<scp>SNR</scp> ‐Enhanced Whole‐Brain Chemical Exchange Saturation Transfer Imaging by Optimized Variable Flip Angles

ABSTRACT Purpose To improve the signal‐to‐noise ratio (SNR) and mitigate T 2 ‐decay‐related blurring in whole‐brain chemical exchange saturation transfer (CEST) imaging by optimizing the refocusing flip angles of a turbo spin echo (TSE) readout, also known as the SPACE‐CEST sequence. Methods The SNR of the SPACE‐CEST sequence was modeled as a function of flip angles, and a resolution penalty term was added to control blurring. Flip angles were optimized under two modes: Resolution‐only and SNR+Resolution mode. The optimized flip angles were compared to conventional variable/constant flip angles regarding transverse magnetization usage efficiency, longitudinal magnetization storage, and specific absorption rate (SAR). The SNR and resolution benefits of the proposed method were validated in a phantom, healthy volunteers, and brain tumor patients. Results The optimized flip angles in the Resolution‐only mode generated a constant signal, validating the framework. The optimized flip angles in SNR+Resolution mode exhibited higher transverse magnetization usage efficiency and greater longitudinal storage. The SNR+Resolution mode produced signals comparable to those from conventional constant flip angles but with significantly lower flip angles. Notably, the SNR+Resolution mode demonstrated high transverse magnetization usage efficiency even with 20% B 1 inhomogeneity and across a wide range T 1 and T 2 values, along with a 32.9% decrease in SAR. On average, the SNR+Resolution mode showed a 14.2% increase in SNR in humans and a 3.6% improvement in spatial resolution. Conclusion Higher transverse magnetization usage efficiency can be achieved by optimizing refocusing flip angles of the SPACE‐CEST sequence, leading to increased SNR and decreased SAR.