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

描述（由申请人提供）：拟议项目的目标是开发一种新的MRI方法来诊断椎间盘源性腰痛。下背痛是一种主要的医疗状况，估计影响高达85%的美国人口。椎间盘（IVD）退变通常与背痛有关。然而，尽管退化的椎间盘可以通过磁共振成像（MRI）来识别，但它们并不总是有症状的。当患者有几个退化的椎间盘时，需要进一步检查以确定疼痛的来源。标准手术包括椎间盘造影术，这是一种非常痛苦的手术，也已知会进一步加速椎间盘退变、椎间盘突出、椎间盘高度损失并影响相邻终板。因此，迫切需要开发用于诊断椎间盘源性疼痛的非侵入性成像工具。已经尝试找到椎间盘源性疼痛和可以使用MRI可视化的特定生物标志物之间的相关性。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竞技场中具有挑战性的MR方法。从椎间盘退变到疼痛的确切途径尚未完全阐明。众所周知，退化的椎间盘由于糖酵解和乳酸分泌水平的增加而更具酸性。最近的研究回避了椎间盘内低pH值水平与下背痛之间的可能联系。因此，我们假设疼痛的椎间盘可以通过使用MRI无创检测低pH值来诊断。我们已经开发了一种新的pH值依赖的MR测量使用T1p（旋转框架中的自旋晶格弛豫）和化学交换饱和转移（CEST）成像的组合。在一项初步研究中，我们证明了在人类患者中通过椎间盘造影检测到的pH水平依赖性MR测量和椎间盘源性疼痛之间存在显著相关性。该项目的目的是进一步改进MR技术，并证明其可以检测患者的椎间盘源性下背痛。我们提出了两个目标：1：开发和验证与IVD中pH值变化相关的MR测量。我们将开发和优化T1p和CEST成像的3D成像技术，以在多个节段上更好地覆盖IVD。这些将在注射乳酸梯度以产生不同pH水平的猪IVD上进行测试。我们还将在猪中使用椎间盘退变模型，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方法可用于准确检测患者的疼痛退变椎间盘。脊柱手术前接受激发性椎间盘造影的患者将接受成像。将MR测量结果与椎间盘造影结果进行比较。将计算诊断灵敏度、特异性和准确性。该项目的成功可能会导致一种新的MRI方案的发展，用于诊断椎间盘源性疼痛。这种方法对患者来说是无痛的，并且可以防止与椎间盘造影术相关的不良反应。

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.