Chemical Exchange Saturation Transfer Imaging in Neuroinflammation: Methods, Challenges, and Recommendations

Chemical Exchange Saturation Transfer (CEST) imaging has emerged as a promising non-invasive molecular MRI technique for investigating neuroinflammation. It offers unique insights into metabolic and molecular alterations in the brain. This review presents a comprehensive overview of CEST principles, methodological developments, and translational applications in neuroinflammation. It covers the basic mechanisms, pulse sequence designs, readout strategies, and various CEST contrasts used to probe molecular changes associated with inflammation. Recent advancements in fast CEST imaging, including optimized undersampling strategies and accelerated reconstruction methods are discussed. Improvements in post-processing and quantification techniques are also highlighted. The growing role of artificial intelligence (AI) in CEST imaging for image reconstruction, artifact correction, and biomarker extraction, is examined. Preclinical and clinical studies show CEST's potential to detect neuroinflammation across neurological disorders. The impact of high-field MRI on enhancing CEST sensitivity and specificity are also discussed. Despite notable progress, several challenges remain. These include sensitivity to field inhomogeneities, lack of acquisition standardization, and limited clinical validation. We outline current limitations, translational barriers, and provide recommendations for improving reproducibility, facilitating clinical adoption, and integrating AI-based approaches for robust molecular characterization. Overall, CEST imaging shows great potential as a non-invasive biomarker for neuroinflammation. It can deepen understanding of the molecular and metabolic mechanisms underlying neurological diseases, while addressing technical and translational challenges remains key for its broader clinical implementation.