Fig 1.
Flow chart of participant inclusion.
Flow chart of the participant inclusion and the number of included muscles for all MRI measures and the number of participants for the functional and strength tests. The total number of segmented muscles per visit and MRI measure is given in gray. BL, baseline; cCSA, contractile cross-sectional area; FF, fat fraction; FVC, forced vital capacity; DTI, diffusion tensor imaging; NSAD, North Star Assessment for Limb-Girdle Type Muscular Dystrophies; 6MWT, 6 minute walk test; 10mWT, 10 m walk test; 4SC, 4 stair climb and descend test.
Fig 2.
Parameter maps from the legs and thighs of a healthy control (54y) and a representative individual with LGMD-R9 (62y, 8.6 years since diagnosis). In the patient elevated FF, water T2, and water T1 are visible in both, legs and thighs. FF, fat fraction; BL, baseline; MD, mean diffusivity.
Table 1.
FF per muscle at each visit. Mean FF (standard deviation, SD) per muscle at each visit and mean change (SD) in FF (ΔFF) after 1-year (1y) and 2-year (2y) follow-up in patients. Only data of the 14 patients who completed all 3 visits are shown here. The mean value of all muscles and the global thigh and leg were added at the bottom. The most and least affected muscles of the thigh and leg and the muscles with the most and least increase over 2 years are highlighted in red and blue, respectively. BL, baseline; FF, fat fraction.
Fig 3.
Bar plots comparing the LGMD-R9 at baseline (blue) and the controls (orange), showing the mean ± standard deviation, for FF, water T2, water T1, cCSA, MD at diffusion time 116.3 ms, and pH, for all muscles. The individual data points are overlaid as dots. Muscles from the thighs and legs are separated by the dotted line. cCSA, contractile cross-sectional area; FF, fat fraction; MD, mean diffusivity. Muscles in the order of appearance: VL, vastus lateralis; VM, vastus medialis, VI, vastus intermedius; RF, rectus femoris; BF, biceps femoris long head; SM, semimembranosus; ST, semitendinosus; AM, adductor magnus; AL, adductor longus; GRA, gracilis; SAR, sartorius; ED, extensor digitorium; TA, tibialis anterior; TP, tibialis posterior; PER, peroneus longus; SOL, soleus; GM, gastrocnemius medialis; GL, gastrocnemius lateralis; QUAD, quadriceps; HSTR, hamstrings; ANT, anterior compartment; FIB, fibularis; TRIC, triceps surae. *p<0.0056 (= 0.05/9). †p<0.05.
Fig 4.
Bar plots comparing the DTI parameters between LGMD-R9 at baseline (blue) and controls (orange) in the global leg at all diffusion times. DTI, diffusion tensor imaging; FA, fractional anisotropy; λ1- λ3, diffusion tensor eigenvalues; MD, mean diffusivity.
Fig 5.
Time course of qMRI, functional, and strength measurs.
Line plots showing the time course over the years since diagnosis. Each line represents an individual with LGMD-R9 and the same colors show the same participant. A. FF in the global thigh and global leg. B. FF in the most and least fat-replaced thigh and leg muscles (AM, VM, GM, TA). C. Functional measures NSAD and FVC. D. Strength tests for knee extension and ankle plantarflexion. The predicted strength is shown. AM, adductor magnus; VM, vastus medialis; GM, gastrocnemius medialis; TA, tibialis anterior; FF, fat fraction; FVC, forced vital capacity; NSAD, North Star Assessment for Limb-Girdle Type Muscular Dystrophies.
Table 2.
Correlation of baseline water T2 and water T1 with disease progression.
Fig 6.
Predictive value of disease activity-sensitive qMRI parameters.
Regression plots of ΔFF with A. Baseline water T2 and B. Baseline water T1 values. The dots represent individuals with LGMD-R9 and the red line indicates the mean value in the controls. AL, adductor longus; GM, gastrocnemius medialis; TP, tibialis posterior; VM, vastus medialis. *p < 0.05, **p < 0.01.
Table 3.
Functional and strength parameters.