This paper reviews state-of-the-art research solutions across the spectrum of medical imaging informatics, discusses clinical translation, and provides future directions for advancing clinical practice. More specifically, it summarizes advances in medical imaging acquisition technologies for different modalities, highlighting the necessity for efficient medical data management strategies in the context of AI in big healthcare data analytics. It then provides a synopsis of contemporary and emerging algorithmic methods for disease classification and organ/ tissue segmentation, focusing on AI and deep learning architectures that have already become the de facto approach. The clinical benefits of in-silico modelling advances linked with evolving 3D reconstruction and visualization applications are further documented. Concluding, integrative analytics approaches driven by associate research branches highlighted in this study promise to revolutionize imaging informatics as known today across the healthcare continuum for both radiology and digital pathology applications. The latter, is projected to enable informed, more accurate diagnosis, timely prognosis, and effective treatment planning, underpinning precision medicine.

The diversity of data management systems affords developers the luxury of building heterogeneous architectures to address the unique needs of big data. It allows one to mix-nmatch systems that can store, query, update, and process data based on specific use cases. However, this heterogeneity brings with it the burden of developing custom interfaces for each data management system. Existing big data frameworks fall short in mitigating these challenges imposed. In this paper, we present Bindaas, a secure and extensible big data middleware that offers uniform access to diverse data sources. By providing a RESTful web service interface to the data sources, Bindaas exposes query, update, store, and delete functionality of the data sources as data service APIs, while providing turn-key support for standard operations involving access control and audit-trails. The research community has deployed Bindaas in various production environments in healthcare. Our evaluations highlight the efficiency of Bindaas in serving concurrent requests to data source instances with minimal overheads.

BACKGROUND AND OBJECTIVE: Morphologic variations of disease are often linked to underlying molecular events and patient outcome, suggesting that quantitative morphometric analysis may provide further insight into disease mechanisms. In this paper a methodology for the subclassification of disease is developed using image analysis techniques. Morphologic signatures that represent patient-specific tumor morphology are derived from the analysis of hundreds of millions of cells in digitized whole slide images. Clustering these signatures aggregates tumors into groups with cohesive morphologic characteristics. This methodology is demonstrated with an analysis of glioblastoma, using data from The Cancer Genome Atlas to identify a prognostically significant morphology-driven subclassification, in which clusters are correlated with transcriptional, genetic, and epigenetic events. MATERIALS AND METHODS: Methodology was applied to 162 glioblastomas from The Cancer Genome Atlas to identify morphology-driven clusters and their clinical and molecular correlates. Signatures of patient-specific tumor morphology were generated from analysis of 200 million cells in 462 whole slide images. Morphology-driven clusters were interrogated for associations with patient outcome, response to therapy, molecular classifications, and genetic alterations. An additional layer of deep, genome-wide analysis identified characteristic transcriptional, epigenetic, and copy number variation events. RESULTS AND DISCUSSION: Analysis of glioblastoma identified three prognostically significant patient clusters (median survival 15.3, 10.7, and 13.0 months, log rank p=1.4e-3). Clustering results were validated in a separate dataset. Clusters were characterized by molecular events in nuclear compartment signaling including developmental and cell cycle checkpoint pathways. This analysis demonstrates the potential of high-throughput morphometrics for the subclassification of disease, establishing an approach that complements genomics.

Pathology is a medical subspecialty that practices the diagnosis of disease. Microscopic examination of tissue reveals information enabling the pathologist to render accurate diagnoses and to guide therapy. The basic process by which anatomic pathologists render diagnoses has remained relatively unchanged over the last century, yet advances in information technology now offer significant opportunities in image-based diagnostic and research applications. Pathology has lagged behind other healthcare practices such as radiology where digital adoption is widespread. As devices that generate whole slide images become more practical and affordable, practices will increasingly adopt this technology and eventually produce an explosion of data that will quickly eclipse the already vast quantities of radiology imaging data. These advances are accompanied by significant challenges for data management and storage, but they also introduce new opportunities to improve patient care by streamlining and standardizing diagnostic approaches and uncovering disease mechanisms. Computer-based image analysis is already available in commercial diagnostic systems, but further advances in image analysis algorithms are warranted in order to fully realize the benefits of digital pathology in medical discovery and patient care. In coming decades, pathology image analysis will extend beyond the streamlining of diagnostic workflows and minimizing interobserver variability and will begin to provide diagnostic assistance, identify therapeutic targets, and predict patient outcomes and therapeutic responses.

OBJECTIVE AND DESIGN: The design and implementation of ImageMiner, a software platform for performing comparative analysis of expression patterns in imaged microscopy specimens such as tissue microarrays (TMAs), is described. ImageMiner is a federated system of services that provides a reliable set of analytical and data management capabilities for investigative research applications in pathology. It provides a library of image processing methods, including automated registration, segmentation, feature extraction, and classification, all of which have been tailored, in these studies, to support TMA analysis. The system is designed to leverage high-performance computing machines so that investigators can rapidly analyze large ensembles of imaged TMA specimens. To support deployment in collaborative, multi-institutional projects, ImageMiner features grid-enabled, service-based components so that multiple instances of ImageMiner can be accessed remotely and federated. RESULTS: The experimental evaluation shows that: (1) ImageMiner is able to support reliable detection and feature extraction of tumor regions within imaged tissues; (2) images and analysis results managed in ImageMiner can be searched for and retrieved on the basis of image-based features, classification information, and any correlated clinical data, including any metadata that have been generated to describe the specified tissue and TMA; and (3) the system is able to reduce computation time of analyses by exploiting computing clusters, which facilitates analysis of larger sets of tissue samples.

The diagnosis of diffuse gliomas requires the careful inspection of large amounts of visual data. Identifying tissue regions that inform diagnosis is a cumbersome task for human reviewers and is a process prone to inter-reader variability. In this paper we present an automatic method for identifying critical diagnostic regions within whole-slide microscopy images of gliomas. We frame the problem of critical region identification as a texture-based content retrieval task in the sense that each image is represented by a set of texture features. Both linear and nonlinear dimensionality reduction techniques are utilized to explore the intrinsic dimensionality of the feature space where images are classified by classification and regression trees with performances improved by a newly extended multi-class gentle boosting (MCGB) mechanism. The proposed method is demonstrated on 1200 sample regions using a five-fold cross validation, achieving a 96.25% classification accuracy.

Design templates that involve discovery, analysis, and integration of information resources commonly occur in many scientific research projects. In this paper we present examples of design templates from the biomedical translational research domain and discuss the requirements imposed on Grid middleware infrastructures by them. Using caGrid, which is a Grid middleware system based on the model driven architecture (MDA) and the service oriented architecture (SOA) paradigms, as a starting point, we discuss architecture directions for MDA and SOA based systems like caGrid to support common design templates.

OBJECTIVES: To develop a security infrastructure to support controlled and secure access to data and analytical resources in a biomedical research Grid environment, while facilitating resource sharing among collaborators. DESIGN: A Grid security infrastructure, called Grid Authentication and Authorization with Reliably Distributed Services (GAARDS), is developed as a key architecture component of the NCI-funded cancer Biomedical Informatics Grid (caBIG). The GAARDS is designed to support in a distributed environment 1) efficient provisioning and federation of user identities and credentials; 2) group-based access control support with which resource providers can enforce policies based on community accepted groups and local groups; and 3) management of a trust fabric so that policies can be enforced based on required levels of assurance. MEASUREMENTS: GAARDS is implemented as a suite of Grid services and administrative tools. It provides three core services: Dorian for management and federation of user identities, Grid Trust Service for maintaining and provisioning a federated trust fabric within the Grid environment, and Grid Grouper for enforcing authorization policies based on both local and Grid-level groups. RESULTS: The GAARDS infrastructure is available as a stand-alone system and as a component of the caGrid infrastructure. More information about GAARDS can be accessed at http://www.cagrid.org. CONCLUSIONS: GAARDS provides a comprehensive system to address the security challenges associated with environments in which resources may be located at different sites, requests to access the resources may cross institutional boundaries, and user credentials are created, managed, revoked dynamically in a de-centralized manner.

This paper describes a new project that systematically addresses the enormous complexity of mapping applications to current and future parallel platforms. By integrating the system layers - domain-specific environment, application program, compiler, run-time environment, performance models and simulation, and workflow manager - and through a systematic strategy for application mapping, our approach exploit the vast machine resources available in such parallel platforms to dramatically increase the productivity of application programmers. This project brings together computer scientists in the areas represented by the system layers (i.e., language extensions, compilers, run-time systems, workflows) together with expertise in knowledge representation and machine learning. With expert domain scientists in molecular dynamics (MD) simulation, we are developing our approach in the context of a specific application class which already targets environments consisting of several hundreds of processors. In this way, we gain valuable insight into a generalizable strategy, while simultaneously producing performance benefits for existing and important applications.

Recent advances in parallel computing have made it possible for scientists to perform atomistic simulations of materials involving billions of atoms. An immersive and interactive virtual environment such as ImmersaDesk is an ideal platform for exploring complex material processes in these simulations. However rendering such large datasets at an interactive speed is a major challenge. To solve this problem we have developed a visualization system by incorporating parallel and distributed computing paradigms. The system uses a parallelized fast visibility-culling algorithm based on the octree data structure to reduce the number of atoms sent to the graphics pipeline. An adaptive multiresolution algorithm based on atomic density is employed to further reduce the load on the graphics pipeline. The resulting system renders a billion-atom system at nearly interactive frame rates on a dual processor SGI Onyx2 with an InfiniteReality2 graphics pipeline connected to a 4-node PC cluster.