Diagnosis of Discogenic Low Back Pain Using pH Level-Dependent MRI

描述(由申请人提供)：建议项目的目标是开发一种新的MRI方法来诊断间盘源性下腰痛。下腰痛是一种主要的医疗疾病，据估计，高达85%的美国人口受到影响。腰椎间盘(IVD)退变通常与背部疼痛有关。然而，尽管退变的椎间盘可以使用磁共振成像(MRI)来识别，但它们并不总是有症状的。当患者有几个退变的椎间盘时，需要进一步检查以确定疼痛的来源。标准程序包括椎间盘造影术，这是一种极其痛苦的程序，也被认为会进一步加速椎间盘退变、椎间盘突出、椎间盘高度损失和影响邻近的终板。因此，迫切需要开发一种非侵入性的影像工具来诊断间盘源性疼痛。人们一直在努力寻找间盘源性疼痛与一种特定的生物标记物之间的关系，这种生物标记物可以用核磁共振成像进行可视化。然而，这些工作要么是在相对较少的患者身上进行的，要么是使用了在临床上具有挑战性的磁共振方法。从椎间盘退变到由此引起的疼痛的确切途径尚未完全阐明。众所周知，由于糖酵解和乳酸分泌水平的增加，退变的椎间盘更具酸性。最近的研究一直未能找到腰椎间盘内低pH值与下腰痛之间可能存在的联系。因此，我们假设可以通过使用MRI无创检测低pH值来诊断疼痛的椎间盘。我们利用旋转标架中的自旋-晶格弛豫(T1P)和化学交换饱和转移(CEST)成像相结合的方法，发展了一种新的依赖于pH水平的磁共振测量方法。在一项初步研究中，我们证明了在人类患者中，依赖于pH水平的MR测量与椎间盘造影术检测到的间盘源性疼痛之间存在显著的相关性。该项目的目标是进一步改进磁共振技术，并证明它可以检测到患者的椎间盘源性下腰痛。我们提出了两个目标：1：开发和验证与IVD中pH变化相关的MR测量。我们将开发和优化T1P和CEST成像的3D成像技术，以便在多个层面上更好地覆盖IVD。这些将在注射了乳酸梯度的猪IVD上进行测试，以产生不同水平的pH。我们还将使用猪的椎间盘退变模型，并评估pH随时间的变化和退变状态的进展。2：验证所提出的MR方法可以准确地检测出患者的疼痛退变椎间盘。在脊柱手术前接受刺激性椎间盘造影术的患者将被成像。MR测量结果将与椎间盘造影术结果进行比较。将计算诊断灵敏度、特异度和准确度。该项目的成功可能会导致开发一种新的MRI方案来诊断间盘源性疼痛。这种方法对患者来说将是无痛的，并防止了与椎间盘造影术相关的不良影响。

DESCRIPTION (provided by applicant): The goal of the proposed project is to develop a novel MRI approach to diagnosing discogenic lower back pain. Lower back pain is a major medical condition estimated to affect up to 85% of the US population. Intervertebral disc (IVD) degeneration is often associated with back pain. However, although degenerate discs can be identified using magnetic resonance imaging (MRI), they are not always symptomatic. When a patient has several degenerate discs, further examination is required to determine the source of the pain. Standard procedures include discography, an extremely painful procedure that is also known to further accelerate disc degeneration, disc herniation, loss of disc height and affect the adjacent endplates. Thus, there is a critical need for the development of non-invasive imaging tools for the diagnosis of discogenic pain. Attempts have been made to find a correlation between discogenic pain and a specific biomarker that can be visualized using MRI. Yet, these works were either performed on a relatively low number of patients or utilized MR methods that are challenging to use in the clinical arena. The exact pathway from disc degeneration to the resulting pain has not been elucidated completely. It is well known that the degenerate disc is more acidic due to increased levels of glycolysis and lactate secretion. Recent studies have eluded to a possible connection between low pH levels within the disc and lower back pain. Therefore, we hypothesized that painful discs could be diagnosed by detecting low pH levels noninvasively using MRI. We have developed a novel pH-level dependent MR measurement using a combination of T1p (spin-lattice relaxation in the rotating frame) and chemical exchange saturation transfer (CEST) imaging. In a pilot study, we demonstrated that there was significant correlation between the pH-level dependent MR measurement and discogenic pain detected by discography in human patients. The objective of the proposed project is to further improve the MR techniques and demonstrate that it can detect discogenic lower back pain in patients. We propose two aims: 1: To develop and validate an MR measurement that is correlated to pH changes in the IVD. We will develop and optimize 3D imaging techniques for both T1p and CEST imaging to allow greater coverage of the IVD at multiple levels. These will be tested on pig IVDs injected with a gradient of lactate to create different levels of pH. We will also use a disc degeneration model in pigs and evaluate pH changes over time and progression of the degenerative state. 2: To validate that the proposed MR method can be used to accurately detect painful degenerate discs in patients. Patients undergoing provocative discography prior to spine surgery will be imaged. MR measurements will be compared to discography results. Diagnostic sensitivity, specificity, and accuracy will be calculated. The success of this project could lead to the development of a novel MRI protocol for the diagnosis of discogenic pain. Such a method will be painless for patients and prevent the adverse effects associated with discography.