High-frequency ultrasound accuracy in preoperative cutaneous melanoma assessment: A meta-analysis.

BACKGROUND: High-frequency ultrasound (HFUS) can safely and efficiently visualize cutaneous tumour characteristics including depth. OBJECTIVES: We aimed to evaluate its accuracy in measuring melanoma depth against the gold standard, histopathology, for treatment planning. METHODS: A review of publications was conducted in March 2023 through five electronic databases. Thirty-six included articles studied patients who received HFUS (≥10 MHz) measurements, melanoma biopsy or excision, and reported a tumour depth correlation coefficient between HFUS and histopathology. We analysed correlation coefficients between HFUS and histopathology, measured tumour depths and shed light on reasons for mismeasurements. Additionally, we identified the reporting of critical metrics including, lesion characteristics, melanoma subtype, type of correlation coefficient, 95% confidence intervals for Pearson coefficients and sample size. RESULTS: The most common tumour imaged was superficial spreading melanoma on the trunk and extremities, followed by head/face. Maximum ultrasound frequencies ranged from 13 MHz to 100 MHz with participants ranging from 5 to 264. Histopathology and HFUS correlation coefficients ranged from 0.417 to 0.997 (median: 0.94, mean: 0.89 and SD: 0.13). Lower frequency probes (10-20 MHz) were less accurate in assessing melanoma thickness, with a cumulative mean correlation coefficient of 0.87 compared to 0.94 (20-25 MHz) and 0.98 (≥70 MHz). Studies demonstrated higher sonographic accuracy in melanomas >0.75 mm. Additionally, ultrasound may report increased melanoma depth compared to histopathology for reasons including lymphocytic infiltration, presence of a nevus and shrinkage during specimen processing. Furthermore, we found a gap in the reporting of details such as fundamental characteristics of lesion populations. Specifically, 86% (31 out of 36) of the studies failed to report one or more critical metrics, such as mean, median or range of lesion depths. CONCLUSIONS: HFUS may serve as a supplementary tool for preoperative melanoma assessment, with increased accuracy in thicker tumours. Frequencies <20 MHz are less reliable in assessing depth. Frequencies ≥70 MHz demonstrate stronger correlations to histopathology. Higher ultrasound accuracy was seen for melanomas with Breslow depth >0.75 mm.

Non-Expert Markings of Active Chronic Graft-Versus-Host Disease Photographs: Optimal Metrics of Training Effects.

Lack of reliable measures of cutaneous chronic graft-versus-host disease (cGVHD) remains a significant challenge. Non-expert assistance in marking photographs of active disease could aid the development of automated segmentation algorithms, but validated metrics to evaluate training effects are lacking. We studied absolute and relative error of marked body surface area (BSA), redness, and the Dice index as potential metrics of non-expert improvement. Three non-experts underwent an extensive training program led by a board-certified dermatologist to mark cGVHD in photographs. At the end of the 4-month training, the dermatologist confirmed that each trainee had learned to accurately mark cGVHD. The trainees' inter- and intra-rater intraclass correlation coefficient estimates were "substantial" to "almost perfect" for both BSA and total redness. For fifteen 3D photos of patients with cGVHD, the trainees' median absolute (relative) BSA error compared to expert marking dropped from 20 cm2 (29%) pre-training to 14 cm2 (24%) post-training. Total redness error decreased from 122 a*·cm2 (26%) to 95 a*·cm2 (21%). By contrast, median Dice index did not reflect improvement (0.76 to 0.75). Both absolute and relative BSA and redness errors similarly and stably reflected improvements from this training program, which the Dice index failed to capture.

Guideline for in vivo assessment of adherent and rolling leukocytes in human skin microvasculature via reflectance confocal videomicroscopy.

OBJECTIVE: To develop a guideline that reliably identifies cutaneous adherent and rolling leukocytes from mimicking scenarios via in vivo reflectance confocal videomicroscopy. METHODS: We used a clinical reflectance confocal microscope, the VivaScope 1500, to acquire 1522 videos of the upper dermal microcirculation from 12 healthy subjects and 60 patients after allogeneic hematopoietic cell transplantation. Blinded to clinical information, two trained raters independently counted the number of adherent and rolling leukocytes in 88 videos. Based on discrepancies in the initial assessments, we developed a guideline to identify both types of leukocyte-endothelial interactions via a modified Delphi method (without anonymity). To test the guideline's ability to improve the inter-rater reliability, the two raters assessed the remaining 1434 videos by using the guideline. RESULTS: We demonstrate a guideline that consists of definitions, a step-by-step flowchart, and corresponding visuals of adherent and rolling leukocytes and mimicking scenarios. The guideline improved the inter-rater reliability of the manual assessment of both interactions. The intraclass correlation coefficient (ICC) of adherent leukocyte counts increased from 0.056 (95% confidence interval: 0-0.236, n = 88 videos, N = 10 subjects) to 0.791 (0.770-0.809, n = 1434, N = 67). The ICC of rolling leukocyte counts increased from 0.385 (0.191-0.550, n = 88, N = 10) to 0.626 (0.593-0.657, n = 1434, N = 67). Intra-rater ICC post-guideline was 0.953 (0.886-0.981, n = 20, N = 12) and 0.956 (0.894-0.983, n = 20, N = 12) for adherent and rolling, respectively. CONCLUSION: The guideline aids in the manual identification of adherent and rolling leukocytes via in vivo reflectance confocal videomicroscopy.

Individual cell motion in healthy human skin microvasculature by reflectance confocal video microscopy.

OBJECTIVE: To describe upper dermal microvasculature of healthy human skin in terms of density and size of cutaneous blood vessels, leukocyte velocity, and leukocyte interactions with the endothelium. METHODS: We used a reflectance confocal microscope, the VivaScope 1500, to acquire videos of individual cell motion. RESULTS: We found no rolling leukocytes in the upper microvasculature of ten healthy subjects. We observed "paused" leukocytes, that is, leukocytes that temporarily stop, coinciding with the simultaneous stopping of the rest of the blood flow. We imaged more paused (median: 1.0 per subject) and adherent (1.5) leukocytes in the forearm than in the chest (median 0 paused and 0 adherent per subject) per 5 minutes of videos per body site. Leukocytes were paused for a median of 7 seconds in the forearm and 3 seconds in the chest, and we found no correlation between this parameter and the blood vessel or leukocyte size. We visualized blood flow change direction. Flowing leukocyte velocities followed a lognormal distribution and were on average higher in the chest (117 µm/s) than in the forearm (66 µm/s). CONCLUSION: The proposed method and reported values in healthy skin provide new insights into intact human skin microcirculation.

Measurement of stress build-up of ion-exchange strengthened lithium aluminosilicate glass.

A recently developed non-destructive method was used to investigate the stress build-up in chemically strengthened lithium aluminosilicate glass. We utilized an updated version of the gradient scattered light method, which now enables more precise determination of the depth coordinates, recovering a more detailed stress profile around the knee. The main motivation of the work was to characterize and optimize the development of the knee-shaped breaking point in stress profile in lithium aluminosilicate glass using Saunders-Kubichan method of 1-step strengthening in a mixture of KNO3+NaNO3 molten salt bath. In the industry, a 2-step process is still commonly used to build such a stress profile. 1-step strengthening will simplify the process as well as save the cost. Compared to previous studies, which used a destructive method based on transmitted light photoelasticity, we found that in the samples ion-exchanged for 24h the knee-shaped breaking points were situated two times deeper whereas the case-depths were 28% shallower. The measured stress profiles were validated by stress equilibrium and by comparison to Na+ ion concentration profiles.

The Anatomic Distribution of Skin Involvement in Patients with Incident Chronic Graft-versus-Host Disease.

Little is known about the anatomic distribution of cutaneous chronic graft-versus-host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes Assessment Study, we describe the frequency and extent of erythema and superficial and deep sclerosis in 8 anatomic sites in patients with incident disease (ie, new cGVHD diagnosis within 3 months of study entry) receiving systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin involvement. When an extremity was involved, the same type of disease was present contralaterally in 92% of cases, revealing a high level of symmetry. As anticipated, erythema was the most common incident feature; however, sclerotic skin involvement at the time of cGVHD diagnosis was more common than has been suggested by previous studies. Erythema occurred in 155 (85%) and sclerosis in 53 (29%) of the patients with skin involvement (46% and 16%, respectively, of the entire cohort of 339 incident cGVHD cases). Erythema was least common on the lower extremities (n = 71; 39% of patients with skin involvement). Moveable sclerosis was rare on the head, neck, and scalp (n = 4; 2%). Deep sclerosis did not occur in this region, and instead was most likely to occur on the upper extremities (n = 14; 8%) and lower extremities (n = 14; 8%). More than one-half of patients with erythema (n = 107; 58.7%) had diffuse involvement (4 or more of 8 sites involved), compared with less than one-third of those with sclerosis (n = 16; 30.2%).

miR-10a-5p is increased in atopic dermatitis and has capacity to inhibit keratinocyte proliferation.

BACKGROUND: miR-10a-5p has been shown to regulate cancer cell proliferation and invasiveness and endothelial cell inflammatory responses. The function of miR-10a-5p in the skin has not been previously studied. The aim of the current study was to examine miR-10a-5p expression, regulation, and function in keratinocytes (KCs) in association with atopic dermatitis (AD). METHODS: The expression of miR-10a-5p and its target genes was analyzed using RT-qPCR, mRNA array analysis, in situ hybridization, and immunofluorescence. The transfection of miRNA mimics, cell cycle distribution analysis, and luciferase assays was used to study miR-10a-5p functions in human primary KCs. RESULTS: miR-10a-5p was found to be upregulated in lesional skin from patients with AD and in proliferating KCs. Array and pathway analysis of IL-1ß-stimulated KCs revealed that miR-10a-5p inhibited many genes that affect cell cycle progression and only a few inflammation-related genes. Accordingly, fewer cells in S-phase and reduced proliferation were detected as characteristics of miR-10a-5p-transfected KCs. The influence of miR-10a-5p on cell proliferation was also evident in KCs induced by AD-related cytokines, including IL-4, IL-17, and IL-1ß, as measured by the capacity to strongly suppress the expression of the proliferation marker Ki-67. Among AD-related putative direct target genes, we verified hyaluronan synthase 3, a damage-associated positive regulator of KC migration and proliferation, as a direct target of miR-10a-5p. CONCLUSIONS: miR-10a-5p inhibits KC proliferation and directly targets hyaluronan synthase 3 and thereby may modulate AD-associated processes in the skin.

Crowdsourcing to delineate skin affected by chronic graft-vs-host disease.

BACKGROUND: Estimating the extent of affected skin is an important unmet clinical need both for research and practical management in many diseases. In particular, cutaneous burden of chronic graft-vs-host disease (cGVHD) is a primary outcome in many trials. Despite advances in artificial intelligence and 3D photography, progress toward reliable automated techniques is hindered by limited expert time to delineate cGVHD patient images. Crowdsourcing may have potential to provide the requisite expert-level data. MATERIALS AND METHODS: Forty-one three-dimensional photographs of three cutaneous cGVHD patients were delineated by a board-certified dermatologist. 410 two-dimensional projections of the raw photos were each annotated by seven crowd workers, whose consensus performance was compared to the expert. RESULTS: The consensus delineation by four of seven crowd workers achieved the highest agreement with the expert, measured by a median Dice index of 0.7551 across all 410 images, outperforming even the best worker from the crowd (Dice index 0.7216). For their internal agreement, crowd workers achieved a median Fleiss's kappa of 0.4140 across the images. The time a worker spent marking an image had only weak correlation with the surface area marked, and very low correlation with accuracy. Percent of pixels selected by the consensus exhibited good correlation (Pearson R = 0.81) with the patient's affected surface area. CONCLUSION: Crowdsourcing may be an efficient method for obtaining demarcations of affected skin, on par with expert performance. Crowdsourced data generally agreed with the current clinical standard of percent body surface area to assess cGVHD severity in the skin.

Reproducibility of the durometer and myoton devices for skin stiffness measurement in healthy subjects.

BACKGROUND: Clinical assessment of skin stiffness is unreliable in many applications. The durometer, an industrial device to measure hardness, has previously been applied in scleroderma. The Myoton is a noninvasive handheld device for assessing soft tissue biomechanical parameters. MATERIALS AND METHODS: We evaluated the reproducibility of both devices in six healthy subjects in the volar forearm, dorsal forearm, upper arm, shin, and calf bilaterally. The intraclass correlation coefficient (ICC) was used as a measure of reproducibility among three observers. RESULTS: The interobserver intraclass correlation coefficient (ICC) of overall stiffness for the Myoton was 0.74 [95% confidence interval (CI) 0.45-1.00] and 0.71 [0.39-1.00] for the durometer. Coefficient of variation (CV) for the Myoton was 6.4% [range 1.3-12.1] and 7.6% [range 4.4-13.8] for the durometer. Myoton and durometer values had a Pearson correlation of 0.69. The intraobserver Myoton ICC was 0.89 [0.74-1.00] and CV 3.1% [range 1.6-5.0]. The 95% confidence minimal detectable change by the Myoton for a single observer is 32.4 N/m, which is 7.6% of the average subject's overall stiffness. CONCLUSION: The Myoton demonstrated high reproducibility, particularly in the overall stiffness parameter, and merits further investigation to assess disease progression and treatment efficacy.

Optical differential temperature measurement with beat frequency phase fluorometry.

We present, to the best of our knowledge, a new method for differential temperature measurement based on thermal sensitivity of the fluorescence lifetime of thermographic phosphors. Pairs of thermographic phosphors are excited with intensity-modulated light at frequencies ω and ω+Δω. The phase shift Δθ of the summary fluorescence intensity beat signal envelope is measured. A prototype of a fluorometric differential temperature sensor is developed, and feasibility of the method is experimentally demonstrated with a Sm2+:SrFCl crystal and the D15->F70 transition for high thermal sensitivity. The observed linear dependence between envelope phase shift Δθ and temperature difference ΔT agrees with the theoretical prediction. Sensitivity of S=-0.97°/°C was achieved. This method could also be applied to differential measurements of any parameter affecting fluorescence lifetime.

Erythematous plaques and papules on a premature infant.

A 2240 gram boy was born at 33.2 weeks gestation with nonblanching, deeply erythematous plaques and papules on the back, flanks, and scalp (Figure 1). His mother was GBS positive and on antibiotic suppression for prior cutaneous MRSA and urinary tract infections. Intrapartum intravenous Penicillin G was administered, and the amniotic sac was artificially ruptured 4 hours prior to delivery to facilitate labor. The delivery was uncomplicated without concern for chorioamnionitis, but the patient initially required CPAP for respiratory distress with 1-minute and 5-minute Apgar scores of 7 and 8, respectively. A skin punch biopsy is shown (Figure 2).

Innovations and Developments in Dermatologic Non-invasive Optical Imaging and Potential Clinical Applications.

Most dermatologists are aware of the benefits of dermoscopy, and a few are familiar with laser-scanning confocal microscopy. Beyond confocal, there are fully 11 different categories of optical techniques that have been applied to clinical dermatology. This article first provides a comprehensive tabular overview of all these optical diagnostic technologies and then details 4 of the lesser known innovations that are already available or still in development (laser Doppler and speckle imaging, Raman spectroscopy, multiphoton microscopy, photoacoustic tomography), with some potential applications in clinical dermatology (blood flow monitoring, skin cancer diagnosis, composition measurements in atopic dermatitis, skin rejuvenation measurement, and noninvasive sentinel lymph node assessment in melanoma). These methods present many advantages, being non-invasive, portable, and rapid. The development of optics in biological and biomedical sciences (i.e. biophotonics) requires not only deep insight into the applications but also synergistic collaboration be-tween engineers and clinicians.

Interference filter tilting to detect a polycyclic aromatic hydrocarbon at the second harmonic of wavelength modulation frequency.

We present a practical implementation of the wavelength-modulation spectroscopy technique with second-harmonic detection for selective detection and concentration measurements of polycyclic aromatic hydrocarbons (PAHs)-common fossil fuel pollutants. The method is based on excitation light wavelength modulation around the maximum of a narrow peak in the absorption spectrum of a PAH and lock-in detection of fluorescence at the second harmonic of the excitation wavelength modulation frequency. A violet LED is used as the excitation source and wavelength modulation is performed via narrowband interference filter tilting. Feasibility is demonstrated with a carcinogenic PAH, benzo(k)fluoranthene. Model computations are presented to estimate the influence of the background signal on the sensitivity of the method.

An Erythematous papular eruption in a woman with Crohn disease treated with infliximab.

We report the case of a 44-year-old woman with a history of Crohn disease treated with infliximab who presented with erythematous papules and plaques on the upper extremities accompanied by fevers. She was subsequently diagnosed with palisaded neutrophilic and granulomatous dermatitis (PNGD). Whereas immune-complex mediated diseases such as rheumatoid arthritis and systemic lupus erythematosus are most commonly associated, inflammatory bowel disease deserves increased consideration as one of the systemic diseases that can present with PNGD. Additionally, PNGD should remain in the differential diagnosis of cutaneous eruptions that develop in the setting of tumor necrosis factor (TNF) antagonist therapy.

mTG-Gelatin phantoms as standardized testbeds for skin biomechanical measurements with Myoton.

Quantitative assessment of skin mechanical properties can play a pivotal role in diagnosing and tracking various dermatological conditions. Myoton is a promising tool that rapidly and noninvasively measures five skin biomechanical parameters. Accurate interpretation of these parameters requires systematic in vitro testing with easy-to-fabricate, cost-effective skin-mimicking phantoms with controllable properties. In this study, we assessed the ability of phantoms made with 5% and 10% gelatin crosslinked with microbial transglutaminase (mTG) to mimic the human skin for Myoton measurements. We discovered that each of the five Myoton parameters displayed moderate to high correlations with shear elastic modulus of the phantoms. Furthermore, Myoton effectively tracked changes in the mechanical properties of these models over time. Additionally, we designed bilayer phantoms incorporating both dermis and subcutaneous tissue-mimicking layers. Myoton successfully distinguished changes in the mechanical properties of the bilayer phantoms due to the introduction of a stiff 2 mm top layer. We also found that 5% mTG-gelatin phantoms mimic Myoton measurements from healthy subjects and 10% phantoms mimic patients with sclerotic chronic graft-versus-host disease (cGVHD). Therefore, multi-layered mTG-gelatin models for skin and soft tissues can serve as standardized testbeds to study different sclerotic skin conditions in a systematic manner.

Mpox-A Rapidly Evolving Disease.

The 2022 mpox outbreak has rapidly emerged onto the global medical scene while the world continues to grapple with the COVID-19 pandemic. Unlike COVID-19, however, most patients with mpox present with skin findings, the evolving clinical presentation of which may be mistaken for other common skin diseases, particularly sexually transmitted infections. This Special Communication provides an overview of the evolution of mpox skin findings from its initial description in humans in 1970 to the present-day multinational outbreak.

Effect of camera distance and angle on color of diverse skin tone-based standards in smartphone photos.

Accurate and reproducible color capture is vital in medical photography. Camera distance and angle are particularly important as they are highly variable in a clinical setting. To account for variability in illumination, camera technology, and geometric effects, color standards are often used for color correction. To explore how geometry affects color, we quantified the change in CIELAB color value of a color standard for diverse skin tones at varying smartphone camera distances and angles. Whereas both chromaticity (a* and b*) and lightness (L*) were affected by angle, distance only affected L* (standard error of measurement, SEM > 1 CIELAB unit). Flash usage did not generally reduce distance and angle associated variability. Compared to compressed (JPG) format, raw (DNG) images had decreased median variability across different distances and angles. These findings suggest that in medical photography, inconsistent camera distance and angle can increase variability in photographed skin appearance over time.

Introduction to the Biophotonics Congress 2022 feature issue.

A feature issue is being presented by a team of guest editors containing papers based on studies presented at the Optica Biophotonics Congress: Biomedical Optics held on April 24-27, 2022 in Fort Lauderdale, Florida, USA.