Abstract
To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31P-MR spectroscopic imaging (MRSI). 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 (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4[Formula: see text]2mm3 and 1.28s, 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. 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. 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.
Highlights
M ITOCHONDRIA play a critical role in biological processes by supplying the energy needed for maintaining tissue viability and functional integrity
The PCr concentration showed exponential recovery kinetics accompanied by a rapid decrease in Pi levels, while ATP levels remained relatively constant, as reported in the literature [4]–[6], [35]
We evaluated the kinetic changes of phosphorous metabolites during two rounds of in vivo experiments performed without electrical stimulation but with data acquisition kept the same
Summary
M ITOCHONDRIA play a critical role in biological processes by supplying the energy needed for maintaining tissue viability and functional integrity. Dynamic 31P-MRSI allows the monitoring of the depletion and resynthesis of PCr during metabolic perturbations such as ischemia/reperfusion or exercise/recovery. The resynthesis of PCr is driven primarily by mitochondrial oxidative metabolism. The rate of PCr resynthesis is a functional biomarker for mitochondrial oxidative capacity [2]. This approach has been shown to be highly reproducible and well correlated with in vitro methods for assessing mitochondrial oxidative capacity [3]. Where ρ(x, f, T ) denotes the dynamic spectroscopic image representing spatial (x), spectral (f ) and temporal (T ) variations; k represents spatial frequency and t is the conjugate variable of f (distinguished from T by its much shorter time-scale).
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