Osamu Togao

Akio Hiwatashi

Degeneration of intervertebral discs (IVDs) is one of the leading causes of low back pain.¹ Surgical treatment has been performed in severe IVD degeneration; however, early-stage IVD degeneration could be treated with regenerative medicine therapy.² Therefore, noninvasive and quantitative imaging methods to detect and monitor changes of IVD degeneration are desirable. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the platform of the cartilage matrix, and they play crucial roles in the function of IVDs. So far, the Pfirrmann grade is widely used to qualitatively asses IVD degeneration on T2-weighted images. However, T2-weighted imaging cannot detect the loss of PGs or GAGs. It has been reported that the loss of PGs can be detected by T1-ρ measurements.

However, the clinical applicability of T1-ρ imaging is limited by the long scan time and the high specific absorption rate required by multiple and long spin-lock pulses.

Chemical exchange saturation transfer (CEST) imaging has drawn considerable attention in the field of molecular imaging as a novel contrast mechanism in MR imaging.³

CEST contrast is achieved by applying a saturation pulse at the resonance frequency of a slow-to-intermediate exchanging proton site (eg, −NH, −OH) of endogenous or exogenous agents, and the resulting saturated spin is transferred to bulk water via a chemical exchange.⁴ CEST imaging of GAGs (ie, gagCEST) is a subset of the endogenous CEST imaging techniques introduced by Ling et al.⁵ GagCEST imaging leverages the proton exchange between the hydroxyl protons (−OH) in GAG units and bulk-water protons. The feasibility of this method for imaging human lumbar IVDs at 3T was demonstrated,⁶ but the quantitative performance of this method in vivo has not yet been evaluated.

In this study, 69 lumbar intervertebral discs in 24 volunteers were examined with T2-weighted and gagCEST imaging and T1-ρ measurements. Our study demonstrated that the gagCEST signal in lumbar IVDs was correlated with both the qualitative visual assessment on T2-weighted images and the quantitative T1-ρ measurement of IVD degeneration. In addition, we found that although both T1-ρ and gagCEST were changed according to the degree of IVD degeneration, the percentage change between Pfirrmann grades I and II was larger in gagCEST (−57%) than in T1-ρ (−8%).

Furthermore, both T1-ρ and gagCEST for Pfirrmann grade I showed the widest variability among all grades, though no obvious degeneration was identified on T2-weighted images. These findings may reflect that T1-ρ and gagCEST could sensitively detect early degenerative changes that were not visible on T2-weighted images. Further investigations including histopathologic assessments are necessary to prove this theory. The relationship between gagCEST imaging findings and the current or future symptoms in patients with IVD degeneration will be needed in larger cohorts.

References

1. Manchikanti L, Singh V, Pampati V, et al. Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician 2001;4:308–316.
2. Phillips FM, An H, Kang JD, et al. Biologic treatment for intervertebral disc degeneration: summary statement. Spine 2003;28:S99, 10.1097/01.BRS.0000076906.82028.03.
3. Ward KM, Aletras AH, Balaban RS. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 2000;143:79–87, 10.1006/jmre.1999.1956.
4. van Zijl PC, Yadav NN. Chemical exchange saturation transfer (CEST): what is in a name and what isn't? Magn Reson Med 2011;65:927–48, 10.1002/mrm.22761.
5. Ling W, Regatte RR, Navon G, et al. Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc Natl Acad Sci U S A 2008;105:2266–70, 10.1073/pnas.0707666105.
6. Haneder S, Apprich SR, Schmitt B, et al. Assessment of glycosaminoglycan content in intervertebral discs using chemical exchange saturation transfer at 3.0 Tesla: preliminary results in patients with low-back pain. Eur Radiol 2013;23:861–68, 10.1007/s00330-012-2660-6.

Read this article at AJNR.org...