Partnership for Magnetic Resonance Spectroscopy Biomarker Development

磁共振波谱生物标志物开发合作

• 批准号: 9134877
• 负责人: Gulin Oz
• 金额: $ 64.53万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134877
• 关键词: Age-associated memory impairment; Alzheimer' s Disease; Area; Atlases; Biochemical; Biological Markers; Biomedical Engineering; Brain; Brain Diseases; Brain region; Central Nervous System Diseases; Cerebrum; Childhood Brain Neoplasm; Clinic; Clinical; Clinical Trials; Collaborations; Consensus; Data; Data Analyses; Data Quality; Dementia; Demyelinating Diseases; Diagnostic; Disease; Early Diagnosis; Early treatment; Effectiveness; Environment; Epilepsy; Florida; Funding; Goals; Health; Hereditary Disease; Imaging technology; Infection; Inherited; Institutes; Institution; International; Investigation; Laboratories; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Metabolic; Methods; Michigan; Minnesota; Monitor; Movement Disorders; Nerve Degeneration; Neurodegenerative Disorders; Pathology; Patients; Performance; Phase; Physicians; Physiologic pulse; Positioning Attribute; Process; Protocols documentation; Protons; Recommendation; Reproducibility; Research; Research Infrastructure; Research Personnel; Sampling; Scanning; Scientist; Site; Software Engineering; Specialized Center; Spinocerebellar Ataxias; Standardization; Stroke; Technology; Testing; Therapeutic Intervention; Training; Translations; United States National Institutes of Health; Universities; Validation; Vendor; base; biomarker development; clinical research site; cohort; data acquisition; healthy volunteer; indium arsenide; method development; mild cognitive impairment; nervous system disorder; neurochemistry; neuroimaging; open source; patient population; prognostic; quantitative imaging; research clinical testing; simulation; therapy development; treatment effect; treatment response

 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.

 描述（由申请人提供）：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的生物标志物而受到阻碍。磁共振波谱（MRS）有潜力直接评估大脑治疗干预的疾病缓解效果。然而，MRS尚未过渡到临床环境，很大程度上是由于数据采集和分析方法缺乏标准化，以及标准临床包获得的数据质量受损，导致神经化学浓度的重现性差。该应用程序的主要目标是通过 MR 物理学家、软件工程师和医师科学家之间的战略联盟，促进先进的 MRS 技术转化为临床环境。 MRS 生物标记物开发合作伙伴关系由 3 个阶段组成，并在相关地点逐步从 MRI/MRS 转向临床专业知识：第一阶段将在两个广泛使用的临床 3T 平台上建立 MR 技术人员就绪的高级 MRS 协议。为此实施选择了优化的半激光 (sLASER) 序列，因为它被 MRS 共识组视为高场推荐的最佳候选序列。第二阶段将评估理想条件下方案的性能（功效），即在 MRI/S 和临床试验专业知识重叠的地点。我们关注遗传性脊髓小脑性共济失调 (SCA)，因为患者群体特征明确，并且最需要进行多中心研究，以便在试验中对患者群体进行充分采样。脊髓小脑性共济失调临床研究联盟 (CRC-SCA) 的四个中心将参与这一阶段，该联盟的成立是为了为常见 SCA 的临床试验提供基础设施。最后，第三阶段将评估该方案在普通条件下的性能（有效性），即在具有轮流 MR 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规模神经影像学研究。该应用程序的重点是翻译。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 MRI 技术、光谱采集和分析方法的验证和可重复性评估以及协助监测脑部疾病治疗反应的非侵入性技术。合作地点包括明尼苏达大学（领先机构）、约翰·霍普金斯大学[第一期和第二期]、杜克大学[第一期]、佛罗里达大学[第二期]、哈佛大学[第二期]、梅奥诊所[第三期]和密歇根大学[第三期]。该项目的交付成果将是一个交钥匙的先进 MRS 数据采集和分析协议，该协议已在多个患者队列、大脑区域、平台和机构（包括临床设置）中进行了全面评估。预计会对神经退行性疾病的早期诊断和治疗产生巨大影响。