Fast in vivo assay of creatine kinase activity in the human brain by P-31 magnetic resonance fingerprinting

A new and efficient magnetisation transfer P-31 magnetic resonance fingerprinting (MT-P-31-MRF) approach is introduced to measure the creatine kinase metabolic rate kCK${k}_{\mathrm{CK}}$ between phosphocreatine (PCr) and adenosine triphosphate (ATP) in human brain. The MRF framework is extended to overcome challenges in conventional P-31 measurement methods in the human brain, enabling reduced acquisition time and specific absorption rate (SAR). To address the challenge of creating and matching large multiparametric dictionaries in an MRF scheme, a nested iteration interpolation method (NIIM) is introduced. As the number of parameters to estimate increases, the size of the dictionary grows exponentially. NIIM can reduce the computational load by breaking dictionary matching into subsolutions of linear computational order. MT-P-31-MRF combined with NIIM provides T1PCr${T}_1{\mathrm{PCr}}$, T1ATP${T}_1{\mathrm{ATP}}$ and kCK${k}_{\mathrm{CK}}$ estimates in good agreement with those obtained by the exchange kinetics by band inversion transfer (EBIT) method and literature values. Furthermore, the test-retest reproducibility results showed that MT-P-31-MRF achieves a similar or better coefficient of variation (%) for T1ATP${T}_1{\mathrm{ATP}}$ and kCK${k}_{\mathrm{CK}}$ measurements in 4 min 15 s, than EBIT with 17 min 4 s scan time, enabling a fourfold reduction in scan time. We conclude that MT-P-31-MRF in combination with NIIM is a fast, accurate, and reproducible approach for in vivo kCK${k}_{\mathrm{CK}}$ assays in the human brain, which enables the potential to investigate energy metabolism in a clinical setting.