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Medizin

骨骼肌疾病的定量磁共振成像

Published: December 18, 2016
doi:
10.3791/52352
, , , , , , , , ,
1Institute of Imaging Science,Vanderbilt University, 2Department of Radiology and Radiological Sciences,Vanderbilt University, 3Department of Biomedical Engineering,Vanderbilt University, 4Department of Molecular Physiology and Biophysics,Vanderbilt University, 5Department of Physical Medicine and Rehabilitation,Vanderbilt University, 6Department of Physics and Astronomy,Vanderbilt University

Summary

神经肌肉疾病常常表现出时间上变化，空间上的异构，和多面病理。该协议的目的是表征使用非侵入性磁共振成像方法本病理。

Abstract

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Introduction

定量磁共振成像（qMRI）描述了开发和使用的MRI量化的物理，化学，和/或生物系统的生物特性。 QMRI要求，一个采用了系统的生物物理模型，感兴趣组织以及MRI脉冲序列组成。脉冲序列被设计为图像“信号强度敏感到的模型中感兴趣的参数。磁共振信号特性（信号强度，频率和/或相位）根据该模型测量和分析。的目标是产生具有连续分布，测量的物理单元的物理或生物参数的无偏，定量估计。常描述系统的方程进行分析和装配在逐个像素的基础上，产生一个图像，其像素值直接反映该变量的值。这样的图像被称为一个参数图。

qMRI的一种常见用法是D才有发展和生物标志物的应用。生物标记物可用于研究疾病机制，建立一个诊断，确定预后，和/或评估治疗反应。它们可以采取内源或外源分子，组织学标本，物理量，或内部图像的浓度或活性的形式。生物标志物的一些总体要求是，他们使用的测量物理单位客观地衡量一个连续分布的变量;有一个清晰的，很好地理解与感兴趣的病理学关系;要改进和临床状态的恶化敏感;并且可以与合适的准确度和精确测量。非侵入性的或微创的生物标志物是特别理想的，因为它们促进患者的舒适度和最小干扰感兴趣的病理。

一个用于开发基于图像的生物标志物的肌肉疾病的目标是，以反映那些complementar方式肌肉疾病y以比更具体地，多空间比选择性的，和/或比现有的方法侵入性更小。在这方面qMRI的一个特定优点是，它具有集成多种类型的信息，从而潜在地表征疾病过程的许多方面的潜力。这种能力是肌肉疾病非常重要，这经常表现出空间上可变的，复杂的病理，包括炎症，坏死和/或萎缩伴脂肪替代，纤维化的肌丝格（“Z盘流”）的破坏和膜损伤。的qMRI方法的另一个优点是，基于对比度的MR图像的定性或半定量描述反映不仅病理学，而且在图像采集参数，硬件差异，和人类感知。最后一个问题的一个例子是由Wokke 等人 ，谁发现脂肪浸润的半定量评估是充满变数和不正确频繁，W证明母鸡定量脂肪/水MRI（FWMRI）相比，1。

在这里描述的协议包括用于测量纵向（T 1）和横向（T 2）弛豫时间常数，定量磁化转移脉冲序列（QMT）参数，使用弥散张量的MRI（DT-MRI）的肌肉结构水的扩散系数，以及使用结构图像和FWMRI。 ，T 1为通过使用反转恢复序列，其中该净磁化矢量被反相并作为系统返回到平衡其幅度进行采样测量。 Ť2是通过重复再聚焦使用再聚焦脉冲，诸如卡尔-赛尔Meiboom-吉尔（CPMG）法的一个列车横向磁化和采样所得到的自旋回波测量。 T1和T2 2的数据可以使用非线性曲线拟合方法，要么承担多项expone的被分析微分方程边值问题的部件先验 （典型地一至三个）或通过使用适合的观测数据的大量衰减指数函数的总和，从而产生信号振幅的频谱的线性逆算法。这种方法需要一个非负最小二乘（NNLS）溶液3，并且通常包括附加正规化，以产生稳定的结果。 T1和T2 2的测量已被广泛用来研究肌肉疾病和损伤4-9。 ŧ1值通常在减少肌肉脂肪浸润地区和发炎地区4-6升高; ŧ2值升高，这两种脂肪浸润和发炎地区的10。

QMT-MRI通过估计高分子的比例来自由水的质子（池大小比率，PSR）表征在组织中的自由水和固体状高分子质子池;内在放松这些池的通货膨胀率;以及它们之间交换的速率。常见的QMT方法包括脉冲饱和度11和选择性反转恢复12,13的方法。下面的协议描述使用脉冲饱和方法，它利用了高分子质子信号的宽线宽，相对于水的质子信号的窄线宽的。通过饱和在谐振频率从水中信号足够不同大分子信号时，水的信号被降低为固体和自由水的质子池之间磁化转移的结果。的数据使用的是定量的生物物理模型进行分析。 QMT已开发和在健康的肌肉14,15应用，而最近出现的抽象描述肌肉疾病16实施。 QMT已被用于研究肌肉炎症的小动物模型，其特征在于它已经表明，炎症减少对PSR 17。因为作为MT既反映了大分子和水分含量，MT的数据也可以反映肝纤维化18,19。

DT-MRI被用于量化具有有序的，细长的细胞组织的水分子的各向异性扩散行为。在DT-MRI，水扩散六个或更多不同的方向测量;然后这些信号被装配到一个张量模型20。的扩散张量，D是对角化，得到3特征值（其是三个主要扩散）和三个特征向量（它指示对应于三个扩散系数的方向）。从D-衍生的这些和其它定量指标提供在微观水平有关组织结构和取向信息。肌肉的扩散性能，特别是D的第三特征值和扩散各向异性程度，反映肌肉发炎17和肌肉损伤由于实验损伤21，劳损22和23,24疾病。对肌肉的扩散性的其他潜在影响包括细胞直径为25和膜通透性的变化而变化。

最后，肌肉萎缩，无或无肉眼可见的脂肪浸润，是许多肌肉疾病的病理学的组成部分。肌肉萎缩可以通过使用结构图象来测量肌肉截面积或体积和FW-MRI评估脂肪浸润来评价。脂肪浸润T中1定性描述-和T2加权图像26，但脂肪和水的信号最好通过形成利用脂肪和水的质子27-29的不同的谐振频率的图像测量。定量脂肪/水的成像方法已在肌肉疾病被应用于诸如肌营养不良1,30,31，并且可以预测在这些患者31下地的损失。

<p类=“jove_content”>此处描述的qMRI协议使用所有这些测量中的自身免疫性炎性肌病性皮肌炎（DM）和多肌炎（PM）来表征肌肉状况。该协议的进一步细节，包括它的再现性，已被先前32发布。该协议包括在我们的系统专门编程标准脉冲序列以及射频（RF）和磁场梯度的对象。作者预期的协议也适用于特征在于肌肉萎缩，炎症和脂肪浸润其他神经肌肉疾病（如肌营养不良症）。

Protocol

注：读者提醒，涉及人类受试者的研究都必须由当地机构审查委员会（IRB）在研究人类受试者使用的批准。研究参与者必须的目的，程序，风险和建议的研究益处通知;替代疗法或程序的可用性;报酬的可用性;以及他们的隐私权，并撤回其同意，并停止其参与。此前MRI测试环节，调查员必须出示一个潜在的研究参与者与IRB批准的知情同意书（ICD），解释其内容，并要求潜在的研究参与者，如果他/她希望参加学习。…

Representative Results

图1示出了在多发性肌炎患者的大腿中部获得代表轴向解剖图像。还示出了垫片体积的面内投影的位置。 7 -代表参数映射每个qMRI方法，都来自同一患者获得，由图2提供。 图2A和2B分别示出了ΔB 0，和章动角场图，。在B 0?…

Discussion

肌肉疾病如肌营养不良症和特发性炎性肌病构成了在异构的病因，并作为单独的实体，在罕见的疾病，发病率组。例如，杜氏肌营养不良症-肌营养不良的最常见的形式-具有1在3500活男婴37,38的入射;皮肌炎，到该协议中得到应用，拥有1 10万39的发病率。这些疾病的高发病率集体然而，他们通常是重叠的病理体征 – 萎缩，炎症，脂肪浸润，膜损伤和纤维化 – 支持一组通用的方法的发?…

Offenlegungen

The authors have nothing to disclose.

Acknowledgements

We acknowledge grant support from the National Institutes of Health: NIH/NIAMS R01 AR050101 (BMD), NIH/NIAMS R01 AR057091 (BMD/JHP), NIH/NIBEB K25 EB013659 (RDD), and the Vanderbilt CTSA award RR024975. We also thank the reviewers for the comments and the subject for participating in these studies.

Materials

Name of Reagent/ Equipment Company Catalog Number Comments/Description
3T human MRI system Philips Medical Systems (Best, the Netherlands) Achieva/Intera
Cardiac phased array receive coil Philips Medical Systems
Pillows, straps, bolsters, and other positioning devices
Computer with MATLAB software The Mathworks, Inc (Natick, MA) r. 2014
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Tags

Keywords: Quantitative MRISkeletal Muscle DiseaseNeuromuscular DiseasesInflammatory MyopathiesMuscular DystrophiesMuscle Strain InjuryMRI ProtocolInformed ConsentSafety ScreeningRF Receiver CoilMotion Limitation
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Damon, B. M., Li, K., Dortch, R. D., Welch, E. B., Park, J. H., Buck, A. K. W., Towse, T. F., Does, M. D., Gochberg, D. F., Bryant, N. D. Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease. J. Vis. Exp. (118), e52352, doi:10.3791/52352 (2016).
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