Quantitative Assessment of Peripheral Oxidative Metabolism With a New Dynamic 1H MRI Technique: A Pilot Study in People With and Without Diabetes Mellitus

Abstract

Background: Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free ¹H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health.

Hypothesis: A ¹H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise.

Study type: Cross-sectional study.

Subjects: Seven subjects without T2DM (T2DM-) and seven age, sex, and BMI-matched subjects with T2DM (T2DM+).

Field strength/sequence: Single-shot rapid acquisition with refocusing echoes (RARE) and single-shot gradient-echo sequences, 3 T.

Assessment: Subjects underwent a rest-exercise-recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, $\tau$ , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to $\tau$ . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed.

Statistical tests: Unpaired t-tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant.

Results: SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. $\tau$ was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM-; this correlation was not significant in T2DM+ (r = -0.23, P = 0.269).

Conclusion: The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM- individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion.

Level of evidence: 1 TECHNICAL EFFICACY: Stage 1.

Keywords: blood flow; diabetes mellitus; phosphocreatine; skeletal muscle.