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: 8824595
• 负责人: Seth A Smith
• 金额: $ 23.55万
• 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/8824595
• 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; research study; simulation; success; targeted imaging; 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）： 项目摘要 本提案的总体目标是在临床场强 (3T) 下开发和实施新型多模态定量磁共振成像 (MRI)，以定量评估多发性硬化症 (MS) 中 SC 病理学和神经功能缺损之间的关系。我们建议可以开发对组织微观结构（髓磷脂）和生物化学敏感的定量 MRI 方法，使其对 MS 中存在的亚体素病理学敏感。然而，SC 是一个具有挑战性的环境，要从中获取高分辨率、定量 MRI 数据。重要的是，先进的 MRI 方法主要是为了评估中枢神经系统的大型结构而开发的，由于其大小、位置和运动，在 SC 中的应用相对较少。然而，我们开展这项研究势在必行，因为人们假设 MS 的大部分临床缺陷是由于 SC 而非大脑的病变造成的。事实上，存在一个临床放射学悖论，即多发性硬化症患者的神经呈现素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来衡量 SC 所遭受的损害程度。其次，由于脊髓是按体位组织的，如果获得足够高质量的MRI数据，我们可以直接探测其结构-功能关系。我们建议开发、实施和评估两种 SC 健康状况的定量 MRI 测量方法，这两种方法都尚未针对 3T 的 SC 开发。首先，我们将开发一种高分辨率、快速、多点和单点定量磁化转移（qMT）实验来推导池大小比（PSR），该比值已被证明与髓磷脂密度直接相关。其次，我们已经证明酰胺质子转移（APT）-化学交换饱和转移（CEST）对高场下正常出现的白质的最早变化敏感。然而，为了使其在临床上可行，必须将其过渡到较低的视野并应用于 SC。因此，我们建议在 SC 中开发和实施高分辨率、稳健的 APT-CEST，以评估病变和其他正常白质中可能发生的变化。总之，该提案的成功将取决于对 MS 患者颈部 SC 的两种新型 MRI 测量的开发、验证和应用，潜在的回报是对晚期 MS 病理学的敏感性（即 qMT 脱髓鞘） ）和潜在的早期 MS 病理学（即 CEST 中的蛋白质积累）。如果成功，我们还将开发并验证 SC 工具箱，以定量评估影响 SC 的各种疾病中的髓磷脂变化、蛋白质（和 pH）变化。值得注意的是，视神经、周围神经和胸/腰脊髓的延伸完全在该提案的结果范围内。

项目成果

7T quantitative magnetization transfer (qMT) of cortical gray matter in multiple sclerosis correlates with cognitive impairment.

多发性硬化症患者皮质灰质的 7T 定量磁化传递 (qMT) 与认知障碍相关。

• DOI: 10.1016/j.neuroimage.2019.116190
• 发表时间: 2019-12
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: McKeithan LJ;Lyttle BD;Box BA;O'Grady KP;Dortch RD;Conrad BN;Thompson LM;Rogers BP;Newhouse P;Pawate S;Bagnato F;Smith SA
• 通讯作者: Smith SA

ZOOM or Non-ZOOM? Assessing Spinal Cord Diffusion Tensor Imaging Protocols for Multi-Centre Studies.

• DOI: 10.1371/journal.pone.0155557
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Samson RS;Lévy S;Schneider T;Smith AK;Smith SA;Cohen-Adad J;Gandini Wheeler-Kingshott CA
• 通讯作者: Gandini Wheeler-Kingshott CA