A framework for rapid, repeatable, and high-fidelity whole-brain multi-pool CEST imaging at 3 T

To develop and validate a framework for rapid, accurate, and repeatable whole-brain, multi-pool chemical exchange saturation transfer (CEST) imaging at 3 T, addressing challenges of long acquisition times and confounding factors.

A single-shot 3D true fast imaging with steady-state precession (True FISP) sequence was optimized for whole-brain multi-pool CEST. Rapid B₀, B₁, and T₁ mapping was performed using a dual-echo modified four-angle method. A feed-forward neural network was developed for rapid B₁ correction, trained against the conventional multi-power method. The apparent exchange-dependent relaxation (AREX) metric was used to correct for T₁ and magnetization transfer (MT) effects. The framework was validated in phantoms and 50 healthy subjects, including a different-day test-retest repeatability assessment.

The True FISP sequence yielded high-quality, whole-brain images with minimal artifacts and distortion in a clinically feasible scan time (∼9 min). Phantom studies confirmed the effectiveness of B₁ correction (coefficient of variation [CV] for the magnetization transfer ratio based on Lorentzian difference (MTR_LD) of the MT pool decreased from 22.49% to 4.61%) and AREX-based confounder correction (CV for APT_AREX reduced from 33.6% to 6.9%). The neural network B₁ correction showed excellent agreement with the conventional multi-power method in vivo (ICC > 0.95). High different-day test-retest repeatability was demonstrated across 96 brain regions, with the average CV for APT_AREX under 10% for 95 of 96 analyzed regions.

A rapid and robust framework for whole-brain quantitative multi-pool CEST imaging was successfully developed and validated. By integrating an efficient acquisition sequence with a streamlined correction pipeline, this approach overcomes key barriers to clinical translation, enabling reliable metabolic imaging for widespread brain pathologies.