Feasibility of Direct Quantitative Magnetic Resonance Imaging of Myelin

描述（由申请人提供）：髓磷脂占白色物质的14%，主要由介电脂质-蛋白质双层组成，这对有效的神经传导至关重要。 目前的运输。髓鞘完整性的缺陷与许多常见的神经系统异常有关。虽然首先想到的是脱髓鞘疾病，但髓鞘异常也与阿尔茨海默病、精神分裂症、创伤性脑损伤、成瘾和痴呆有关。因此，改进的髓鞘成像可能对许多CNS疾病的表征产生深远的影响。几乎所有目前的，非侵入性的，用于评估髓鞘的完整性的方法依赖于间接的措施，主要是磁化传递和髓鞘水分数。这两种测量方法都显示出与染色组织切片中的光密度在不同程度上相关，但都有缺点。重要的是，这些替代物的生物物理机制尚未完全理解，从而使数据解释复杂化。它们还需要满足许多条件，这些条件可能不适用于一系列髓鞘异常，并且绝对定量的实现充其量也是值得怀疑的。在这里，我们假设直接检测和定量髓鞘是可行的。初步工作的基础上，表征质子和31 P信号从液晶基质的髓鞘脂质双层，并显示其可检测性的超短回波时间（UTE）成像的9.4 T实验室微成像系统，我们描绘了一个路径，以图像为基础的髓鞘定量的临床成像系统。 该提案的核心是开发和评估3D零回波时间（ZTE）定量MRI采集和分析方法，包括组织水抑制和压缩感知重建，随后转换为3 T临床成像仪。通过UTE和ZTE方法对重建的髓鞘和完整的神经组织进行的初步结果证明了所提出的方法的可行性。这项工作的长期目标是将其转化为临床，作为一种替代和可能的上级技术，用于髓鞘异常患者的局部髓鞘定量，并提供评估治疗效果的方法。

DESCRIPTION (provided by applicant): Myelin, accounting for 14% of white matter, is predominantly composed of a dielectric lipid-protein bilayer that is paramount to efficient neural current transport. Defects in myelin integrity are associated with numerous common neurologic abnormalities. Although demyelinating diseases first come to mind, myelin abnormalities have also been implicated in Alzheimer's disease, schizophrenia, traumatic brain injury, addiction, and dementias. Thus, improved myelin imaging may have profound impact on characterization of many CNS diseases. Virtually all current, noninvasive, methods for evaluating the integrity of the myelin sheath rely on indirect measures, principally magnetization transfer and myelin water fraction. Both measures have been shown to correlate to varying degrees with optical density in stained histological sections but both have shortcomings. Importantly, the biophysical mechanisms of these surrogates are not completely understood, thereby complicating data interpretation. They further require a number of conditions to be satisfied that may not apply across a range of myelin abnormalities, and achievement of absolute quantification is questionable at best. Here, we hypothesize that direct detection and quantification of myelin is practical. Building on preliminary work characterizing the proton and 31P signal from the liquid-crystalline matrix of the myelin lipid bilayer, and showing its detectability by ultra-short echo-time (UTE) imaging on a 9.4T laboratory micro- imaging system, we delineate a path toward image-based myelin quantification on a clinical imaging system. Central to this proposal is the development and evaluation of 3D zero-echo-time (ZTE) quantitative MRI acquisition and analysis methods involving tissue water suppression and compressed sensing reconstruction, with subsequent translation to a 3T clinical imager. Initial results on reconstituted myelin and intact neural tissue performed by UTE and ZTE methods demonstrate the proposed method's feasibility. The work's longer- term goal is translation to the clinic as an alternative and possily superior technique for regional myelin quantification in patients with myelin abnormalities and for providing means to evaluate treatment effectiveness.