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

Abstract

BackgroundType 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.HypothesisA 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 TypeCross‐sectional study.SubjectsSeven subjects without T2DM (T2DM−) and seven age, sex, and BMI‐matched subjects with T2DM (T2DM+).Field Strength/SequenceSingle‐shot rapid acquisition with refocusing echoes (RARE) and single‐shot gradient‐echo sequences, 3 T.AssessmentSubjects 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, , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed.Statistical TestsUnpaired t‐tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant.ResultsSMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. 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).ConclusionThe 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 Evidence1Technical EfficacyStage 1