Search Results (930)

There is an increasing demand for ultrasound imaging technologies, particularly wearable and portable systems, for continuous physiological monitoring applications. Although some recent flexible ultrasound devices have adopted polymer encapsulations, typical rigid transducer designs still include metal housings and costly electrodes, contributing to increased device weight and fabrication cost. To address these limitations, we developed an aluminum-electrode/3D-printed polymer-housing ultrasound transducer (APUT) utilizing a polyvinylidene fluoride piezoelectric film. Compared to a gold-electrode/metal-housing ultrasound transducer, the APUT material costs and total weight were approximately 66% and 86% lower, respectively. Acoustic evaluation revealed a center frequency of 24.5 MHz and a fractional bandwidth of 60.9%, with axial and lateral resolutions of 51 and 152 μm, respectively. Furthermore, during a 3-h pulsed operation test, the APUT exhibited an initial increase in capacitance followed by a relatively stable response, with no progressive surface-temperature increase detected within the accuracy of the measurement method. Finally, successful ex vivo imaging of chicken breast tissue confirms the APUT’s biomedical applicability, highlighting its potential as a wearable, portable, and disposable ultrasound platform. Full article

Magnetic Particle Imaging (MPI) detects superparamagnetic nanoparticles, enabling bimodal contrast with MRI. Resovist^®/Ferucarbotran, still used in research, has clinical safety compatibility but suboptimal MPI performance due to many small 5 nm SPIO cores. Magnetic fractionation can enrich larger cores, improving MPI signal and supporting cellular imaging applications. To enable bimodal MRI/MPI and assess in vivo extracellular vesicle (EV) labelling, we characterized the imaging sensitivity and cell-labelling performance of VivoTrax, a commercial formulation similar to Resovist^®, and VivoTrax Plus, obtained by magnetic fractionation. VivoTrax Plus showed higher MRI transverse relaxivity and MPI sensitivity than VivoTrax, and both formulations displayed low toxicity toward adipose-derived stem cells (ASCs). VivoTrax Plus allowed MRI detection of small cell numbers, around 100 cells, in agarose phantoms with greater sensitivity than VivoTrax. However, EVs of 30–150 nm isolated from ASCs labelled with VivoTrax Plus did not retain SPIONs, whereas EVs from VivoTrax-labelled ASCs did. Preliminary in vivo experiments in SOD-G93A mice showed MRI-detectable signal voids in the brain after intranasal EV administration, suggesting EV migration to lesioned areas. Overall, magnetic fractionation improves SPION imaging sensitivity but may alter relevant biological properties. Full article

Because lesions associated with digestive system diseases are often deeply seated, embedded within complex luminal milieus, and protected by substantial local delivery barriers, conventional diagnostic and therapeutic modalities remain constrained in their targeting capability, minimal invasiveness, and precision. Microrobots, leveraging micro-scale motion, active navigation, programmable controllability, and theranostic integration, open a new avenue for the precise diagnosis and treatment of digestive system diseases. Here, we review the major actuation modalities and structural designs of microrobots and discuss recent advances in their use across the gastrointestinal and hepatopancreatobiliary systems, focusing on targeted drug delivery, biospecimen harvesting, lesion detection, and interventional treatment. We further discuss the major obstacles to progress in this field, including robust operation in complex in vivo settings, real-time imaging and closed-loop feedback control, biosafety, degradability, and eventual clinical implementation. With continued advances in high-performance materials, multimodal actuation, intelligent control, and convergence with endoscopic and medical imaging technologies, microrobots are poised to accelerate the transition of digestive disease care toward precision, intelligence, and minimally invasive intervention. Full article

Background/Objectives: White-light cystoscopy remains central to bladder cancer detection and surveillance, but diagnostic uncertainty persists in detecting flat lesions, particularly carcinoma in situ, distinguishing inflammatory mimics, and targeting biopsies. Optical spectroscopy and spectral imaging may provide objective tissue information beyond visual inspection. This scoping review mapped the diagnostic evidence and translational readiness of these technologies. Methods: A scoping review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed, Embase and Web of Science were searched from inception to 31 July 2026. Eligible articles evaluated wavelength-dependent optical signals directly in human bladder tissue in clinically relevant in vivo or ex vivo settings. Related articles with the same, overlapping or expanded datasets were grouped into study families. Results: Forty-seven articles were organised into 39 study families. Raman spectroscopy showed the clearest progression from ex vivo discrimination to in vivo cystoscopic feasibility and device development. Fluorescence and reflectance provided early in vivo evidence, although specificity was often limited by inflammation and benign changes. Infrared and near-infrared techniques remained mainly specimen-based, while multimodal systems were evaluated mostly ex vivo. Evidence for spectral imaging was limited, and no clinically integrated endoscopic hyperspectral-imaging study meeting the criteria was identified. Conclusions: Optical spectroscopy and spectral imaging show diagnostic potential for bladder cancer tissue characterisation, but evidence remains heterogeneous and insufficient for routine implementation. Among the included techniques, Raman spectroscopy appears most translationally mature, whereas wide-field spectral imaging remains underdeveloped. Future studies should prioritise prospective in vivo evaluation, standardised acquisition, histopathological correlation, external patient-level validation and clinically meaningful endpoints. Full article

Osteoarthritis (OA) causes irreversible cartilage damage, highlighting the need for early and sensitive assessment. Current imaging modalities are limited in detecting early-stage changes. Ultrasound (US) provides a non-invasive and accessible alternative, but its clinical adoption is limited by the lack of standardized protocols and reliable cartilage assessment. Simulations can be used to address these challenges by enabling system design, acquisition optimization and validation by providing ground truth when in vivo ground truth is unavailable. The aim of this study is to develop an in silico framework for realistic US imaging of healthy and OA cartilage by combining accurate acoustic wave modeling with a 2D microstructural cartilage phantom. The model was calibrated to healthy cartilage using first-order speckle statistics and extended to simulate degeneration through changes in structural and acoustic properties. As a proof-of-concept study, simulations were evaluated against limited ex vivo US data from healthy and OA cartilage and compared with literature data. The simulations reproduced key OA-related features and trends, including changes in reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscatter (AIB), and gray level distributions. These findings demonstrate the feasibility of using microstructure-based tissue phantoms to model healthy and OA cartilage. The framework provides a platform for systematic investigation of cartilage microstructure and US-derived features and may support future generation of synthetic datasets for data-driven and AI-based OA assessment. Full article

Background/Objectives: Rapid optical assessment of freshly excised basal cell carcinoma (BCC) specimens may shorten the interval between excision and margin evaluation. This prospective pilot study estimated the diagnostic performance of ex vivo line-field confocal optical coherence tomography (LC-OCT) for detecting residual BCC at lateral surgical margins, using histopathology as the reference standard. Methods: Fifty-five clinically suspicious lesions from 48 patients were examined at two centers. Results were analyzed for the complete cohort and for a post-training inclusion phase comprising 32 lesions from 31 patients. Overall lesion-level consensus classifications were recorded separately from classifications of the four clock-face quadrants. Lesions with a negative overall LC-OCT assessment and at least one non-evaluable quadrant were classified as indeterminate and excluded from the primary lesion-level analysis. Thirteen lesions also underwent exploratory ex vivo fusion confocal microscopy (evFCM). Results: In the inclusion phase, 125 of 128 quadrants were evaluable. Thirteen true-positive, 106 true-negative, 2 false-negative, and 4 false-positive quadrant results yielded 86.7% sensitivity, 96.4% specificity, and 95.2% accuracy. At the lesion level, 2 of 32 results were indeterminate. Among the remaining 30 lesions, LC-OCT yielded 5 true-positive, 22 true-negative, 2 false-negative, and 1 false-positive results, corresponding to 71.4% sensitivity, 95.7% specificity, and 90.0% accuracy. The evFCM analysis was descriptive because the subset was small and nonconsecutive. Conclusions: Ex vivo LC-OCT showed promising specificity and overall accuracy for assessing lateral BCC margins after training. The limited number of margin-positive lesions, indeterminate results, clustered quadrant data, and absence of systematic deep-margin imaging require cautious interpretation. LC-OCT should not replace histopathological margin assessment on the basis of the present data. Full article

Background/Objectives: Distinguishing melanoma from benign melanocytic nevi remains a central diagnostic challenge, and vascular features may provide additional information beyond surface morphology. Super-resolution ultrasound using the erythrocytes (SURE) is a contrast-free imaging technique that uses endogenous erythrocyte scattering signals to reconstruct microvascular architecture beyond the conventional diffraction limit. This study evaluated the feasibility of SURE for in vivo visualization and quantitative assessment of dermal microvasculature in clinically benign nevi. Methods: Eleven participants with 35 clinically benign dermal nevi were included. All lesions underwent clinical and dermoscopic assessment, conventional B-mode ultrasound, color and power Doppler imaging, and SURE imaging. Eight larger nevi were imaged in two imaging planes, resulting in 43 SURE acquisitions. SURE reconstructions were assessed qualitatively for microvascular morphology and quantitatively for vessel diameter and erythrocyte flow velocity in proximal, intermediate, and distal visible intralesional vessel segments. Results: Dermoscopic and conventional ultrasound images were acquired for all lesions. SURE reconstructions of sufficient quality for quantitative analysis were obtained for all included acquisitions, yielding 129 vessel diameter measurements and 129 corresponding velocity measurements. Conventional Doppler demonstrated absent or minimal detectable vascular signal in the majority of lesions, whereas SURE visualized branching structures consistent with dermal microvascular networks in all the lesions. The mean vessel diameter was 85.0 ± 20.2 µm, with measured diameters ranging from 48.1 to 173.0 µm. The median flow velocity was 1.80 [1.30–2.50] mm/s. No significant differences in vessel diameter or velocity were observed between proximal, intermediate, and distal intralesional segments. Conclusions: SURE enabled contrast-free in vivo visualization and quantitative assessment of low-velocity dermal microvasculature in clinically benign nevi. These findings support the feasibility of SURE for microvascular mapping of melanocytic lesions and provide a basis for future studies including malignant lesions, volumetric imaging, and histopathological validation. Full article

Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers. Full article

Reperfusion after acute ischemic stroke (AIS) triggers a series of ferroptosis-related molecular events, including iron dyshomeostasis, oxidative/nitrative stress, antioxidant depletion, and membrane lipid peroxidation. Conventional ferroptosis assays mainly rely on ex vivo or endpoint measurements, limiting their ability to dynamically monitor the spatiotemporal evolution of these events during ischemia–reperfusion. Recent advances in chemical sensing and optical imaging have enabled in situ detection of key ferroptosis-related nodes, such as Fe²⁺/labile iron pool, ROS/ONOO⁻, GSH/Cys/GPX4, H₂S/Cys–Met metabolism, and lipid peroxidation. In this review, we summarize sensing targets, reaction-based probe design, near-infrared and two-photon imaging, photoacoustic imaging, and multimodal validation strategies for AIS-related ferroptosis. Representative probes for H₂O₂, ONOO⁻, H₂S, Fe²⁺, and lipid peroxidation are discussed in the context of cellular models, oxygen-glucose deprivation/reoxygenation, middle cerebral artery occlusion/reperfusion, and in vivo brain imaging. We emphasize that a single probe signal cannot independently confirm ferroptosis and should be interpreted together with GPX4/ACSL4 alterations, MDA/4-HNE levels, tissue injury, neurological outcomes, and Fer-1/Lip-1 rescue experiments. Finally, we discuss current challenges, including limited tissue penetration, blood–brain barrier delivery, quantitative stability, probe safety, and clinical translation, and highlight future directions involving ratiometric, NIR/NIR-II, two-photon, multitarget, and imaging-guided validation strategies. Full article

Upper tract urothelial carcinoma (UTUC) represents 5–10% of urothelial malignancies and poses significant diagnostic challenges. Ureterorenoscopy (URS) remains essential for definitive diagnosis, tumor characterization, and selection of candidates for kidney-sparing surgery. Recent advances in endoscopic image-enhancement technologies aim to overcome the limitations of conventional white-light URS. The aim of this study is to review the current evidence on advanced endoscopic imaging techniques for the diagnosis and management of UTUC. This narrative literature review summarizes current evidence on advanced endoscopic imaging techniques for UTUC. A comprehensive search of PubMed/MEDLINE, EMBASE, and Scielo databases was conducted to identify studies evaluating photodynamic diagnosis (PDD), narrow band imaging (NBI), Image1-S™-Spies™, optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), and endoluminal ultrasonography (ELUS). Data were qualitatively synthesized by modality. Macroscopic enhancement techniques (PDD, NBI, Image1-S™) improve visualization of urothelial surfaces and vascular patterns during URS. PDD demonstrates the highest diagnostic accuracy, with sensitivities up to 95.8%, and a pooled sensitivity and specificity of 0.96 and 0.86. NBI increases tumor detection rates, identifying up to 22.7% additional lesions in early studies. Microscopic imaging modalities provide complementary information. OCT enables high-resolution cross-sectional imaging with 93% concordance with pathological staging. CLE offers in vivo optical biopsy with near-histological resolution, achieving concordance rates of 100% for low-grade and 83–86% for high-grade tumors. ELUS allows deeper tissue assessment but with lower spatial resolution. Enhanced endoscopic imaging technologies are promising, improving tumor detection, characterization, and intraoperative risk stratification. However, current evidence remains limited and heterogeneous, highlighting the need for large prospective multicenter studies to define their impact on oncological outcomes. Full article

Background: Processed extracellular lipid–protein preparations require rigorous analytical characterization to determine whether their compositional profile, processing stability, and short-term cellular compatibility are preserved across storage and handling conditions. Methods: In this study, we quantitatively characterized a processed phospholipoproteic secretome-derived formulation under fresh, concentrated, cryopreserved, and lyophilized conditions. Results: Label-free quantitative proteomic analyses performed using timsTOF Pro mass spectrometry coupled to dia-PASEF acquisition identified 574 human proteins across all experimental conditions following predefined analytical quality criteria. Comparative analyses demonstrated preservation of the overall structural proteomic profile following processing and storage procedures, with retention of membrane-associated and extracellular structural proteins consistently exceeding 90% relative to the fresh reference condition. Quantitative reproducibility remained high across all experimental groups, with coefficients of variation ranging from 3.0% to 4.5% and strong inter-replicate Pearson correlations. Principal component analysis, hierarchical clustering, peptide/protein overlap analyses, and differential expression profiling demonstrated limited proteomic divergence while preserving the majority of quantified proteins within conserved abundance ranges. Complementary real-time live-cell kinetic imaging performed in non-malignant dermal-derived cells using the IncuCyte^® S3 platform demonstrated stable short-term confluence kinetics and cellular viability exceeding 92% over 48 h across all evaluated formulations. No sustained proliferative suppression or detectable morphological evidence of cytotoxicity was observed. Collectively, these findings support the preservation of compositional stability, analytical reproducibility, and short-term ex vivo cellular compatibility across defined processing and storage conditions. These integrated proteomic and kinetic datasets provide a quantitative framework for the analytical evaluation of processed extracellular phospholipoproteic preparations, while functional barrier activity, membrane incorporation, lipid raft engagement, and long-term tissue-level effects remain to be addressed in dedicated future studies. Full article

Nanoparticles combining gold and iron oxide are promising for a wide range of biomedical applications, including photothermal therapy, radiotherapy enhancement, drug delivery, and diagnostic imaging. However, their long-term biodistribution and safety profile remain largely unexplored. Here, we synthesized Fe₃O₄@AuNP core–satellite nanoparticles (Fe₃O₄@AuNPs) using femtosecond laser ablation, functionalized them with 15 kDa polyethylene glycol (PEG), and characterized them using a panel of physicochemical techniques. Healthy C57BL/6 mice received an intravenous injection of Fe₃O₄@AuNPs at 730 mg Au/kg and 82 mg Fe/kg, respectively. Biodistribution was monitored by computed tomography (CT) and magnetic resonance imaging (MRI) over 12 months, after which gold and iron concentrations were measured ex vivo, and long-term toxicity was assessed via histology and blood biochemistry. Nanoparticles accumulated predominantly in the liver and spleen. Quantitative analysis of CT images revealed a gradual decrease in gold content, while MRI showed a progressive reduction in negative contrast in the liver between 6 and 12 months, suggesting possible changes in the Fe₃O₄ core structure. Over the one-year observation period, no differences in behavior or body weight gain were detected between the treated and control groups. Histological examination revealed no pathological changes other than mild age-related alterations. These findings provide a baseline for the long-term behavior of laser-ablated core–satellite Fe₃O₄@AuNPs, which is essential for their further development in diagnostic and theranostic applications. Full article

Background/Objectives: Metal artifacts from dental implants degrade CBCT image quality and may impair detection of peri-implant bone defects. Zirconia implants produce stronger artifacts than titanium due to its higher atomic number. This study evaluated the impact of a native MAR algorithm (SMARF) on CBCT detection of buccal fenestration and dehiscence of varying sizes adjacent to zirconia versus titanium implants. Methods: In this ex vivo pilot study, two 4 mm × 12 mm implants (one titanium and one zirconia) were implanted in a dry human mandible. Artificial fenestration and dehiscence defects were created at the buccal surface of right and left premolar regions, in three sizes (small 2 mm × 2 mm× 1 mm; medium 2 mm × 4 mm× 1 mm; large 2 mm × 6 mm× 1 mm). Scans were acquired with a Papaya 3D (Genoray) CBCT using a single-tooth FOV (4 cm× 4 cm × 5 cm), 83 kVp, 10 mA, 0.1 mm voxel; each condition was imaged with MAR on and off (six repeats each). Two trained observers scored defect presence on a five-point Likert scale. Sensitivity, specificity, inter- and intraobserver agreement (Cohen’s kappa), and comparisons across conditions were calculated. Results: Interobserver κ = 0.65 (substantial); intraobserver κ = 0.87–1.00 (excellent). For titanium implants, sensitivity and specificity were 100% across all defect types, sizes, and MAR settings. For zirconia implants, fenestration sensitivity with MAR off increased with size (small 50%, medium 75%, large 100%); MAR on raised sensitivity to 100% for all sizes, with a significant improvement for small fenestrations (p = 0.005). Dehiscence sensitivity for zirconia was 100% across sizes and MAR conditions. Specificity for zirconia defects was 83.3% with MAR off and decreased to 66.6% with MAR on (p = 0.07). Conclusions: With the Papaya 3D system used in this pilot study, MAR was unnecessary for defect detection adjacent to titanium implants but affected performance for zirconia implants: MAR increased sensitivity for small fenestrations while reducing specificity (although not statistically significant). Clinicians should weigh the sensitivity–specificity trade off when applying MAR around zirconia implants. Full article

In this study, a mitochondria-targeting near-infrared (NIR) fluorescent probe, Mito-V, based on an oxanthrene-like hybrid structure was designed and synthesized, for detecting viscosity with pH-cooperative response characteristics. Upon increasing viscosity, Mito-V exhibits a significant NIR fluorescence enhancement with a high signal-to-noise ratio and excellent selectivity. Under weakly acidic conditions, the viscosity response is further enhanced, demonstrating a pH-cooperative effect that improves detection sensitivity. Cellular imaging experiments confirmed that Mito-V can effectively monitor fluctuations in intracellular viscosity, and co-localization studies revealed its high specificity for mitochondria, with a Pearson’s coefficient of 0.89. Furthermore, the pH-cooperative effect on viscosity detection was verified at the cellular level. In vivo imaging in zebrafish successfully visualized viscosity variations, demonstrating the probe’s applicability and biosafety for monitoring viscosity in biological systems. These findings indicate that Mito-V holds great potential for studying viscosity-related processes in live cells and organisms. Full article

Vaginal dysbiosis, particularly bacterial vaginosis (BV), is associated with altered immune responses that may influence the formation of extracellular traps (ETs). This study aimed to characterize neutrophil and macrophage extracellular traps (NETs and METs) in vaginal discharge samples obtained from women with normal microbiota (NM) and BV, with particular emphasis on Gardnerella vaginalis (GV) detection. An ex vivo analysis was performed using vaginal smears from 14 patients previously classified according to the Nugent criteria. Immunofluorescence assays targeting neutrophil elastase (NE), citrullinated histone H3 (Citr-H3), CD15, and CD68 were conducted, and quantitative image analysis was performed using the TissueFAXS and StrataQuest platforms. NETs were classified into three morphotypes: spread (spr), diffuse (diff), and aggregated (agg). BV samples exhibited a substantially higher mean NET count than NM samples (842.43 vs. 91.86). The number of diffNETs was significantly higher in BV samples than in NM samples (p = 0.004), whereas GV-positive samples showed increased sprNET abundance compared with that in negative samples (248 vs. 8; p < 0.05). CD68⁺ cell counts were significantly higher in BV samples (p = 0.026), whereas no significant differences in NE or Citr-H3 fluorescence intensity were observed between groups. MET structures were also identified, suggesting macrophage involvement in the local immune response. Collectively, these findings indicate that vaginal dysbiosis and GV presence are associated with enhanced NET formation and distinct morphotype distributions, supporting a role for ETs in the immunopathology of BV. Full article