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

使用 pH 值依赖的 MRI 诊断椎间盘源性腰痛

• 批准号: 8722766
• 负责人: DAN GAZIT
• 金额: $ 60.52万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8722766
• 关键词: Adverse effects; Affect; Anesthesia procedures; Animal Model; Back Pain; Biochemical; Biological Markers; Brain Neoplasms; Chemicals; Clinical; Control Groups; Detection; Development; Diagnosis; Diagnostic Procedure; Diagnostic Sensitivity; Environment; Family suidae; Fiber; Future; Glycolysis; Glycosaminoglycans; Goals; Health; Height; Human; Image; Imaging Device; Intervertebral disc structure; Intestines; Lead; Link; Low Back Pain; Magnetic Resonance Imaging; Measurement; Measures; Medical; Methods; Modeling; Morphologic artifacts; Motion; Needles; Operative Surgical Procedures; Outcome Measure; Pain; Painless; Pathway interactions; Patients; Pilot Projects; Play; Population; Procedures; Proteoglycan; Protocols documentation; Relaxation; Role; Sensitivity and Specificity; Signal Transduction; Slice; Source; Spinal; Stem cells; System; Techniques; Testing; Three-Dimensional Imaging; Time; Tissues; Variant; Vertebral column; Weight; Work; base; data acquisition; disc regeneration; gene therapy; healthy volunteer; imaging modality; improved; in vivo; innovation; intervertebral disk degeneration; meter; non-invasive imaging; novel; pressure; prevent; prognostic; success

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.

描述（由申请人提供）：拟议项目的目的是开发一种新型的MRI方法来诊断椎间盘的下背部疼痛。下背部疼痛是一种主要的医疗状况，估计会影响多达85％的美国人群。椎间盘（IVD）变性通常与背痛有关。但是，尽管可以使用磁共振成像（MRI）鉴定退化圆盘，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根源。标准程序包括唱片，这是一种极度痛苦的程序，也已知可以进一步加速椎间盘变性，椎间盘催眠，椎间盘高度损失并影响相邻的终结物。因此，对于开发非侵入性成像工具的迫切需要，以诊断出椎间盘痛的疼痛。已经尝试找到粘附疼痛与可以使用MRI可视化的特定生物标志物之间的相关性。然而，这些作品要么是在相对较少的患者中进行的，要么是在临床领域使用挑战的MR方法。从椎间盘变性到产生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，退化的椎间盘更具酸性。最近的研究避免了椎间盘内低pH值与下背部疼痛之间的可能联系。因此，我们假设可以通过使用MRI毫无创作的低pH水平来诊断疼痛的椎间盘。我们使用T1P（旋转框架中的自旋晶格松弛）和化学交换饱和转移（CEST）成像的组合开发了一种新型的pH级依赖性MR测量。在一项试点研究中，我们证明了人类患者唱片检测到的pH级依赖性MR测量和二聚体疼痛之间存在显着相关性。拟议项目的目的是进一步改善MR技术，并证明它可以检测患者的椎间盘下背痛。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测量值。我们将针对T1P和CEST成像开发并优化3D成像技术，以使IVD在多个级别上进行更大的覆盖范围。这些将在注射乳酸梯度的猪IVD上进行测试，以创建不同水平的pH值。我们还将在猪中使用椎间盘变性模型，并评估pH变化随时间的变化和退化状态的进展。 2：验证所提出的MR方法可用于准确检测患者的疼痛变性椎间盘。将在脊柱手术前接受挑衅性唱片的患者成像。 MR测量将与唱片结果进行比较。将计算诊断灵敏度，特异性和准确性。该项目的成功可能导致开发一种新型MRI方案，以诊断椎间盘痛。这种方法对于患者而言是无痛的，并防止与唱片相关的不利影响。