Imaging Biomarkers of Treatment Response

Imaging Biomarkers of Treatment Response PDF

Author:

Publisher:

Published: 2015

Total Pages: 294

ISBN-13:

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Quantitative imaging biomarkers -- numerical measurements derived from medical imaging that can be interpreted by clinicians - are a critical component of treatment response assessment in oncology. They can also play an important role in the design and interpretation of clinical trials, provided that they are measured following a standardized set of best practices. In this thesis, we have demonstrated the successful application of imaging biomarkers of treatment response to a clinical trial assessing the pharmacodynamics and pharmacokinetics of the anti-angiogenic TKI therapeutic Axitinib. We have illustrated the challenges facing quantitative imaging biomarkers in general, and gained valuable insights into anti-angiogenic therapy in particular. We have characterized the pharmacodynamics of "withdrawal flare," a rapid increase in tumor proliferation following cessation of anti-angiogenic therapy, using quantitative imaging biomarkers derived from FLT PET. This is the first time in humans that the temporal dynamics of Axitinib withdrawal flare have been characterized, a critical step in optimizing the use of this drug in combination therapy. Although we demonstrated that significant flare occurs in patients treated with Axitinib, we also observed substantial inter-patient heterogeneity in imaging response during withdrawal. Among the sub-set of patients experiencing withdrawal flare, it was found to occur at two days post-cessation of Axitinib, with relatively little additional flare between days 2 and 7 of withdrawal. Moreover, withdrawal flare was found to be associated with poor clinical outcome. We directly compared the results of the Axitinib trial with an earlier trial of a related anti-angiogenic drug, Sunitinib, which had used the same imaging biomarkers of treatment response. The proliferative and vascular response during withdrawal of Axitinib and Sunitinib was found to be nearly identical, and there is not sufficient evidence to support any significant difference in proliferative response during treatment. We also explored intra-patient, inter-lesion response heterogeneity. However, when comparing the imaging response with pre-treatment phenotypes, no significant correlations were observed, suggesting that some underlying biological mechanisms may be driving the inter-lesion differences in response. The insights gained from this original work support several hypotheses for how to improve patient treatment. These hypotheses will be partially addressed in three new ongoing clinical trials at the University of Wisconsin.

Evolution of Translational Omics

Evolution of Translational Omics PDF

Author: Institute of Medicine

Publisher: National Academies Press

Published: 2012-09-13

Total Pages: 354

ISBN-13: 0309224187

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Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.

Medical Imaging Informatics

Medical Imaging Informatics PDF

Author: Alex A.T. Bui

Publisher: Springer Science & Business Media

Published: 2009-12-01

Total Pages: 454

ISBN-13: 1441903852

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Medical Imaging Informatics provides an overview of this growing discipline, which stems from an intersection of biomedical informatics, medical imaging, computer science and medicine. Supporting two complementary views, this volume explores the fundamental technologies and algorithms that comprise this field, as well as the application of medical imaging informatics to subsequently improve healthcare research. Clearly written in a four part structure, this introduction follows natural healthcare processes, illustrating the roles of data collection and standardization, context extraction and modeling, and medical decision making tools and applications. Medical Imaging Informatics identifies core concepts within the field, explores research challenges that drive development, and includes current state-of-the-art methods and strategies.

Radiomics and Radiogenomics

Radiomics and Radiogenomics PDF

Author: Ruijiang Li

Publisher: CRC Press

Published: 2019-07-09

Total Pages: 420

ISBN-13: 1351208268

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Radiomics and Radiogenomics: Technical Basis and Clinical Applications provides a first summary of the overlapping fields of radiomics and radiogenomics, showcasing how they are being used to evaluate disease characteristics and correlate with treatment response and patient prognosis. It explains the fundamental principles, technical bases, and clinical applications with a focus on oncology. The book’s expert authors present computational approaches for extracting imaging features that help to detect and characterize disease tissues for improving diagnosis, prognosis, and evaluation of therapy response. This book is intended for audiences including imaging scientists, medical physicists, as well as medical professionals and specialists such as diagnostic radiologists, radiation oncologists, and medical oncologists. Features Provides a first complete overview of the technical underpinnings and clinical applications of radiomics and radiogenomics Shows how they are improving diagnostic and prognostic decisions with greater efficacy Discusses the image informatics, quantitative imaging, feature extraction, predictive modeling, software tools, and other key areas Covers applications in oncology and beyond, covering all major disease sites in separate chapters Includes an introduction to basic principles and discussion of emerging research directions with a roadmap to clinical translation

Quantitative Magnetic Resonance Imaging

Quantitative Magnetic Resonance Imaging PDF

Author: Nicole Seiberlich

Publisher: Academic Press

Published: 2020-11-18

Total Pages: 1094

ISBN-13: 0128170581

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Quantitative Magnetic Resonance Imaging is a ‘go-to’ reference for methods and applications of quantitative magnetic resonance imaging, with specific sections on Relaxometry, Perfusion, and Diffusion. Each section will start with an explanation of the basic techniques for mapping the tissue property in question, including a description of the challenges that arise when using these basic approaches. For properties which can be measured in multiple ways, each of these basic methods will be described in separate chapters. Following the basics, a chapter in each section presents more advanced and recently proposed techniques for quantitative tissue property mapping, with a concluding chapter on clinical applications. The reader will learn: The basic physics behind tissue property mapping How to implement basic pulse sequences for the quantitative measurement of tissue properties The strengths and limitations to the basic and more rapid methods for mapping the magnetic relaxation properties T1, T2, and T2* The pros and cons for different approaches to mapping perfusion The methods of Diffusion-weighted imaging and how this approach can be used to generate diffusion tensor maps and more complex representations of diffusion How flow, magneto-electric tissue property, fat fraction, exchange, elastography, and temperature mapping are performed How fast imaging approaches including parallel imaging, compressed sensing, and Magnetic Resonance Fingerprinting can be used to accelerate or improve tissue property mapping schemes How tissue property mapping is used clinically in different organs Structured to cater for MRI researchers and graduate students with a wide variety of backgrounds Explains basic methods for quantitatively measuring tissue properties with MRI - including T1, T2, perfusion, diffusion, fat and iron fraction, elastography, flow, susceptibility - enabling the implementation of pulse sequences to perform measurements Shows the limitations of the techniques and explains the challenges to the clinical adoption of these traditional methods, presenting the latest research in rapid quantitative imaging which has the possibility to tackle these challenges Each section contains a chapter explaining the basics of novel ideas for quantitative mapping, such as compressed sensing and Magnetic Resonance Fingerprinting-based approaches

Brain Tumor Imaging

Brain Tumor Imaging PDF

Author: Elke Hattingen

Publisher: Springer

Published: 2015-09-02

Total Pages: 166

ISBN-13: 3642450407

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This book describes the basics, the challenges and the limitations of state of the art brain tumor imaging and examines in detail its impact on diagnosis and treatment monitoring. It opens with an introduction to the clinically relevant physical principles of brain imaging. Since MR methodology plays a crucial role in brain imaging, the fundamental aspects of MR spectroscopy, MR perfusion and diffusion-weighted MR methods are described, focusing on the specific demands of brain tumor imaging. The potential and the limits of new imaging methodology are carefully addressed and compared to conventional MR imaging. In the main part of the book, the most important imaging criteria for the differential diagnosis of solid and necrotic brain tumors are delineated and illustrated in examples. A closing section is devoted to the use of MR methods for the monitoring of brain tumor therapy. The book is intended for radiologists, neurologists, neurosurgeons, oncologists and other scientists in the biomedical field with an interest in neuro-oncology.

Biomarkers in Drug Development

Biomarkers in Drug Development PDF

Author: Michael R. Bleavins

Publisher: John Wiley & Sons

Published: 2011-09-20

Total Pages: 559

ISBN-13: 1118210425

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Discover how biomarkers can boost the success rate of drug development efforts As pharmaceutical companies struggle to improve the success rate and cost-effectiveness of the drug development process, biomarkers have emerged as a valuable tool. This book synthesizes and reviews the latest efforts to identify, develop, and integrate biomarkers as a key strategy in translational medicine and the drug development process. Filled with case studies, the book demonstrates how biomarkers can improve drug development timelines, lower costs, facilitate better compound selection, reduce late-stage attrition, and open the door to personalized medicine. Biomarkers in Drug Development is divided into eight parts: Part One offers an overview of biomarkers and their role in drug development. Part Two highlights important technologies to help researchers identify new biomarkers. Part Three examines the characterization and validation process for both drugs and diagnostics, and provides practical advice on appropriate statistical methods to ensure that biomarkers fulfill their intended purpose. Parts Four through Six examine the application of biomarkers in discovery, preclinical safety assessment, clinical trials, and translational medicine. Part Seven focuses on lessons learned and the practical aspects of implementing biomarkers in drug development programs. Part Eight explores future trends and issues, including data integration, personalized medicine, and ethical concerns. Each of the thirty-eight chapters was contributed by one or more leading experts, including scientists from biotechnology and pharmaceutical firms, academia, and the U.S. Food and Drug Administration. Their contributions offer pharmaceutical and clinical researchers the most up-to-date understanding of the strategies used for and applications of biomarkers in drug development.

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