Download or read book Development and Validation of PH and Oxygen Sensitive Magnetic Resonance Imaging for Metabolic Characterization of Glioma written by Jingwen Yao and published by . This book was released on 2021 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: The reprogrammed energy metabolism and the dysfunctional vascular network of tumors create a hypoxic and acidic microenvironment, which is related to various malignant properties of cancer and poor patient prognosis. We have developed an amine chemical exchange saturation transfer (CEST) sequence with spin-and-gradient echo (SAGE) echo-planar imaging (EPI) readout to evaluate tumor acidity and hypoxia in human gliomas simultaneously. Amine CEST provided pH-sensitivity through labeling the endogenous amine protons that undergo chemical exchange with water protons, with a pH-dependent exchange rate. On the other hand, the reversible transverse relaxation rate quantified using the multi-echo EPI readout reflects oxygen extraction through sensitivity to paramagnetic deoxyhemoglobin. This dissertation focused on developing and validating this novel dual-function imaging technique, mainly from three aspects: the technical development and validation, the biological validation, and the clinical validation of the proposed pH- and oxygen-sensitive CEST-SAGE-EPI technique in human gliomas. We have developed a new post-processing method for improved $B_0$ correction. A customized CEST physical phantom was designed and developed with validated temporal stability. We also evaluated the CEST contrast variability in healthy volunteers and the normal-appearing contralateral brain regions in glioma patients. The proposed pH- and oxygen-sensitive imaging biomarkers showed significant correlations with the tumor cell metabolomics features and MRI-guided biopsy tissue biomarkers, which validated the biological bases of the imaging biomarkers. Additionally, we have examined the association between tumor acidity with tumor vascularity, as measured by perfusion MRI. Lastly, we investigated the clinical usefulness of the biomarkers to characterize different glioma genotypes, predict patient prognosis, and monitor treatment responses. In summary, this dissertation demonstrated that the novel dual-function pH- and oxygen-sensitive imaging technique reflects the abnormal metabolism in glioma patients and has the potential to provide clinical values for patient diagnosis, prognosis, and treatment efficacy assessment.
Download or read book PH weighted Molecular Magnetic Resonance Imaging in Gliomas written by Robert John Harris and published by . This book was released on 2016 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic resonance imaging is an integral part of medical diagnoses, treatment, and evaluation of patients with brain tumors. While standard anatomical imaging is useful, it does not provide information about molecular-level tumor characteristics that may spatially and temporally vary throughout the tumor. As such, there remains a need for the development of novel MRI techniques that can be used for evaluation of tumor growth and treatment response in patients with glioma undergoing radiochemotherapy. Extracellular acidosis is a hallmark of cancer and is intertwined with other common characteristics of the tumor microenvironment including hypoxia and angiogenesis. Therefore, the central objective of this dissertation was to develop a non-invasive imaging technique for identifying regions of acidosis within glioma and surrounding tissues using MRI. The most common types of glioma are highly aggressive and often require radiochemotherapy, which can result in variable responses across the patient population. Information about the acidity characteristics of these gliomas and the surrounding tissue may allow us to more accurately select targets for biopsy and radiation therapy, identify which patients are responding well to treatment, and predict prognosis. Chemical exchange saturation transfer (CEST) MRI is a molecular imaging technique that generates contrast indirectly from protons on labile functional groups such as amines, amides, and hydroxyls. CEST image contrast is dependent on the exchange rate between bulk water protons and these functional groups, which is in turn dependent upon local pH. Because of this, we hypothesized that we could utilize CEST MRI for pH-weighted imaging in human tissues. By developing simulations of the Bloch-McConnell equations governing chemical exchange, we have shown that the CEST contrast generated by fast-exchanging amino acid amine protons increases with decreasing pH within a physiologically relevant range (6.0-7.4). We have also incorporated experimental scan parameters into these simulations to more accurately simulate the CEST contrast obtained during clinical data acquisition. Data were acquired in amino acid phantoms at varying pH and concentration, verifying our image contrast was dependent on pH. Our pH-weighted MRI sequence was also applied in animal models of glioma, providing evidence it can be used to generate unique contrast within tumors and can serve as a potential biomarker for response to treatment. Our CEST MRI method was then applied serially in a cohort of glioblastoma patients undergoing treatment with standard radiochemotherapy, along with select cases of patients undergoing targeted biopsy. Results showed that tumor acidity characteristics were predictive of progression-free survival in the glioblastoma patient cohort. Acidity of targets selected for biopsy on pH-weighted images was indicative of tumor within those biopsy samples. To improve the imaging time of our sequence, we then upgraded the readout to utilize echo-planar imaging (EPI) rather than the standard gradient echo method. This allowed for whole brain coverage and multiple averages within a reduced scan time. The pH-weighted CEST-EPI sequence was applied in healthy volunteers and in a cohort of glioma patients prior to biopsy, in order to select targets for biopsy in regions of acidic and non-acidic tumor tissue. A subset of these patients also underwent PET imaging using 18F-FDOPA, an amino acid analog, near the time of their their pH-weighted scan. 18F-FDOPA uptake was shown to correlate quantitatively and qualitatively with regions of acidity, although pH-weighted imaging provided unique contrast in some cases. pH-weighted MRI was also acquired in recurrent glioblastoma patients before and after the start of treatment with bevacizumab. Acidity was shown to decrease after bevacizumab treatment, and in some cases acidic regions with no apparent contrast enhancement were shown to develop contrast enhancement on follow-up images, indicating that acidic lesions on pH-weighted MRI may be predictive of further tumor growth. Two additional advanced pH-weighted CEST MRI techniques were also implemented. CEST-EPI with a multi-echo readout was developed and acquired in a small cohort of glioma patients. The short and long echoes can provide sensitivity to more and less restricted water molecules, respectively. Separately, our CEST simulation incorporating T1 and T2 maps was used to quantitatively calculate estimates of pH in each image voxel for a subset of patients and animal models. This allows us to correct for T1 and T2 effects and generate numerical estimates of pH rather than pH-weighted images. Together, these experiments and results present a comprehensive description of pH-weighted molecular MRI in gliomas. This technique has the potential to be implemented clinically for detection of acidosis in gliomas and other brain pathologies.
Download or read book Glioma Imaging written by Whitney B. Pope and published by Springer Nature. This book was released on 2019-11-11 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers physiologic, metabolic and molecular imaging for gliomas. Gliomas are the most common primary brain tumors. Imaging is critical for glioma management because of its ability to noninvasively define the anatomic location and extent of disease. While conventional MRI is used to guide current treatments, multiple studies suggest molecular features of gliomas may be identified with noninvasive imaging, including physiologic MRI and amino acid positron emission tomography (PET). These advanced imaging techniques have the promise to help elucidate underlying tumor biology and provide important information that could be integrated into routine clinical practice. The text outlines current clinical practice including common scenarios in which imaging interpretation impacts patient management. Gaps in knowledge and potential areas of advancement based on the application of more experimental imaging techniques will be discussed. In reviewing this book, readers will learn: current standard imaging methodologies used in clinical practice for patients undergoing treatment for glioma and the implications of emerging treatment modalities including immunotherapy the theoretical basis for advanced imaging techniques including diffusion and perfusion MRI, MR spectroscopy, CEST and amino acid PET the relationship between imaging and molecular/genomic glioma features incorporated in the WHO 2016 classification update and the potential application of machine learning about the recently adopted and FDA approved standard brain tumor protocol for multicenter drug trials of the gaps in knowledge that impede optimal patient management and the cutting edge imaging techniques that could address these deficits
Download or read book Magnetic Resonance Spectroscopic Imaging of Metabolism and PH for Tumor Characterization in Vivo Using Hyperpolarized 13C labelled Biosensors written by Stephan Maximilian Düwel and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Imaging Gliomas After Treatment written by Tommaso Scarabino and published by Springer Science & Business Media. This book was released on 2012-03-12 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: This atlas is a detailed guide to the imaging appearances of gliomas following treatment with neurosurgery, radiation therapy, and chemotherapy. Normal and pathological findings are displayed in detailed MR images that illustrate the potential modifications due to treatment. Particular emphasis is placed on characteristic appearances on the newer functional MR imaging techniques, including MR spectroscopy, diffusion-weighted imaging, and perfusion imaging. These techniques are revolutionizing neuroradiology by going beyond the demonstration of macroscopic alterations to the depiction of preceding metabolic changes at the cellular and subcellular level, thereby allowing earlier and more specific diagnosis. A key section comprising some 40 clinical cases and more than 500 illustrations offers an invaluable clinical and research tool not only for neuroradiologists but also for neurosurgeons, radiotherapists, and medical oncologists.
Download or read book Brain Tumor Imaging written by Elke Hattingen and published by Springer. This book was released on 2015-09-02 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Advanced Imaging Biomarkers for the Characterisation of Glioma written by Gerard Thompson and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Glioblastoma multiform (GBM) is an aggressive primary brain tumour. Despite treatment advances in recent years, outcomes remain poor. Disease progression tends to occur adjacent to the original tumour or surgical resection bed, usually within the radiotherapy planning field. This local recurrence and progression is believed to be the result of invasive disease in the surrounding tissue at the time of diagnosis and treatment, which is not currently detectable by conventional non-invasive methods. A number of novel therapies are currently under development which target specific aspects of the tumour behaviour, to try and improve outcomes from this devastating disease. Imaging biomarkers are under development, therefore, in order to provide a non-invasive assessment of tumour extent and behaviour, to provide bespoke image-guided therapies, and detect recurrence or treatment failure at the earliest opportunity. These are also of value in the context of novel therapeutics, which may have a very specific affect on an aspect of tumour behaviour that is not readily apparent on standard clinical imaging. Key to the progression of GBM is the invasion into surrounding white matter. This is followed by a period of tumour growth and subsequent angiogenesis in which microvasculature is produce that is distinct from the highly regulated blood-brain barrier. This thesis covers the development of suite of advanced magnetic resonance imaging (MRI) techniques aimed at characterising those very traits of GBM responsible for the aggressiveness and treatment resistance. Repeatability studies are undertaken to determine the performance of the biomarkers in healthy tissues, and also in a range of gliomas. Dynamic Contrast Enhanced (DCE-) and dynamic susceptibility-enhanced (DSC-)MRI are used to provide estimates of perfusion and permeability in the tumour. In order to address the reasons behind preferential invasion of the corpus callosum, they are used in conjunction with ASL to non-invasively map perfusion territories and watershed regions in the brain through perfusion timing parameters. Diffusion Tensor Imaging (DTI) and quantitative magnetisation transfer (qMT) are used to provide complementary information about white matter integrity, in order to identify changes occurring with glioma invasion as early as possible and direct image-guided treatments at presentation. Their complementary nature is assessed by comparing the two parameters simultaneously in white matter. Additionally, one of the qMT parameters which may be related to tissue pH is shown to be sensitive and specific for the detection of high-grade tumour tissue. Finally, a novel multiparametric imaging biomarker is introduced. Tumour surface mapping assesses the boundary between the solid tumour and surrounding tissue in order to identify areas of potential aggressiveness and invasion. Multiple imaging parameters can be combined to improve specificity and sensitivity. Using the diffusion-weighted imaging parameter, mean diffusivity (MD - also referred to as the apparent diffusion coefficient (ADC)), it is shown to be predictive of clinical outcome in a retrospective and prospective study, while a multiparametric example is given indicating the utility as a predicative biomarker for regions of progression and recurrence, and as potential spatial discriminator for image-guided therapies.
Download or read book Regulation of Tissue Oxygenation Second Edition written by Roland N. Pittman and published by Biota Publishing. This book was released on 2016-08-18 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.
Download or read book Metabolism in Cancer written by Thorsten Cramer and published by Springer. This book was released on 2016-08-24 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.
Download or read book MRI written by Brian M. Dale and published by John Wiley & Sons. This book was released on 2015-08-06 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fifth edition of the most accessible introduction to MRI principles and applications from renowned teachers in the field provides an understandable yet comprehensive update. Accessible introductory guide from renowned teachers in the field Provides a concise yet thorough introduction for MRI focusing on fundamental physics, pulse sequences, and clinical applications without presenting advanced math Takes a practical approach, including up-to-date protocols, and supports technical concepts with thorough explanations and illustrations Highlights sections that are directly relevant to radiology board exams Presents new information on the latest scan techniques and applications including 3 Tesla whole body scanners, safety issues, and the nephrotoxic effects of gadolinium-based contrast media
Download or read book Angiogenesis Assays written by Carolyn A. Staton and published by John Wiley & Sons. This book was released on 2007-01-11 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.
Download or read book Methodologies for Metabolomics written by Norbert W. Lutz and published by Cambridge University Press. This book was released on 2013-01-21 with total page 641 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolomics, the global characterisation of the small molecule complement involved in metabolism, has evolved into a powerful suite of approaches for understanding the global physiological and pathological processes occurring in biological organisms. The diversity of metabolites, the wide range of metabolic pathways and their divergent biological contexts require a range of methodological strategies and techniques. Methodologies for Metabolomics provides a comprehensive description of the newest methodological approaches in metabolomic research. The most important technologies used to identify and quantify metabolites, including nuclear magnetic resonance and mass spectrometry, are highlighted. The integration of these techniques with classical biological methods is also addressed. Furthermore, the book presents statistical and chemometric methods for evaluation of the resultant data. The broad spectrum of topics includes a vast variety of organisms, samples and diseases, ranging from in vivo metabolomics in humans and animals to in vitro analysis of tissue samples, cultured cells and biofluids.
Download or read book Molecular Epidemiology written by Paul A. Schulte and published by Academic Press. This book was released on 2012-12-02 with total page 609 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will serve as a primer for both laboratory and field scientists who are shaping the emerging field of molecular epidemiology. Molecular epidemiology utilizes the same paradigm as traditional epidemiology but uses biological markers to identify exposure, disease or susceptibility. Schulte and Perera present the epidemiologic methods pertinent to biological markers. The book is also designed to enumerate the considerations necessary for valid field research and provide a resource on the salient and subtle features of biological indicators.
Download or read book Biomedical Magnetic Resonance written by Thomas L. James and published by . This book was released on 1984 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Diffuse Low Grade Gliomas in Adults written by Hugues Duffau and published by Springer Science & Business Media. This book was released on 2013-03-19 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the latest research pertaining to the diagnosis, therapy and management of diffuse low-grade gliomas (DLGG) in adults, with a particular focus on the path towards individualised therapy for this kind of tumour. Recent research on the natural history of DLGGs and their interaction with the brain has led to new diagnostic and therapeutic strategies which increase survival and quality of life of the patient, and these methods are described in this book.
Download or read book Growth Hormone Deficiency in Adults written by Jens O. L. Jørgensen and published by Karger Medical and Scientific Publishers. This book was released on 2005-01-01 with total page 241 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has been known for over 40 years that GH-deficient-children benefit from replacement with the hormone. But GH, essential for longitudinal growth, also plays a role after completion of final height. With the introduction of biosynthetic human GH 20 years ago, the use of GH was no longer restricted to severe growth retardation in hypopituitary children. This book will take the reader behind the myths of GH and into the real world of clinical endocrinology. The contributions stem from recognized clinicians and scientists who have been working in the field for decades. The contents encompass traditional end points of GH therapy such as body composition, bone biology and physical performance. Attention is also devoted to diagnostic aspects and side effects. Additional features range from clinical epidemiology to quality of life, and novel areas such as the impact of traumatic brain injury on pituitary function are also covered. The present volume of Frontiers of Hormone Research is essential reading for health care professionals interested in clinical endocrinology and GH.
Download or read book In Vivo NMR Spectroscopy written by Robin A. de Graaf and published by John Wiley & Sons. This book was released on 2019-03-11 with total page 584 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presents basic concepts, experimental methodology and data acquisition, and processing standards of in vivo NMR spectroscopy This book covers, in detail, the technical and biophysical aspects of in vivo NMR techniques and includes novel developments in the field such as hyperpolarized NMR, dynamic 13C NMR, automated shimming, and parallel acquisitions. Most of the techniques are described from an educational point of view, yet it still retains the practical aspects appreciated by experimental NMR spectroscopists. In addition, each chapter concludes with a number of exercises designed to review, and often extend, the presented NMR principles and techniques. The third edition of In Vivo NMR Spectroscopy: Principles and Techniques has been updated to include experimental detail on the developing area of hyperpolarization; a description of the semi-LASER sequence, which is now a method of choice; updated chemical shift data, including the addition of 31P data; a troubleshooting section on common problems related to shimming, water suppression, and quantification; recent developments in data acquisition and processing standards; and MatLab scripts on the accompanying website for helping readers calculate radiofrequency pulses. Provide an educational explanation and overview of in vivo NMR, while maintaining the practical aspects appreciated by experimental NMR spectroscopists Features more experimental methodology than the previous edition End-of-chapter exercises that help drive home the principles and techniques and offer a more in-depth exploration of quantitative MR equations Designed to be used in conjunction with a teaching course on the subject In Vivo NMR Spectroscopy: Principles and Techniques, 3rd Edition is aimed at all those involved in fundamental and/or diagnostic in vivo NMR, ranging from people working in dedicated in vivo NMR institutes, to radiologists in hospitals, researchers in high-resolution NMR and MRI, and in areas such as neurology, physiology, chemistry, and medical biology.
