Infrared imaging spectroscopy of skin cancer lesions

Skin cancer is a disease of the twenty-first century since, unfortunately, being tan is associated to be healthy and good looking. UV radiation produces one of the most aggressive kinds of skin cancer: melanoma; once the damage is done there is no other solution that a rapid and effective diagnosis. Clinical examination and biopsies have shown to be slow and costly in many ways, so the possibility of getting a non-invasive optical detection of skin melanomas became a hot topic in biophotonics. In this context, multispectral imaging systems have approached the problem, but none of them worked inside the infrared range. Hence, this work has been proposed as an interesting, long-term project to further investigate about the possibilities of infrared imaging spectroscopy for the early detection of skin cancer through the development of such a system based on an InGaAs camera

Initial results of finger imaging using Photoacoustic Computed Tomography

We present a photoacoustic computed tomography investigation on a healthy human finger, to image blood vessels with a focus on vascularity across the interphalangeal joints. The cross-sectional images were acquired using an imager specifically developed for this purpose. The images show rich detail of the digital blood vessels with diameters between 100 $\mu$m and 1.5 mm in various orientations and at various depths. Different vascular layers in the skin including the subpapillary plexus could also be visualized. Acoustic reflections on the finger bone of photoacoustic signals from skin were visible in sequential slice images along the finger except at the location of the joint gaps. Not unexpectedly, the healthy synovial membrane at the joint gaps was not detected due to its small size and normal vascularization. Future research will concentrate on studying digits afflicted with rheumatoid arthritis to detect the inflamed synovium with its heightened vascularization, whose characteristics are potential markers for disease activity.Comment: 2 figure

Multidimensional imaging for skin tissue surface characterization

Human skin, the outer and largest organ covering our body, can be described in terms of both its 3D spatial topography and its 2D spectral reflectance. Such a characterization normally requires the application of separate procedures using different kinds of equipment, where spectral reflectance can only be obtained from a small patch of the skin surface. This paper investigates the integration of multiple imaging modalities to simultaneously capture both spectral and spatial information from the skin surface over a wide area. By extending the imaging spectrum from the visible to the near-infrared (NIR), we improve general recovery, obtain a more detailed skin profile, and are able to identify the distribution of various principal chromophores within the deeper dermal layers. Experiments show that new dimensions of skin characterization can be generated through the recovered geometrical and spectral information, so that an enhanced visibility of important skin physiological phenomena can be achieved. © 2013 Elsevier B.V. All rights reserved

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

Non-Invasive Measurement of Frog Skin Reflectivity in High Spatial Resolution Using a Dual Hyperspectral Approach

Background:Most spectral data for the amphibian integument are limited to the visible spectrum of light and have been collected using point measurements with low spatial resolution. In the present study a dual camera setup consisting of two push broom hyperspectral imaging systems was employed, which produces reflectance images between 400 and 2500 nm with high spectral and spatial resolution and a high dynamic range.Methodology/Principal Findings:We briefly introduce the system and document the high efficiency of this technique analyzing exemplarily the spectral reflectivity of the integument of three arboreal anuran species (Litoria caerulea, Agalychnis callidryas and Hyla arborea), all of which appear green to the human eye. The imaging setup generates a high number of spectral bands within seconds and allows non-invasive characterization of spectral characteristics with relatively high working distance. Despite the comparatively uniform coloration, spectral reflectivity between 700 and 1100 nm differed markedly among the species. In contrast to H. arborea, L. caerulea and A. callidryas showed reflection in this range. For all three species, reflectivity above 1100 nm is primarily defined by water absorption. Furthermore, the high resolution allowed examining even small structures such as fingers and toes, which in A. callidryas showed an increased reflectivity in the near infrared part of the spectrum.Conclusion/Significance:Hyperspectral imaging was found to be a very useful alternative technique combining the spectral resolution of spectrometric measurements with a higher spatial resolution. In addition, we used Digital Infrared/Red-Edge Photography as new simple method to roughly determine the near infrared reflectivity of frog specimens in field, where hyperspectral imaging is typically difficult. © 2013 Pinto et al

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

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

Quantification and influence of skin chromophores for remote detection of anemic conditions

Current standards for diagnosing and monitoring anemia are relatively invasive. The superficial symptoms of this condition are due to an underlying deficiency of red blood cells (RBC) or erythrocytes, and hemoglobin in the blood. This results in an inadequate supply of oxygen to the body’s tissues. For point-of-care diagnostic systems, remote determination of blood conditions will depend on an understanding of the interaction of light with hemoglobin. However, the skin acts as the first barrier for this detection. In this study, we pursue the possibility of detecting anemic conditions from the perfused blood in the dermis using optical models and Monte Carlo (MC) methods. The skin is composed of two primary layers, the epidermis and the dermis. The avascular epidermis absorbs light due to its primary chromophore, melanin. Subsequently, the absorption in the dermis layer is quantified by hematocrit and hemoglobin concentrations. Two-layer models of the human skin are set up and optical properties are assigned to these models. The optical variability across these models are defined by six melanin (epidermis) and two erythrocytes (dermis) concentrations. The twelve combinations of optical properties are assessed at six wavelengths of interest in the Virtual Tissue Simulator (VTS) environment. The chosen wavelengths range across the visible and near-infrared spectrum, which is a known and important diagnostic window for biological tissues. In this study, we explore the variability of light interactions for healthy and anemic blood conditions quantified in the dermis while accounting for variable melanin concentrations in the epidermis

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

Photoacoustic microscopy

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies