权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of Quantitative Deuterium MRS Imaging for Human Brain Tumor Application at Ultrahigh Field

超高场定量氘 MRS 成像在人脑肿瘤应用中的发展

基本信息

批准号：
10468203
负责人：
Clark Chin-Chung Chen
金额：
$ 53万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10468203
关键词：
3-Dimensional Adult Animal Experimentation Animals Area Basic Science Biochemical Biological Biopsy Specimen Brain Brain Neoplasms Caring Cell Respiration Cells Cerebrum Chemotherapy and/or radiation Citric Acid Cycle Clinic Clinical Clinical Treatment Computer software Data Detection Deuterium Development Diagnosis Disease Energy Metabolism Engineering Fatality rate Functional disorder Funding Future Glioblastoma Glucose Glutamates Glutamine Glycolysis Goals Human Human body Ice Image Imaging Techniques Imaging technology Immune Intake Interdisciplinary Study Intravenous infusion procedures Label Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Malignant Neoplasms Malignant neoplasm of brain Measurement Measures Metabolic Metabolic Marker Methods Minnesota Mitochondria Modality Modeling Monitor Mutation Neurosurgeon Noise Normal tissue morphology Operative Surgical Procedures Oral Outcome Pathologic Pathology Patients Physiologic pulse Pilot Projects Positron-Emission Tomography Production Prognosis Property Pyruvate RF coil Radiation therapy Research Research Personnel Resistance Resolution Sensitivity and Specificity Signal Transduction Site Specificity Specimen Techniques Technology Testing Time Training United States National Institutes of Health Universities Warburg Effect Work aerobic glycolysis anticancer research base brain disorder diagnosis brain morphology brain tissue cancer cell clinical diagnosis contrast imaging cost effective data analysis pipeline expectation fluorodeoxyglucose glucose metabolism glucose uptake human imaging image processing imaging modality imaging study improved in vivo indexing innovation kinetic model magnetic field magnetic resonance spectroscopic imaging metabolic imaging metabolic rate neuro-oncology neurochemistry neuroimaging neuropathology novel novel imaging technique novel therapeutics oxidation quantitative imaging software development spatiotemporal spectroscopic imaging success therapeutic development tool treatment response tumor tumor heterogeneity tumor progression

项目摘要

PROJECT SUMMARY Glioblastoma (GBM) is the most aggressive form of human cancers with very high fatality rate and short survival time, and the cancer cells aggressively infiltrate the brain and are intrinsically resistant to chemotherapy and radiation therapy. Intra-tumoral heterogeneity is a major challenge in therapeutic development for GBM patients because surgical acquisition of clinical specimens cannot be used to monitor the tumor progression and/or the underlying metabolic changes. Various neuroimaging methods have been used to study the morphology of the brain tumors. However, the need for noninvasively characterizing the brain tumors and their metabolic features has not been met, which should be critical for prognosis or for monitoring the tumor progression and response to treatment. It is well known that a common hallmark of the cancer cells is disrupted glucose metabolism, in which upregulated glycolysis is accompanied by inhibited mitochondrial oxidation, i.e., the “Warburg effect”. Imaging the “Warburg effect” and its spatial variability in brain tumors is a new attempt that can have a major impact on cancer research, particularly in the treatment of GBM, because therapies aimed at reversing the Warburg effect have shown promise in GBM ; however, great efforts are needed to develop novel metabolic imaging techniques to achieve the capabilities sought by clinicians. We have recently initiated a project aiming to develop a neuroimaging technique based on deuterium (2H) MRS (DMRS) detection of 2H-labeled brain metabolites following an administration of D-Glucose-6,6-d2 (d66). Our preliminary results indicate that the dynamic DMRS imaging can determine the cerebral metabolic rates of glucose (CMRGlc) and TCA cycle (VTCA), thus, the lactate production rate (CMRLac) in addition to the concentrations of deuterium-labeled glucose (Glc), mixed glutamate/glutamine (Glx) and lactate (Lac) in living brains. Furthermore, we demonstrated for the first time that the uncoupling between the glycolysis and oxidation in brain tumor can be quantitatively imaged via mapping the [Lac]/[Glx] ratio defined as an index of Warburg effect (IWE); and it has been shown that IWE is highly sensitive for distinguishing brain tumor from surrounding normal tissues. In this application, we are seeking NIH funding support to move forward with the DMRS imaging development through: i) integrated hardware and software development and the ultrahigh field MR technology to further boost signal-to-noise ratio (SNR), spectral resolution and spatiotemporal resolution; ii) testing the ultrahigh resolution DMRS imaging in healthy subject, and tumor patients and establishing a quantification model and imaging processing pipeline for future application; and iii) comparing the DMRS imaging results with the neuropathological and immunohistochemical findings of the biospecimens to understand the correlation between the DMRSI measurements and biological features of brain tumor. Our interdisciplinary research team with unique expertise is ready for a full-scale development of this highly innovative and cost-effective neuroimaging essential for basic research and clinic application in neuro-oncology.

项目总结