RESUMO
AIM: To examine how the location where reading takes place and the availability of prior images can affect performance in breast test-set reading. MATERIALS AND METHODS: Under optimized viewing conditions, 10 expert screen readers each interpreted a reader-specific set of images containing 200 mammographic cases. Readers, randomly divided into two groups read images under one of two pairs of conditions: clinical read with prior images and laboratory read with prior images; laboratory read with prior images and laboratory read without prior images. Region-of-interest (ROI) figure-of-merit (FOM) was analysed using JAFROC software. Breast side-specific sensitivity and specificity were tested using Wilcoxon matched-pairs signed rank tests. Agreement between pairs of readings was measured using Kendall's coefficient of concordance. RESULTS: Group performances between test-set readings demonstrated similar ROI FOMs, sensitivity and specificity median values, and acceptable levels of agreement between pairs of readings were shown (W = 0.75-0.79, p < 0.001) for both pairs of reading conditions. On an individual reader level, two readers demonstrated significant decreases (p < 0.05) in ROI FOMs when prior images were unavailable. Reading location had an inconsistent impact on individual performance. CONCLUSION: Reading location and availability of prior images did not significantly alter group performance.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Competência Clínica , Mamografia , Garantia da Qualidade dos Cuidados de Saúde , Intensificação de Imagem Radiográfica , Competência Clínica/normas , Tomada de Decisões , Feminino , Humanos , Variações Dependentes do Observador , Garantia da Qualidade dos Cuidados de Saúde/normas , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: While the cause of Parkinson's disease (PD) remains unknown, evidence suggests certain environmental factors, such as well water drinking, herbicides, pesticides exposure and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause Parkinsonism. To investigate the possible impact of environmental risk factors for idiopathic PD, a case-control study was performed in the Eastern India. METHODS: During the period from January 1st, 2006 and December 10th, 2009, 175 PD patients (140 men, 35 women) and 350 non-Parkinson age-sex matched controls were included in the study. Subjects were given a structured neurological examination and completed an administered questionnaire which elicited detailed information on demographic data, pesticides, herbicides family history, occupation, dietary and smoking habits. RESULTS: The multivariate analysis revealed that family history of PD, pesticide exposure, exposure to toxins other than pesticides and herbicides, rural living and previous history of depression were associated with increased risk of PD, whereas, smoking appeared to be a protective factor. Well water drinking for at least five years, though a significant risk factor on univariate analysis (OR = 4.5, 95% CI = 2.1-9.9), could not be proved significant in multivariate analysis. Head trauma, vegetarian dietary habit, occupation involving physical exertion and exposure to domestic pets were not as significant risk factors. CONCLUSION: Results of our study support the hypothesis of multifactorial etiology of PD with environmental factors acting on a genetically susceptible host.
Assuntos
Exposição Ambiental , Saúde da Família , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença de Parkinson/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários , Adulto JovemRESUMO
Oxidative stress is implicated as a major factor for nigral neuronal cell death. Metabolic failure in antioxidant mechanisms could hypothetically facilitate the chemical processes that lead to lipid peroxidation. To elucidate whether elevated lipid peroxidation rates might increase risk of developing Parkinson's disease (PD), the Authors determined plasma levels of malondialdehyde (MDA) in 80 PD patients and 80 controls. There was a significant difference between the plasma MDA levels of PD patients and controls (7.48 +/- 1.55 vs 5.1 +/- 1.26 nmol/ml). Plasma MDA levels were inversely related to the age of the PD patients (r = -0.46; p < 0.01) and age of onset but in the control group, no such correlation was observed between the plasma MDA and age. However, there was no significant correlation between plasma MDA levels and the duration of disease, Hoehn and Yahr stages and the Unified Parkinson's Disease Rating Scale (UPDRS). Thus, the results suggest that high plasma lipid peroxidation rates might contribute as a risk factor for PD in West Bengal.
Assuntos
Peroxidação de Lipídeos , Malondialdeído/sangue , Estresse Oxidativo , Doença de Parkinson/metabolismo , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Doença de Parkinson/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Substância Negra/fisiopatologiaRESUMO
In 1996 Swensson published an observer model that predicted receiver operating characteristic (ROC), localization ROC (LROC), free-response ROC (FROC) and alternative FROC (AFROC) curves, thereby achieving "unification" of different observer performance paradigms. More recently a model termed initial detection and candidate analysis (IDCA) has been proposed for fitting computer aided detection (CAD) generated FROC data, and recently a search model for human observer FROC data has been proposed. The purpose of this study was to derive IDCA and the search model based expressions for operating characteristics, and to compare the predictions to the Swensson model. For three out of four mammography CAD data sets all models yielded good fits in the high-confidence region, i.e., near the lower end of the plots. The search model and IDCA tended to better fit the data in the low-confidence region, i.e., near the upper end of the plots, particularly for FROC curves for which the Swensson model predictions departed markedly from the data. For one data set none of the models yielded satisfactory fits. A unique characteristic of search model and IDCA predicted operating characteristics is that the operating point is not allowed to move continuously to the lowest confidence limit of the corresponding Swensson model curves. This prediction is actually observed in the CAD raw data and it is the primary reason for the poor FROC fits of the Swensson model in the low-confidence region.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Modelos Biológicos , Curva ROC , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Simulação por Computador , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Search is a basic activity that is performed routinely in many different tasks. In the context of medical imaging it involves locating lesions in images under conditions of uncertainty regarding the number and locations of lesions that may be present. A search model is presented that applies to situations, as in the free-response paradigm, where on each image the number of normal regions that could be mistaken for lesions is unknown, and the number of observer generated localizations of suspicious regions (marks) is unpredictable. The search model is based on a two-stage model that has been proposed in the literature, according to which, at the first stage (the preattentive stage) the observer uses mainly peripheral vision to identify likely lesion candidates, and at the second stage the observer decides (i.e., cognitively evaluates) whether or not to report the candidates. The search model regards the unpredictable numbers of lesion and non-lesion localizations as random variables and models them via appropriate statistical distributions. The model has three parameters quantifying the lesion signal-to-noise ratio, the observer's expertise at rejecting non-lesion locations, and the observer's expertise at finding lesions. A figure-of-merit quantifying the observer's search performance is described. The search model bears a close resemblance to the initial detection and candidate analysis (IDCA) model that has been recently proposed for analysing computer aided detection (CAD) algorithms. The ability to analytically model and quantify the search process would enable more powerful assessment and optimization of performance in these activities, which could be highly significant.
Assuntos
Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiologia/métodos , Radiologia/normas , Algoritmos , Humanos , Distribuição Normal , Variações Dependentes do Observador , Distribuição de Poisson , Curva ROC , Percepção VisualRESUMO
In imaging tasks where the observer is uncertain whether lesions are present, and where they could be present, the image is searched for lesions. In the free-response paradigm, which closely reflects this task, the observer provides data in the form of a variable number of mark-rating pairs per image. In a companion paper a statistical model of visual search has been proposed that has parameters characterizing the perceived lesion signal-to-noise ratio, the ability of the observer to avoid marking non-lesion locations, and the ability of the observer to find lesions. The aim of this work is to relate the search model parameters to receiver operating characteristic (ROC) curves that would result if the observer reported the rating of the most suspicious finding on an image as the overall rating. Also presented are the probability density functions (pdfs) of the underlying latent decision variables corresponding to the highest rating for normal and abnormal images. The search-model-predicted ROC curves are 'proper' in the sense of never crossing the chance diagonal and the slope is monotonically changing. They also have the interesting property of not allowing the observer to move the operating point continuously from the origin to (1, 1). For certain choices of parameters the operating points are predicted to be clustered near the initial steep region of the curve, as has been observed by other investigators. The pdfs are non-Gaussians, markedly so for the abnormal images and for certain choices of parameter values, and provide an explanation for the well-known observation that experimental ROC data generally imply a wider pdf for abnormal images than for normal images. Some features of search-model-predicted ROC curves and pdfs resemble those predicted by the contaminated binormal model, but there are significant differences. The search model appears to provide physical explanations for several aspects of experimental ROC curves.
Assuntos
Curva ROC , Radiologia/métodos , Algoritmos , Área Sob a Curva , Interpretação Estatística de Dados , Humanos , Funções Verossimilhança , Modelos Estatísticos , Distribuição Normal , Variações Dependentes do Observador , Radiologia/normas , Percepção VisualRESUMO
PURPOSE: To evaluate nodule detection in an anthropomorphic chest phantom in computed tomography (CT) images reconstructed with adaptive iterative dose reduction 3D (AIDR(3D)) and filtered back projection (FBP) over a range of tube current-time product (mAs). METHODS: Two phantoms were used in this study: (i) an anthropomorphic chest phantom was loaded with spherical simulated nodules of 5, 8, 10, and 12 mm in diameter and +100, -630, and -800 Hounsfield units electron density; this would generate CT images for the observer study; (ii) a whole-body dosimetry verification phantom was used to ultimately estimate effective dose and risk according to the model of the BEIR VII committee. Both phantoms were scanned over a mAs range (10, 20, 30, and 40), while all other acquisition parameters remained constant. Images were reconstructed with both AIDR(3D) and FBP. For the observer study, 34 normal cases (no nodules) and 34 abnormal cases (containing 1-3 nodules, mean 1.35 ± 0.54) were chosen. Eleven observers evaluated images from all mAs and reconstruction methods under the free-response paradigm. A crossed-modality jackknife alternative free-response operating characteristic (JAFROC) analysis method was developed for data analysis, averaging data over the two factors influencing nodule detection in this study: mAs and image reconstruction (AIDR(3D) or FBP). A Bonferroni correction was applied and the threshold for declaring significance was set at 0.025 to maintain the overall probability of Type I error at α = 0.05. Contrast-to-noise (CNR) was also measured for all nodules and evaluated by a linear least squares analysis. RESULTS: For random-reader fixed-case crossed-modality JAFROC analysis, there was no significant difference in nodule detection between AIDR(3D) and FBP when data were averaged over mAs [F(1, 10) = 0.08, p = 0.789]. However, when data were averaged over reconstruction methods, a significant difference was seen between multiple pairs of mAs settings [F(3, 30) = 15.96, p < 0.001]. Measurements of effective dose and effective risk showed the expected linear dependence on mAs. Nodule CNR was statistically higher for simulated nodules on images reconstructed with AIDR(3D) (p < 0.001). CONCLUSIONS: No significant difference in nodule detection performance was demonstrated between images reconstructed with FBP and AIDR(3D). mAs was found to influence nodule detection, though further work is required for dose optimization.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Observação , Fatores de TempoRESUMO
Numerous eyeglass lens materials have been recommended for protection of radiologists' eyes from the cataractogenic effect of radiation during fluoroscopic procedures. For the most part, these lenses coincidentally attenuate x-ray beams because they contain elements of high atomic number that are added to increase refractive index. With a bean hardened to simulate scatter, direct transmission ratios were measured for 32 commercially available lens materials. Scatter to the eye, both through and around the glass lenses and secondary scatter to the eye from the radiologist's head, was determined with lenses mounted on a head phantom and a 1-cm3 ion chamber in the position of the eye. Transmission ratios for the various lenses ranged from 3% to 98% for an 80 kVp x-ray beam (HVL = 4.5 mm Al). Measurements with the head phantom in place show that secondarily scattered radiation from the fluoroscopist's head contributes significantly to ocular exposure. Optimal radiation protection of the eyes during fluoroscopy depends not only on eyeglasses with leaded glass, but also on shielding of sufficient size and shape to reduce exposure to the surrounding head.
Assuntos
Catarata/prevenção & controle , Dispositivos de Proteção dos Olhos/normas , Fluoroscopia , Doenças Profissionais/prevenção & controle , Equipamentos de Proteção/normas , Proteção Radiológica/instrumentação , Humanos , Modelos Estruturais , Doses de Radiação , Espalhamento de RadiaçãoRESUMO
An ROC study is described which compares the performance of three types of images--conventional screen-film, single-energy digital and dual energy bone cancelled (soft tissue) digital--in detecting subtle interstitial pulmonary disease. Marginally detectable nodular and reticulonodular patterns (12 different patterns of each) were superimposed over the lungs of a frozen human chest phantom to simulate the clinical situation. The digital images were formatted on film at full size (ie, 35 cm X 43 cm). A total of 156 images (52 of each type, of which 28 were normal and 24 had simulated pathology) were used in the study and read by five experienced chest radiologists. Using a paired t-test, the areas under the individual ROC curves were compared for three combinations of images--single-energy digital and conventional, soft tissue digital and conventional, and soft tissue and single-energy digital. No statistically significant difference was observed between the conventional and single-energy digital images. The readers performed better with both conventional and single-energy digital images than with the soft tissue digital images at statistically significant levels (P = 0.05 for conventional vs. soft tissue digital and P = 0.02 for single-energy digital vs. soft tissue digital). The results suggest that there is no advantage in employing dual-energy soft tissue images to assist in diagnosing interstitial disease in the clinical setting. They also suggest that spatial resolution requirements are less demanding in digital chest systems that obtain scatter-free images than in digital systems utilizing conventional scatter control techniques.
Assuntos
Fibrose Pulmonar/diagnóstico por imagem , Radiografia Torácica , Estudos de Avaliação como Assunto , Humanos , Modelos Estruturais , Intensificação de Imagem RadiográficaRESUMO
Receiver operating characteristic (ROC) methodology is widely used in evaluating medical imaging modalities. While appropriate in some cases, it has several drawbacks when the detection task, e.g., nodule detection, involves localizing the abnormality. Free-response receiver operating characteristic (FROC) methodology offers a more natural framework to describe observer performance in such studies and has other advantages. Due to the lack of a statistical analysis procedure comparable to the maximum likelihood procedure (ROCFIT program) available for ROC studies, the FROC method has not gained widespread acceptance. This work presents and solves a two parameter model for the statistical analysis of FROC data. The model assumes that the probability density of the signal stimuli is normally distributed, as is the probability density for producing one or more false positives per image. A program (FROCFIT) is described for estimating the parameters and their uncertainties from experimental data. An index of performance is proposed to quantify observer performance in FROC experiments. Application of this methodology to several FROC data sets produced good to excellent fits.
Assuntos
Curva ROC , Estatística como Assunto , Humanos , SoftwareRESUMO
The purpose of this investigation was to apply the recently developed CAMPI (computer analysis of mammography phantom images) method to a Fischer Mammotest Stereotactic Digital Biopsy machine. Another aim was to further elucidate the nature of the empirically introduced CAMPI measures. Images of an American College of Radiology (ACR) accreditation phantom centered on the largest two speck groups were obtained on this machine under a variety of x-ray conditions. An additional measure, alternative SNR (ASNR) is introduced which is complementary to the SNR measure. Analyses of the Mammotest images revealed that the mAs and kVp dependencies of the CAMPI measures could be understood from basic imaging physics principles. It is shown that: (1) the measures reflect the expected linearity of the digital detector and Poisson photon statistics; (2) under automatic exposure control (AEC) conditions the signal (SIG) measure is proportional to subject contrast; and (3) under AEC conditions the noise (NOI) measure is proportional to the square root of the average absorbed photon energy. Correspondence with basic imaging physics principles shows that the measures are significantly free of artifacts. Precision of the CAMPI measures exceeds that of human observers by orders of magnitude. CAMPI measures are expected to be more relevant to clinical mammography than Fourier metrics as the measurements are done on objects of arbitrary shape and size that were designed by the manufacturer to resemble various detection tasks in mammography. It is concluded that CAMPI can perform objective and highly precise evaluations of phantom image quality in mammography. It could be used as a sophisticated quality control tool, as a replacement for the current ACR/MQSA phantom evaluation program, and to evaluate the rapidly evolving digital mammography technology.
Assuntos
Doenças Mamárias/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Mamografia/métodos , Mamografia/estatística & dados numéricos , Intensificação de Imagem Radiográfica/métodos , Fenômenos Biofísicos , Biofísica , Neoplasias da Mama/diagnóstico por imagem , Estudos de Avaliação como Assunto , Feminino , Humanos , Imagens de Fantasmas , Tecnologia RadiológicaRESUMO
A method is described for determining and correcting the spatial distortion affecting images acquired with image-intensified video systems. The distortion is separated into two physically distinct components, a predominant one originating from the projection of the x-ray image onto the curved input phosphor, and a smaller component corresponding to the mapping from the input phosphor to the output phosphor and the digital image matrix. The former is determined geometrically and the latter is modeled with four empirical parameters. A method for determining the two components from calibration images of a grid phantom is presented. The model of the image intensifier distortion was found to be in good agreement with the measured distortion in the images. The correction is applicable to arbitrary angulations of the x-ray beam with respect to the image intensifier tube, and consequently is directly applicable to digital tomosynthesis. The correction allows one to obtain accurate positional information with fluorography and may also be useful in radiation therapy treatment planning and quantitative digital subtraction angiography.
Assuntos
Intensificação de Imagem Radiográfica/métodosRESUMO
The methodology employed to calculate radiographic signal-to-noise ratio (SNR) for the commonly used disk-shaped test object is reviewed. Although the "matched" aperture yields the maximum SNR, its shape is difficult to achieve experimentally. On the other hand, a circular aperture having the same size as the object is much simpler to realize. We have performed a numerical analysis of the SNRs obtained with matched and circular apertures for two screen/film systems (a mammographic and a general purpose combination) for a range of test-object sizes. We find that for object sizes greater than 0.5 mm in diameter, there is a less than 4% difference between the SNRs obtained with the two apertures. The shapes of some of the matched apertures are also presented. We conclude that the SNR determined with the circular aperture is a simpler and more useful determinant of system performance for the screen/film combinations studied.
Assuntos
Intensificação de Imagem Radiográfica , Ecrans Intensificadores para Raios X , Teoria da Informação , Intensificação de Imagem Radiográfica/instrumentação , Pesos e MedidasRESUMO
Two methods of dual-photon absorptiometry (DPA) utilizing an x-ray tube instead of a radionuclide source have recently been introduced. In one method kVp switching is employed and two transmitted intensities at each pixel are determined. In the other method, K-edge filtration combined with a single kVp spectrum is used, but photons in two energy windows are counted. We present a theoretical analysis of the two methods, focusing on a figure of merit which is essentially the exposure efficiency (the precision for a given entrance exposure) and tube loading. We also compare their exposure efficiencies to theoretical limits that no DPA system can exceed. Our study indicates that the K-edge-filtered method is more exposure efficient by about a factor of 2. The switched-kVp method requires less heat units per scan by about a factor of 3. A hybrid K-edge switched-kVp method is suggested which achieves the same exposure efficiency as the K-edge-filtered method at lesser tube loading. Our theoretical model is based on published x-ray spectra and attenuation coefficients and is in good agreement with other simulation work. It is of interest that a point source of Gd-153 would be even more exposure efficient, achieving about 90% of the theoretical limit. However, in practice, the Gd source is of finite size and limited strength, and consequently the radionuclide method cannot achieve as good a precision as either x-ray method in similar scan times.
Assuntos
Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Modelos Teóricos , Humanos , Matemática , Radiografia , Cintilografia , Raios XRESUMO
The precision of quantitative and subjective evaluations of phantom image quality has been studied. Twenty-seven images of the American College of Radiology (ACR) mammography accreditation phantom were acquired under different x-ray techniques and digitized. Several quantitative image quality measures were obtained from each image by analyzing microcalcification and nodule target objects in the phantom. All images were also scored subjectively by 8 observers, each of whom provided a count of the number of objects seen in each target class (fibrils, microcalcifications, and nodules). An analysis was performed to predict the subjective measurements from the quantitative measurements and to estimate their variabilities. It was found that the subjective measures could be well predicted by the quantitative measures and that the variance of the quantitative measures was significantly smaller than that of the subjective measure, by almost a factor of 10. The implication for the ACR accreditation program for mammography is that a substantial improvement is possible in the image quality evaluation process by performing computerized analysis of the phantom images in addition to subjective analysis.
Assuntos
Mamografia/normas , Imagens de Fantasmas , Acreditação , Feminino , Humanos , Controle de Qualidade , Radiologia , Análise de Regressão , Reprodutibilidade dos Testes , Sociedades Médicas , Estados UnidosRESUMO
A cassette for simultaneously acquiring dual-energy mammographic images is proposed and studied utilizing a theoretical noise analysis model. The cassette consists of a sandwich of two storage phosphor plates separated by a copper filter. The front, low atomic number, plate was assumed to be comprised of SrFBr and the rear, high atomic number, plate of commercially available BaFBr (98 mg/cm2 coating weight). Assuming a constant x-ray tube voltage of 50 kVp and a typical breast thickness, the theoretical model yielded a front SrFBr phosphor coating weight of approximately 21 mg/cm2. The study indicates that a relatively large separation in the average of x-ray photon energies absorbed in the two plates can be obtained. It also indicates that both a high-quality conventional (single energy) digital image and a tissue canceled digital image (i.e., a calcium image) can be obtained at dose levels comparable to those currently employed. The latter image could potentially improve the early detection of cancerous microcalcifications and also lends itself to computer aided diagnosis.
Assuntos
Mamografia/instrumentação , Intensificação de Imagem Radiográfica/instrumentação , Feminino , HumanosRESUMO
A semiempirical model for generating tungsten target x-ray spectra is presented. This model extends earlier work in two significant areas. First, both bremsstrahlung and characteristic x-ray production are assumed to occur at varying depths within the target. Second, optimal parameters for the model were determined from experimental spectra utilizing nonlinear least-squares techniques. As a result, good agreement is obtained between calculated and measured x-ray tube spectra and output for different target angles and a wide range of x-ray tube potentials. Such is not the case with previously published models.
Assuntos
Modelos Teóricos , Radiografia , Matemática , Rênio , Tungstênio , Raios XRESUMO
Needle-shaped thermoseeds have been manufactured from an alloy consisting of 70.4% nickel and 29.6% copper. The magnetic properties of the alloy were measured at various temperatures and from this the heating power produced by a thermoseed exposed to an electromagnetic induction field was computed as a function of the seed temperature. Calorimetric measurements were also performed. From these data, temperature distributions in simple tumor models assumed to be heated by an array of nickel-copper implants were computed. It was found that the nickel-copper implants produce substantially better temperature homogeneity than readily available constant power seeds, especially in tumors with unpredictable rates of blood perfusion or when the implant arrangement is not perfectly regular. Since such conditions are likely to be present in actual patients, the nickel-copper implants should be very useful in clinical hyperthermia.
Assuntos
Temperatura Alta/uso terapêutico , Neoplasias/terapia , Ligas , Calorimetria , Cobre , Humanos , Níquel , TemperaturaRESUMO
The abnormal urinary indole profile induced by hydroquinone has been found to be reversed by psoralene, a pigmentogenic drug in vitiligo.
Assuntos
Hidroquinonas/farmacologia , Indóis/urina , Vitiligo/urina , Animais , Bufonidae , Ficusina/farmacologia , Hidroquinonas/antagonistas & inibidores , Masculino , Fatores de Tempo , Vitiligo/induzido quimicamenteRESUMO
Tryptophan pyrrolase, a microsomal enzyme responsible for the break-down of tryptophan, has been detected in Bufo melanostictus. The enzyme has been found to be deactivated under influence of antivitiligo drug psoralene and activated by hydroquinone, an inhibitor of tyrosinase. Tryptophan pyrrolase has been found to have an antagonistic relationship with tyrosinase in Bufo melanostictus. The implication of the results has been discussed in relation to melanogenesis in vitiligo.