Partnership for Magnetic Resonance Spectroscopy Biomarker Development

 描述(申请人提供)：神经退行性疾病的临床试验因缺乏反映大脑治疗效果的定量和客观生物标记物而受阻。磁共振波谱(MRS)有可能直接评估脑内治疗干预的疾病改善效果。然而，MRS尚未过渡到临床环境，这主要是由于缺乏标准化的数据采集和分析方法，以及使用标准临床程序包获得的数据质量下降，导致神经化学浓度的重复性较差。该应用程序的主要目标是促进先进的MRS技术在MR物理学家、软件工程师和内科科学家之间的战略联盟中转化为临床环境。MRS Biomarker开发的这一合作伙伴关系由3个阶段组成，包括在相关地点从MRI/MRS向临床专业知识的逐步转变：第一阶段将在两个广泛使用的临床3T平台上建立一个MR技术员准备好的高级MRS协议。优化的半激光(SLASER)序列被选择用于该实施，因为它被MRS共识小组认为是推荐高场的最佳候选者。第二阶段将评估方案在理想条件下(疗效)的表现，即在磁共振成像/S和临床试验专业知识重叠的地点。我们将重点放在遗传性脊髓小脑性共济失调(SCA)上，因为患者队列具有良好的特征，他们最需要多中心研究来在试验中对患者群体进行充分抽样。脊髓小脑性共济失调临床研究联盟(CRC-SCA)的四个站点将参与这一阶段，该联盟成立的目的是为常见SCA的临床试验提供基础设施。最后，第三阶段将评估协议在普通条件下的性能(有效性)，即在有轮流磁共振技术人员的临床环境中。这一阶段将重点关注阿尔茨海默病(AD)，这是与年龄相关的认知能力下降和痴呆的最常见原因，并利用正在进行的大型神经成像研究。这个应用程序有一个翻译重点。该项目的生物工程重点领域包括用于神经成像应用的先进高场磁共振技术、光谱采集和分析方法的验证和重复性评估，以及帮助监测脑部疾病治疗反应的非侵入性技术。合作地点是明尼苏达大学(主要机构)、约翰霍普金斯大学[第一阶段和第二阶段]、杜克大学[第一阶段]、佛罗里达大学[第二阶段]、哈佛大学[第二阶段]、梅奥诊所[第三阶段]和密歇根大学[第三阶段]。该项目的成果将是一个交钥匙的高级MRS数据采集和分析协议，该协议已经在多个患者队列、大脑区域、平台和机构(包括临床设置)中进行了全面评估。预计在神经退行性疾病的早期诊断和治疗方面将产生很大影响。

 DESCRIPTION (provided by applicant): Clinical trials for neurodegenerative diseases are hampered by the lack of quantitative and objective biomarkers that reflect treatment effects in the brain. Magnetic resonance spectroscopy (MRS) has potential to directly assess disease-modifying effects of therapeutic interventions in the brain. However, MRS has not made the transition to the clinical setting, largely due to lack of standardization of data acquisition and analysis methods and compromised data quality obtained with standard clinical packages, which result in poor reproducibility of neurochemical concentrations. The primary objective of this application is to facilitate translation of advanced MRS technology to the clinical setting ina strategic alliance between MR physicists, software engineers and physician scientists. This Partnership for MRS Biomarker Development is comprised of 3 phases and incorporates a gradual shift from MRI/MRS to clinical expertise at the sites involved: Phase I will establish an MR-technologist ready advanced MRS protocol on two widely-used clinical 3T platforms. An optimized semi-LASER (sLASER) sequence was chosen for this implementation because it is considered a top candidate for recommendation for high fields by the MRS Consensus Group. Phase II will assess the performance of the protocol under ideal conditions (efficacy), namely at sites where MRI/S and clinical trial expertise overlap. We focus on hereditary spinocerebellar ataxias (SCA) because the patient cohorts are well-characterized and they present the greatest need for multi-center investigations to sufficiently sample the patient population in trials. Four sites of the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which was formed to provide infrastructure for clinical trials in the common SCAs, will participate in this phase. Finally, Phase III will assess the performance of the protocol under ordinary conditions (effectiveness), i.e. in a clinical setting with rotating MR technologists. This phase will focus o Alzheimer disease (AD), the most common cause of age associated cognitive decline and dementia, and take advantage of large ongoing neuroimaging investigations. This application has a translational focus. The bioengineering focus areas of this project include advanced high field MRI technology for neuroimaging applications, validation and reproducibility assessment of spectral acquisition and analysis methods and non-invasive technology to assist monitoring treatment response in brain disorders. The partnership sites are the University of Minnesota (leading institution), Johns Hopkins University [Phases I and II], Duke University [Phase I], University of Florida [Phase II], Harvard University [Phase II], Mayo Clinic [Phase III] and University of Michigan [Phase III]. The deliverable of this project will be a turn-key advanced MRS data acquisition and analysis protocol that has been comprehensively evaluated in multiple patient cohorts, brain regions, platforms, and institutions, including the clinical settin. A high impact is expected in early diagnosis and treatment of neurodegenerative diseases.