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松弛的关键生物物理参数。近年来，MPF作为神经组织中髓磷脂的潜在生物标志物引起了人们的极大兴趣。然而，由于缺乏快速可靠的体内测量该参数的方法，MPF可能的临床应用受到阻碍。这个项目建立在我们之前的美国国立卫生研究院资助的R21研究的基础上，在那里我们开发、组织学验证和临床测试了一种全新的快速而强大的全脑MPF制图方法。该方法仅利用一个非共振饱和数据点来测量MPF，从而大大提高了时间效率。该项目的总体目标是开发一种快速和临床有用的方法来绘制人类脊髓的MPF图谱。所提出的方法的技术概念是基于我们小组最初为脑成像开发的单点强积金映射原理。然而，由于兴趣解剖结构的小尺寸和运动问题，这种方法在脊髓成像中的实施是具有挑战性的。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。具体而言，我们将建立新的脊髓MPF映射方法，该方法结合了多回波求和、并行成像、缩小视场采集和一种新的合成参考原理，该原理基于将获取的参考图像替换为由互补T1和质子密度图导出的计算图像进行数据归一化。基于这些解决方案，我们将实现一种亚毫米空间分辨率和临床负担得起的扫描时间的颈椎和上胸脊髓MPF制图方案。在第二个目标中，我们将进行一项试点研究，旨在建立脊髓MPF图谱在多发性硬化症（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脑和脊髓的MPF图谱。我们将进一步比较MS患者与对照组、复发缓解型与继发性进展型患者脊髓的MPF，确定脊髓MPF与普遍接受的MS临床状态量表之间的关系，并检验包括脑和脊髓MPF的联合模型比单独基于脑MPF的模型更能解释MS患者临床状态的假设。本项目开发的MPF制图方法有望在多发性硬化症、脊髓损伤、脊髓型颈椎病等引起脊髓髓磷脂损伤的疾病诊断和治疗监测中发挥重要作用。

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.