TY - JOUR
T1 - High-Resolution Dynamic 31P-MR Spectroscopic Imaging for Mapping Mitochondrial Function
AU - Clifford, Bryan
AU - Gu, Yuning
AU - Liu, Yuchi
AU - Kim, Kihwan
AU - Huang, Sherry
AU - Li, Yudu
AU - Lam, Fan
AU - Liang, Zhi Pei
AU - Yu, Xin
N1 - Funding Information:
Manuscript received June 19, 2019; revised October 30, 2019 and December 19, 2019; accepted January 14, 2020. Date of publication January 28, 2020; date of current version September 18, 2020. This work was supported in part by the National Institutes of Health (R01EB023704 and R21EB021013) and the UIUC Yang Award. (Bryan Clifford and Yuning Gu contributed equally to this work.) (Corresponding authors: Zhi-Pei Liang; Xin Yu.) B. Clifford and Y. Li are with the Department of Electrical and Computer Engineering and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign.
Publisher Copyright:
© 1964-2012 IEEE.
PY - 2020/10
Y1 - 2020/10
N2 - Objective: To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31P-MR spectroscopic imaging (MRSI). Methods: 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. Results: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4{}\times \text{4} \times{ 2 mm3 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.
AB - Objective: To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31P-MR spectroscopic imaging (MRSI). Methods: 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. Results: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4{}\times \text{4} \times{ 2 mm3 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.
KW - Magnetic resonance spectroscopic imaging
KW - dynamic phosphorus-31 MRSI
KW - low rank models
KW - metabolic imaging
KW - mitochondrial oxidative capacity
KW - subspace models
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U2 - 10.1109/TBME.2020.2969892
DO - 10.1109/TBME.2020.2969892
M3 - Article
C2 - 32011244
AN - SCOPUS:85091264085
SN - 0018-9294
VL - 67
SP - 2745
EP - 2753
JO - IRE transactions on medical electronics
JF - IRE transactions on medical electronics
IS - 10
M1 - 8972401
ER -