Title
High-Resolution Dynamic 31 P-MR Spectroscopic Imaging for Mapping Mitochondrial Function
Abstract
<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective:</italic> 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). <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Methods:</italic> 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 <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(k, t, T)</italic> -space; image reconstruction was accomplished using a low-rank tensor-based framework. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Results:</italic> The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${}\times \text{4} \times{}$</tex-math></inline-formula> 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 <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</italic> mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</italic> experiments were performed to demonstrate reproducibility, and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</italic> experiments were used to validate the accuracy of the estimated metabolite maps. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Conclusions:</italic> A new model-based method is proposed to achieve 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 proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">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 xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</italic> and longitudinal studies of mitochondrial dysfunction in disease development and progression.
Year
DOI
Venue
2020
10.1109/TBME.2020.2969892
IEEE Transactions on Biomedical Engineering
Keywords
DocType
Volume
Imaging,Spatial resolution,Biological system modeling,Mathematical model,In vivo,Rats,Image reconstruction
Journal
67
Issue
ISSN
Citations 
10
0018-9294
0
PageRank 
References 
Authors
0.34
0
9
Name
Order
Citations
PageRank
Bryan Clifford121.38
Yuning Gu200.34
Yuchi Liu300.34
Kihwan Kim400.34
Sherry Huang511.07
Yudu Li600.34
Fan Lam7509.14
Zhi-Pei Liang852264.94
Xin Yu922.43