Share:
Share this content in WeChat
X
Clinical Article
Phosphorus-31 magnetic resonance spectroscopy assessment of calf skeletal muscle energy metabolism in patients with lower extremity peripheral artery disease
ZHONG Siyi  ZHANG Qinhe  WANG Shigeng  LIN Liangjie  PENG Jing  XU Xiaofang  SONG Qingwei  WANG Jiazheng  JI Donghua  LIU Ailian 

Cite this article as: ZHONG S Y, ZHANG Q H, WANG S G, et al. Phosphorus-31 magnetic resonance spectroscopy assessment of calf skeletal muscle energy metabolism in patients with lower extremity peripheral artery disease[J]. Chin J Magn Reson Imaging, 2026, 17(9): 144-151. DOI:10.12015/issn.1674-8034.2026.09.019.


[Abstract] Objective To evaluate energy metabolism impairment in the gastrocnemius (GM) and soleus (SOL) muscles of the calf in patients with lower-extremity peripheral artery disease (PAD) and healthy volunteers using phosphorus-31 magnetic resonance spectroscopy (31P-MRS).Materials and Methods This prospective study enrolled 15 PAD patients (patient group) and 16 age-, sex-, and BMI-matched healthy volunteers (control group) who met the inclusion and exclusion criteria. All subjects underwent resting-state 31P-MRS multi-voxel scanning of the posterior calf muscles on the left side using a 3.0 T MR scanner with a 31P surface coil. Two observers independently selected GM and SOL voxels for post-processing analysis using JMRUI software, obtaining the peak area under the curve for metabolites including phosphocreatine (PCr), adenosine triphosphate (ATP) (with the total area under the three ATP peaks recorded as tATP), phosphodiesters (PDE), and inorganic phosphate (Pi). Metabolite ratios were subsequently calculated, including Pi/tATP, PCr/tATP, Pi/PCr, and PDE/PCr. Statistical analyses were performed using GraphPad Prism 10.1.2 and MedCalc 15.2.2. Inter-observer agreement was assessed using the intra-class correlation coefficient (ICC). Within-group differences in metabolic parameters between GM and SOL were compared using paired t-tests for normally distributed data and the Wilcoxon signed-rank test for non-normally distributed data. Between-group differences in GM and SOL metabolic parameters were assessed using independent t-tests or Mann-Whitney U tests, as appropriate, with Cohen's d effect sizes calculated to evaluate the sensitivity of each metabolic indicator in discriminating PAD. Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) were computed to further quantify diagnostic performance, with sensitivity and specificity derived via the Youden index. Differences between AUCs were compared using the DeLong test, and McNemar test was used to compare sensitivity and specificity across metabolic indicators.Results Inter-observer agreement was good for all metabolic parameters in both groups (all ICC > 0.80). No significant within-group differences in metabolic parameters between GM and SOL were observed in either group (all P > 0.05). Compared with the control group, the patient group demonstrated significantly elevated GM Pi/tATP (0.223 ± 0.050 vs. 0.170 ± 0.066, P = 0.007), Pi/PCr (0.154 ± 0.036 vs. 0.105 ± 0.036, P = 0.002), and PDE/PCr (0.158 ± 0.056 vs. 0.076 ± 0.028, P < 0.001). Similarly, SOL Pi/tATP (0.223 ± 0.051 vs. 0.161 ± 0.045, P = 0.004), Pi/PCr (0.147 ± 0.037 vs. 0.105 ± 0.026, P = 0.005), and PDE/PCr (0.143 ± 0.040 vs. 0.073 ± 0.025, P < 0.001) were all significantly elevated, with SOL PDE/PCr showing the largest Cohen's d effect size among all between-group comparisons (d = 2.1). ROC curve analysis showed that PDE/PCr in both GM and SOL (AUC = 0.896 and 0.942, respectively) achieved better diagnostic performance than the other metabolic indices. DeLong test showed that the AUC difference between SOL Pi/PCr and PDE/PCr was statistically significant (P = 0.044), while differences among all other pairs of metabolic indices were not significant (all P > 0.05). McNemar test showed that, for sensitivity, SOL PDE/PCr (93.3%) was significantly higher than SOL Pi/PCr (53.3%, P = 0.031) but did not differ significantly from SOL Pi/tATP (86.7%, P > 0.05). No significant differences in sensitivity were found between GM PDE/PCr (80.0%) and GM Pi/tATP (100.0%) or Pi/PCr (86.7%, all P > 0.05). For specificity, GM PDE/PCr (87.5%) was significantly higher than GM Pi/tATP (50.0%, P = 0.031) but did not differ significantly from GM Pi/PCr (68.8%, P > 0.05); no significant differences in specificity were found among the SOL metabolic indices (all P > 0.05).Conclusions This study preliminarily demonstrates that 31P-MRS has the potential to assess changes in skeletal muscle energy metabolism in patients with PAD, and the increase in PDE/PCr ratio in SOL can serve as a potentially sensitive indicator for evaluating energy metabolism disorders in PAD.
[Keywords] lower extremity peripheral artery disease;multi-nuclear magnetic resonance imaging;energy metabolism;31P magnetic resonance spectroscopy

ZHONG Siyi1, 2, 3   ZHANG Qinhe1, 2   WANG Shigeng1, 2   LIN Liangjie4   PENG Jing4   XU Xiaofang4   SONG Qingwei1, 2   WANG Jiazheng2   JI Donghua3   LIU Ailian1, 2*  

1 Department of Radiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China

2 Technology Innovation Center of Hyperpolarized MRI, Liaoning Province, Dalian 116011, China

3 Department of Interventional Radiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China

4 Philips (China) Investment Co., Ltd, Beijing 100016, China

Corresponding author: LIU A L, E-mail: cjr.liuailian@vip.163.com

Conflicts of interest   None.

Received  2026-04-29
Accepted  2026-08-17
DOI: 10.12015/issn.1674-8034.2026.09.019
Cite this article as: ZHONG S Y, ZHANG Q H, WANG S G, et al. Phosphorus-31 magnetic resonance spectroscopy assessment of calf skeletal muscle energy metabolism in patients with lower extremity peripheral artery disease[J]. Chin J Magn Reson Imaging, 2026, 17(9): 144-151. DOI:10.12015/issn.1674-8034.2026.09.019.

[1]
CRIQUI M H, MATSUSHITA K, ABOYANS V, et al. Lower extremity peripheral artery disease: Contemporary epidemiology, management gaps, and future directions: a scientific statement from the American heart association[J/OL]. Circulation, 2021, 144(9): e171-e191 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/34315230/. DOI: 10.1161/CIR.0000000000001005.
[2]
GBD 2019 Peripheral Artery Disease Collaborators. Global burden of peripheral artery disease and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019[J/OL]. Lancet Glob Health, 2023, 11(10): e1553-e1565 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/37734799/. DOI: 10.1016/S2214-109X(23)00355-8.
[3]
CALLEGARI S, FEHER A, SMOLDEREN K G, et al. Multi-modality imaging for assessment of the microcirculation in peripheral artery disease: Bench to clinical practice[J/OL]. Am Heart J Plus Cardiol Res Pract, 2024, 42: 100400 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/38779485/. DOI: 10.1016/j.ahjo.2024.100400.
[4]
PARK S Y, PEKAS E J, ANDERSON C P, et al. Impaired microcirculatory function, mitochondrial respiration, and oxygen utilization in skeletal muscle of claudicating patients with peripheral artery disease[J/OL]. Am J Physiol Heart Circ Physiol, 2022, 322(5): H867-H879 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/35333113/. DOI: 10.1152/ajpheart.00690.2021.
[5]
WILBURN D, FLETCHER E, PAPOUTSI E, et al. Ultrastructural alterations and mitochondrial dysfunction in skeletal muscle of peripheral artery disease patients: implications for early therapeutic interventions[J]. EXCLI J, 2024, 23: 1208-1225. DOI: 10.17179/excli2024-7592.
[6]
KIM K, ANDERSON E M, SCALI S T, et al. Skeletal muscle mitochondrial dysfunction and oxidative stress in peripheral arterial disease: A unifying mechanism and therapeutic target[J/OL]. Antioxidants, 2020, 9(12): 1304 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/33353218/. DOI: 10.3390/antiox9121304.
[7]
SCHIAFFINO S, CHEMELLO F, REGGIANI C. The diversity of skeletal muscle fiber types[J/OL]. Cold Spring Harb Perspect Biol, 2025, 17(8): a041477 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/39134381/. DOI: 10.1101/cshperspect.a041477.
[8]
KUPRIYANOVA Y, SCHRAUWEN-HINDERLING V. Advances in in vivo magnetic resonance spectroscopy for metabolic disorders[J/OL]. Front Endocrinol, 2025, 16: 1578333 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/40756506/. DOI: 10.3389/fendo.2025.1578333.
[9]
MEYERSPEER M, BOESCH C, CAMERON D, et al. 31P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations[J/OL]. NMR Biomed, 2021, 34(5): e4246 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/32037688/. DOI: 10.1002/nbm.4246.
[10]
SINGH M, JHAJHARIA A, PRUTHI R, et al. 31P-MRS-measured phosphocreatine recovery kinetics in human muscles in health and disease: a systematic review and meta-analysis[J/OL]. NMR Biomed, 2025, 38(5): e70023 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/40189235/. DOI: 10.1002/nbm.70023.
[11]
SPORKIN H L, PATEL T R, BETZ Y, et al. Chemical exchange saturation transfer magnetic resonance imaging identifies abnormal calf muscle-specific energetics in peripheral artery disease[J/OL]. Circ Cardiovasc Imaging, 2022, 15(7): e013869 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/35861977/. DOI: 10.1161/CIRCIMAGING.121.013869.
[12]
GREINER J V, SNOGREN T I, GLONEK T. The 31P spectral modulus (PSM) as an assay of metabolic status[J/OL]. Biology, 2025, 14(2): 152 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/40001920/. DOI: 10.3390/biology14020152.
[13]
GOLDEN L E, XU J, MAGNOTTA V A, et al. Decreased cerebral ATP in pre-motor manifest Huntington's disease: A pilot study[J/OL]. Park Relat Disord, 2025, 140: 108040 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/40974859/. DOI: 10.1016/j.parkreldis.2025.108040.
[14]
JONUSCHEIT M, KORZEKWA B, SCHÄR M, et al. 31P-MRS saturation transfer for assessing human hepatic ATP synthesis at clinical field strength[J/OL]. Eur Radiol Exp, 2025, 9: 51 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/40360906/. DOI: 10.1186/s41747-025-00588-9.
[15]
VALKOVIČ L, CHMELÍK M, UKROPCOVÁ B, et al. Skeletal muscle alkaline Pi pool is decreased in overweight-to-obese sedentary subjects and relates to mitochondrial capacity and phosphodiester content[J/OL]. Sci Rep, 2016, 6: 20087 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/26838588/. DOI: 10.1038/srep20087.
[16]
BRADLEY C E, FLETCHER E, WILKINSON T, et al. Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy[J]. EXCLI J, 2024, 23: 523-533. DOI: 10.17179/excli2024-7004.
[17]
AFFOURTIT C, CARRÉ J E. Mitochondrial involvement in sarcopenia[J/OL]. Acta Physiol, 2024, 240(3): e14107 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/38304924/. DOI: 10.1111/apha.14107.
[18]
ZHAO S, DONG Y J, JIANG B Y, et al. Cerebral phosphorus metabolite as imaging biomarkers in Alzheimer's disease: a 31P magnetic resonance spectroscopy study[J/OL]. NeuroImage Clin, 2025, 48: 103904 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/41260015/. DOI: 10.1016/j.nicl.2025.103904.
[19]
PAYNE T, BURGESS T, BRADLEY S, et al. Multimodal assessment of mitochondrial function in Parkinson's disease[J]. Brain, 2024, 147(1): 267-280. DOI: 10.1093/brain/awad364.
[20]
KRŠŠÁK M, LINDEBOOM L, SCHRAUWEN-HINDERLING V, et al. Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations[J/OL]. NMR Biomed, 2021, 34(5): e4266 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/32022964/. DOI: 10.1002/nbm.4266.
[21]
DIVAKARAN S, HARMS H J, ROBERTSON M, et al. Post-walking exercise skeletal muscle perfusion and energetics in patients with symptomatic lower extremity peripheral artery disease[J/OL]. J Nucl Cardiol, 2025, 46: 102143 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/39889951/. DOI: 10.1016/j.nuclcard.2025.102143.
[22]
ELSAID N M H, PETERS D C, GALIANA G, et al. Clinical physiology: the crucial role of MRI in evaluation of peripheral artery disease[J]. Am J Physiol Heart Circ Physiol, 2024, 326(5): H1304-H1323. DOI: 10.1152/ajpheart.00533.2023.
[23]
BAKERMANS A J, WESSEL C H, ZHENG K H, et al. Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease[J]. J Magn Reson Imaging, 2020, 51(1): 98-107. DOI: 10.1002/jmri.26841.
[24]
HINKLEY J M, CORNNELL H H, STANDLEY R A, et al. Older adults with sarcopenia have distinct skeletal muscle phosphodiester, phosphocreatine, and phospholipid profiles[J/OL]. Aging Cell, 2020, 19(6): e13135 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/32468656/. DOI: 10.1111/acel.13135.
[25]
LANZA I R, SUNDBERG C W, KENT J A. Reduced oxidative capacity of skeletal muscle IS NOT an inevitable consequence of adult ageing[J]. J Physiol, 2025, 603(1): 21-24. DOI: 10.1113/JP285042.
[26]
RONTOYANNI V G, BLEARS E, NUNEZ LOPEZ O, et al. Skeletal muscle bioenergetics in critical limb ischemia and diabetes[J]. J Surg Res, 2023, 288: 108-117. DOI: 10.1016/j.jss.2023.02.015.
[27]
SPEICHINGER F, GRATL A, RAUDE B, et al. Mitochondrial respiration in peripheral arterial disease depends on stage severity[J/OL]. J Cell Mol Med, 2024, 28(8): e18126 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/38534092/. DOI: 10.1111/jcmm.18126.
[28]
JONUSCHEIT M, WIERICHS S, ROTHE M, et al. Reproducibility of absolute quantification of adenosine triphosphate and inorganic phosphate in the liver with localized 31P-magnetic resonance spectroscopy at 3-T using different coils[J/OL]. NMR Biomed, 2024, 37(8): e5120 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/38404058/. DOI: 10.1002/nbm.5120.
[29]
JAMES J J, MELLOW M L, BUECKERS E P, et al. Sex differences in human skeletal muscle fiber types and the influence of age, physical activity, and muscle group: A systematic review and meta-analysis[J/OL]. Physiol Rep, 2025, 13(21): e70616 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/41178056/. DOI: 10.14814/phy2.70616.
[30]
KUZNETSOV A V, MARGREITER R, HAGENBUCHNER J, et al. Energy metabolism in different skeletal muscles and muscle fibers: implications for injury and dietary supplementation[J]. Pflugers Arch, 2025, 477(10): 1231-1240. DOI: 10.1007/s00424-025-03112-5.
[31]
POPOV D V, MAKHNOVSKII P A, ZGODA V G, et al. Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion[J]. J Appl Physiol (1985), 2023, 134(5): 1256-1264. DOI: 10.1152/japplphysiol.00048.2023.
[32]
KOSMAC K, WANG R D, STEWART J, et al. Gastrocnemius myofiber type and mitochondrial alterations associated with peripheral artery disease severity[J/OL]. Function (Oxf), 2025, 6(6): zqaf047 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/41051228/. DOI: 10.1093/function/zqaf047.
[33]
SCHRAMA E J, HOOIJMANS M T, VAN DE VELDE N M, et al. Skeletal muscle membrane permeability markers derived from 31P-MRS may reflect disease activity in Becker muscular dystrophy[J/OL]. NMR Biomed, 2025, 38(11): e70155 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/41058238/. DOI: 10.1002/nbm.70155.
[34]
VAN DE CASTEELE F, VAN THIENEN R, HORWATH O, et al. Does one biopsy cut it Revisiting human muscle fiber type composition variability using repeated biopsies in the vastus lateralis and gastrocnemius medialis[J]. J Appl Physiol (1985), 2024, 137(5): 1341-1353. DOI: 10.1152/japplphysiol.00394.2024.
[35]
FLETCHER J R, STRZALKOWSKI N D J. The neuromechanics of the soleus for fall prevention in aging[J/OL]. Front Physiol, 2025, 16: 1743559 [2026-04-27]. https://pubmed.ncbi.nlm.nih.gov/41574195/. DOI: 10.3389/fphys.2025.1743559.
[36]
WANG X H, CHEN C, LU H N, et al. The changes of healthy adults delayed onset muscle soreness 31P-MR spectroscopy and correlation between serum creatine kinase and soreness index[J]. Chin J Radiol, 2014, 48(1): 17-20. DOI: 10.3760/cma.j.issn.1005-1201.2014.01.006.
[37]
KIM K, THOME T, PASS C, et al. Multiomic analysis of calf muscle in peripheral artery disease and chronic kidney disease[J]. Circ Res, 2025, 136(7): 688-703. DOI: 10.1161/CIRCRESAHA.124.325642.

PREV Magnetic resonance image compilation combined with MUSE-DWI for preoperative evaluation of neurovascular invasion in rectal cancer: Quantitative analysis of intratumoral and peritumoral parameters
NEXT Neuroprotective therapy and visualization of acute ischemic stroke based on inflammation-targeted MRI molecular probe in mice
  



Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn