High-Resolution Dynamic 31P-MR Spectroscopic Imaging for Mapping Mitochondrial Function

<italic>Objective:</italic> To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using ³¹P-MR spectroscopic imaging (MRSI). <italic>Methods:</italic> We developed a novel method for high-resolution dynamic ³¹P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spiral trajectories and sparse sampling of <italic>(k, t, T)</italic>-space; image reconstruction was accomplished using a low-rank tensor-based framework. <italic>Results:</italic> The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4<inline-formula><tex-math notation="LaTeX">${}\times \text{4} \times{}$</tex-math></inline-formula>2 mm³ and 1.28 s, respectively. This allowed for <italic>in vivo</italic> mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of <italic>in vivo</italic> experiments were performed to demonstrate reproducibility, and <italic>in vitro</italic> experiments were used to validate the accuracy of the estimated metabolite maps. <italic>Conclusions:</italic> A new model-based method is proposed to achieve high-resolution dynamic ³¹P-MRSI. The proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. <italic>Significance:</italic> Abnormal mitochondrial metabolism is a key cellular dysfunction in many prevalent diseases such as diabetes and heart disease; however, current understanding of mitochondrial function is mostly gained from studies on isolated mitochondria under nonphysiological conditions. The proposed method has the potential to open new avenues of research by allowing <italic>in vivo</italic> and longitudinal studies of mitochondrial dysfunction in disease development and progression.