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: 8039181
• 负责人: Alexey Samsonov
• 金额: $ 31.5万
• 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/8039181
• 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; Health; 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; developmental disease; 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; 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）：多发性硬化症的高级定量磁化传递成像多发性硬化症（MS）是一种复杂的神经退行性疾病，其症状、临床病程和神经组织的潜在病理变化高度可变。虽然磁共振成像（MRI）已成为一个重要的诊断工具，提供非侵入性证据的MS病变，常规MRI相关性较差的临床残疾，其预后价值是非常有限的。需要立即使用特异性和更灵敏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。这些生物标志物也是衡量新兴的神经保护和髓鞘修复方法（如干细胞移植）的有效性所必需的。最终，开发这些生物标志物将允许识别最有可能从疾病修饰疗法的早期治疗中受益的患者。磁化传递成像（MTI）探头可以通过对传统MRI无法测量的固定结合质子产生敏感性，揭示对脱髓鞘和轴突丢失的其他隐匿性治疗效果。MT对比度对大分子组织成分的细微变化敏感，不仅在常规MRI可见的病变内，而且在常规MRI扫描可见的病变外，并且显示出预测残疾和检测MS病理的前景。然而，MR系统依赖性因素和MRI的多参数性质产生了混淆因素，限制了MTI的特异性和准确性，从而限制了其作为评估MS的生物标志物的临床实用性。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，则真正的定量MTI（qMTI）方法可以规避这些严重的缺陷。此外，定量成像需要沿参数维度沿着重复采样，这产生了需要扫描时间几倍增加的临床上不切实际的方法。该提案的总体目标是通过开发基于磁化转移的临床可行的定量MRI方法，生成具有改进特异性的真正定量生物标志物。我们已经注意到，可以通过新的图像估计重建方法来利用参数采样维中的冗余信息，以显著地加速成像方法。具体来说，我们的第一个目标是开发提供固有校准的定量MRI方法。目标集中在开发与并行成像能力兼容的强大的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，但更重要的是通过在第二个目标中开发的基于模型的图像重建算法为加速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，并能够在MS患者和年龄匹配的对照的小群体中早期检测病理。该项目将利用几个独特的资源和能力，在一个广泛的MS研究计划在UW-麦迪逊。如果成功，该技术不仅将改变MS的护理和治疗发展，而且还将用于其他白色物质为基础的疾病，包括神经退行性疾病，肿瘤，发育和精神疾病的研究，诊断和临床管理。公共卫生关系：多发性硬化症（MS）是困扰美国年轻人的单一最常见的衰弱性神经系统疾病。它是不可治愈的，并且在成年人的黄金时期发作（患者通常在20多岁、30多岁或40多岁时被诊断出），导致生活质量的惊人损失和美国每年68亿美元的总经济成本（1998年估计）。MS治疗的发展由于缺乏病程的非侵入性措施而受到很大阻碍，在患者或其医生的客观体征或症状变得明显之前，病程可能会大幅进展。这种对疾病的非侵入性措施的关键需求可以通过MRI技术的进步来满足;本研究的总体目标是确定MS疾病的敏感和特异性MRI标记物，这些标记物将指导当前疗法的应用，并促进有前途的新治疗方法（如干细胞移植）的发展。