Progress Update: MRI measurement to identify disease initiation in FSHD

by Prof. Dr. Arend Heerschap

See grant Intramuscular pattern of fat infiltration measured by MRI to identify disease initiation in FSHD

L. Heskamp1, A. Ogier2,3, A. Le Troter2, D. Bendahan2, A. Heerschap1

1Department of Radiology and Nucleair Medicine, Radboud university medical center, Nijmegen, Netherlands

2Aix Marseille University CNRS URM 7339 Centre de Resonance Magnetique Biologique et Medicale Faculte de Medecine 27 Bd J. Moulin 13005 Marseille France

3Aix Marseille Univ, Université de Toulon, CNRS, LIS, Marseille, France



A major question in FSHD is in which muscles and where in a muscle DUX4 starts to be harmful. Discovering the location of DUX4 initiation in a muscle could indicate what the reason is for DUX4 expression and guide therapy development in FSHD.


As fat infiltration is the ultimate consequence of DUX4 expression we determined the intramuscular fat infiltration pattern, as a surrogate to find the location of DUX4 initiation, in 396 lower extremity muscles of 9 FSHD patients from tendon to tendon using quantitative MRI and semi-automatic muscle segmentation.


Per muscle, on average 44 slices (thickness: 5mm) were semi-automatically segmented on 2pt-Dixon fat fraction (FF) maps to determine the FF per slice. Subsequently, each muscle was divided in five proximo-distal segments.


For each muscle we determined the overall average fat fraction (FF). For a normal muscle the FF is below 10%, as depicted by the blue line in the figure for the gastrocnemius muscles that we have analyzed. A FF above 60% represents a complete fat infiltrated muscle (green line in de figure). Subsequently we determined the FF for each image slice along the muscle and plotted this as a function of the overall FF (see colored lines in the figure for the gastrocnemius). For an overall FF of 10 – 20% we see that the highest fat fractions appear in slices positioned distally (red lines In the figure). The higher the overall FF the more the curves shift proximally (to the right in the figure). In other words the muscles exhibited a fat infiltration front, being most evident in intermediately fat infiltrated muscles (10%

We have found this typical pattern of distal to proximal movement of fat infiltration not only in the gastrocnemius muscle, but in nearly all muscles of the leg.


Leg muscles in FSHD patients exhibit a fat infiltration front that starts distally, indicating that this is the location of the initial DUX4 expression. The reason could be the higher strain and/or lower oxygen levels in the distal part of the muscles as we have discovered in another ongoing study of healthy persons.

The fat infiltration pattern in FSHD is distinct from fat infiltration in other muscular dystrophies in which fat infiltration is either diffuse or starting equally from both ends of the muscle.

Heerschap - fig 1