Quantitative Visualization and Detection of Skin Cancer Using Dynamic Thermal Imaging

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death ¹. To date, the only effective treatment for melanoma remains surgical excision, therefore, the key to extended survival is early detection ^2,3. Considering the large numbers of patients diagnosed every year and the limitations in accessing specialized care quickly, the development of objective in vivo diagnostic instruments to aid the diagnosis is essential. New techniques to detect skin cancer, especially non-invasive diagnostic tools, are being explored in numerous laboratories. Along with the surgical methods, techniques such as digital photography, dermoscopy, multispectral imaging systems (MelaFind), laser-based systems (confocal scanning laser microscopy, laser doppler perfusion imaging, optical coherence tomography), ultrasound, magnetic resonance imaging, are being tested. Each technique offers unique advantages and disadvantages, many of which pose a compromise between effectiveness and accuracy versus ease of use and cost considerations. Details about these techniques and comparisons are available in the literature ⁴.Infrared (IR) imaging was shown to be a useful method to diagnose the signs of certain diseases by measuring the local skin temperature. There is a large body of evidence showing that disease or deviation from normal functioning are accompanied by changes of the temperature of the body, which again affect the temperature of the skin ^5,6. Accurate data about the temperature of the human body and skin can provide a wealth of information on the processes responsible for heat generation and thermoregulation, in particular the deviation from normal conditions, often caused by disease. However, IR imaging has not been widely recognized in medicine due to the premature use of the technology ^7,8 several decades ago, when temperature measurement accuracy and the spatial resolution were inadequate and sophisticated image processing tools were unavailable. This situation changed dramatically in the late 1990s-2000s. Advances in IR instrumentation, implementation of digital image processing algorithms and dynamic IR imaging, which enables scientists to analyze not only the spatial, but also the temporal thermal behavior of the skin ⁹, allowed breakthroughs in the field.In our research, we explore the feasibility of IR imaging, combined with theoretical and experimental studies, as a cost effective, non-invasive, in vivo optical measurement technique for tumor detection, with emphasis on the screening and early detection of melanoma ^10-13. In this study, we show data obtained in a patient study in which patients that possess a pigmented lesion with a clinical indication for biopsy are selected for imaging. We compared the difference in thermal responses between healthy and malignant tissue and compared our data with biopsy results. We concluded that the increased metabolic activity of the melanoma lesion can be detected by dynamic infrared imaging.     

Morbidity and Mortality in 7,684 Women According to Personal Hair Dye Use: The Copenhagen City Heart Study followed for 37 Years

Background

Permanent hair dye contains aromatic amines which are carcinogenic, and can cause allergic skin reactions. In the long term personal use of hair dye might therefore influence both morbidity and mortality.

Objectives

We tested the hypothesis that personal use of hair dye in women is associated with increased morbidity and mortality in the general population.

Methods

We included 7,684 women from the Copenhagen City Heart Study with information on the use of personal hair dye. We assessed the risk of cancer, skin diseases, other morbidities, and mortality during a median follow-up of 27 years (range 0–37).

Results

The multivariable adjusted hazard ratio for malignant melanoma in women with versus without personal use of hair dye was 2.07 (95% confidence interval 1.25–3.42). There was no increased risk of other cancer types. For other skin diseases and other major causes of morbidity we found no differences between the two groups, except for a minor excess of digestive diseases and increased risk of Parkinson’s disease among women using hair dye. Finally, we found no difference in all-cause mortality comparing women using personal hair dye or not. After correction for multiple comparisons, none of the results remained significant. However, in sensitivity analysis the excess risk of malignant melanoma remained increased with a hazard ratio of 2.58 (95%CI 1.33–5.03) among users of personal hair dye.

Conclusions

Personal use of hair dye does not have major influences on morbidity and mortality. Our finding of a 2-fold risk of malignant melanoma in women using hair dye is hypothesis generating.     

MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters

The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high‐penetrance genes, like CDKN2A, and allelic variation in low‐penetrance genes like the melanocortin‐1 receptor gene, MC1R. Red‐hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population. The study cohort consisted of sporadic primary melanoma patients, familial melanoma patients and a control group. An allele‐dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed. This elevated risk was found to be significantly associated with an increased frequency of dysplastic nevi (DN) among familial patients compared to sporadic patients. MC1R variation was found to be less frequent among acral lentiginous melanomas (ALM) and dependent on tumour localisation. No association was found between CDKN2A gene variants and general melanoma risk. Two new variants in the POMC gene were identified in red haired individuals without RHC alleles.     

An expert system for the early detection of melanoma using knowledge-based image analysis

Melanoma is the most lethal skin cancer; however, nearly all patients can be saved and cured by early detection and prompt surgical treatment. It has been demonstrated that the major diagnostic and prognostic parameters of melanoma are the vertical thickness, three-dimensional (3D) size and shape, and color of the lesion. The other characteristic features of early melanoma are irregularities in the boundary of the lesion and the appearance of nonuniform pigmentation (with a variety of color). During early stages of development of the melanoma, the changes in these parameters are very difficult to assess since no good tool exists for measuring them in situ and analyzing them for malignancy. A novel optical instrument called the "Nevoscope" has been developed to obtain multiple views of the transilluminated skin lesion from several angles. These views have been used to measure the thickness and 3D size of the skin lesion without excision. A knowledge-based image analysis and interpretation system is being developed to analyze images of the skin lesion for a set of diagnostic and prognostic features: thickness, 3D size, color and margin, boundary and surface characteristics. This analysis combined with the patient's history, such as occurrence of melanoma or dysplastic nevi in the family, life style, skin type, etc., is used by the knowledge-based expert system to detect early or potentially malignant lesions. The diagnostic and prognostic knowledge bases for the early detection of melanoma are being developed with the help of expert dermatologists and published case studies.     

Skin lesion prevalence of estuarine common bottlenose dolphins (Tursiops truncatus) in North Carolina,with comparisons to other east coast study sites

Common bottlenose dolphins (Tursiops truncatus) are sentinels of environmental health. Skin lesions may indicate disease and can be used to infer population health. We estimated the prevalence of skin lesions and identified major lesion types on coastal bottlenose dolphins in Roanoke Sound, North Carolina, over a 3-year period using photo-identification. Boat-based surveys were conducted from April 2012 through October 2014. High quality images of distinctive fins were examined for overall prevalence (P) of any skin lesion (n = 169, P = 0.49, 95% CI = 0.42–0.57). Lesion prevalence estimates varied little between years (2012 P = 0.45, 2013 P = 0.56, 2014 P = 0.52) and most lesions were observed in the spring (P = 0.79, 95% CI: 0.57–0.92). Of six lesion types examined, pale lesions were most common (P = 0.41, 95% CI: 0.30–0.52). Annual lesion prevalence estimates for dolphins in Roanoke Sound were comparable to published estimates for T. truncatus in Charleston, South Carolina, Brunswick, Georgia, and Sarasota, Florida (p ≥ .05), although, seasonal differences in lesion occurrence and type were observed (p < .05). Future studies should examine relationships between lesions and environmental variables and use stranded dolphins to investigate skin lesion etiology.     

Clinical and Histopathological Characterization of Cutaneous Melanomas in the Melanoblastoma‐Bearing Libechov Minipig Model

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma‐bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59–67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti‐cancerous self‐defense.     

Coral disease physiology: the impact of Acroporid white syndrome on <Emphasis Type="Italic">Symbiodinium</Emphasis>

Acroporid white syndrome, a disease-like syndrome from the Great Barrier Reef, results from degenerative host tissue at lesion borders. Tissue preceding lesion borders appears visually healthy, but it is currently unclear whether the endosymbiotic zooxanthellae (Symbiodinium) are physiologically impacted. Compared to healthy colonies, this study found no significant differences in symbiont density, mitotic index or chlorophyll a content in tissue bordering (0 cm), and 8 cm away from white syndrome lesions. Using chlorophyll a fluorescence techniques, the border tissue did not appear to be photosynthetically compromised, and Symbiodinium extracted from this area were photosynthetically competent. Transmission electron microscopy revealed extensive degeneration of host tissues surrounding symbionts in affected areas, however, Symbiodinium cells were structurally intact with no sign of in situ degradation. Collectively, these results suggest that Symbiodinium at white syndrome lesion borders exist in a dynamic intra-cellular state during active host tissue loss, yet remain physiologically uncompromised.     

Evaluation of aid to diagnosis of pigmented skin lesions in general practice: controlled trial randomised by practice

Objectives To determine whether an aid to the diagnosis of pigmented skin lesions reduces the ratio of benign lesions to melanomas excised in general practice.Design Controlled trial randomised by practice.Setting General practices in Perth, Western Australia.Participants 468 general practitioners in 223 practices.Interventions Intervention practices were given an algorithm and instant camera to assist with the diagnosis of pigmented skin lesions. All practices were given national guidelines on managing melanoma.Main outcome measures Ratio of benign pigmented lesions to melanomas excised. Analyses conducted with and without inclusion of seborrhoeic keratoses.Results At baseline the ratios of benign to malignant lesions were lower in the intervention group than in the control group. During the trial period the ratios were higher in the intervention group (19:1 v 17:1 without seborrhoeic keratoses and 29:1 v 26:1 with seborrhoeic keratoses). After adjustment for patients'' age, sex, and socioeconomic status, the ratio was 1.02 times higher (95% confidence interval 0.68 to 1.51, P = 0.94) in the intervention group when seborrhoeic keratoses were not included and 1.03 times higher (0.71 to 1.50, P = 0.88) when seborrhoeic keratoses were included. General practitioners in the intervention group were less likely than those in the control group to excise the most recent pigmented skin lesion they managed (22% v 48%, P < 0.001) and to refer the patient to a specialist (16% v 27%, P = 0.06).Conclusions Provision of the algorithm and camera did not decrease the ratio of benign pigmented skin lesions to melanomas excised by general practitioners.     

Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing Libechov minipig model

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59-67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti-cancerous self-defense.     

Genetic risk factors for melanoma

The genetic basis of melanoma is complex and has both inherited and acquired components. Different genomic approaches have been used to identify a number of inherited risk factors, which can be stratified by penetrance and prevalence. Rare high-penetrance factors are expressed in familial clustering of melanoma and include mutations in CDKN2A (encoding p16^INK4a and p14^ARF) and CDK4. These genes are involved in cell-cycle arrest and melanocyte senescence and are nearly invariably targeted by somatic mutations during melanoma progression. Low-penetrance factors are common in the general population and include single-nucleotide polymorphisms in or near MC1R, ASIP, TYR and TYRP1. These genes are major determinants of hair and skin pigmentation, but their role in melanoma development remains unclear. This review describes the efforts that have led to the current understanding of melanoma susceptibility as the result of complex gene–gene and gene–environment interactions. Despite the significant advances, the majority of familial cases remain unaccounted for.     

A comparison of methods for inoculating bean plants with Elsinoë phaseoli and some factors affecting infection

Bean (Phaseolus vulgaris) leaves were inoculated with a conidial suspension of Elsinoe phaseoli by spraying, by applying a 10 μl drop, by a cotton wool technique or by using a camel hair brush. Spray application resulted in a uniform distribution of lesions over the leaf surface and gave consistent levels of infection between repetitions. Drop application allowed good control of the amount of inoculum applied. Although brush or cotton wool techniques gave high levels of infection it was not possible to control the amount of inoculum. Only immature tissues were susceptible to infection. Five cultivars were inoculated with two isolates and disease was scored on the basis of numbers of lesions and lesion type (scab severity). The small white cvs PAN 181 and Teebus were the most resistant; lesions were small and generally fewer than on the large-seeded red speckled sugar bean cvs Umlazi and Umvoti. The value of the different inoculation techniques in studies on bean scab is discussed.     

A case report of an unrecognized nevoid melanoma in a young woman--clinicopathological diagnostic challenge

Nevoid melanoma is a rare form of melanoma histologically resembling benign melanocytic nevi and may be overlooked in routine histological sections. Authors are presenting a case of a 31-year-old woman who presented with bizarre pigmented skin lesions in the area of the postoperative scar on the back where, 6 years earlier, a "nevus pigmentosus epidermo-dermalis" was excised and hystologically confirmed in outer institution. The lesions were surgically removed and histopathological findings were characteristic for nevoid melanoma. Additionally, specimen of primary removed lesion was reexamined and primary nevoid melanoma was then recognized, therefore indicating that the lesions our patient presented with are nevoid melanoma recidivisms. Extensive diagnostic procedures showed no signs of melanoma dissemination. Three months later, the patient returned for consultation and presented with two new brownish-pigmented papules in the area of the new postoperative scar. The lesions were excised and new nevoid melanoma recidivism was confirmed. The patient remained under the regular follow up and, almost 9 years after the removal of primary nevoid melanoma, followed by two cutaneous recidivisms, remains disease-free. This case aims to highlight the problematic area in the analysis of pigmented skin lesions where nevoid melanoma represents one of the clinical and pathological diagnostic challenges.     

Hair morphology and systematics ofPhysalis (Solanaceae)

Hair morphology was exammed on developing seedlings and mature plants of ten species from five of seven series inPhysalis. The taxonomic importance of hair development and the distribution of hair types then was evaluated with respect to other comparative data. Two classes of hair types were observed, as found in earlier investigations ofSolanum andRhododendron. The first hair class comprises a sequence from unbranched hairs to dendroid-stelliform hairs. Hairs of this class show considerable variability among taxa in size, presence or absence of glandular tips, and presence and degree of branching, and so were useful in making taxonomic comparisons. The second hair class consists of short hairs, each tipped with a multicellular gland. This second hair class was not useful taxonomically because of its lack of variability in morphology and its often rare occurrence on a plant. The taxa studied exhibit distinctive trichome features which serve to distinguish series and, in some cases together with other data, provided new insight into previously enigmatic species relationships.     

Minimally invasive non‐thermal laser technology using laser‐induced optical breakdown for skin rejuvenation

We describe a novel, minimally invasive laser technology for skin rejuvenation by creating isolated microscopic lesions within tissue below the epidermis using laser induced optical breakdown. Using an in‐house built prototype device, tightly focused near‐infrared laser pulses are used to create optical breakdown in the dermis while leaving the epidermis intact, resulting in lesions due to cavitation and plasma explosion. This stimulates a healing response and consequently skin remodelling, resulting in skin rejuvenation effects. Analysis of ex‐vivo and in‐vivo treated human skin samples successfully demonstrated the safety and effectiveness of the microscopic lesion creation inside the dermis. Treatments led to mild side effects that can be controlled by small optimizations of the optical skin contact and treatment depth within the skin. The histological results from a limited panel test performed on five test volunteers show evidence of microscopic lesion creation and new collagen formation at the sites of the optical breakdown. This potentially introduces a safe, breakthrough treatment procedure for skin rejuvenation without damaging the epidermis with no or little social down‐time and with efficacy comparable to conventional fractional ablative techniques. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Associations between fish health and Pfiesteria spp. in Chesapeake Bay and mid-Atlantic estuaries

In response to concerns that there may be an association between harmful algal bloom (HAB) species and fish health, including the widespread use of fish health as one indicator of a possible HAB warranting further investigation, evidence for such an association was evaluated in Chesapeake Bay and other mid-Atlantic estuaries (1999–2001). A statistical approach was used, without invoking causality, to test whether there is an association between the prevalence of externally-visible lesions in fish populations above background levels and the presence of Pfiesteria spp. in co-located water and fish samples. Externally visible anomalies (e.g. ulcers, necrosis, parasites, etc.) were recorded for Atlantic menhaden (Brevoortia tyrannus) and all other fish collected. Polymerase chain reaction (PCR) techniques were used to test for the presence of Pfiesteria spp. in water samples collected at routine and rapid response sampling events. No actively toxic Pfiesteria was found during this study. Fine-scale (within a given sample site) and broad-scale (estuary-wide sampling) comparisons showed positive associations between externally-visible fish lesions in menhaden populations and the presence of Pfiesteria spp. in co-located samples. Logistic regression modeling of Pfiesteria detection probabilities as a function of prevalence of menhaden with lesions was significant (P = 0.0096). Reductions in the false positive (tests indicating Pfiesteria presence when its absent) and false negative (tests indicating Pfiesteria is absent when it is actually present) rates occurred when the minimum sample size threshold increased from 1 to 30 fish (P = 0.003–0.001). This association served as a useful field indicator of potential HAB activity that could warrant further field investigation and testing.     

Ret transgenic mouse model of spontaneous skin melanoma: focus on regulatory T cells

Ret transgenic mouse model of skin malignant melanoma is characterized by the overexpression of the human ret transgene in melanin‐containing cells. Transgenic mice spontaneously develop skin tumors with metastases in lymph nodes, lungs, liver, brain, and the bone marrow. Tumor lesions show typical melanoma morphology and express melanoma‐associated antigens. Although transgenic mice demonstrate an accumulation of melanoma antigen‐specific memory and effector T cells, their anti‐tumor effects could be blocked by highly immunosuppressive leukocytes enriched in the tumor microenvironment and in the periphery. Here, we discuss the role of one of the most potent immunosuppressive subset, regulatory T cells, in the melanoma progression in this model.     

Noninvasive diagnosis of melanoma with tensor decomposition-based feature extraction from clinical color image

We propose a method for feature extraction from clinical color images, with application in classification of skin lesions. Proposed feature extraction method is based on tensor decomposition of the clinical color image of skin lesion. Since color image is naturally represented as a three-way tensor, it is reasonable to use multi-way techniques to capture the underlying information contained in the image. Extracted features are elements of the core tensor in the corresponding multi-way decomposition, and represent spatial-spectral profile of the lesion. In contrast to common methods that exploit either texture or spectral diversity of the tumor only, the proposed approach simultaneously captures spatial and spectral characteristics. The procedure is tested on a problem of noninvasive diagnosis of melanoma from the clinical color images of skin lesions, with overall sensitivity 82.1% and specificity 86.9%. Our method compares favorably with the state of the art results reported in the literature and provides an interesting alternative to the existing approaches.     

Dermatophytosis of tiger caused by microsporum canis

Microsporum canis was isolated from the inflammatory skin lesions of a Bengal tiger in April, 1979. In clinical findings rounded area of alopecia, 3 to 8 cm in size was observed on the right haúnch and the tail. The skin lesions were covered with thin scales, but the inflammatory changes were not severe. Findings, on physical examination, were unremarkable and the animal appeared healthy except for the skin lesions. The infected hairs were invaded by the fungal elements and arthroconidia were around the hair shaft. Cuticles and cortex of the infected hairs were brittle. They were evidently digested and were easily pulled out from the hair follicles. In mycological findings numerous and typical macroconidia were observed. By cross mating of a isolate from tiger andNannizzia otae(–) strain, cleistothecia were produced. Both organic iodide and undecylenic acid ointment were effective for therapy. In this paper the dermatophytosis of tiger caused byM. canis is described.     

An accurate and effective FMM-based approach for freehand 3D ultrasound reconstruction

Freehand three-dimensional ultrasound imaging is a highly attractive research area because it is capable of volumetric visualization and analysis of tissues and organs. The reconstruction algorithm plays a key role to the construction of three-dimensional ultrasound volume data with higher image quality and faster reconstruction speed. However, a systematic approach to such problem is still missing. A new fast marching method (FMM) for three-dimensional ultrasound volume reconstruction using the tracked and hand-held probe is proposed in this paper. Our reconstruction approach consists of two stages: bin-filling stage and hole-filling stage. Each pixel in the B-scan images is traversed and its intensity value is assigned to its nearest voxel in the bin-filling stage. For the efficient and accurate reconstruction, we present a new hole-filling algorithm based on the fast marching method. Our algorithm advances the interpolation boundary along its normal direction and fills the area closest to known voxel points in first, which ensure that the structural details of image can be preserved. Experimental results on both ultrasonic abdominal phantom and in vivo urinary bladder of human subject and comparisons with some popular algorithms are used to demonstrate its improvement in both reconstruction accuracy and efficiency.