In Vivo Quantification of Creatine Kinase Kinetics in Mouse Brain Using P-MRS at 7 T.

P-MRS is a method of choice for studying neuroenergetics in vivo, but its application in the mouse brain has been limited, often restricted to ultrahigh field (> 7 T) MRI scanners. Establishing its feasibility on more readily available preclinical 7-T scanners would create new opportunities to study metabolism and physiology in murine models of brain disorders. Here, we demonstrate that the apparent forward rate constant (k) of creatine kinase (CK) can be accurately quantified using a progressive saturation-transfer approach in the mouse brain at 7 T. We also find that a 20% reduction in respiration of anesthetized mice can lead to 36% increase in k attributable to a drop in cellular pH and mitochondrial ATP production. To achieve this, we used a test-retest analysis to assess the reliability and repeatability of P-MRS acquisition, analysis, and experimental design protocols. We report that many P-containing metabolites can be reliably measured using a localized 3D-ISIS sequence, which showed highest SNR amplitude, SNR consistency, and minimal T relaxation signal loss. Our study identifies key physiological factors influencing mouse brain energy homeostasis in vivo and provides a methodological basis to guide future studies interested in implementing P-MRS on preclinical 7-T scanners.