UCSF

Low back pain is an expensive, widespread healthcare concern. The mechanisms of its progression and association with intervertebral disc degeneration are not fully understood, but recent studies suggest that lactate accumulation and a subsequent drop in pH may be initiating events. Chemical exchange saturation transfer (CEST) of glycosaminoglycans (gagCEST) has emerged as way to quantify glycosaminoglycan (GAG) concentrations in the intervertebral disc, but no studies have examined its dependency on pH. This study seeks to assess the pH-dependence of gagCEST and use iopromide, a common contrast agent used in CT imaging, as a pH-sensitive CEST probe to explore these agents' potential to measure pH of the intervertebral discs. We first create chondroitin sulfate and Ultravist® phantoms over a range of pH values to explore the pH-dependency of the CEST imaging of these probes and apply these findings to porcine intervertebral disc specimens. Our results demonstrate the non-linear dependence of gagCEST on pH and a linear regression of the Iopromide CEST effect with pH (R2 = 0.95). Iopromide was then infused into the disc and the calibration created by the phantom studies was used to determine pH in the disc.

These findings provide what is to our knowledge the first description of the pH dependence of gagCEST imaging and the first use of the iopromide contrast agent in the CEST MR imaging of the intervertebral disc specimen. Because iopromide CEST imaging is independent of the local concentration of macromolecules, it particularly shows great potential in reporting pH in intervertebral disc specimen studies. The ability to report pH in a tissue non-invasively by one of these methods could be valuable in better understanding disease progression.