電阻抗和雷射掃描顯微術在皮膚科之應用

Abstract

Skin diseases are diverse, and it is important to make diagnoses early. The methods include physical examinations and histopathology of skin tissue. Physical examinations are based on physical signs and appearances of skin lesions; skin biopsy provides tissue-level characters and has become the standard. However, it is an invasive procedure. Based on the clinical requirements, we provide two alternative methods as screening tools for the infectious diseases. The first part of the dissertation is electrical impedance in dermatology. Similar clinical appearances prevent accurate diagnosis of two common skin diseases, clavus and verruca. In this study, electrical impedance was employed as a novel tool to generate a predictive model for estimating the probability of being verruca. A total of 57 samples, comprised of 29 clavus and 28 varruca lesions, were used. To obtain impedance variables, an LCR-meter system was applied to measure capacitance (C), resistance (Re), impedance (Z) and phase angle (θ). The thickness (d) of the lesions was an additional variable. These variables of clavus and verruca were then compared by fitting the univariate logistic regression models with the generalized estimating equations (GEE) method. In model generation, log ZSD and θSD were formulated as predictors by fitting multiple logistic regression models with the same GEE method. Moreover, the model is validated by the good-of fit (GOF) assessments and the generalized additive models (GAM). The result suggests that the generated model could provide a rapid, relatively low-cost, safe and non-invasive screening tool in clinic use. After that, we designed a portable and low-cost impedance measurement device that can be applied on human nails which have very high impedance in nature. The circuit is designed based on the voltage divider theory. A sine wave with amplitude of 1V and frequency ranging from 500 to 7k Hz was used for excitation. By using an AD converter card installed in a laptop computer, the results can be analyzed quantitatively. For portability considerations, the bias current of our circuit is less than 1mA, so it is suitable for battery power. By changing the compatible resistance to match different range of impedance value, the designed circuit has more versatility on measuring impedance of samples. The results show that our circuit has more capability to measure the impedance of nails than an LCR-meter. The second part concerns the imaging study of skin fungal infection with laser-scanning microscopy. Fungal hyphae or spores can be observed in the skin when it becomes infected by fungi. Traditional transmission microscope can only provide the 2-D image of the specimen, which makes the appreciation of spatial arrangement of fungal elements difficult. Furthermore, in most circumstances, keratinolytic agents should be used on the specimen to make the examination of fungi easier. However, this specimen treatment makes the observation of the natural conformation of fungi in human tissue impossible. We used a confocal-and-multiphoton microscopy to check the specimen of tinea capitis, tinea corposis and onychomycosis, and constructed the fungal stereo images. We found that laser-scanning microscopy is an ideal tool in constructing the real fungal invasive pattern in human tissue.