Yin and Yang of skin microbiota in "swimmer acne".

Cutibacterium acnes (C. acnes) is an organism implicated in the pathogenesis of acne. Despite regular immersion in antimicrobial chlorine, adolescent swimmers suffer from acne and tend to be resistant to standard therapies. Given the presence of Pseudomonas within swimming facilities, we hypothesized that "swimmer acne" is potentially driven by a different microbial mechanism. In this study, we aimed to examine the microbial dynamics of C. acnes and Pseudomonadaceae, a family of gram-negative bacteria (includes Pseudomonas aeruginosa), in swimmers and its potential contribution to the pathogenesis of acne in this population. Using fluorescence photography that measures the Coproporphyrin III (CPIII), we quantitated an absolute abundance of C. acnes present on the face of each participant pre- and post-swimming. In addition, 16S rRNA gene sequencing was utilized to assess relative abundance of the skin microbiota on each participant pre- and post-swimming. 16 swimmers (8 girls and 8 boys) completed the study. Seven had acne on the face. The CPIII fluorescence levels decreased for all swimmers after 1 h of swimming (p-value <0.001). In contrast, the relative abundance of C. acnes remained unchanged, while that of Pseudomonadaceae increased after swimming (p-value =0.027). Comparing the relative abundances of Pseudomonadaceae before swimming, there was a significant increase in variance from the mean in acne group as compared to no acne group (p-value <0.001). Taken together, we conclude that the skin dysbiosis resulting from repeated decolonization and colonization of C. acnes and Pseudomonadaceae, respectively, can potentially be associated with the pathogenesis of acne in swimmers.

Effects of swimming on facial sebum in adolescents.

Swimmers often complain of dry skin, consistent with decreased skin sebum levels, and yet may also have acne, which is commonly related to elevated sebum levels. Sixteen adolescent swimmers with and without acne were enrolled to examine two markers of facial sebum levels before and after 1 hour of swimming. Swimmers with acne did not have significant decreases in their sebum levels or shine measurements after swimming, whereas swimmers without acne did. Overall, swimming may remove superficial sebum more than follicular sebum and therefore leave swimmers subject to both dry skin and acne simultaneously.

Parametric Acne Severity (PAS) Score and Lesion Counts From Multi-Modality Facial Image Analysis Correlates Strongly with Investigator Assessment.

Variability in acne lesion counting and assessing global severity necessitates large sample sizes that increase trial costs. Lack of standardized measures for these outcomes precludes the conduct of meta-analyses needed to compare efficacy of acne treatments. The goal of this study was to evaluate objective measures of lesion counts and global severity using analysis of multimodal photography. An algorithm for counting lesions was trained and validated in 30 acne subjects and compared to parallel assessments by 2 expert raters. A composite of photographic data representative of acne lesion topography, erythema, and C Acnes fluorescence was used to generate a Parametric Acne Severity (PAS) score. No relationship was identified between lesion counts and IGA. The correlation coefficients between raters and the algorithm when compared per view for the inflammatory and non-inflammatory lesion counts were 0.77 (P=0.001) and 0.85 (P=0.001), respectively. The correlation coefficient between the raters’ IGA grades and the PAS score was 0.82 (P<0.05). These data demonstrate that the lesion counting, and PAS are objective measures that strongly correlate with investigator assessments. Inclusion of these measure in clinical trials may reduce variability, standardize outcomes, and provide insights into treatment effects on photographic parameters associated with acne. J Drugs Dermatol. 2021;20(6):642-647. doi:10.36849/JDD.6165.

Quantitative measurement of skin surface oiliness and shine using differential polarized images.

Excess amounts of skin surface oil can lead to adverse psychological consequences. Grease-spot photometry-based techniques measure sebum production rate. However, besides being tedious, these measurements are influenced by contact area, applied pressure, and time of application. Image analysis of polarized images has the potential to provide objective, quantitative information of skin oiliness. This study was designed to set up an imaging device for capturing and enhancing the changes in skin surface oiliness and to clinically and quantitatively, (via image analysis), evaluate varying levels of skin surface oiliness. Mineral oil was used to simulate skin surface oil. 40.5 µL of the mineral oil was applied within a two inch square area of interest on facial skin in twelve steps, from 1 to 40.5 µL, at 40% increments. The results indicate a strong correlation between the quantitative skin surface oiliness measurements and the clinical assessments. This sensitive technique has the potential to be utilized in future studies to evaluate product efficacies in reducing skin oiliness.

Measuring acne using Coproporphyrin III, Protoporphyrin IX, and lesion-specific inflammation: an exploratory study.

Propionibacterium acnes: (P. acnes) produce Porphyrins; however, fluorescence measurement of Porphyrins from Ultraviolet-A (UVA) images has failed to establish a correlation. Acne clinical research and imaging has ignored the spectral excitation-emission characteristics and the exact pattern of the Porphyrins synthesized by P. acnes. In this exploratory study, for the first time, the possible relationships of Coproporphyrin III (CpIII) and Protoporphyrin IX (PpIX) fluorescence as well as acne lesion-specific inflammation measurements with clinical signs of acne are investigated. Furthermore, the sensitivity of these measurements in tracking and differentiating the known treatment effects of Benzoyl Peroxide (BPO) 5%, and combination of Clindamycin + BPO are also evaluated. Comedonal and papulopustular lesions identified by investigators during a live assessment of 24 mild-to-severe acne subjects were compared with fluorescence and inflammation measurements obtained from analysis of VISIA®-CR images. CpIII fluorescence spots showed a strong correlation (r = 0.69-0.83), while PpIX fluorescence spots showed a weak correlation (r = 0.19-0.27) with the investigators' comedonal lesion counts. A strong correlation was also observed between the investigators' papulopustular lesion counts and acne lesion-specific inflammation (r = 0.76). Our results suggest that CpIII fluorescence and acne lesion-specific-inflammation measurement can provide objective indication of comedonal and papulopustular acne severity, respectively. Furthermore, these measurements may be more sensitive and specific in evaluating treatment effects and early signs of acne lesion progression compared to investigators' lesion counts.

Auto-classification of acne lesions using multimodal imaging.

Differentiating inflammatory and non-inflammatory acne lesions and obtaining lesion counts is pivotal part of acne evaluation. Manual lesion counting has reliably demonstrated the clinical efficacy of anti-acne products for decades. However, maintaining assessment consistency within and across acne trials is an important consideration since lesion counting can be subjective to the individual evaluators, and the technique has not been rigorously standardized. VISIA-CR is a multi-spectral and multi-modal facial imaging system. It captures fluorescence images of Horn and Porphyrin, absorption images of Hemoglobin and Melanin, and skin texture and topography characterizing broad-spectrum polarized and non-polarized images. These images are analyzed for auto-classification of inflammatory and non-inflammatory acne lesion, measurement of erythema, and post-acne pigmentation changes. In this work the accuracy of this acne lesion auto-classification technique is demonstrated by comparing the auto-detected lesions counts with those counted by expert physicians. The accuracy is further substantiated by comparing and confirming the facial location and type of every auto-identified acne lesion with those identified by the physicians. Our results indicate a strong correlation between manual and auto-classified lesion counts (correlation coefficient >0.9) for both inflammatory and non inflammatory lesions This technology has the potential to eliminate the tedium of manual lesion counting, and provide an accurate, reproducible, and clinically relevant evaluation of acne lesions. As an aid to physicians it will allow development of a standardized technique for evaluating acne in clinical research, as well as accurately choosing treatment options for their patients according to the severity of a specific lesion type in clinical practice

In vivo fluorescence lifetime tomography.

Local molecular and physiological processes can be imaged in vivo through perturbations in the fluorescence lifetime (FLT) of optical imaging agents. In addition to providing functional information, FLT methods can quantify specific molecular events and multiplex diagnostic and prognostic information. We have developed a fluorescence lifetime diffuse optical tomography (DOT) system for in vivo preclinical imaging. Data is captured using a time-resolved intensified charge coupled device (ICCD) system to measure fluorescence excitation and emission in the time domain. Data is then converted to the frequency domain, and we simultaneously reconstruct images of yield and lifetime using an extension to the normalized Born approach. By using differential phase measurements, we demonstrate DOT imaging of short lifetimes (from 350 ps) with high precision (+/-5 ps). Furthermore, this system retains the efficiency, speed, and flexibility of transmission geometry DOT. We demonstrate feasibility of FLT-DOT through a progressive series of experiments. Lifetime range and repeatability are first measured in phantoms. Imaging of subcutaneous implants then verifies the FLT-DOT approach in vivo in the presence of inhomogeneous optical properties. Use in a common research scenario is ultimately demonstrated by imaging accumulation of a targeted near-infrared (NIR) fluorescent-labeled peptide probe (cypate-RGD) in a mouse with a subcutaneous tumor.

Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier.

The quantitative accuracy of fluorescence and bioluminescence imaging of small animals can be improved by knowledge of the in situ optical properties of each animal. Obtaining in situ optical property maps is challenging, however, due to short propagation distances, requirements for high dynamic range, and the need for dense spatial, temporal, and spectral sampling. Using an ultrafast gated image intensifier and a pulsed laser source, we have developed a small animal diffuse optical tomography system with multiple synthetic modulation frequencies up to >1 GHz. We show that amplitude and phase measurements with useful contrast-to-noise ratios can be obtained for modulation frequencies over the range of approximately 250 to 1250 MHz. Experiments with tissue simulating phantoms demonstrate the feasibility of reconstructing the absorption and scattering optical properties in a small animal imaging system.

Quantitative small animal fluorescence tomography using an ultrafast gated image intensifier.

Optical approaches to small animal in vivo molecular imaging provide high sensitivity, stable non-radioactive probes, and an extensive array of functional reporting strategies. However, quantitative whole body assays remain illusive. The quantitative accuracy of optical imaging is affected by the depth of the buried target and the heterogeneity of tissue optical properties. Tomography approaches, to obtaining in-vivo optical property maps, and whole body distributions of fluorescing probes, provide a strategy for improving the quality and quantitative accuracy of small animal optical imaging. Here we present a time-resolved, charged coupled device (CCD) based system for quantitative small animal fluorescence tomography.

Monte Carlo simulation of light-tissue interaction: three-dimensional simulation for trans-illumination-based imaging of skin lesions.

Three-dimensional, voxel-based, and wavelength-dependent skin lesion models are developed and simulated using Monte Carlo techniques. The optical geometry of the Nevoscope with trans-illumination is used in the simulations for characterizing the lesion thickness. Based on the correlation analysis between the lesion thickness and the diffuse reflectance, optical wavelengths are selected for multispectral imaging of skin lesions using the Nevoscope. Tissue optical properties reported by various researchers are compiled together to form a voxel library. Tissue models used in the simulations are developed using the voxel library which offers flexibility in updating the optical properties and adding new media types into the models independent of the Monte Carlo simulation code.

Multi-spectral image analysis and classification of melanoma using fuzzy membership based partitions.

The sensitivity and specificity of melanoma diagnosis can be improved by adding the lesion depth and structure information obtained from the multi-spectral, trans-illumination images to the surface characteristic information obtained from the epi-illumination images. Wavelet transform based bi-modal channel energy features obtained from the images are used in the analysis. Methods using both crisp and fuzzy membership based partitioning of the feature space are evaluated. For this purpose, the ADWAT classification method that uses crisp partitioning is extended to handle multi-spectral image data. Also, multi-dimensional fuzzy membership functions with Gaussian and Bell profiles are proposed for classification. Results show that the fuzzy membership functions with Bell profile are more effective than the extended ADWAT method in discriminating melanoma from dysplastic nevus.

Multi-spectral imaging and analysis for classification of melanoma.

Wavelengths in the visible spectrum are selected for multi-spectral trans-illumination imaging of the skin lesions using the Nevoscope. The multi-spectral image data is analyzed using crisp and fuzzy partitioning techniques for classification of melanoma. It is shown that the multi-spectral images add the lesion depth and structural information to the superficial lesion characteristics obtained from the surface illumination images and hence, improve the sensitivity and specificity of melanoma diagnosis.

Classification of melanoma using tree structured wavelet transforms.

This paper presents a wavelet transform based tree structure model developed and evaluated for the classification of skin lesion images into melanoma and dysplastic nevus. The tree structure model utilizes a semantic representation of the spatial-frequency information contained in the skin lesion images including textural information. Results show that the presented method is effective in discriminating melanoma from dysplastic nevus. The results are also compared with those obtained using another method of developing tree structures utilizing the maximum channel energy criteria with a fixed energy ratio threshold.