Novel Method for Imaging Cartilage

软骨成像新方法

基本信息

批准号：
7727838
负责人：
Ravinder Regatte
金额：
$ 19.02万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7727838
关键词：
Affect Age American Amides Amines Biochemical Biological Assay Biological Models Bovine Cartilage Cartilage Chemicals Chondroitin Sulfates Clinical Clinical Trials Collagen Collagen Fibril Contrast Media Cytoskeleton Degenerative polyarthritis Deposition Detection Development Diagnostic Disease Elderly Event Exercise Frequencies Functional Imaging Gadolinium Glycosaminoglycans Goals Healthcare Systems Hydroxyl Radical Image Imaging Techniques Individual Injection of therapeutic agent Joints Knowledge Magnetic Resonance Imaging Measures Mediating Methodology Methods Modality Modeling Modification Molecular NMR Spectroscopy Outcome Penetration Physiological Pilot Projects Population Positioning Attribute Proteoglycan Protons Quality of life Radio Relaxation Research Proposals Secondary to Signal Transduction Site Slice Sodium Specificity Specimen Spectrum Analysis Staging Surface Techniques Thick Time Tissues Water Weight Work base clinical application design effective therapy imaging modality in vivo innovation macromolecule magnetic field novel progesterone 11-hemisuccinate-(2-iodohistamine)public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this explorative research proposal (R21) is to develop a novel proton based method for quantifying the early biochemical changes of cartilage via chemical exchange dependent saturation transfer (CEST). Osteoarthritis (OA) affects over 50 million Americans and has a substantial impact on the economy and the health care system. Currently, there is no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. The conventional MR techniques have shown promise for the identification of more subtle morphologic alterations as determined by cartilage volume, or surface fibrillation. However, they even the more innovative of these conventional techniques have not been consistent in detecting the earliest stages (biochemical/functional integrity) of cartilage degeneration Newer techniques, such as delayed gadolinium (Gd)-enhanced MRI of cartilage (dGEMRIC), spin-lattice relaxation in the rotating frame (T1A) and sodium imaging have focused on more physiologic imaging of cartilage. However, dGEMRIC and T1A have some limitations for clinical applications. For example; dGEMRIC requires exogenous contrast agent as well as 90 minute waiting period while T1A has significant radio-frequency (RF) energy deposition and requires a long acquisition time. Although, sodium MRI is highly specific to PG, it requires RF hardware modification and high static magnetic fields (Bo) and has inherently low sensitivity, all of which limit this techniques clinical utility. Based on these limitations of both conventional as well as more innovative MR techniques, we recently developed a new proton method based on chemical exchange dependent saturation transfer (CEST). In this developmental R21 project, we will lay the ground work for a novel proton based method for quantifying glycosaminoglycan (GAG) of cartilage via CEST imaging. This project will allow us to identify an appropriate chemical exchange site (sites) that could be developed for use as an endogenous CEST contrast under physiological conditions and validate in model systems (chondroitin sulfate and collagen phantoms) as well as excised bovine cartilage specimens undergoing sequential enzymatic depletion. The results will be correlated with currently utilized MRI techniques (dGEMRIC, T1A and sodium MR) and respective biochemical assays. Our preliminary results indicate that the CEST based approach will provide unique, endogenous contrast mechanism, and determine a clear connection between CEST contrast and early degenerative changes in cartilage tissue. Once the CEST methodology is developed and validated in model systems (chondroitin sulfate, collagen phantoms, and excised bovine cartilage with sequential depletion), the proposed technique will have the potential to detect early biochemical changes of cartilage in vivo. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) affects more than half of the population above the age of 65 and has a significant negative impact on their quality of life. Currently there is no cure for this debilitating disease and the effective treatment is, at best, focused on symptomatic relief. The proposed R21 developmental project will allow us to establish a new method via chemical exchange dependent saturation transfer (CEST) contrast modality for detecting early degenerative changes in cartilage.

描述（由申请人提供）：该探索性研究建议的长期目标（R21）是开发一种基于质子的新方法，用于通过化学交换依赖性饱和转移（CEST）来量化软骨的早期生化变化。骨关节炎（OA）影响了超过5000万美国人，并对经济和医疗保健系统产生了重大影响。当前，这种使这种使人衰弱的疾病无法治愈，有效治疗充其量是症状缓解。常规的MR技术显示出有望鉴定通过软骨体积或表面纤颤确定的更微妙的形态改变。 However, they even the more innovative of these conventional techniques have not been consistent in detecting the earliest stages (biochemical/functional integrity) of cartilage degeneration Newer techniques, such as delayed gadolinium (Gd)-enhanced MRI of cartilage (dGEMRIC), spin-lattice relaxation in the rotating frame (T1A) and sodium imaging have focused on more physiologic imaging软骨。但是，Dgemric和T1a对临床应用有一些局限性。例如; Dgemric需要外源性对比剂以及90分钟的等待期，而T1A具有明显的射频（RF）能量沉积，并且需要长时间的收购时间。虽然，钠MRI对PG高度特异性，但它需要RF硬件修改和高静态磁场（BO），并且具有固有的敏感性低，所有这些都限制了该技术临床实用性。基于传统和更具创新性的MR技术的这些局限性，我们最近开发了一种基于化学交换依赖性饱和转移（CEST）的新质子方法。在这个发展性R21项目中，我们将为基于质子的新方法奠定基础工作，以通过CEST成像量化软骨的糖胺聚糖（GAG）。该项目将使我们能够识别一个适当的化学交换位点（位点），该地点可以用作生理条件下的内源性CEST对比度，并在模型系统（硫酸软骨素和胶原蛋白幻影）中验证以及切除的牛软骨样品以及经过顺序综合消耗的情况。结果将与当前使用的MRI技术（DGemric，T1A和MR）和各自的生化测定相关。我们的初步结果表明，基于CEST的方法将提供独特的内源性对比机制，并确定CEST对比度与软骨组织的早期退行性变化之间的明显联系。一旦在模型系统（硫酸软管，胶原蛋白幻象和切除的牛软骨）中开发并验证了CEST方法论，则提出的技术将有可能检测体内软骨的早期生化变化。公共卫生相关性：骨关节炎（OA）影响超过65岁以上人口的一半以上，对其生活质量产生了重大负面影响。当前，这种使人衰弱的疾病无法治愈，有效治疗充其量是症状缓解。拟议的R21发展项目将使我们能够通过化学交换依赖饱和转移（CEST）对比度建立一种新方法，以检测软骨的早期退行性变化。