Fast macromolecular proton fraction mapping of the human spinal cord

描述(申请人提供)：大分子质子分数(MPF)是决定组织中水和大分子之间交叉松弛的关键生物物理参数。近年来，MPF作为髓鞘在神经组织中的潜在生物标志物引起了人们的极大兴趣。然而，由于缺乏能够快速、可靠地在体内测量这一参数的方法，MPF可能的临床应用受到了阻碍。这个项目建立在我们之前由NIH资助的R21研究的基础上，我们在那里开发、组织学验证和临床测试了一种新的快速和健壮的全脑MPF成像方法。该方法只利用一个非共振饱和数据点来测量MPF，从而在时间效率上有了很大的提高。这个项目的总体目标是开发一种快速且临床有用的方法来绘制人类脊髓的MPF图。该方法的技术概念是基于本课题组最初为脑成像开发的单点MPF映射的原理。然而，由于感兴趣的解剖结构的小尺寸和运动问题，这种方法对于脊髓成像的实现是具有挑战性的。该项目包含两个具体目标。在第一个目标中，我们将实施一系列技术解决方案，这些解决方案将在提高空间分辨率和信噪比的同时，降低扫描时间和运动灵敏度。具体地说，我们将建立一种新的脊髓MPF映射方法，该方法结合了多回波求和、并行成像、缩小视场采集和合成参考图像的新原理，该原理基于用从互补T1图和质子密度图得到的计算参考图像来替换获取的参考图像来进行数据归一化。基于这些解决方案，我们将为颈椎和上胸段脊髓实施MPF标测方案，空间分辨率为亚毫米，扫描时间临床负担得起。在第二个目标中，我们将进行一项先导性研究，旨在建立脊髓MPF标测在多发性硬化症(MS)中的临床应用。为此，我们将从多发性硬化症患者和健康对照人群中获取大脑和脊髓的MPF图。我们将进一步比较MS患者和对照组以及复发-缓解和继发性疾病病程患者之间的脊髓MPF，确定脊髓MPF与普遍接受的MS临床状态量表之间的关联，并检验包括脑和脊髓MPF的联合模型比仅基于脑MPF的模型更好地解释MS患者的临床状态的假设。在本项目中开发的MPF映射方法有望对导致脊髓髓鞘损伤的疾病诊断和治疗监测非常有益，例如多发性硬化症、脊髓损伤和脊髓型颈椎病。

DESCRIPTION (provided by applicant): Macromolecular proton fraction (MPF) is a key biophysical parameter determining cross-relaxation between water and macromolecules in tissues. Over recent years, MPF has attracted significant interest as a potential biomarker of myelin in neural tissues. However, possible clinical applications of MPF have been hampered due to the absence of methods allowing fast and reliable in vivo measurements of this parameter. This project builds on our previous NIH-funded R21 study, where we developed, histologically validated, and clinically tested a principally new fast and robust method for whole-brain MPF mapping. This method achieves critical improvement in time efficiency by utilizing only one off-resonance saturation data point to measure MPF. The overall goal of this project is to develop a fast and clinically useful method for MPF mapping of the human spinal cord. The technical concept of the proposed method is based on the principle of single-point MPF mapping initially developed by our group for the brain imaging. However, implementation of this approach for the spinal cord imaging is challenging due to the small size of the anatomical structure of interest and motion problems. The project contains two specific aims. In the first aim, we will implement a series of technical solutions, which will allow improvements in spatial resolution and signal-to-noise ratio with simultaneous reduction of the scan time and motion sensitivity. Specifically, we will build the new spinal cord MPF mapping method on a combination of multi-echo summation, parallel imaging, reduced field-of-view acquisition, and a novel principle of synthetic reference, which is based on the replacement of an acquired reference image for data normalization by a calculated one derived from complimentary T1 and proton density maps. Based on these solutions, we will implement an MPF mapping protocol for the cervical and upper thoracic spinal cord with sub-millimeter spatial resolution and clinically affordable scan time. In the second aim, we will conduct a pilot study aimed to establish clinical utility of spinal cord MPF mapping in multiple sclerosis (MS). For this purpose, we will acquire MPF maps of the brain and spinal cord from a population of MS patients and healthy controls. We will further compare MPF in the spinal cord between MS patients and controls and between patients with relapsing-remitting and secondary-progressive disease courses, determine associations between spinal cord MPF and commonly accepted MS clinical status scales, and test the hypothesis that combined models including brain and spinal cord MPF better explain clinical status of MS patients than the models based on brain MPF alone. The MPF mapping method developed in this project is expected to be highly beneficial for disease diagnosis and treatment monitoring in conditions causing myelin damage in the spinal cord, such as MS, spinal cord injury, and cervical spondylotic myelopathy.