Electrical impedance spectroscopy is a technique that has been investigated as a potential method for the diagnosis of epithelial carcinomas. Finite element modelling can provide an insight into the patterns of current flow in normal and pathological epithelium and hence aid in the process of probe design optimization. In order to develop a finite element model of the structure of normal and precancerous cervical squamous epithelium, it was first necessary to obtain the mean values and ranges of a number of morphological tissue parameters. The most important parameters in discriminating normal from neoplastic tissue were identified as being cell size and shape distribution, nuclear-to-cytoplasmic volume ratio and volume of extracellular space. A survey of the literature revealed an absence of reliable quantitative data for these parameters. We therefore present the results of our own basic image analysis on normal and pathological tissue sections, which we hope will be of use to other workers wishing to model cervical squamous epithelium, or other similar tissue structures.
Electrical impedance spectroscopy has been developed as a potential method for the diagnosis of carcinoma in epithelial tissues. An understanding of the influence of structural changes in the tissue on the properties measured using this technique is essential for interpreting measured data and optimization of probe design. In contrast to other tissue types, carcinoma in situ of the bladder gives rise to an increase in electrical impedance over the kHz-MHz frequency range in comparison to normal tissue. Finite element models of the urothelium and the underlying superficial lamina propria have been constructed and solved in order to ascertain the influence of structural changes associated with malignancy, oedema and inflammation on the measured electrical properties of the tissue. Sensitivity analysis of results from a composite tissue model suggests that the increase in lymphocyte density in the lamina propria associated with an inflammatory response to the infiltration of urine into the tissue may explain these unusual electrical properties.
In this study we sought to develop a computational modeling paradigm in order to describe the influence of calcium on normal and transformed keratinocyte proliferation and differentiation. Keratinocytes and HaCat cells were grown in monolayer cultures with low and physiologic calcium concentrations, and levels of proliferation and involucrin expression were assessed. Both types of cells grew as monolayers under a low-calcium environment, and stratified in media with physiologic levels of calcium. However, keratinocytes were more proliferative in low rather than physiologic levels of calcium, whereas the opposite was true for HaCat cells. Normal keratinocytes differentiated as calcium levels increased. HaCat cells showed little differentiation at any calcium concentration. However, while the computer simulation could be modified to describe the effect of calcium on the growth of normal keratinocytes, our findings did not support the hypothesis that simply "turning off" the ability of HaCat cells to differentiate would account for the growth characteristics of these transformed cells. This demonstrates the application of computational modeling to hypothesis testing in biological systems.