Imaging phenotypes predict overall survival in glioma more accurate than basic demographic and cell mutation profiles.

BACKGROUND: Magnetic resonance imaging (MRI), digital pathology imaging (PATH), demographics, and IDH mutation status predict overall survival (OS) in glioma. Identifying and characterizing predictive features in the different modalities may improve OS prediction accuracy. PURPOSE: To evaluate the OS prediction accuracy of combinations of prognostic markers in glioma patients. MATERIALS AND METHODS: Multi-contrast MRI, comprising T1-weighted, T1-weighted post-contrast, T2-weighted, T2 fluid-attenuated-inversion-recovery, and pathology images from glioma patients (n = 160) were retrospectively collected (1983-2008) from TCGA alongside age and sex. Phenotypic profiling of tumors was performed by quantifying the radiographic and histopathologic descriptors extracted from the delineated region-of-interest in MRI and PATH images. A Cox proportional hazard model was trained with the MRI and PATH features, IDH mutation status, and basic demographic variables (age and sex) to predict OS. The performance was evaluated in a split-train-test configuration using the concordance-index, computed between the predicted risk score and observed OS. RESULTS: The average age of patients was 51.2years (women: n = 77, age-range=18-84years; men: n = 83, age-range=21-80years). The median OS of the participants was 494.5 (range,3-4752), 481 (range,7-4752), and 524.5 days (range,3-2869), respectively, in complete dataset, training, and test datasets. The addition of MRI or PATH features improved prediction of OS when compared to models based on age, sex, and mutation status alone or their combination (p < 0.001). The full multi-omics model integrated MRI, PATH, clinical, and genetic profiles and predicted the OS best (c-index= 0.87). CONCLUSION: The combination of imaging, genetic, and clinical profiles leads to a more accurate prognosis than the clinical and/or mutation status.

Learning histopathological patterns.

AIMS: The aim was to demonstrate a method for automated image analysis of immunohistochemically stained tissue samples for extracting features that correlate with patient disease. We address the problem of quantifying tumor tissue and segmenting and counting cell nuclei. MATERIALS AND METHODS: Our method utilizes a flexible segmentation method based on sparse coding trained from representative image samples. Nuclei counting is based on a nucleus model that takes size, shape, and nucleus probability into account. Nuclei clustering and overlays are resolved using a gray-weighted distance transform. We obtain a probability measure for pixels belonging to a nucleus from our segmentation procedure. Experiments are carried out on two sets of immunohistochemically stained images - one set based on the estrogen receptor (ER) and the other on antigen KI-67. For the nuclei separation we have selected 207 ER image samples from 58 tissue micro array-cores corresponding to 58 patients and 136 KI-67 image samples also from 58 cores. The images are hand-annotated by marking the center position of each nucleus. For the ER data we have a total of 1006 nuclei and for the KI-67 we have 796 nuclei. Segmentation performance was evaluated in terms of missing nuclei, falsely detected nuclei, and multiple detections. The proposed method is compared to state-of-the-art Bayesian classification. STATISTICAL ANALYSIS USED: The performance of the proposed method and a state-of-the-art algorithm including variations thereof is compared using the Wilcoxon rank sum test. RESULTS: For both the ER experiment and the KI-67 experiment the proposed method exhibits lower error rates than the state-of-the-art method. Total error rates were 4.8 % and 7.7 % in the two experiments, corresponding to an average of 0.23 and 0.45 errors per image, respectively. The Wilcoxon rank sum tests show statistically significant improvements over the state-of-the-art method. CONCLUSIONS: We have demonstrated a method and obtained good performance compared to state-of-the-art nuclei separation. The segmentation procedure is simple, highly flexible, and we demonstrate how it, in addition to the nuclei separation, can perform precise segmentation of cancerous tissue. The complexity of the segmentation procedure is linear in the image size and the nuclei separation is linear in the number of nuclei. Additionally the method can be parallelized to obtain high-speed computations.