The rate of progress in improving survival of patients with solid tumors is slow due to late stage diagnosis and poor tumor characterization processes that fail to effectively reflect the nature of tumor before treatment or the subsequent change in its dynamics because of treatment. Further advancement of targeted therapies relies on advancements in biomarker research. In the context of solid tumors, bio-specimen samples such as biopsies serve as the main source of biomarkers used in the treatment and monitoring of cancer, even though biopsy samples are susceptible to sampling error and more importantly, are local and offer a narrow temporal scope.

Because of its established role in cancer care and its non-invasive nature imaging offers the potential to complement the findings of cancer biology. Over the past decade, a compelling body of literature has emerged suggesting a more pivotal role for imaging in the diagnosis, prognosis, and monitoring of diseases. These advances have facilitated the rise of an emerging practice known as Radiomics: the extraction and analysis of large numbers of quantitative features from medical images to improve disease characterization and prediction of outcome. It has been suggested that radiomics can contribute to biomarker discovery by detecting imaging traits that are complementary or interchangeable with other markers.

This thesis seeks further advancement of imaging biomarker discovery. This research unfolds over two aims: I) developing a comprehensive methodological pipeline for converting diagnostic imaging data into mineable sources of information, and II) investigating the utility of imaging data in clinical diagnostic applications. Four validation studies were conducted using the radiomics pipeline developed in aim I. These studies had the following goals: (1 distinguishing between benign and malignant head and neck lesions (2) differentiating benign and malignant breast cancers, (3) predicting the status of Human Papillomavirus in head and neck cancers, and (4) predicting neuropsychological performances as they relate to Alzheimer’s disease progression. The long-term objective of this thesis is to improve patient outcome and survival by facilitating incorporation of routine care imaging data into decision making processes.

ABSTRACT BACKGROUND AND PURPOSE: Sinonasal inverted papilloma (IP) can harbor squamous cell carcinoma (SCC). Consequently, differentiating these tumors is important. The objective of this study was to determine if MRI-based texture analysis can differentiate SCC from IP and provide supplementary information to the radiologist. MATERIALS AND METHODS: Adult patients who had IP or SCC resected were eligible (coexistent IP and SCC were excluded). Inclusion required tumor size greater than 1.5 cm and a pre-operative MRI with axial T1, axial T2, and axial T1 post-contrast sequences. Five well- established texture analysis algorithms were applied to an ROI from the largest tumor cross- section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. Based on three separate blinded reviews of the ROI, isolated tumor, and entire images, two neuroradiologists predicted tumor type in consensus. RESULTS: The IP and SCC cohorts were matched for age and gender, while SCC tumor volume was larger (p=0.001). The best classification model achieved similar accuracies for training (17 SCC, 16 IP) and validation (7 SCC, 6 IP) datasets of 90.9% and 84.6% respectively (p=0.537). The machine-learning accuracy for the entire cohort (89.1%) was better than that of the neuroradiologist ROI review (56.5%, p=0.0004) but not significantly different from the neuroradiologist review of the tumors (73.9%, p=0.060) or entire images (87.0%, p=0.748). CONCLUSION: MRI-based texture analysis has potential to differentiate SCC from IP and may provide incremental information to the neuroradiologist, particularly for small or heterogeneous tumors.

Background: Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.

Methods: We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei) for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.

Results: We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients). The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients).

Conclusion: Multi-parametric MRI and texture analysis can help characterize and visualize GBM’s spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.