Parameter-based transfer learning for severity classification of atopic dermatitis using hyperspectral imaging.

BACKGROUND/PURPOSE: Because atopic dermatitis (AD) is a chronic inflammatory skin condition that causes structural changes, there is a growing need for noninvasive research methods to evaluate this condition. Hyperspectral imaging (HSI) captures skin structure features by exploiting light wavelength variations in penetration depth. In this study, parameter-based transfer learning was deployed to classify the severity of AD using HSI. Therefore, we aimed to obtain an optimal combination of classification results from the four models after constructing different source- and target-domain datasets. METHODS: We designated psoriasis, skin cancer, eczema, and AD datasets as the source datasets, and the set of images acquired via hyperspectral camera as the target dataset for wavelength-specific AD classification. We compared the severity classification performances of 96 combinations of sources, models, and targets. RESULTS: The highest classification performance of 83% was achieved when ResNet50 was trained on the augmented psoriasis dataset as the source, with the resulting parameters used to train the model on the target Near-infrared radiation (NIR) dataset. The second highest classification accuracy of 81% was achieved when ResNet50 was trained on the unaugmented psoriasis dataset as the source, with the resulting parameters used to train the model on the target R dataset. ResNet50 demonstrated potential as a generalized model for both the source and target data, also confirming that the psoriasis dataset is an effective training resource. CONCLUSION: The present study not only demonstrates the feasibility of the severity classification of AD based on hyperspectral images, but also showcases combinations and research scalability for domain exploration.

Superoxide Dismutase-Mimetic Polyphenol-Based Carbon Dots for Multimodal Bioimaging and Treatment of Atopic Dermatitis.

Polyphenols have been investigated for their potential to mitigate inflammation in the context of atopic dermatitis (AD). In this study, epigallocatechin-3-gallate (EGCG)-based carbon dots (EGCG@CDs) were developed to enhance transdermal penetration, reduce inflammation, recapitulate superoxide dismutase (SOD) activity, and provide antimicrobial effects for AD treatment. The water-soluble EGCG@CDs in a few nanometers size exhibit a negative zeta potential, making them suitable for effective transdermal penetration. The fluorescence properties, including an upconversion effect, make EGCG@CDs suitable imaging probes for both in vitro and in vivo applications. By mimicking the SOD enzyme, EGCG@CDs scavenge reactive oxygen species (ROS) and actively produce hydrogen peroxide through a highly catalytic capability toward the oxygen reduction reaction, resulting in the inhibition of bacterial growth. The enhanced antioxidant properties, high charge mobility, and various functional groups of EGCG@CDs prove effective in reducing intracellular ROS in an in vitro AD model. In the mouse AD model, EGCG@CDs incorporated into a hydrogel actively penetrated the epidermal layer, leading to ROS scavenging, reduced mast cell activation, and histological recovery of skin barriers. This research represents the versatile potential of EGCG@CDs in addressing AD and advancing tissue engineering.

Zinc penetration through the skin barrier in atopic dermatitis and rosacea using reflectance confocal microscopy.

Atopic dermatitis (AD) is a chronic, recurrent eczematous disorder with a complex pathophysiology caused by skin barrier abnormalities. Rosacea is a common chronic immune-mediated inflammatory disorder that results in diminished skin barrier function. Reflectance confocal microscopy (RCM) is a non-invasive method for visualizing the dynamic status of epidermal and upper dermal structures. In this study, we compared skin barrier permeability among normal, AD and rosacea groups. To assess skin barrier permeability, zinc was applied to lesional skin and the RCM reflectance intensity of zinc penetration was measured. Reflectance confocal microscopy revealed that the intensity in patients with rosacea and AD was higher than that in the normal group at depths of 8-24 µm in both the face and forearm, which were considered as the stratum corneum (SC) and tight junction (TJ) level (p < 0.0001). When comparing AD and rosacea, the intensity of rosacea was higher than that of AD at a depth of 8 µm in the face (p < 0.0001). The intensity of AD was higher than that of rosacea at a depth of 24 µm (p = 0.009). This suggests that skin barrier permeability is increased in the upper epidermis of patients with AD and rosacea. On the face, patients with rosacea had more SC weakness than did those with AD, whereas patients with AD had more TJ weakness than those with rosacea.

In vivo non-invasive staining-free visualization of dermal mast cells in healthy, allergy and mastocytosis humans using two-photon fluorescence lifetime imaging.

Mast cells (MCs) are multifunctional cells of the immune system and are found in skin and all major tissues of the body. They contribute to the pathology of several diseases including urticaria, psoriasis, atopic dermatitis and mastocytosis where they are increased at lesional sites. Histomorphometric analysis of skin biopsies serves as a routine method for the assessment of MC numbers and their activation status, which comes with major limitations. As of now, non-invasive techniques to study MCs in vivo are not available. Here, we describe a label-free imaging technique to visualize MCs and their activation status in the human papillary dermis in vivo. This technique uses two-photon excited fluorescence lifetime imaging (TPE-FLIM) signatures, which are different for MCs and other dermal components. TPE-FLIM allows for the visualization and quantification of dermal MCs in healthy subjects and patients with skin diseases. Moreover, TPE-FLIM can differentiate between two MC populations in the papillary dermis in vivo-resting and activated MCs with a sensitivity of 0.81 and 0.87 and a specificity of 0.85 and 0.84, respectively. Results obtained on healthy volunteers and allergy and mastocytosis patients indicate the existence of other MC subpopulations within known resting and activated MC populations. The developed method may become an important tool for non-invasive in vivo diagnostics and therapy control in dermatology and immunology, which will help to better understand pathomechanisms involving MC accumulation, activation and degranulation and to characterize the effects of therapies that target MCs.

From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin.

The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients' bedsides. These 'optical biopsies' generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.

Topical tacrolimus vs medium-dose ultraviolet A1 phototherapy in the treatment of atopic dermatitis - a preliminary study in relation to parameters of the epidermal barrier function and high-frequency ultrasonography.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, relapsing skin disorder, which is characterized by intense pruritus, skin dryness and concomitant epidermal barrier dysfunction. The basic therapy involves the application of anti-inflammatory topical drugs like; glucocorticosteroids and calcineurin inhibitors. Phototherapy in AD is regarded as an additional form of treatment. The latest invention, ultraviolet A1-UVA1 phototherapy (340-400 nm), was introduced to the treatment of AD by Krutmann et al in 1992. It appears that the main mode of action of UVA1 phototherapy in AD is through activation of apoptosis of T lymphocytes. Additionally, new studies show that UVA1 can also inhibit the activity of calcineurin phosphatase, similarly to calcineurin inhibitors such as cyclosporin A or tacrolimus. The aim of this study is to, for the first time, compare the efficacy of medium dose UVA1 phototherapy and tacrolimus ointment in patients with moderate-severe AD. PATIENTS AND METHODS: This study involved 20 AD patients. Half of the patients were treated with UVA1 phototherapy, while another 10 participants were treated with the application of tacrolimus ointment. The severity of the disease progress was assessed on the basis of EASI score (Eczema Area Severity Index). Moreover, the clinical condition of patients was assessed using non-invasive techniques such as measurement of transepidermal water loss - TEWL and skin capacitance, as well as high-frequency ultrasonography (20 MHz). RESULTS: This study described above confirmed the beneficial influence of both therapies on the course of moderate-severe AD. Tacrolimus induced a greater reduction in TEWL, while phototherapy caused the reduction of subepidermal low echogenic band-SLEB within sites affected with pathological lesions. CONCLUSIONS: Both tacrolimus and phototherapy treatment seemed to significantly reduce EASI.

Comparison between high-frequency ultrasonography (Dermascan C, version 3) and histopathology in atopic dermatitis.

BACKGROUND: The main purpose of this study was the exact comparison of B-scan images obtained from 16 patients suffering from AD with histological. METHODS: Sixteen patients diagnosed with AD aged between 14 and 57 years, were chosen for the study. In all patients before the introduction of proper treatment regimen, the high frequency skin ultrasonography (Derma Scan Cortex Technology, version 3, Hadsund, Germany) has been performed and then a 5 mm wide punch biopsies have been taken from the area of scanned lesions. Control group consisted of 15 healthy individuals without any signs of atopic and chronic diseases. RESULTS: There was 7.8 ± 0.4% mean skin echogenicity from lesional antecubital skin in AD patients (min value 7.2%, max value 8.5%). The skin hypoechoic band was detected in fifteen out of sixteen patients (93.7%). There were statistically significant correlations between the hypoechoic band thickness and the following parameters: degree of epidermal hyperplasia, the degree of epidermal hyperkeratosis, the degree of parakeratosis and the degree of spongiosis as well as the intensity of inflammatory infiltrates. Skin echogenicity strongly correlated negatively with the intensity of inflammatory infiltrates. CONCLUSION: On the basis of analysis of 16 specimens we can conclude that all pathological changes of AD influence ultrasound image and in addition, the USG picture depends on the phase of disease process.

Atopic myelitis: a clinical, biological, radiological and histopathological diagnosis.

We describe a young patient with an unusual intramedullary lesion filled with eosinophils. The 21-year-old man developed chronic myelitis without optic neuritis or signs of systemic or infectious disease. A spinal biopsy was conducted because of the progressive extension and pseudo-tumoural aspect of the lesion. Histopathological analysis of the biopsy specimen revealed a severe inflammatory process with macrophages and numerous eosinophils. The eosinophil count in the blood and cerebrospinal fluid (CSF) were normal. Clinical, laboratory and radiological data did not correspond with the usual causes of eosinophilic myelitis. Abnormal mite antigen-specific IgE levels and features similar to Japanese cases of atopic myelitis suggested an allergic origin. Despite normal total IgE levels, this case may be the second case of atopic myelitis reported in a Caucasian patient. Striking differences with the first reported case are the absence of a typical history of atopy and normal total IgE levels. This case highlights that atopic myelitis should be considered in myelopathy occurring in Caucasian patients even in the absence of hyperIgEaemia.

Reactivity to nickel sulfate at sodium lauryl sulfate pretreated skin sites is higher in atopics: an echographic evaluation by means of image analysis performed on 20 MHz B-scan recordings.

The aim of this study was to establish an objectively assessable procedure simulating simultaneous exposure to irritants and allergens in domestic and occupational environments, in order to evaluate differences in the reactivity to the combination of these substances in atopic and non-atopic nickel-sensitized subjects. Thirty-four nickel-sensitive patients, 20 of whom were affected by atopic dermatitis, underwent four patch tests with NiSO4 0.05% aq. on two adjacent sites of both volar forearms, with a 24-h application time. Two of the test sites were treated with sodium lauryl sulfate (SLS) 5% for 30 min, before application of the nickel sulfate preparation. Echographic recordings were performed by a 20-MHz B-scanner and processed by an image analysis program, providing a numerical representation of the picture data, based on the attribution of fictional values to the amplitudes of the echoes. The dermal inflammatory reaction was quantified by an amplitude band, marking the hypo-reflecting part of the dermis, whereas epidermal damage was assessed by a band highlighting the entrance echo. Pre-treatment with SLS of the skin area where nickel sulfate was subsequently applied greatly enhanced the allergic response at 24 and 72 h, both in subjects with atopic dermatitis and in subjects with allergic contact dermatitis. However, in atopics, the increase in the allergic reactivity after irritation of the skin was more pronounced both by clinical and by echographic evaluation. These observations stress the importance of the concurrent action of irritants and allergens in maintaining the dermatitis in atopics.

Results of lymphography in early mycosis fungoides.

Lymphography was performed in 28 patients with mycosis fungoides. In 22 of the patients, the investigation took place prior to 2 months after the diagnosis was established, and in 7 of these lymphography was made before the histological verification of mycosis fungoides was possible. Five patients with widespread, persistent and severe atopic dermatitis served as controls. Eighteen patients with mycosis fungoides (64%) had abnormal lymphograms, while all 5 controls had normal lymphograms. Abnormal findings were diagnosed in 12 of 22 patients at the earliest time possible during the course of their disease and even found in 5 of 7 patients who only had premycotic lesions at the time of investigation. These results may have some bearing on therapy, suggesting that systemic treatment could possibly be introduced at a far earlier disease stage than is the custom at present.