Advanced Magnetization Transfer Imaging in Multiple Sclerosis Disease

多发性硬化症的先进磁化转移成像

• 批准号: 7635079
• 负责人: Alexey Samsonov
• 金额: $ 32.14万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7635079
• 关键词: Acceleration; Acute; Adult; Age; Algorithms; Binding; Biological Markers; Calibration; Caring; Central Nervous System Diseases; Clinic; Clinical; Clinical Management; Clinical Research; Clinical Trials; Communities; Complement; Complex; Computer software; Conflict (Psychology); Data; Databases; Demyelinations; Detection; Development; Diagnosis; Diagnostic; Dimensions; Disease; Disease Progression; Early Diagnosis; Early treatment; Edema; Employee Strikes; Enhancing Lesion; Evolution; Fostering; Foundations; Goals; Hospitals; Hour; Image; Imaging Techniques; Imaging technology; Inflammation; Lesion; Life; Magnetic Resonance Imaging; Measurement; Measures; Mental disorders; Methods; Metric; Modeling; Monitor; Motion; Multiple Sclerosis; Multiple Sclerosis Lesions; Myelin; Nature; Nerve Degeneration; Neurodegenerative Disorders; Outcome Measure; Pathologic; Pathology; Patients; Performance; Phase I/II Trial; Physicians; Physiologic pulse; Population; Process; Protocols documentation; Protons; Quality of life; Radial; Reporting; Research; Resolution; Resources; Sampling; Scanning; Series; Specificity; Staging; Stem cell transplant; Symptoms; System; Techniques; Time; Tissues; Universities; Validation; Wisconsin; base; clinically relevant; density; design; disability; economic cost; effectiveness measure; experience; image reconstruction; imaging modality; imaging probe; improved; innovation; meetings; model development; neoplastic; nervous system disorder; neuropathology; neuroprotection; novel; novel therapeutic intervention; prognostic; programs; public health relevance; reconstruction; relating to nervous system; repaired; therapy development; tool; treatment effect; white matter; young adult

DESCRIPTION (provided by applicant): Advanced Quantitative Magnetization Transfer Imaging in Multiple Sclerosis Disease Multiple sclerosis (MS) is a complex neurodegenerative disease that is highly variable in symptoms, clinical course, and underlying pathological changes in neural tissues. While magnetic resonance imaging (MRI) has become an important diagnostic tool providing noninvasive evidence of MS lesions, conventional MRI correlates poorly with clinical disability and its prognostic value is very limited. Specific and more sensitive imaging biomarkers are needed immediately to monitor disease progression, provide early outcome measures in clinical trials, and guide clinical decisions regarding current treatment options, particularly during the early stages of the disease. These biomarkers are also necessary to measure the effectiveness of emerging approaches to neuroprotection and myelin repair, such as stem cell transplantation. Ultimately, developing these biomarkers will allow identification of patients who are most likely to benefit from early treatment with disease-modifying therapy. Magnetization transfer imaging (MTI) probes can reveal otherwise occult treatment effects on demyelination and axonal loss by creating sensitivity to immobile bound protons immeasurable by conventional MRI. MT contrast is sensitive to subtle changes in macromolecular tissue composition, not only within but also beyond lesions visible in conventional MRI, and shows promise for prediction of disability and detection of MS pathology before it becomes visible on conventional MRI scans. However, MR system-dependent factors and the multi-parametric nature of MRI create confounding factors that limit the specificity and accuracy of MTI and thus restrict its clinical utility as a biomarker in assessing MS. Truly quantitative MTI (qMTI) methods can circumvent these crippling deficiencies if rapid calibration and measurement of other MR parameters can be obtained in a reasonable scan time. In addition, quantitative imaging requires repetitive sampling along a parametric dimension, creating a clinically impractical method that requires a several-fold increase in scan time. The overarching aim of this proposal is to generate truly quantitative biomarkers with improved specificity through the development of clinically feasible, quantitative MRI methods based on magnetization transfer. We have noticed that redundant information in the parametric sampling dimension can be exploited through new image estimation reconstruction methods to dramatically accelerate imaging methods. Specifically, our first aim will develop quantitative MRI methods that provide inherent calibration. The aim centers on developing robust 3D radial imaging methods compatible with parallel imaging capabilities. The variable sampling density with these trajectories allows acceleration through undersampling, but more importantly provides a foundation for accelerating qMTI through model-based image reconstruction algorithms developed in the second aim. Finally, the third aim will measure the ability of qMT biomarkers to predict clinical disability and lesion evolution and enable early detection of pathology in a small population of MS patients and age-matched controls. The project will leverage several unique resources and capabilities in a broad MS research program at UW- Madison. If successful, the techniques will not only change care and treatment development in MS, but will also be useful for the study, diagnosis, and clinical management of other white matter-based diseases including neurodegenerative, neoplastic, developmental and psychiatric disorders. PUBLIC HEALTH RELEVANCE: Multiple sclerosis (MS) is the single most common debilitating neurological disease afflicting young adults in the U.S. It is incurable and it strikes during the prime years of adult life (patients are typically diagnosed in their 20's, 30's or 40's), resulting in a staggering loss of quality of life and a total economic cost to the U.S. of $6.8 billion annually (1998 estimate). The development of therapies for MS is greatly impeded by the lack of noninvasive measures of the disease course, which can progress substantially before objective signs or symptoms become apparent to the patient or his physician. This critical need for noninvasive measures of the disease can be met through advances in MRI technology; the overarching aim of this research is to identify sensitive and specific MRI markers for MS disease that will guide the application of current therapies and foster the development of promising new therapeutic approaches such as stem cell transplantation.

描述（由申请人提供）：多发性硬化症（MS）是一种复杂的神经退行性疾病，在症状、临床过程和神经组织的潜在病理改变方面具有高度的可变性。虽然磁共振成像（MRI）已成为一种重要的诊断工具，为MS病变提供无创证据，但常规MRI与临床残疾的相关性较差，其预后价值非常有限。立即需要特异性和更敏感的成像生物标志物来监测疾病进展，在临床试验中提供早期结果测量，并指导有关当前治疗方案的临床决策，特别是在疾病的早期阶段。这些生物标志物对于测量新兴的神经保护和髓磷脂修复方法的有效性也是必要的，例如干细胞移植。最终，开发这些生物标志物将允许识别最有可能从疾病改善疗法的早期治疗中受益的患者。磁化转移成像（MTI）探针可以通过对常规MRI无法测量的固定结合质子产生敏感性，从而揭示脱髓鞘和轴突损失的其他隐蔽治疗效果。MT对比对大分子组织组成的细微变化很敏感，不仅在常规MRI可见的病变内，而且在常规MRI扫描可见病变之外，并且有望在常规MRI扫描可见病变之前预测残疾和检测MS病理。然而，MR系统依赖因素和MRI的多参数特性产生了混淆因素，限制了MTI的特异性和准确性，从而限制了其作为ms评估生物标志物的临床应用。真正的定量MTI （qMTI）方法可以避免这些严重的缺陷，如果可以在合理的扫描时间内获得其他MR参数的快速校准和测量。此外，定量成像需要沿着参数维度重复采样，这是一种临床上不切实际的方法，需要将扫描时间增加几倍。该提案的总体目标是通过开发临床可行的、基于磁化转移的定量MRI方法，产生具有更高特异性的真正定量的生物标志物。我们注意到，通过新的图像估计重建方法可以利用参数采样维度中的冗余信息，从而大大加快成像方法。具体来说，我们的第一个目标是开发定量MRI方法，提供固有的校准。目标集中于开发与并行成像能力兼容的鲁棒3D径向成像方法。这些轨迹的可变采样密度允许通过欠采样加速，但更重要的是为通过第二个目标中开发的基于模型的图像重建算法加速qMTI提供了基础。最后，第三个目标将测量qMT生物标志物预测临床残疾和病变演变的能力，并在一小部分MS患者和年龄匹配的对照组中实现早期病理检测。该项目将在威斯康星大学麦迪逊分校的一个广泛的MS研究项目中利用几个独特的资源和能力。如果成功，这些技术不仅将改变MS的护理和治疗发展，而且还将有助于其他白质疾病的研究、诊断和临床管理，包括神经退行性疾病、肿瘤、发育和精神疾病。公共卫生相关性：多发性硬化症（MS）是困扰美国年轻人的最常见的一种使人衰弱的神经系统疾病。它是无法治愈的，它发生在成年人的黄金时期（患者通常在20多岁、30多岁或40多岁被诊断出来），导致生活质量的惊人损失，每年给美国造成68亿美元的总经济损失（1998年估计）。由于缺乏对病程的非侵入性测量，MS治疗的发展受到很大阻碍，病程可以在患者或其医生发现客观体征或症状之前实质性进展。MRI技术的进步可以满足这种对疾病无创测量的迫切需求；这项研究的总体目标是确定MS疾病的敏感和特异性MRI标记物，这将指导当前治疗方法的应用，并促进有前途的新治疗方法的发展，如干细胞移植。