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.

Public Health Relevance

Provocative discography is a painful and damaging diagnostic procedure often used to identify the cause of discogenic back pain. We propose to develop a non-invasive magnetic resonance imaging (MRI) method for the diagnosis of back pain, which is based on the detection of pH levels within the spinal discs.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AR066517-01
Application #
8722766
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lester, Gayle E
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90048