3D Creatine Kinase Imaging (CKI) for In Vivo Whole-Brain Mapping of Creatine Kinase Reaction Rates with 31P-Magnetization Transfer MR Fingerprinting

The creatine kinase (CK) is a key enzyme involved in brain bioenergetics, but imaging its activity noninvasively in the human brain remains a significant challenge. This study aims to advance the magnetization transfer (MT)-31P magnetic resonance fingerprinting (MRF) framework for 3D Creatine Kinase Imaging (CKI), delivering the first whole-brain CK reaction rate maps. The method was implemented and validated on a clinical 7 Tesla MRI scanner with a 49:30-minute acquisition time and the within-session reproducibility was assessed. The CKI method successfully enables the whole-brain mapping of CK reaction rates, showing robust reproducibility with coefficients of variation (CV) below 11% for 25-minute scan sessions. Furthurmore, CKI acquisition provided simultaneous mapping of adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrationratios, PCr longitudinal relaxation time (T ₁ ^PCr ), and phosphorus-based B0 maps at a 7.2 × 7.2 × 20 mm ³ resolution. CKI provides, for the first time,3D whole-brain mapping of k _CK rates in high resolution, using a user-friendly, push-button approach. A functional CKI (fCKI) study demonstrated the first CK activation cluster map in response to visual stimulation, revealing a mean 17% increase in CK rates in the visual cortex. The novel imaging modalities, CKI and fCKI, have the potential to offer new insights into brain bioenergetics both at rest and during activity.