Fast macromolecular proton fraction mapping of the human spinal cord

描述（由申请人提供）：大分子质子分数（MPF）是决定组织中水和大分子之间交叉弛豫的关键生物物理参数。近年来，MPF作为神经组织中髓鞘的潜在生物标志物引起了人们的极大兴趣。然而，可能的MPF的临床应用受到阻碍，由于缺乏方法，允许快速和可靠的体内测量这个参数。该项目建立在我们之前的NIH资助的R21研究的基础上，在该研究中，我们开发了一种用于全脑MPF映射的主要新的快速和强大的方法。该方法通过仅利用一个非共振饱和数据点来测量MPF，实现了时间效率的关键改进。本项目的总体目标是开发一种快速且临床上有用的人类脊髓MPF映射方法。所提出的方法的技术概念是基于单点MPF映射的原则，最初由我们的小组开发的脑成像。然而，由于感兴趣的解剖结构的小尺寸和运动问题，这种方法用于脊髓成像的实现是具有挑战性的。该项目有两个具体目标。在第一个目标中，我们将实施一系列技术解决方案，这将允许提高空间分辨率和信噪比，同时减少扫描时间和运动灵敏度。具体来说，我们将建立新的脊髓MPF映射方法的组合多回波求和，并行成像，减少视场采集，和一个新的原则的合成参考，这是基于一个计算的一个来自免费的T1和质子密度图的数据标准化所获得的参考图像的替代。基于这些解决方案，我们将实现一个MPF映射协议的颈部和上胸脊髓亚毫米空间分辨率和临床负担得起的扫描时间。在第二个目标，我们将进行一项试点研究，旨在建立脊髓MPF映射在多发性硬化症（MS）的临床效用。为此，我们将从MS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患者和对照组之间以及复发缓解型和继发进展型疾病病程患者之间脊髓中的MPF，确定脊髓MPF和普遍接受的MS临床状态量表之间的关联，并检验包括脑和脊髓MPF的组合模型比仅基于脑MPF的模型更好地解释MS患者的临床状态的假设。在该项目中开发的MPF映射方法预计将非常有益于在脊髓中引起髓鞘损伤的条件下的疾病诊断和治疗监测，例如MS、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.