In Vivo Macromolecular and Protein-Based MRI in the Spinal Cord of MS Patients

多发性硬化症患者脊髓的体内大分子和蛋白质 MRI

• 批准号: 8684183
• 负责人: Seth A Smith
• 金额: $ 19.59万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8684183
• 关键词: Active Biological Transport; Address; Adrenomyeloneuropathy; Affect; Amides; Atrophic; Biochemistry; Brain; Cervical; Cervical spinal cord structure; Chemicals; Chest; Clinical; Data; Data Set; Demyelinations; Dependency; Development; Diffusion Magnetic Resonance Imaging; Disease; Environment; Esthesia; Goals; Health; Hip region structure; Histocompatibility Testing; Human; Image; Impairment; Inflammation; Lesion; Location; Lumbar spinal cord structure; Magnetic Resonance Imaging; Malignant Neoplasms; Manuscripts; Measures; Methods; Microscopic; Modeling; Motion; Motivation; Multiple Sclerosis; Myelin; Myelin Proteins; Nervous System Physiology; Neuraxis; Neurologic; Neurologic Dysfunctions; Neuromyelitis Optica; Noise; Optic Nerve; Pathology; Patients; Peptides; Peripheral Nerves; Physiologic pulse; Proteins; Protons; Reporting; Reproducibility; Resolution; Scanning; Severities; Signal Transduction; Site; Spinal Canal; Spinal Cord; Spinal Cord Column; Spinal Cord Diseases; Spinal cord damage; Spinal cord injury; Staging; Stroke; Structure; Structure-Activity Relationship; Swelling; Technology; Testing; Time; Tissues; Toes; Transverse Myelitis; Validation; Vertebral column; Water; base; burden of illness; cell motility; cohort; density; dorsal column; emerging adult; experience; gray matter; healthy volunteer; imaging modality; in vivo; indexing; insight; lateral column; nervous system disorder; neurochemistry; neurological pathology; novel; public health relevance; research study; simulation; success; ventral column; vibration; white matter

DESCRIPTION (provided by applicant): Project Summary The overall goal of this proposal is to develop and implement novel, multi-modal, quantitative magnetic resonance imaging (MRI) in the human spinal cord (SC) at clinical field strengths (3T) to quantitatively assess the relationship between SC pathology and neurological deficit in multiple sclerosis (MS). We propose that quantitative MRI methods sensitive to tissue microstructure (myelin) and biochemistry can be developed to be sensitive to sub-voxel pathology that is present in MS. However, the SC is a challenging environment from which to obtain high-resolution, quantitative MRI data. Importantly, advanced MRI methods have mainly been developed to assess large structures of central nervous system and relatively few have been applied in the SC due to its size, location, and motion. Yet it is imperative that we embark on this study as it has been hypothesized that the bulk of clinical deficit in MS comes as a result of lesions in the SC rather than the brain. In fact, a clinical radiological paradox exists in that the neurological presentatin in patients with MS does not always match the severity of radiological findings. We propose that this is due to the lack of quantitative and sensitive markers for the magnitude of damage that the SC experiences. Secondly, since the spinal cord is somatotopically organized, if sufficient quality MRI data are obtained, we can directly probe the structure- function relationship. We propose to develop, implement and evaluate two quantitative MRI measures of the health of the SC, neither of which have been developed for the SC at 3T. First, we will develop a high- resolution, rapid, multi- and single-point quantitative magnetization transfer (qMT) experiment to derive the pool size ratio (PSR), which has been shown to be directly correlated with myelin density. Secondly, we have shown that amide proton transfer (APT) - chemical exchange saturation transfer (CEST) is sensitive to the earliest changes in normal appearing white matter at high field. Nevertheless, for this to be clinically viable, it must be transitioned to lower fied and applied to the SC. Thus, we propose to develop and implement high- resolution, robust APT-CEST in the SC to assess the changes that may occur in lesions and in otherwise normal appearing white matter. Together, the success of this proposal will be determined by the development, validation, and application of two novel MRI measures to the cervical SC of patients with MS with the potential pay-off being sensitivity to late-stage MS pathology (i.e. demyelination from qMT) and potentially early stage MS pathology (i.e. protein accumulation from CEST). If successful, we will also have developed and validated a SC toolbox to quantitatively assess myelin changes, protein (and pH) changes in a variety of diseases that affect the SC. It should not go with out notice that extensions to the optic nerve, peripheral nerves, and thoracic/lumbar spinal cord are well within the scope of the results of this proposal.

描述（由申请人提供）：项目总结本提案的总体目标是在临床场强（3 T）下开发和实施人体脊髓（SC）中的新型、多模态、定量磁共振成像（MRI），以定量评估多发性硬化（MS）中SC病理与神经功能缺损之间的关系。我们建议，定量MRI方法敏感的组织微观结构（髓鞘）和生物化学可以开发敏感的亚体素病理是存在于MS。然而，SC是一个具有挑战性的环境，从中获得高分辨率，定量MRI数据。重要的是，先进的MRI方法主要用于评估中枢神经系统的大型结构，由于其大小，位置和运动，相对较少应用于SC。然而，我们必须开始这项研究，因为它已经假设，MS的大部分临床缺陷是由于SC而不是大脑的病变。事实上，临床放射学存在一个矛盾，即MS患者的神经系统表现并不总是与放射学结果的严重程度相匹配。我们认为，这是由于缺乏定量和敏感的标记物的损伤程度，SC的经验。第二，由于脊髓是在体视学上组织的，如果获得足够质量的MRI数据，我们可以直接探讨结构-功能关系。我们建议开发，实施和评估两个定量MRI措施的健康的SC，这两个都没有开发的SC在3 T。首先，我们将开发一个高分辨率，快速，多点和单点定量磁化转移（qMT）实验，以获得池尺寸比（PSR），这已被证明是直接相关的髓鞘密度。其次，我们已经表明，酰胺质子转移（APT）-化学交换饱和转移（CEST）是敏感的最早出现的白色物质在高场的变化。然而，这是临床上可行的，它必须过渡到较低的fied和应用于SC。因此，我们建议开发和实施高分辨率，强大的APT-CEST在SC中，以评估可能发生的变化，在病变和其他正常的外观白色的问题。总之，该提案的成功将取决于两种新型MRI测量方法的开发、验证和应用，以及对MS患者的宫颈SC的潜在回报，即对晚期MS病理（即qMT脱髓鞘）和潜在早期MS病理（即CEST蛋白质蓄积）的敏感性。如果成功，我们还将开发和验证一个SC工具箱，以定量评估髓鞘变化，蛋白质（和pH值）的变化，在各种疾病的影响SC。它不应该没有注意到，延伸到视神经，周围神经，和胸/腰脊髓是在本提案的结果范围内。