Gene Expressions, Hippocampal Volume Loss, and MMSE Scores in Computation of Progression and Pharmacologic Therapy Effects for Alzheimer's Disease.

We build personalized relevance parameterization method (prep-ad) based on artificial intelligence (ai) techniques to compute Alzheimer's disease (ad) progression for patients at the mild cognitive impairment (mci) stage. Expressions of ad related genes, mini mental state examination (mmse) scores, and hippocampal volume measurements of mci patients are obtained from the Alzheimer's Disease Neuroimaging Initiative (adni) database. In evaluation of cognitive changes under pharmacological therapies, patients are grouped based on available clinical measurements and the type of therapy administered, namely donepezil monotherapy and polytherapy of donepezil with memantine. Average leave one out cross validation (loocv) error rates are calculated for prep-ad results as less than 8 percent when mmse scores are used to compute disease progression for a 60 month period, and 3 percent with hippocampal volume measurements for 12 months. Statistical significance is calculated as p = 0.003 for using ad related genes in disease progression and as for the results computed by prep-ad. These relatively small average loocv errors and p-values suggest that our prep-ad methods employing gene expressions, mmse scores and hippocampal volume loss measurements can be useful in supporting pharmacologic therapy decisions during early stages of ad.

Spatial Heterogeneity Analysis in Evaluation of Cell Viability and Apoptosis for Colorectal Cancer Cells.

In evaluation of cell viability and apoptosis, spatial heterogeneity is quantified for cancerous cells cultured in 3-D in vitro cell-based assays under the impact of anti-cancer agents. In 48-h experiments using human colorectal cancer cell lines of HCT-116, SW-620, and SW-480, incubated cells are divided into control and drug administered groups, to be grown in matrigel and FOLFOX solution, respectively. Our 3-D cell tracking and data acquisition system guiding an inverted microscope with a digital camera is utilized to capture bright field and fluorescent images of colorectal cancer cells at multiple time points. Identifying the locations of live and dead cells in captured images, spatial point process and Voronoi tessellation methods are applied to extract morphological features of in vitro cell-based assays. For the former method, spatial heterogeneity is quantified with the second-order functions of Poisson point process, whereas the deviation in the area of Voronoi polygons is computed for the latter. With both techniques, the results indicate that the spatial heterogeneity of live cell locations increases as the viability of in in vitro cell cultures decreases. On the other hand, a decrease is observed for the heterogeneity of dead cell locations with the decrease in cell viability. This relationship between morphological features of in vitro cell-based assays and cell viability can be used for drug efficacy measurements and utilized as a biomarker for 3-D in vitro microenvironment assays.

Mathematical models of tumor growth using Voronoi tessellations in pathology slides of kidney cancer.

The impact of patient-specific spatial distribution features of cell nuclei on tumor growth characteristics was analyzed. Tumor tissues from kidney cancer patients were allowed to grow in mice to apply H&E staining and to measure tumor volume during preclinical phase of our study. Imaging the H&E stained slides under a digital light microscope, the morphological characteristics of nuclei positions were determined. Using artificial intelligence based techniques, Voronoi features were derived from diagrams, where cell nuclei were considered as distinct nodes. By identifying the effect of each Voronoi feature, tumor growth was expressed mathematically. Consistency between the computed growth curves and preclinical measurements indicates that the information obtained from the H&E slides can be used as biomarkers to build personalized mathematical models for tumor growth.