High-Resolution Dynamic <sup>31</sup>P-MR Spectroscopic Imaging for Mapping Mitochondrial Function
Bryan Clifford, Yuning Gu, Yuchi Liu, Ki-Hwan Kim, Sherry Huang, Yudu Li, Fan Lam, Zhi‐Pei Liang, Xin Yu
Abstract
Objective: To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sup> P-MR spectroscopic imaging (MRSI). Methods: We developed a novel method for high-resolution dynamic <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sup> P-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 (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. Results: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4 × 4 × 2 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> and 1.28 s, respectively. This allowed for in vivo mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of in vivo experiments were performed to demonstrate reproducibility, and in vitro experiments were used to validate the accuracy of the estimated metabolite maps. Conclusions: 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. Significance: 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 in vivo and longitudinal studies of mitochondrial dysfunction in disease development and progression.