Saima Rathore

Ahmad Chaddad, Paul Daniel Mingli Zhang, Saima Rathore et al.

Imaging biomarkers offer a non-invasive way to predict the response of immunotherapy prior to treatment. In this work, we propose a novel type of deep radiomic features (DRFs) computed from a convolutional neural network (CNN), which capture tumor characteristics related to immune cell markers and overall survival. Our study uses four MRI sequences (T1-weighted, T1-weighted post-contrast, T2-weighted and FLAIR) with corresponding immune cell markers of 151 patients with brain tumor. The proposed method extracts a total of 180 DRFs by aggregating the activation maps of a pre-trained 3D-CNN within labeled tumor regions of MRI scans. These features offer a compact, yet powerful representation of regional texture encoding tissue heterogeneity. A comprehensive set of experiments is performed to assess the relationship between the proposed DRFs and immune cell markers, and measure their association with overall survival. Results show a high correlation between DRFs and various markers, as well as significant differences between patients grouped based on these markers. Moreover, combining DRFs, clinical features and immune cell markers as input to a random forest classifier helps discriminate between short and long survival outcomes, with AUC of 72\% and p=2.36$\times$10$^{-5}$. These results demonstrate the usefulness of proposed DRFs as non-invasive biomarker for predicting treatment response in patients with brain tumors.

Saima Rathore, Jatin Chaudhary, Boning Tong et al.

Cerebral microbleeds, markers of brain damage from vascular and amyloid pathologies, are linked to cognitive decline in aging, but their role in Alzheimer's disease (AD) onset and progression remains unclear. This study aimed to explore whether the presence and location of lobar microbleeds are associated with amyloid-$β$ (A$β$)-PET, tau tangle formation (tau-PET), and longitudinal cognitive decline. We analyzed 1,573 ADNI participants with MR imaging data and information on the number and location of microbleeds. Associations between lobar microbleeds and pathology, cerebrospinal fluid (CSF), genetics, and cognition were examined, focusing on regional microbleeds and domain-specific cognitive decline using ordinary least-squares regression while adjusting for covariates. Cognitive decline was assessed with ADAS-Cog11 and its domain-specific sub-scores. Participants underwent neuropsychological testing at least twice, with a minimum two-year interval between assessments. Among the 1,573 participants (692 women, mean age 71.23 years), 373 participants had microbleeds. The presence of microbleeds was linked to cognitive decline, particularly in the semantic, language, and praxis domains for those with temporal lobe microbleeds. Microbleeds in the overall cortex were associated with language decline. Pathologically, temporal lobe microbleeds were associated with increased tau in the overall cortex, while cortical microbleeds were linked to elevated A$β$ in the temporal, parietal, and frontal regions. In this mixed population, microbleeds were connected to longitudinal cognitive decline, especially in semantic and language domains, and were associated with higher baseline A$β$ and tau pathology. These findings suggest that lobar microbleeds should be included in AD diagnostic and prognostic evaluations.

Ahmad Chaddad, Saima Rathore, Mingli Zhang et al.

This paper proposes to use deep radiomic features (DRFs) from a convolutional neural network (CNN) to model fine-grained texture signatures in the radiomic analysis of recurrent glioblastoma (rGBM). We use DRFs to predict survival of rGBM patients with preoperative T1-weighted post-contrast MR images (n=100). DRFs are extracted from regions of interest labelled by a radiation oncologist and used to compare between short-term and long-term survival patient groups. Random forest (RF) classification is employed to predict survival outcome (i.e., short or long survival), as well as to identify highly group-informative descriptors. Classification using DRFs results in an area under the ROC curve (AUC) of 89.15% (p<0.01) in predicting rGBM patient survival, compared to 78.07% (p<0.01) when using standard radiomic features (SRF). These results indicate the potential of DRFs as a prognostic marker for patients with rGBM.

Saima Rathore, Muhammad Aksam Iftikhar, Zissimos Mourelatos

Cancer histology reveals disease progression and associated molecular processes, and contains rich phenotypic information that is predictive of outcome. In this paper, we developed a computational approach based on deep learning to predict the overall survival and molecular subtypes of glioma patients from microscopic images of tissue biopsies, reflecting measures of microvascular proliferation, mitotic activity, nuclear atypia, and the presence of necrosis. Whole-slide images from 663 unique patients [IDH: 333 IDH-wildtype, 330 IDH-mutants, 1p/19q: 201 1p/19q non-codeleted, 129 1p/19q codeleted] were obtained from TCGA. Sub-images that were free of artifacts and that contained viable tumor with descriptive histologic characteristics were extracted, which were further used for training and testing a deep neural network. The output layer of the network was configured in two different ways: (i) a final Cox model layer to output a prediction of patient risk, and (ii) a final layer with sigmoid activation function, and stochastic gradient decent based optimization with binary cross-entropy loss. Both survival prediction and molecular subtype classification produced promising results using our model. The c-statistic was estimated to be 0.82 (p-value=4.8x10-5) between the risk scores of the proposed deep learning model and overall survival, while accuracies of 88% (area under the curve [AUC]=0.86) were achieved in the detection of IDH mutational status and 1p/19q codeletion. These findings suggest that the deep learning techniques can be applied to microscopic images for objective, accurate, and integrated prediction of outcome for glioma patients. The proposed marker may contribute to (i) stratification of patients into clinical trials, (ii) patient selection for targeted therapy, and (iii) personalized treatment planning.

Saima Rathore, Muhammad A. Iftikhar, Metin N. Gurcan et al.

Both radiographic (Rad) imaging, such as multi-parametric magnetic resonance imaging, and digital pathology (Path) images captured from tissue samples are currently acquired as standard clinical practice for glioblastoma tumors. Both these data streams have been separately used for diagnosis and treatment planning, despite the fact that they provide complementary information. In this research work, we aimed to assess the potential of both Rad and Path images in combination and comparison. An extensive set of engineered features was extracted from delineated tumor regions in Rad images, comprising T1, T1-Gd, T2, T2-FLAIR, and 100 random patches extracted from Path images. Specifically, the features comprised descriptors of intensity, histogram, and texture, mainly quantified via gray-level-co-occurrence matrix and gray-level-run-length matrices. Features extracted from images of 107 glioblastoma patients, downloaded from The Cancer Imaging Archive, were run through support vector machine for classification using leave-one-out cross-validation mechanism, and through support vector regression for prediction of continuous survival outcome. The Pearson correlation coefficient was estimated to be 0.75, 0.74, and 0.78 for Rad, Path and RadPath data. The area-under the receiver operating characteristic curve was estimated to be 0.74, 0.76 and 0.80 for Rad, Path and RadPath data, when patients were discretized into long- and short-survival groups based on average survival cutoff. Our results support the notion that synergistically using Rad and Path images may lead to better prognosis at the initial presentation of the disease, thereby facilitating the targeted enrollment of patients into clinical trials.