Melanin and Hemoglobin Identification for Skin Disease Analysis

International audienceThis paper proposes a novel method to extract melanin and hemoglobin concentrations of human skin, using bilateral decomposition with the knowledge of a multiple layered skin model and absorbance characteristics of major chromophores. Different from state-of-art approaches, the proposed method enables to address highlight and strong shading usually existing in skin color images captured under uncontrolled environment. The derived melanin and hemoglobin indices, directly related to the pathological tissue conditions, tend to be less influenced by external imaging factors and are effective for describing pigmentation distributions. Experiments demonstrate the value of the proposed method for computer-aided diagnosis of different skin diseases. The diagnostic accuracy of melanoma increases by 9-15% for conventional RGB lesion images, compared to techniques using other color descriptors. The discrimination of inflammatory acne and hyperpigmentation reveals acne stage, which would be useful for acne severity evaluation. It is expected that this new method will prove useful for other skin disease analysis

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs. Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma

Digital Image Analysis of Vitiligo for Monitoring of Vitiligo Treatment

Vitiligo is an acquired pigmentary skin disorder characterized by depigmented macules that result from damage to and destruction of epidermal melanocytes. Visually, the vitiligous areas are paler in contrast to normal skin or completely white due to the lack of pigment melanin. The course of vitiligo is unpredictable where the vitiligous skin lesions may remain stable for years before worsening. Vitiligo treatments have two objectives, to arrest disease progression and to re-pigment the vitiligous skin lesions. To monitor the efficacy of the treatment, dermatologists observe the disease directly, or indirectly using digital photos. Currently there is no objective method to determine the efficacy of the vitiligo treatment. Physician's Global Assessment (PGA) scale is the current scoring system used by dermatologists to evaluate the treatment. The scale is based on the degree of repigmentation within lesions over time. This quantitative tool however may not be help to detect slight changes due to treatment as it would still be largely dependent on the human eye and judgment to produce the scorings. In addition, PGA score is also subjective, as it varies with dermatologists. The progression of vitiligo treatment can be very slow and can take more than 6 months. It is observed that dermatologists find it visually hard to determine the areas of skin repigmentation due to this slow progress and as a result the observations are made after a longer time frame. The objective of this research is to develop a tool that enables dermatologists to determine and quantify areas of repigmentation objectively over a shorter time frame during treatment. The approaches towards achieving this objective are based on digital image processing techniques. Skin color is due to the combination of skin histological parameters, namely pigment melanin and haemoglobin. However in digital imaging, color is produced by combining three different spectral bands, namely red, green, and blue (RGB). It is believed that the spatial distribution of melanin and haemoglobin in skin image could be separated. It is found that skin color distribution lies on a two-dimensional melanin-haemoglobin color subspace. In order to determine repigmentation (due to pigment melanin) it is necessary to perform a conversion from RGB skin image to this two-dimensional color subspace. Using principal component analysis (PCA) as a dimensional reduction tool, the two-dimensional subspace can be represented by its first and second principal components. Independent component analysis is employed to convert the twodimensional subspace into a skin image that represents skin areas due to melanin and haemoglobin only. In the skin image that represents skin areas due to melanin, vitiligous skin lesions are identified as skin areas that lack melanin. Segmentation is performed to separate the healthy skin and the vitiligous lesions. The difference in the vitiligous surface areas between skin images before and after treatment will be expressed as a percentage of repigmentation in each vitiligo lesion. This percentage will represent the repigmentation progression of a particular body region. Results of preliminary and pre-clinical trial study show that our vitiligo monitoring system has been able to determine repigmentation progression objectively and thus treatment efficacy on a shorter time cycle. An intensive clinical trial is currently undertaken in Hospital Kuala Lumpur using our developed system. VI

Sensitivity of Diffuse Reflectance Spectroscopy to Dose- and Depth-dependent Changes in Tumor Oxygenation after Radiation Therapy

Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities, there is no established technique that would enable early identification of tumor radioresistance. Tumor oxygenation plays a crucial role for radiotherapy efficiency. We hypothesize that diffuse reflectance spectroscopy (DRS) enabling repeated non-invasive measurements of tumor vascular oxygen saturation can provide surrogate measures of tumor oxygenation to predict tumor response to therapy. The goal of this study is to determine the sensitivity of diffuse reflectance spectroscopy to changes in tumor oxygenation after single-dose radiation therapy in a preclinical tumor xenograft model. We established three specific aims addressing the ability of DRS to provide accurate measures of tumor properties. The first aim is to determine the effect skin thickness on the extraction of optical parameters using one-layer Lookup Table (LUT) model. The second aim is to determine depth- and dose-dependent changes in DRS-measured vascular oxygenation during radiotherapy. The third aim is to determine the association between DRS-measured vascular oxygenation and immunohistochemically assessed intracellular hypoxia. Our results demonstrate a significant impact of skin thickness on the extraction of optical parameters for short source-detector separations caused by the one-layer assumption of the LUT model. We also detected LUT model failure to identify the absence of melanin when skin is mechanically removed. These findings suggest that existing LUT model needs to be modified to account for the effect of the skin layer. Measurements with different source-detector separations revealed higher concentration of hemoglobin in superficial layer of tumors and blood supply disruption after exposure to 8 Gy of radiation

Raman spectroscopy and diffuse reflectance spectroscopy for diagnosis of human cancer and acanthosis nigricans

Cancer and diabetes are common chronic diseases in today\u27s world causing numerous deaths in adults as well as children. Most common types of cancers in adults include prostate, lung, breast, colorectal and head and neck squamous cell carcinoma, while among children; leukemia, and brain and central nervous system cancers are quite common. In each of these cases, early detection of the cancer or disease dramatically increases the chances of successful treatment. In recent years, there has been much interest in using Raman spectroscopy and diffuse reflectance spectroscopy as analytical optical spectroscopic methods for early diagnosis of diseases. Raman spectroscopy can be used to measure changes in the bio-molecular composition of a tissue specimen, and diffuse reflectance spectroscopy can measure chromophores of the skin. In this research, archived (formalin-fixed paraffin processed) tissues of head and neck squamous cell carcinoma, prostate, and pediatric tumors have been investigated using Raman spectroscopy. We have utilized statistical methods such as principal component analysis (PCA) and discriminant function analysis (DFA) to analyze the spectral output and distinguish between normal and cancerous tissues. The results show cancerous tissues can be successfully distinguished from normal tissues in three cancer types in ex vivo. However, due to loss of biochemical in the tissue processing (paraffinizing and deparaffinizing procedure), the prediction ability of the archived tissues are less compared to frozen tissues as observed in the pediatric tumor investigation. We also investigated the diagnostic capability of diffuse reflectance spectroscopy and colorimetry on a skin disease, acanthosis nigricans in vivo. The aim is to quantify and characterize the skin color change associated with acanthosis nigricans skin disease in insulin-resistant obese individuals. We observe both the instruments can be utilized to detect acanthosis nigricans with more than 87% sensitivity and 94% specificity when combined with advanced chemometric methods

Feature Selection on Hyperspectral Data for Dismount Skin Analysis

Many security applications require the ability to accurately identify dismounts based on their distinctive identification properties. A dismount can be identified by many personal characteristics to include clothing, height, and gait. In particular, a dismount\u27s skin can be used as an identifying feature because of the vast variability of skin pigmentation amongst individuals. Hyperspectral data, which is comprised of hundreds of spectral channels sampled from a nearly contiguous electromagnetic spectrum, is used to detect skin spectral variability amongst dismounts. However, hyperspectral data is often highly correlated and computationally expensive to process. Feature selection methods can be employed to reduce the data to a manageable size. This thesis presents the results of applying the fast correlation based filter (FCFB) [51] to a data set that contains hyperspectral data from the forearms of 62 subjects. The reduced data is used to train an artificial neural network (ANN) to discriminate a dismount of interest (DOI) amongst a group of 4 non-DOI\u27s. The trained model is then tested to find the same DOI amongst a group of 62 new non-DOI\u27s. The FCBF selected four features (1014, 1024, 1033, and 1348nm) to discriminate amongst the dismounts. Using these four features, the ANN on average misclassified dismounts amongst four separate DOI validation tests. More specifically, the amount of possible DOI suspects was reduced from 62 to 4 dismounts. The FCBF outperformed three other feature selection methods with 4 times less misclassified instances

In vivo real-time imaging of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness with visible spatially modulated light

We present the real-time single snapshot multiple frequency demodulation - spatial frequency domain imaging (SSMD-SFDI) platform implemented with a visible digital mirror device that is capable of imaging and monitoring dynamic turbid medium and processes over a large field of view. One challenge in quantitative imaging of biological tissue such as the skin is the complex structure rendering techniques based on homogeneous medium models to fail. To address this difficulty we have also developed a novel method that maps the layered structure to a homogeneous medium for spatial frequency domain imaging. The varying penetration depth of spatially modulated light on its wavelength and modulation frequency is used to resolve the layered structure. The efficacy of the real-time SSMD-SFDI platform and this two-layer model is demonstrated by imaging forearms of 6 healthy subjects under the reactive hyperemia protocol. The results show that our approach not only successfully decouples light absorption by melanin from that by hemoglobin and yields accurate determination of cutaneous hemoglobin concentration and oxygen saturation, but also provides reliable estimation of the scattering properties, the melanin content and the epidermal thickness in real time. Potential applications of our system in imaging skin physiological and functional states, cancer screening, and microcirculation monitoring are discussed at the end. © 2017 Optical Society of Americ

Fast estimation of the spectral optical properties of rabbit pancreas and pigment content analysis

The pancreas is a highly important organ, since it produces insulin and prevents the occurrence of diabetes. Although rare, pancreatic cancer is highly lethal, with a small life expectancy after being diagnosed. The pancreas is one of the organs less studied in the field of biophotonics. With the objective of acquiring information that can be used in the development of future applications to diagnose and treat pancreas diseases, the spectral optical properties of the rabbit pancreas were evaluated in a broad-spectral range, between 200 and 1000 nm. The method used to obtain such optical properties is simple, based almost on direct calculations from spectral measurements. The optical properties obtained show similar wavelength dependencies to the ones obtained for other tissues, but a further analysis on the spectral absorption coefficient showed that the pancreas tissues contain pigments, namely melanin, and lipofuscin. Using a simple calculation, it was possible to retrieve similar contents of these pigments from the absorption spectrum of the pancreas, which indicates that they accumulate in the same proportion as a result of the aging process. Such pigment accumulation was camouflaging the real contents of DNA, hemoglobin, and water, which were precisely evaluated after subtracting the pigment absorption