was used to investigate the cardiac activity in broad whitefish larvae (Coregonus nasus) under acute exposure to cadmium and phenol. We identified contamination-induced abnormalities in the rhythms of the ventricle and atrium. Our results allow introducing additional endpoints to evaluate the cardiac dysfunction in fish larvae and contribute to the non-invasive evaluation of the toxic effects of industrial pollutants on bioaccumulation and aquatic life.

Orientation selectivity mapping in the visual cortex.

The orientation map is one of the most well-studied functional maps of the visual cortex. However, results from the literature are of different qualities. Clear boundaries among different orientation domains and blurred uncertain distinctions were shown in different studies. These unclear imaging results will lead to an inaccuracy in depicting cortical structures, and the lack of consideration in experimental design will also lead to biased depictions of the cortical features. How we accurately define orientation domains will impact the entire field of research. In this study, we test how spatial frequency (SF), stimulus size, location, chromatic, and data processing methods affect the orientation functional maps (including a large area of dorsal V4, and parts of dorsal V1) acquired by intrinsic signal optical imaging. Our results indicate that, for large imaging fields, large grating stimuli with mixed SF components should be considered to acquire the orientation map. A diffusion model image enhancement based on the difference map could further improve the map quality. In addition, the similar outcomes of achromatic and chromatic gratings indicate two alternative types of afferents from LGN, pooling in V1 to generate cue-invariant orientation selectivity.

Convolutional neural network for automated tooth segmentation on intraoral scans.

BACKGROUND: Tooth segmentation on intraoral scanned (IOS) data is a prerequisite for clinical applications in digital workflows. Current state-of-the-art methods lack the robustness to handle variability in dental conditions. This study aims to propose and evaluate the performance of a convolutional neural network (CNN) model for automatic tooth segmentation on IOS images. METHODS: A dataset of 761 IOS images (380 upper jaws, 381 lower jaws) was acquired using an intraoral scanner. The inclusion criteria included a full set of permanent teeth, teeth with orthodontic brackets, and partially edentulous dentition. A multi-step 3D U-Net pipeline was designed for automated tooth segmentation on IOS images. The model's performance was assessed in terms of time and accuracy. Additionally, the model was deployed on an online cloud-based platform, where a separate subsample of 18 IOS images was used to test the clinical applicability of the model by comparing three modes of segmentation: automated artificial intelligence-driven (A-AI), refined (R-AI), and semi-automatic (SA) segmentation. RESULTS: The average time for automated segmentation was 31.7 ± 8.1 s per jaw. The CNN model achieved an Intersection over Union (IoU) score of 91%, with the full set of teeth achieving the highest performance and the partially edentulous group scoring the lowest. In terms of clinical applicability, SA took an average of 860.4 s per case, whereas R-AI showed a 2.6-fold decrease in time (328.5 s). Furthermore, R-AI offered higher performance and reliability compared to SA, regardless of the dentition group. CONCLUSIONS: The 3D U-Net pipeline was accurate, efficient, and consistent for automatic tooth segmentation on IOS images. The online cloud-based platform could serve as a viable alternative for IOS segmentation.

Enhanced optical imaging and fluorescent labeling for visualizing drug molecules within living organisms.

The visualization of drugs in living systems has become key techniques in modern therapeutics. Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization. At the subcellular level, super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs. Moving beyond subcellular imaging, researchers have integrated multiple modes, like optical near-infrared II imaging, to study the complex spatiotemporal interactions between drugs and their surroundings. By combining these visualization approaches, researchers gain supplementary information on physiological parameters, metabolic activity, and tissue composition, leading to a comprehensive understanding of drug behavior. This review focuses on cutting-edge technologies in drug visualization, particularly fluorescence imaging, and the main types of fluorescent molecules used. Additionally, we discuss current challenges and prospects in targeted drug research, emphasizing the importance of multidisciplinary cooperation in advancing drug visualization. With the integration of advanced imaging technology and molecular design, drug visualization has the potential to redefine our understanding of pharmacology, enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

Oligonucleotide probes for imaging and diagnosis of bacterial infections.

The rise of infectious diseases as a public health concern has necessitated the development of rapid and precise diagnostic methods. Imaging techniques like nuclear and optical imaging provide the ability to diagnose infectious diseases within the body, eliminating delays caused by sampling and pre-enrichments of clinical samples and offering spatial information that can aid in a more informed diagnosis. Traditional molecular probes are typically created to image infected tissue without accurately identifying the pathogen. In contrast, oligonucleotides can be tailored to target specific RNA sequences, allowing for the identification of pathogens, and even generating antibiotic susceptibility profiles by focusing on drug resistance genes. Despite the benefits that nucleic acid mimics (NAMs) have provided in terms of stabilizing oligonucleotides, the inadequate delivery of these relatively large molecules into the cytoplasm of bacteria remains a challenge for widespread use of this technology. This review summarizes the key advancements in the field of oligonucleotide probes for in vivo imaging, highlighting the most promising delivery systems described in the literature for developing optical imaging through in vivo hybridization.

Target-triggered assembly of plasmon resonance nanostructures for quantitative detection of lncRNA in liver cancer cells via surface enhanced Raman spectroscopy.

Long-stranded non-coding RNAs (lncRNA) have important roles in disease as transcriptional regulators, mRNA processing regulators and protein synthesis factors. However, traditional methods for detecting lncRNA are time-consuming and labor-intensive, and the functions of lncRNA are still being explored. Here, we present a surface enhanced Raman spectroscopy (SERS) based biosensor for the detection of lncRNA associated with liver cancer (LC) as well as in situ cellular imaging. Using the dual SERS probes, quantitative detection of lncRNA (DAPK1-215) can be achieved with an ultra-low detection limit of 952 aM by the target-triggered assembly of core-satellite nanostructures. And the reliability of this assay can be further improved with the R2 value of 0.9923 by an internal standard probe that enables the signal dynamic calibration. Meanwhile, the high expression of DAPK1-215 mainly distributed in the cytoplasm was observed in LC cells compared with the normal ones using the SERS imaging method. Moreover, results of cellular function assays showed that DAPK1-215 promoted the migration and invasion of LC by significantly reducing the expression of the structural domain of death associated protein kinase. The development of this biosensor based on SERS can provide a sensitive and specific method for exploring the expression of lncRNA that would be a potential biomarker for the screening of LC.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .

Rapid Assessment of Bio-distribution and Antitumor Activity of the Photosensitizer Bremachlorin in a Murine PDAC Model: Detection of PDT-induced Tumor Necrosis by IRDye® 800CW Carboxylate, Using Whole-Body Fluorescent Imaging.

Photodynamic therapy (PDT) is a light-based anticancer therapy that can induce tumor necrosis and/or apoptosis. Two important factors contributing to the efficacy of PDT are the concentration of the photosensitizer in the tumor tissue and its preferential accumulation in the tumor tissue compared to that in normal tissues. In this study, we investigated the use of optical imaging for monitoring whole-body bio-distribution of the fluorescent (660 nm) photosensitizer Bremachlorin in vivo, in a murine pancreatic ductal adenocarcinoma (PDAC) model. Moreover, we non-invasively, examined the induction of tumor necrosis after PDT treatment using near-infrared fluorescent imaging of the necrosis avid cyanine dye IRDye®-800CW Carboxylate. Using whole-body fluorescence imaging, we observed that Bremachlorin preferentially accumulated in pancreatic tumors. Furthermore, in a longitudinal study we showed that 3 hours after Bremachlorin administration, the fluorescent tumor signal reached its maximum. In addition, the tumor-to-background ratio at all-time points was approximately 1.4. Ex vivo, at 6 hours after Bremachlorin administration, the tumor-to-muscle or -normal pancreas ratio exhibited a greater difference than it did at 24 hours, suggesting that, in terms of efficacy, 6 hours after Bremachlorin administration was an effective time point for PDT treatment of PDAC. In vivo administration of the near infrared fluorescence agent IRDye®-800CW Carboxylate showed that PDT, 6 hours after administration of Bremachlorin, selectively induced necrosis in the tumor tissues, which was subsequently confirmed histologically. In conclusion, by using in vivo fluorescence imaging, we could non-invasively and longitudinally monitor, the whole-body distribution of Bremachlorin. Furthermore, we successfully used IRDye®-800CW Carboxylate, a near-infrared fluorescent necrosis avid agent, to image PDT-induced necrotic cell death as a measure of therapeutic efficacy. This study showed how fluorescence can be applied for optimizing, and assessing the efficacy of, PDT.

Red blood cell flickering activity locally controlled by holographic optical tweezers.

Red blood cells possess a singular mechanobiology, enabling efficient navigation through capillaries smaller than their own size. Their plasma membrane exhibits non-equilibrium shape fluctuation, often reported as enhanced flickering activity. Such active membrane motion is propelled by motor proteins that mediate interactions between the spectrin skeleton and the lipid bilayer. However, modulating the flickering in living red blood cells without permanently altering their mechanical properties represents a significant challenge. In this study, we developed holographic optical tweezers to generate a force field distributed along the equatorial membrane contour of individual red blood cells. In free-standing red blood cells, we observed heterogeneous flickering activity, attributed to localized membrane kickers. By employing holographic optical forces, these active kickers can be selectively halted under minimal invasion. Our findings shed light on the dynamics of membrane flickering and established a manipulation tool that could open new avenues for investigating mechanotransduction processes in living cells.

Broadband Negative Photoconductive Response in Carbon Nanodots.

Due to the broadband response and low selectivity of external light, negative photoconductivity (NPC) effect holds great potential applications in photoelectric devices. Herein, different photoresponsive carbon nanodots (CDs) are prepared from diverse precursors and the broadband response from the NPC CDs are utilized to achieve the optoelectronic logic gates and optical imaging for the first time. In detail, the mcu-CDs which are prepared by the microwave-assisted polymerization of citric acid and urea possess the large specific surface area and abundant hydrophilic groups as sites for the adsorption of H2O molecules and thereby present a high conductivity in dark. Meanwhile, the low affinity of mcu-CDs to H2O molecules permits the light-induced desorption of H2O molecules by heat effect and thus endow the mcu-CDs with a low conductivity under illumination. The easy absorption and desorption of H2O molecules contribute to the extraordinary NPC of mcu-CDs. With the broadband NPC response in CDs, the optoelectronic logic gates and flexible optical imaging system are established, achieving the applications of "NOR" or "NAND" logic operations and high-quality optical images. These findings unveil the unique optoelectronic properties of CDs, and have the potential to advance the applications of CDs in optoelectronic devices.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: theoretical development and in silico validation.

Objective.Effective early treatment-within 3-5 months of disease onset-significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 1 in 3 patients experiences treatment failure which takes 3-6 months to detect with current monitoring techniques. The aim of this work is to develop a method for extracting quantitative features from data obtained with time-domain diffuse optical imaging (TD-DOI), and demonstrate their sensitivity to RA disease activity.Approach.80 virtual phantoms of the proximal interphalangeal joint-obtained from a realistic tissue distribution derived from magnetic resonance imaging-were created to simulate RA-induced alterations in 5 physiological parameters. TD-DOI images were generated using Monte Carlo simulations, and Poisson noise was added to each image. Subsequently, each image was convolved with an instrument response function (IRF) to mimic experimental measurements. Various spatiotemporal features were extracted from the images (i.e. statistical moments, temporal Fourier components), corrected for IRF effects, and correlated with the disease index (DI) of each phantom.Main results.Spatiotemporal Fourier components of TD-DOI images were highly correlated with DI despite the confounding effects of noise and the IRF. Moreover, lower temporal frequency components (⩽0.4 GHz) demonstrated greater sensitivity to small changes in disease activity than previously published spatial features extracted from the same images.Significance.Spatiotemporal components of TD-DOI images may be more sensitive to small changes in RA disease activity than previously reported DOI features. TD-DOI may enable earlier detection of RA treatment failure, which would reduce the time needed to identify treatment failure and improve patient prognosis.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: experimental validation in tissue-mimicking finger phantoms.

Objective.Effective treatment within 3-5 months of disease onset significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 30% of RA patients fail their first treatment, and it takes 3-6 months to identify failure with current monitoring techniques. Time-domain diffuse optical imaging (TD-DOI) may be more sensitive to RA disease activity and could be used to detect treatment failure. In this report, we present the development of a TD-DOI hand imaging system and validate its ability to measure simulated changes in RA disease activity using tissue-mimicking finger phantoms.Approach.A TD-DOI system was built, based on a single-pixel camera architecture, and used to image solid phantoms which mimicked a proximal interphalangeal finger joint. For reference,in silicoimages of virtual models of the solid phantoms were also generated using Monte Carlo simulations. Spatiotemporal Fourier components were extracted from both simulated and experimental images, and their ability to distinguish between phantoms representing different RA disease activity was quantified.Main results.Many spatiotemporal Fourier components extracted from TD-DOI images could clearly distinguish between phantoms representing different states of RA disease activity.Significance.A TD-DOI system was built and validated using finger-mimicking solid phantoms. The findings suggest that the system could be used to monitor RA disease activity. This single-pixel TD-DOI system could be used to acquire longitudinal measures of RA disease activity to detect early treatment failure.

Structurally Modulated Formation of Cyanine J-Aggregates with Sharp and Tunable Spectra for Multiplexed Optoacoustic and Fluorescence Bioimaging.

J-aggregation brings intriguing optical and electronic properties to molecular dyes and significantly expands their applicability across diverse domains, yet the challenge for rationally designing J-aggregating dyes persists. Herein, we developed a large number of J-aggregating dyes from scratch by progressively refining structure of a common heptamethine cyanine. J-aggregates with sharp spectral bands (full-width at half-maximum≤38 nm) are attained by introducing a branched structure featuring a benzyl and a trifluoroacetyl group at meso-position of dyes. Fine-tuning the benzyl group enables spectral regulation of J-aggregates. Analysis of single crystal data of nine dyes reveals a correlation between J-aggregation propensity and molecular arrangement within crystals. Some J-aggregates are successfully implemented in multiplexed optoacoustic and fluorescence imaging in animals. Notably, three-color multispectral optoacoustic tomography imaging with high spatiotemporal resolution is achieved, owing to the sharp and distinct absorption bands of the J-aggregates.