CEST MRI: Translational prospects for intervertebral disc degeneration - from basic research to clinical applications

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is characterized by metabolic and biochemical alterations within the intervertebral disc (IVD) microenvironment. Conventional magnetic resonance imaging (MRI) is limited in its ability to accurately evaluate and precisely quantify changes these small-molecule changes. Chemical exchange saturation transfer (CEST) is an emerging MRI modality that exploits exchangeable protons (such as-OH, -NH, and -NH₂ groups) within tissues. It has garnered widespread clinical attention for its ability to generate imaging contrast at the molecular level in vivo by targeting the exchangeable groups of specific metabolites. This review summarizes the application of CEST imaging in IVDD. We begin by comparing various IVD imaging modalities to highlight the unique advantages of CEST. Next, we outline the fundamental concepts, theoretical basis, and quantitative methods of CEST, followed by an overview of various CEST contrast agents. By correlating IVDD pathology with CEST imaging principles, we explore the modality's potential to identify key biomarkers, including glycosaminoglycan content, pH variations, microenvironmental shifts, and pain-generating IVDs. Furthermore, we discuss standardization of CEST and clinical decision system for IVDD. Finally, we analyze the current challenges facing CEST technology and evaluate its future translational prospects-particularly its integration with artificial intelligence (AI) and multimodal imaging-to highlight future research directions.

CEST generates specific molecular imaging contrast in tissues rich in exchangeable protons with suitable water exchange rates. It offers a distinct advantage in non-invasively quantifying in vivo metabolic changes within the cartilage microenvironment. However, due to existing technical bottlenecks, CEST remains largely confined to preclinical research. The future integration of CEST with AI and multimodal imaging holds the potential to overcome these limitations, enabling the precise evaluation and prediction of degenerative diseases such as IVDD and osteoarthritis. This will drive a fundamental leap in CEST MRI assessment, transitioning from macroscopic 'structure and composition' to microscopic "molecular concentration and chemical environment" analysis and "intelligent prediction". Such advancements will not only provide robust molecular imaging evidence for ultra-early diagnosis and precision targeted therapy but also establish CEST as an irreplaceable tool in the future of precision medicine and intelligent imaging diagnostics.