Multiparametric Aging Study Across Adulthood in the Leg Through Quantitative MR Imaging, ¹H Spectroscopy, and ³¹P Spectroscopy at 3T

Background: Improved characterization of healthy muscle aging is needed to establish early biomarkers in age-related diseases.

Purpose: To quantify age-related changes on multiple MRI and clinical variables evaluated in the same cohort and identify correlations among them.

Study type: Prospective.

Population: 70 healthy subjects (30 men) from 20 to 81 years old.

Field strength/sequence: 3T/water T₂ (multiecho SE, multi-TE STEAM), water T₁ (GRE MR Fingerprinting), fat-fraction (multiecho GRE, multi-TE STEAM), carnosine (PRESS), multicomponent water T₂ (ISIS-CPMG SE train), and ³¹P pulse-acquire spectroscopy.

Assessment: Age- and sex-related changes on: Imaging: fat-fraction (FF_MRI), water T₁ (T_1-H2O), and T₂ (T_2-H2O-MRI) and their heterogeneities ΔT_1-H2O and ΔT_2-H2O-MRI in the posterior compartment (PC) and anterior compartment (AC) of the leg. ¹H spectroscopy: Carnosine concentration, pH, water T₂ components (T_2-H2O-CPMG), fat-fraction (FF_MRS), and water T₂ (T_2-H2O-MRS) in the gastrocnemius medialis. ³¹P spectroscopy: Phosphodiesters (PDE), phosphomonoesters, inorganic phosphates (Pi), and phosphocreatine (PCr) normalized to adenosine triphosphate (ATP) and pH in the calf. Clinical evaluation: Body-mass index (BMI), gait speed (GS), plantar flexion strength, handgrip strength (HS), HS normalized to wrist circumference (HS_norm), physical activity assessment.

Statistical tests: Multilinear regressions with sex and age as fixed factors. Spearman correlations calculated between variables. Benjamini-Hochberg procedure for false positives reduction (5% rate). A P < 0.05 significance level was used.

Results: Significant age-related increases were found for BMI (ρ_Age = 0.04), HS_norm (ρ_Age = -0.01), PDE/ATP (ρ_Age = 2.8 × 10^-3), Pi/ATP (ρ_Age = 2.0 × 10^-3), Pi/PCr (ρ_Age = 0.3 × 10^-3), T_2-H2O-MRS (ρ_Age = 0.051 msec), FF_MRS (ρ_Age = 0.036) the intermediate T_2-H2O-CPMG component time (ρ_Age = 0.112 msec), and fraction (ρ_Age = -0.3 × 10^-3); and in both compartments for FF_MRI (ρ_Age = 0.06, PC; ρ_Age = 0.06, AC), T_2-H2O-MRI (ρ_Age = 0.05, PC; ρ_Age = 0.05, AC; msec), ΔT_2-H2O-MRI (ρ_Age = 0.02, PC; ρ_Age = 0.02, AC; msec), T_1-H2O (ρ_Age = 1.08, PC; ρ_Age = 1.06, AC; msec), and ΔT_1-H2O (ρ_Age = 0.22, PC; ρ_Age = 0.37, AC; msec). The best age predictors, accounting for sex-related differences, were HS_norm (R² = 0.52) and PDE/ATP (R² = 0.44). In both leg compartments, the imaging measures and HS_norm were intercorrelated. In PC, T_2-H2O-MRS and FF_MRS also showed numerous correlations to the imaging measures. PDE/ATP correlated to T_1-H2O, T_2-H2O-MRI, ΔT_2-H2O-MRI, FF_MRI, FF_MRS, the intermediate T_2-H2O-CPMG, BMI, Pi/PCr, and HS_norm.

Data conclusion: Our multiparametric MRI approach provided an integrative view of age-related changes in the leg and revealed multiple correlations between these parameters and the normalized HS.

Level of evidence: 1 TECHNICAL EFFICACY: Stage 3.