Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study

Abstract

We conducted a prospective multinational study of muscle pathology using magnetic resonance imaging (MRI) in patients with limb-girdle muscular dystrophy 2I (LGMD2I). Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP) gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by qualitative grading for 15 individual lower limb muscles and quantitative Dixon imaging was analysed on 14 individual lower limb muscles by region of interest analysis. We described the pattern and appearance of muscle pathology and gender differences, not previously reported for LGMD2I. Diffuse fat infiltration of the gastrocnemii muscles was demonstrated in females, whereas in males fat infiltration was more prominent in the medial than the lateral gastrocnemius (p = 0.05). In the anterior thigh of males, in contrast to females, median fat infiltration in the vastus medialis muscle (45.7%) exceeded that in the vastus lateralis muscle (11.2%) (p<0.005). MRI is non-invasive, objective and does not rely on patient effort compared to clinical and physical measures that are currently employed. We demonstrated (i) that the quantitative Dixon technique is an objective quantitative marker of disease and (ii) new observations of gender specific patterns of muscle involvement in LGMD2I.

Conflict of interest statement

Competing Interests: JV has given lectures for and received travel expenses from Genzyme. VS serves on the advisory boards of Genzyme and Acceleron, on the Joint Imaging Committee of Prosensa for which he receives research support, and has presented lectures for Genzyme. All other authors report no disclosures. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. T1 weighted images of the lower leg in LGMD2I patients with increasing severity in pathology (a–e), and in a control subject (f).

In image (a) there is involvement of medial gastrocnemius and soleus compared to image (e) where all muscles but tibialis anterior are severely affected. (TA =  tibialis anterior, SOL =  soleus, PL =  peroneus longus, LG =  lateral gastrocnemius, MG =  medial gastrocnemius).

Figure 2. T1 weighted images of the thigh in LGMD2I patients with increasing stages of severity and fat content (a–e), and in a control subject (f).

In (a) this is almost normal, however in (e) only sparing of gracilis and sartorius is seen. (VL =  vastus lateralis, SM =  semimembranosus, ST =  semitendinosus, BFLH =  biceps femoris long head, SAR =  sartorius, GRAC =  gracilis, RF =  rectus femoris).

Figure 3. The grey bars illustrate the quantitative fat fractions for LGMD2I patients with median qualitative score at the left of the bars.

The grey box indicates the lower and upper quartiles, with the median represented as a bar within the grey box and the stems the range (the outliers more than 1.5 interquartile range are marked separately as dots). (BFLH =  biceps femoris long head, ST =  semitendinosus, SM =  semimembranosus, BFSH =  biceps femoris short head, SAR =  sartorius, VM =  vastus medialis, GRAC =  gracilis, VL =  vastus lateralis, RF =  rectus femoris, MG =  medial gastrocnemius, LG =  lateral gastrocnemius, PL =  peroneus longus, SOL =  soleus, TA =  tibialis anterior).

Figure 4. Quantitative fat images of the thigh in LGMD2I patients with increasing stages of severity and increasing fat fraction (a–e), and in a control subject (f).

In (a) this is almost normal, however in (e) only sparing of gracilis (fat fraction 13.7%) and sartorius (24.0%) is seen. (SM =  semimembranosus, ST =  semitendinosus, GRAC =  gracilis, SAR =  sartorius).

Figure 5. This figure compares the results of quantitative Dixon imaging with the semi-quantitative grading, demonstrating the wide range of fat fractions that can exist within the same grade (rs = 0.87, p<0.01).

The grey bars represent the middle 50% of the distribution between the upper and lower quartile and their corresponding fat fraction. The dots and stars represent outliers beyond 1.5 and 3.0 times the interquartile range beyond the upper quartile respectively.

Figure 6. Comparison of the thigh muscles in (a) a male LGMD2I patient with more advanced pathology and increased fat content seen in the vastus medialis muscle (72.2%) and (b) preservation of the vastus medialis muscle (9.7%) of a female LGMD2I patient.

(VM =  vastus medialis, VL =  vastus lateralis).

Figure 7. Strong correlation between knee flexion strength (in pounds) and hamstring average fat fraction, r = −.73 (p

Figure 8. Strong correlation between 6 minute walk distance (6MWD) and hamstring average fat fraction, r = −.79 (p