HIGHLY EFFICIENT CEREBRAL PERFUSION MRI

描述（由申请人提供）：MRI脑灌注成像是一项广泛应用于几乎所有MRI扫描仪上的技术，用于临床脑疾病诊断和神经科学研究。在过去的五年中，动脉自旋标记（ASL）在临床诊断中的应用显著增加，而静脉注射钆造影剂在临床上仍被广泛使用。两种脑灌注方法，ASL和DSC技术，都涉及快速成像，以识别血液通过毛细血管室。图像信噪比（SNR）受到组织体积中血液的小分数（例如3%）的限制。这个比例很小，但第二个限制是成像的时间窗口，对于血液通道的毛细血管阶段，它被限制在大约500-700毫秒。因此，血液流入的快速成像至关重要。因此，基于DSC对比的方法和多层二维EPI的ASL不能令人满意地显示全脑的图像灌注，除了厚片，因此降低了空间分辨率。因此，3D成像已被开发为2D EPI的替代方案。然而，如果存在患者运动伪影，则2D图像与3D图像相比具有某些理想的特征。为了克服这些限制，我们建议开发新的技术来同时获取图像，而不是单独获取图像。这种被称为同时多层成像ASL （SMS ASL）和SMS DSC的方法在毛细血管灌注阶段有限的时间窗口内获得的图像数量增加了数倍，因此可以对整个大脑进行成像。SMS-ASL的另一个好处是，扫描大脑的时间可以大大减少，避免重复扫描不同的大脑区域，从而减少运动伪影。该项目的第二个主要创新是Hadamard编码ASL，它在临床研究中非常有用，因为在正常衰老的人群中，血动脉传递时间（ATT）是未知的。Hadamard-ASL在几个不同的流入时间（TI）获取图像，以确保在至少一组图像中捕获血液的毛细血管灌注阶段。通过在标记周期的定义良好的子块划分中获取不同的TI值，它们的组合在不同的TI上获得分离的图像，其信噪比基本上是当前方法所需的两倍，净扫描时间是当前方法所需的一半，该方法独立且顺序地获取每个TI数据集。Hadamard和SMS都可以结合起来进一步提高信噪比、速度和空间分辨率。这将严重影响灌注技术在临床应用中的可及性和稳健性。新的同步灌注成像技术的可用性将使临床医生和研究人员能够对患者进行显着改进的MRI灌注测量，这些改进将影响许多不同脑部疾病的诊断，包括中风、脑白质病和退行性疾病；即阿尔茨海默病和帕金森病。定量脑血流（CBF）和ATT的灌注测量是重要的定量生物标志物，可作为脑疾病新药治疗评价的生理成像指标。这一系列新的灌注成像技术利用更有效的脉冲序列，在分辨率、切片覆盖、信噪比和速度方面具有主要优势。新的同步成像将具有很高的实用性，并在世界各地的临床扫描仪上使用是非常理想的。改进的定量MRI灌注成像总体上提高了效率，这是高度商业化的，因为它们提供了改进的诊断方法来评估脑部疾病，并进一步提高了MRI神经放射学检查的特异性和敏感性。新序列将在AMRIT的1.5特斯拉、加州大学伯克利分校的3T、加州大学旧金山医学中心的3T和7T、马萨诸塞州总医院的马蒂诺斯生物医学成像中心和哈佛医学院的MRI扫描仪上进行设计、实施和评估。一旦新的灌注序列得到优化，将在UCSF医学中心、UCLA和宾夕法尼亚大学的协同临床试验点进一步评估和优化。除了在神经放射学检查中确立其价值外，它们还将成为基础和临床神经科学研究的有用工具。

DESCRIPTION (provided by applicant): MRI cerebral perfusion imaging is a widely disseminated technique on nearly all MRI scanners used for clinical diagnosis of brain disease and for neuroscience research. Over the last five years there has been considerably increased use of arterial spin labeling (ASL) for clinical diagnosis, while still i.v. injections of a gadoliium based contrast bolus are widely used clinically. Both brain perfusion methods, ASL and DSC techniques, involve making images very fast to identify the passage of blood through the capillary compartment. The image signal-to-noise ratio (SNR) is limited by the small (e.g., 3%) fraction of blood in tissue volumes. This is proportionately small but a second limitation is the time window of imaging, which is constrained to about 500-700 milliseconds for the capillary phase of blood passage. Therefore, rapid imaging of blood inflow is essential. For this reason DSC contrast based methods and ASL with multi-slice 2D EPI have not been able to satisfactorily image perfusion in the entire brain except with thick slices hence reduced spatial resolution. 3D imaging has therefore been developed as an alternative to 2D EPI. However, 2D images have certain desirable characteristics compared with 3D if there are patient motion artifacts. To overcome these limitations we propose to develop novel technology to acquire images simultaneously instead of separately. This approach called simultaneous multi-slice imaging ASL (SMS ASL) and SMS DSC increases by several fold the number of images that are acquired during the limited time window of capillary perfusion phase so the whole brain can be imaged. Another benefit of SMS-ASL is that the time to scan the brain can be greatly reduced by avoiding repeated scans of different brain areas, thus, reducing motion artifacts. A second major innovation in this project is the Hadamard encoded ASL, which is highly useful in clinical studies where the blood arterial transit time (ATT) is not known as in normal aging of people. The Hadamard-ASL acquires images at several different inflow times (TI) to be sure to capture the capillary perfusion phase of blood in at least one set of images. By acquiring the different TI values in a well-defined sub-bolus partitioning of the labeling period, their combination gives separated images at the distinct TI with essentially 2x the SNR and half the net scan time as required by current methodology which acquires each TI data set independently and sequentially. Both the Hadamard and the SMS can be combined for further improvements in SNR, speed and spatial resolution. This will highly impact the accessibility to patients and the robustness of the perfusion technology in clinical use. The availability of the new simultaneous perfusion imaging technology will give clinicians and researchers the capability of performing significantly improved MRI perfusion measurements in patients and these improvements will impact the diagnosis of many different brain diseases, including stroke, leukoencephalopathies and degenerative diseases; i.e., Alzheimer's disease and Parkinson's disease. Perfusion measurements of quantitative cerebral blood flow (CBF) and ATT are important quantitative biomarkers useful as physiological imaging in evaluating new drug therapies for brain diseases. This family of new perfusion imaging techniques utilizes more efficient pulse sequences that provide major advantages in resolution, slice coverage, SNR and speed. The new simultaneous imaging will have high utility and be highly desirable for use on clinical scanners worldwide. The improved quantitative MRI perfusion imaging offers overall increased efficiency that is highly commercializable given they provide improved diagnostic approaches to evaluate brain disease and further improve specificity and sensitivity in MRI neuroradiological exams. The new sequences will be designed, implemented and evaluated on MRI scanners operating at 1.5 Tesla at AMRIT, at 3T at University of California Berkeley and at 3T and 7T at University of California, San Francisco Medical Center and at Martinos Center for Biomedical Imaging, Massachusetts General Hospital, and Harvard Medical School. Once the new perfusion sequences are optimized they will be further evaluated and optimized in collaborative clinical test sites of UCSF Medical Center, UCLA and University of Pennsylvania. In addition to establishing their value in neuroradiology exams, they will be made into useful tools for basic and clinical neuroscience research.