Enhanced Temporal-Resolution CEST Imaging for reliable mapping of muscle OXPHOS

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Abstract

Purpose

Creatine-weighted CEST (CrCEST) MRI maps the recovery rate of creatine (T Cr ) in exercised muscle, reflecting mitochondrial oxidative phosphorylation (OXPHOS). However, its limited temporal resolution can cause discrepancies with T PCr measurements 31P-MRS. This study introduces Fast-CrCEST, a novel method for reliable, high-temporal-resolution mapping of skeletal muscle OXPHOS.

Methods

Our proposed Fast-CrCEST method acquires Cr maps at a temporal resolution of 10s by applying RF saturation (B 1 ) at only ±1.8 ppm, in contrast to the conventional CrCEST protocol, which employs six frequency offsets and requires 30s per acquisition. Given that magnetization transfer ratio asymmetry (MTR asym ) depends on B 0 inhomogeneity, we modeled the pre-exercise MTR asym for each muscle as a function of the corresponding B 0 inhomogeneity. This model was subsequently used to correct pixel-wise post-exercise B 0 shifts, allowing isolation of signal changes specifically associated with exercise-induced alterations in creatine levels. Seven subjects performed plantar flexion exercise at 3T, while CrCEST, fast-CrCEST, and 31P-MRS were performed. Recovery time constants in the gastrocnemius muscles, obtained from CrCEST (T Cr ) and fast-CrCEST (T fCr ), were compared with those derived from 31 P-MRS (T PCr ). To compare the accuracy of Cr recovery time constant measurements between CrCEST and fast-CrCEST, we performed simulations using 10s and 30s sampling intervals, incorporating experimentally measured noise levels.

Results

T fCr showed a significant 1:1 correlation with T PCr (R 2 = 0.57, p = 0.048), whereas T Cr values were approximately three times higher than T PCr , with a weaker correlation (R 2 =0.47, p=0.087).

Conclusion

We present a novel method for correcting exercise-induced B 0 shifts in fast-CrCEST. This approach enables reliable assessment of post-exercise creatine recovery, outperforming the conventional CrCEST protocol and demonstrating strong agreement with the gold-standard 31 P-MRS.

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