Partnership for Magnetic Resonance Spectroscopy Biomarker Development

磁共振波谱生物标志物开发合作伙伴关系

• 批准号: 8929438
• 负责人: Gulin Oz
• 金额: $ 69.06万
• 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/8929438
• 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; Development; Diagnostic; Disease; Early Diagnosis; Early treatment; Effectiveness; Environment; Epilepsy; Florida; Funding; Goals; 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; 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; public health relevance; 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（由适用提供）：缺乏反映大脑治疗效果的定量和客观生物标志物，阻碍了神经退行性疾病的临床试验。磁共振光谱（MRS）具有直接评估大脑治疗干预措施的疾病改良作用的潜力。但是，MRS并未过渡到临床环境，这主要是由于缺乏数据采集和分析方法的标准化以及使用标准临床包装获得的数据质量损害，这导致神经化学浓度的可重复性差。该应用的主要目的是促进先进的MRS技术向临床环境转换为MR物理学家，软件工程师和物理科学家之间的战略联盟。这种针对生物标志物夫人开发的合作伙伴关系完成了3个阶段，并在所涉及的网站上纳入了从MRI/MRS到临床专业知识的年级转变：I期将在两个广泛使用的临床3T平台上建立MR-TECHNOCGER REACH ADVACH MRS MRS协议。为此实现选择了优化的半激光（Slaser）序列，因为MRS共识组被认为是高场推荐的最高候选者。第二阶段将在理想条件（功效）下评估协议的性能，即MRI/S和临床试验专业知识重叠的地点。我们专注于Herditary Spinocerebellar共济失调（SCA），因为患者队列的表征良好，并且它们对多中心投资的最大需求是在试验中充分对患者人群进行充分的品尝。形成的四个脊椎动物共济失调（CRC-SCA）的临床研究联盟的四个地点将参与此阶段。最后，第三阶段将在普通条件下（有效性），即在旋转MR技术的临床环境中评估协议的性能。这一阶段将集中于阿尔茨海默氏病（AD），这是年龄相关的认知能力下降和痴呆症的最常见原因，并利用大量持续的神经影像学调查。该应用程序具有翻译重点。该项目的生物工程重点领域包括用于神经影像应用的高级高场MRI技术，光谱获取和分析方法的验证和可重复性评估以及非侵入性技术，以帮助监测脑疾病中的治疗反应。合作伙伴关系站点是明尼苏达大学（领先的机构），约翰·霍普金斯大学[阶段I和II]，杜克大学[I阶段]，佛罗里达大学[第二阶段]，哈佛大学[第二阶段]，Mayo Clinic [III期]和密歇根大学[III期]和密歇根大学[III期]。该项目的可交付将是一个交钥匙高级MRS数据采集和分析方案，在包括临床定居在内的多个患者同类，大脑区域，平台和机构中都经过了全面评估。预计在早期诊断和神经退行性疾病的治疗中会产生很大的影响。