Ex vivo porcine model to measure pH dependence of chemical exchange saturation transfer effect of glycosaminoglycan in the intervertebral disc

Abstract

Purpose Studies have linked low pH and loss of glycosaminoglycan (GAG) in the intervertebral discs (IVDs) of patients with discogenic back pain. The purpose of the present study is to determine whether the chemical exchange saturation transfer (CEST) effect of GAG (gagCEST) is pH-dependent and whether it can be used to detect pH changes in IVD specimens. Iopromide, a FDA approved agent for CT/X-Ray, was also evaluated as a pH-sensitive CEST probe to explore the agents’ potential to measure IVD pH. Methods The pH dependency of the CEST effect of chondroitin sulfate (containing GAG) and Iopromide phantoms was investigated at 7 T. Z-spectra from porcine IVD specimens were acquired before and after manipulating the pH with sodium lactate. Iopromide was injected into the specimens and the calibration curve was used to determine the pH status. Results Chondroitin sulfate showed a non-linear dependence of gagCEST effect with pH and gagCEST signal differences were detected in the specimens. The CEST effect of Iopromide resulted in a sigmoidal relation with pH and was used to measure pH. Conclusion gagCEST is sensitive to pH and enables investigation of the IVD pH status. Iopromide CEST is independent of the local GAG concentration and has the potential for measuring pH in the IVD.

Age‐dependency of glycosaminoglycan content in lumbar discs: A 3t gagcEST study

“…The gagCEST effect is considered sensitive to changes in pH value, which has been established in an ex vivo porcine model. 28 CEST imaging using the contrast agent iopamidol is a recently developed MRI technique that enables in vivo pH determination using a ratiometric approach. 29,30 The present study is limited by the lack of pH assessment in order to avoid the application of contrast agent.…”

Detection of extracellular matrix degradation in intervertebral disc degeneration by diffusion magnetic resonance spectroscopy

“…Compared with T2 mapping, T1ρ imaging possesses a better dynamic range and, hence, a better sensitivity to tissue hydration and PG content change during IVDD . Chemical exchange saturation transfer (CEST) imaging can detect GAG loss, and several studies have demonstrated the feasibility of CEST imaging of GAG content and pH changes during IVDD . The use of 23 Na MRI has also been explored for measuring the sodium concentration in intervertebral disc as an index for fixed charge density and GAG content in the ECM .…”

Detection of low back pain using pH level-dependent imaging of the intervertebral disc using the ratio of R1ρdispersion and −OH chemical exchange saturation transfer (RROC)

“…The GAG phantoms scan in our study is different from that reported by Melkus et al (17). First, their study was performed at 7.0T, which has a larger resonance frequency separation between ÀOH and water protons than 3.0T.…”

“…In fact, a roughly linear relationship between ÀOH CEST and GAG concentration was discovered on phantoms (24,25). The pH dependence of ÀOH CEST has also been shown at 7.0T by Melkus et al (17), yet no effort has been made to characterize such relationship at 3.0T.…”