Abstract
ABSTRACT
Background
Myofibrillar myopathies (MFM) form a large group of clinically and genetically heterogeneous protein aggregate diseases. We investigated whether a novel quantitative MRI protocol can reveal new aspects of structural and biochemical muscle pathology in three classic MFM subtypes.
Methods
MRI of the lower legs was performed in nine MFM patients with filamin‐C (
FLNC
;
n
= 5), desmin (
DES
,
n
= 2) and LIM domain binding 3 (
LDB3
;
n
= 2) gene mutations, one patient with non‐MFM, filamin‐C related distal myopathy (4 males, 6 females, 51.0 ± 7.7 years) and 10 age‐matched healthy control subjects (5 males, 5 females, 50.0 ± 11.0 years).
1
H MRI at 3 T addressed fatty replacement and edema‐like changes as well as quantitative measurements of proton density fat fraction (PDFF) and water T
2
relaxation times.
39
K/
23
Na MRI at 7 T was employed to determine apparent tissue potassium and tissue sodium concentrations (aTPC/aTSC).
Results
T
1
‐weighted and T
2
‐weighted STIR imaging showed the highest degree of fat replacement in the soleus and gastrocnemius medialis muscle regions and the highest degree of edema‐like changes in the extensor regions in all 10 myopathy patients. The lowest degree of fat replacement and edema‐like changes was present in the gastrocnemius lateralis muscles. Marked fatty replacement of peroneus muscles was also present in DES‐related MFM and
FLNC
‐related distal myopathy. Muscular PDFF values were significantly increased in all MFM patients (
p
= 0.003 ‐ 10% and > 50%). When excluding the muscles with PDFF > 50%, the median water T
2
was significantly increased in all muscle regions of MFM patients with the exception of the tibialis anterior and posterior muscles. Fat‐corrected aTSC values in MFM patients were significantly increased compared to healthy controls (55.6 ± 16.3 mM vs. 23.2 ± 5.5 mM,
p
p
Conclusions
Quantitative PDFF measurements and water T
2
mapping serve as valuable tools to objectively quantify fat and edema‐like changes in MFM. Furthermore, changes in potassium/sodium ion balance in the lower leg muscles of MFM patients could serve as new markers to quantify the extent of biochemical changes in individual muscle regions. Further longitudinal evaluation is required to validate whether they are sensitive to changes prior to a high degree of fat replacement.