The University of Pennsylvania Glioblastoma (UPenn-GBM) cohort: Advanced MRI, clinical, genomics, & radiomics

Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during routine clinical practice, at the University of Pennsylvania Health System, (b) accompanying clinical, demographic, and molecular information, (d) perfusion and diffusion derivative volumes, (e) computationally-derived and manually-revised expert annotations of tumor sub-regions, as well as (f) quantitative imaging (also known as radiomic) features corresponding to each of these regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments

A framework for 3D vessel analysis using whole slide images of liver tissue sections

Three-dimensional (3D) high resolution microscopic images have high potential for improving the understanding of both normal and disease processes where structural changes or spatial relationship of disease features are significant. In this paper, we develop a complete framework applicable to 3D pathology analytical imaging, with an application to whole slide images of sequential liver slices for 3D vessel structure analysis. The analysis workflow consists of image registration, segmentation, vessel cross-section association, interpolation, and volumetric rendering. To identify biologically-meaningful correspondence across adjacent slides, we formulate a similarity function for four association cases. The optimal solution is then obtained by constrained Integer Programming. We quantitatively and qualitatively compare our vessel reconstruction results with human annotations. Validation results indicate a satisfactory concordance as measured both by region-based and distance-based metrics. These results demonstrate a promising 3D vessel analysis framework for whole slide images of liver tissue sections

Quality of Radiomic Features in Glioblastoma Multiforme: Impact of Semi-Automated Tumor Segmentation Software.

ObjectiveThe purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software.Materials and methodsMR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic.ResultsOur study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC < 0.5). Most first order statistics and morphometric features showed moderate-to-high NDR (4 > NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant.ConclusionThe use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics

A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer.

Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

Radiogenomics Framework for Associating Medical Image Features with Tumour Genetic Characteristics

Significant progress has been made in the understanding of human cancers at the molecular genetics level and it is providing new insights into their underlying pathophysiology. This progress has enabled the subclassification of the disease and the development of targeted therapies that address specific biological pathways. However, obtaining genetic information remains invasive and costly. Medical imaging is a non-invasive technique that captures important visual characteristics (i.e. image features) of abnormalities and plays an important role in routine clinical practice. Advancements in computerised medical image analysis have enabled quantitative approaches to extract image features that can reflect tumour genetic characteristics, leading to the emergence of ‘radiogenomics’. Radiogenomics investigates the relationships between medical imaging features and tumour molecular characteristics, and enables the derivation of imaging surrogates (radiogenomics features) to genetic biomarkers that can provide alternative approaches to non-invasive and accurate cancer diagnosis. This thesis presents a new framework that combines several novel methods for radiogenomics analysis that associates medical image features with tumour genetic characteristics, with the main objectives being: i) a comprehensive characterisation of tumour image features that reflect underlying genetic information; ii) a method that identifies radiogenomics features encoding common pathophysiological information across different diseases, overcoming the dependence on large annotated datasets; and iii) a method that quantifies radiogenomics features from multi-modal imaging data and accounts for unique information encoded in tumour heterogeneity sub-regions. The present radiogenomics methods advance radiogenomics analysis and contribute to improving research in computerised medical image analysis

Assessment of brain cancer atlas maps with multimodal imaging features.

BACKGROUND: Glioblastoma Multiforme (GBM) is a fast-growing and highly aggressive brain tumor that invades the nearby brain tissue and presents secondary nodular lesions across the whole brain but generally does not spread to distant organs. Without treatment, GBM can result in death in about 6 months. The challenges are known to depend on multiple factors: brain localization, resistance to conventional therapy, disrupted tumor blood supply inhibiting effective drug delivery, complications from peritumoral edema, intracranial hypertension, seizures, and neurotoxicity. MAIN TEXT: Imaging techniques are routinely used to obtain accurate detections of lesions that localize brain tumors. Especially magnetic resonance imaging (MRI) delivers multimodal images both before and after the administration of contrast, which results in displaying enhancement and describing physiological features as hemodynamic processes. This review considers one possible extension of the use of radiomics in GBM studies, one that recalibrates the analysis of targeted segmentations to the whole organ scale. After identifying critical areas of research, the focus is on illustrating the potential utility of an integrated approach with multimodal imaging, radiomic data processing and brain atlases as the main components. The templates associated with the outcome of straightforward analyses represent promising inference tools able to spatio-temporally inform on the GBM evolution while being generalizable also to other cancers. CONCLUSIONS: The focus on novel inference strategies applicable to complex cancer systems and based on building radiomic models from multimodal imaging data can be well supported by machine learning and other computational tools potentially able to translate suitably processed information into more accurate patient stratifications and evaluations of treatment efficacy

Texture Analysis Platform for Imaging Biomarker Research

abstract: 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.Dissertation/ThesisDoctoral Dissertation Biomedical Informatics 201