Cellular Molecular And Metabolic Magnetic Resonance Imaging

This dissertation, "Cellular, Molecular and Metabolic Magnetic Resonance Imaging: Techniques and Applications" by Mei-kwan, April, Chow, 周美君, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. DOI: 10.5353/th_b4490114 Subjects: Magnetic resonance imaging

Magnetic resonance imaging (MRI) is a non-invasive imaging tool that provides excellent soft tissue contrast with submillimeter spatial resolution. However, its potential of therapeutic interventions and diagnostic applications can be limited by the low sensitivities in detecting cellular, molecular and metabolic changes. Development of novel MR contrast agents with desired targeting or drug delivery capabilities for cellular and molecular imaging may be beneficial for higher sensitivity and specificity. Spectroscopic imaging at high-field MRI may be advantageous in identifying and quantifying metabolic changes with increased signal-to-noise ratio and spectral resolution. In this book, novel techniques for cellular, molecular and metabolic MRI are investigated and demonstrated to be valuable in various applications.

The ability of molecular and cellular imaging to track the survival, migration, and differentiation of cells in vivo as well as monitor particular gene expression in living subjects is rapidly moving from the research laboratory into daily clinical settings. The interdisciplinary nature of the field mandates a constant dialogue among molecular and

Standard magnetic resonance imaging (MRI) is a prominent clinical imaging modality used to diagnose and study diseases in vivo. It is principally based on the detection of the nuclei of hydrogen atoms (the proton; symbol 1H) in water molecules in tissues. X-nuclei MRI (also called non-proton MRI) is based on the detection of the nuclei of other atoms (X-nuclei) in the body, such as sodium (23Na), phosphorus (31P), chlorine (35Cl), potassium (39K), deuterium (2H), oxygen (17O), lithium (7Li), and fluorine (19F) using modified software and hardware. X-nuclei MRI can provide fundamental, new metabolic information related to cellular energetic metabolism and ion homeostasis in tissues that cannot be assessed using standard hydrogen MRI. This book is an introduction to the techniques and biomedical applications of X-nuclei MRI. It describes the theoretical and experimental basis of X-nuclei MRI, the limitations of this technique, and its potential biomedical applications for the diagnosis and prognosis of many disorders or for quantitative monitoring of therapies in a wide range of diseases. The book is divided into four parts. Part I includes a general description of X-nuclei nuclear magnetic resonance physics and imaging. Part II deals with the MRI of endogenous nuclei such as 23Na, 31P, 35Cl, and 39K; Part III, the MRI of endogenous/exogenous nuclei such as 2H and 17O; and Part IV, the MRI of exogenous nuclei such as 7Li and 19F. The book is illustrated throughout with many representative figures and includes references and reading suggestions in each section. It is the first book to introduce X-nuclei MRI to researchers, clinicians, students, and general readers who are interested in the development of imaging methods for assessing new metabolic information in tissues in vivo in order to diagnose diseases, improve prognosis, or measure the efficiency of therapies in a timely and quantitative manner. It is an ideal starting point for a clinical or scientific research project in non-proton MRI techniques.

Leading experts in the use of MRI explain its basic principles and demonstrate its power to understand biological processes with numerous cutting-edge applications. To illustrate its capability to reveal exquisite anatomical detail, the authors discuss MRI applications to developmental biology, mouse phenotyping, and fiber architecture. MRI can also provide information about organ and tissue function based on endogenous cantrast mechanisms. Examples of brain, kidney, and cardiac function are included, as well as applications to neuro and tumor pathophysiology. In addition, the volume demonstrates the use of exogenous contrast material in functional assessment of the lung, noninvasive evaluation of tissue pH, the imaging of metabolic activity or gene expression that occur on a molecular level, and cellular labeling using superparamagnetic iron oxide contrast agents.

The inclusion of oncogene-driven reprogramming of energy metabolism within the list of cancer hallmarks (Hanahan and Weinberg, Cell 2000, 2011) has provided major impetus to further investigate the existence of a much wider metabolic rewiring in cancer cells, which not only includes deregulated cellular bioenergetics, but also encompasses multiple links with a more comprehensive network of altered biochemical pathways. This network is currently held responsible for redirecting carbon and phosphorus fluxes through the biosynthesis of nucleotides, amino acids, lipids and phospholipids and for the production of second messengers essential to cancer cells growth, survival and invasiveness in the hostile tumor environment. The capability to develop such a concerted rewiring of biochemical pathways is a versatile tool adopted by cancer cells to counteract the host defense and eventually resist the attack of anticancer treatments. Integrated efforts elucidating key mechanisms underlying this complex cancer metabolic reprogramming have led to the identification of new signatures of malignancy that are providing a strong foundation for improving cancer diagnosis and monitoring tumor response to therapy using appropriate molecular imaging approaches. In particular, the recent evolution of positron emission tomography (PET), magnetic resonance spectroscopy (MRS), spectroscopic imaging (MRSI), functional MR imaging (fMRI) and optical imaging technologies, combined with complementary cellular imaging approaches, have created new ways to explore and monitor the effects of metabolic reprogramming in cancer at clinical and preclinical levels. Thus, the progress of high-tech engineering and molecular imaging technologies, combined with new generation genomic, proteomic and phosphoproteomic methods, can significantly improve the clinical effectiveness of image-based interventions in cancer and provide novel insights to design and validate new targeted therapies. The Frontiers in Oncology Research Topic “Exploring Cancer Metabolic Reprogramming Through Molecular Imaging” focusses on current achievements, challenges and needs in the application of molecular imaging methods to explore cancer metabolic reprogramming, and evaluate its potential impact on clinical decisions and patient outcome. A series of reviews and perspective articles, along with original research contributions on humans and on preclinical models have been concertedly included in the Topic to build an open forum on perspectives, present needs and future challenges of this cutting-edge research area.

This issue of MRI Clinics of North America focuses on Functional MRI in Oncology. Articles will include: Functional MRI techniques in oncology in the era of personalized medicine, MRI biomarkers and surrogate endpoints in oncology clinical trials, Therapy monitoring with functional MRI, Multiparametric MRI in the assessment of brain tumors, Multiparametric MRI of breast cancer, Functional MRI in chest malignancies, Multiparametric MRI in abdominal malignancies, Assessment of musculoskeletal malignancies with functional MRI, Evaluation of head and neck tumors with functional MRI, Role of multiparametric MRI in malignancies of the urogenital tract, Diffusion-weighted imaging in oncology, Functional MRI in gynecologic cancer, Assessment of angiogenesis with MRI: DCE-MRI and beyond, Imaging of tumor metabolism: MR spectroscopy, and more!

This book presents advanced molecular imaging techniques used to assess metabolic function. Covering state-of-the art modalities, it discusses the evaluation of a wide range of diseases that have a metabolic component, including cancer, inflammatory conditions, diabetes, neurodegeneration, and cardiovascular disorders. Imaging provides a quantitative perspective to the assessment of metabolic function and complements genetic analysis of disorders related to disrupted metabolism. Organized into four parts, the book highlights basic principles in molecular imaging techniques; metabolic imaging approaches, including magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and hybrid modalities; metabolic diseases; and future perspectives. Featuring contributions from leading authorities in radiology, oncology, cardiology, and neurology, Imaging and Metabolism is a pioneering exploration of the role of imaging modalities in assessing the physiological status of abnormal cells and diagnosing disease.