Perfusion MRI for Multi-site Studies of Brain Function

描述(申请人提供)：动脉自旋标记(ASL)灌注核磁共振显示了广泛可用的静息脑功能的定量测量，可用作精神和神经疾病的神经相关性的生物标记物，用于测量大脑中的药物效果，并最终用于对个别患者的诊断和治疗监测。尽管ASL灌注MRI技术目前已在大多数MRI扫描仪平台上实施，但社区对各种技术实施的性能差异以及如何最好地跨中心和MRI扫描仪平台使用该技术的不确定性限制了其在临床研究中的常规应用。基于我们在前一个资金周期中成功开发了跨平台的量化方法和标准序列，我们建议将重点放在限制ASL多中心研究的关键问题上。我们的第一个目标是通过比较不同的ASL实现的重复性以及它们对两种测试干预的反应来衡量ASL的相对敏感度。这一目标的结果将是对检测区域影响的力量进行定量计算，以及实施的选择将如何影响力量和所需的样本量。第二个目标是利用定制的图像采集和灌注模体的构建来开发质量评估方法。质量保证是跨部位成像研究的一个关键因素，但目前还没有确定的方法来测试ASL的灌注性能。在我们的最终目标中，我们的目标是表征和减少与研究干预无关的大脑活动变化引起的可变灌注信号，即所谓的生理噪声。我们将确定在ASL扫描期间执行中等要求的警戒任务是否有助于控制受试者的精神状态，减少变异性，而不过度刺激大脑的特定区域。我们还将研究大脑中网络活动引起的血流灌注的静息波动，以确定在图像处理过程中识别和消除这些波动是否会改善重复性。这一目的也将决定静息波动的幅度是否反映静息灌流。由于血液氧合敏感MRI测量的静息脑波动越来越多地被用作静息功能的指标，建立波动与平均静息活动之间的关系将解决功能成像中的一个突出问题。这些目标的实现将加速和改善ASL作为脑功能生物标记物在疾病中的使用，并将极大地改进使用ASL的众多计划和积极的多地点研究的设计。

DESCRIPTION (provided by applicant): Arterial Spin Labeling (ASL) perfusion MRI shows promise as a widely available and quantitative measure of resting brain function that can be used as a biomarker for the neural correlates of psychiatric and neurologic diseases, for the measurement of drug effects in the brain, and ultimately for diagnosis and treatment monitoring in individual patients. Although ASL perfusion MRI technologies are now implemented on most MRI scanner platforms, uncertainty in the community on the performance differences of various technical implementations and how to best use the technology across centers and MRI scanner platforms has limited its dissemination into routine use in clinical research. Building upon our successful development of quantification methods and standard sequences across platforms in the prior funding cycle, we propose to focus on the key issues limiting multi-center studies with ASL. Our first aim is to measure the relative sensitivity of different implementations of ASL by comparing their reproducibility and their response to 2 test interventions, citalopram or alprazolam administration. The result of this aim will be a quantitative calculation of power for detection of regional effects and how the choice of implementation will affect the power and required sample size. The second aim is to develop quality assessment methods using customized image acquisitions and the construction of a perfusion phantom. Quality assurance is a key element of imaging studies across sites, but there are no established methods for testing ASL perfusion performance. In our final aim, we target the characterization and reduction of variable perfusion signal induced by changes in brain activity unrelated to study interventions, so-called physiological noise. We will determine whether performing a moderately demanding vigilance task during the ASL scan will help control the subject's mental state and reduce variability without excessively stimulating particular regions of the brain. We will also study resting fluctuations in perfusion induced by network activity in the brain to determine if identifying and removing these fluctuations during image processing improves reproducibility. This aim will also determine if the amplitude of resting fluctuations is reflective of resting perfusion. Since resting brain fluctuations as measured by blood oxygenation sensitive MRI are increasingly being used as an indicator of resting function, establishing a relationship between fluctuations and average resting activity will address an outstanding question in functional imaging. Achievement of these aims will accelerate and improve the use of ASL as a biomarker for brain function in disease and will greatly improve the design of numerous planned and active multi-site studies employing ASL.