Imaging of Muscle Disease
Volker Straub
What’s the role of MRI
in the diagnosis of genetic muscle diseases?
Volker Straub
Pattern recognition – the quiz
MRI is a tool for different applications
Pattern recognition  e.g. T1w
outcome measures 
quantitative MRI, e.g. Dixon
technique, T2
Pathophysiology  contrast
agents, Diffusion tensor imaging
texture analysis  algorithms
Fundamentals of MRI
1.5 vs 3–tesla MRI
High field strength MRI provides
a better signal to noise ratio.
At the same resolution, images
on a higher field strength
magnet can be acquired faster.
mritechniciansite.com
Fundamentals of MRI
Frontal or coronal plane
divides the body or an organ into
front (anterior) and back (posterior)
portions
Transverse (cross-sectional),
axial or horizontal plane
divides the body or an organ into
upper (superior) or lower (inferior)
portions
Whole Body MRI
Cardiac MRI
http://upload.wikimedia.org/
Mohit Joshi, 08/21/2010, www.topnews.in/health/
Pattern recognition by muscle MRI –
a diagnostic or a research indication?
51 y. of age
15 y. history of weakness
CK 680 U/l
Bethlem myopathy
43 y. of age
6 y. history of weakness
CK 840 U/l
Pompe disease
diagnostic procedures in muscle diseases
clinical history
clinical examination
investigations
 blood tests
 electrophysiology
 cardiac function
 lung function
 imaging
 muscle biopsy
 protein analysis
 genetic analysis
confirmed diagnosis
diagnostic procedures in muscle diseases
clinical history
clinical examination
investigations
 blood tests
 genetic analysis
 electrophysiology
 cardiac function
 lung function
 imaging
 muscle biopsy
 protein analysis
confirmed diagnosis
Stanford MSK MRI Atlas 1.0
Stanford MSK MRI Atlas 1.0
which diseases might a muscle MRI help to diagnose?
 Muscular Dystrophies
 Myofibrillar Myopathies
 (congenital) Myopathies
LGMD2I - Descriptive analysis
Thigh muscles; T1 weighted
LGMD2I - Descriptive analysis
Calf muscles; T1 weighted
LGMD2I - quantitative analysis
Muscle
Biceps Femoris long head
(BFLH)
Semitendinosis (ST)
Semimembranosis (SM)
Biceps Femoris short head
(BFSH)
Sartorius (SAR)
Vastus Medialis (VM)
Gracilis (GRAC)
Vastus Lateralis (VL)
Rectus Femoris (RF)
Medial Gastrocnemius (MG)
Lateral Gastrocnemius (LG)
Peroneus Longus (PL)
Soleus (SOL)
Tibialis Anterior (TA)
Median
LGMD2I
69.7
Median
Control
3.9
49.0
48.6
25.5
2.3
2.9
3.2
24.2
23.3
16.4
14.3
9.4
25.1
19.4
16.0
10.5
5.9
3.9
5.5
3.0
2.9
3.3
2.2
2.0
4.9
3.0
2.8
thigh
lower leg
Table 2; The median values of fat infiltration (%) in the patient group and the control group.
Willis T. et al., PLOS one 2013
LGMD2I
thigh
LGMD2I
–
assessment of muscle pathology by MRI
Selective pattern of involvement
LGMD2L – anoctamin5
proximal weakness of lower limbs + high CK!
LGMD2L – anoctamin5
UK9
UK7A
UK5B
Sarkozy A. et al., Neuromuscul Disord 2012
LGMD2L – anoctamin5
UK5A
UK1A
UK11
Sarkozy A. et al., Neuromuscul Disord 2012
LGMD2L – anoctamin5
Schematic representation of muscle involvement. Red: most
severely affected muscles; green: least affected muscles
29 y old female, CK 2.500 U/l, limb girdle weakness
LGMD2A
Typically involvement of the
hamstring and the medial
gastrocnemius and soleus muscles
46 y old male, high CK, limb girdle weakness
Sparing of the lower leg muscles
in a patient with limb girdle
muscular dystrophy:
Think of the sarcoglycanopathies
or Pompe disease!
 Myofibrillar Myopathies
(desminopathies, protein surplus
myopathies)
Desmin
Myotilin
ZASP
B-Crystalin
Filamin C
BAG3
DNAJB6
Titin
VCP
Desmin associated myopathy
The most affected muscles are:
Thigh: the semitendinosus, sartorius and gracilis muscles
Calf: the extensor digitorum longus musles
Myotilin associated myopathy
The most affected muscles are:
Thigh: the adductor magnus and semimembranosus muscles
Calf: the soleus, medial gastrocnemius and tibialis anterior musles
50 y old female with sequence variants in
ZASP, titin, myotilin and desmin
desmin
myotilin
Straub et al., Neuromuscul Disord 2012
Myofibrillar Myopathies
MUSCLES
DES
CRYAB
MYOT ZASP
Peroneus
9/9
3/4
6/11
1/2
Soleus
1/9
2/4
11/11
2/2
Semitendinosus
9/9
4/4
0/11
0/2
Semimembranosus
0/9
0/4
11/11
1/2
Sartorius
9/9
3/4
2/11
0/2
Gracilis
6/9
4/4
0/11
0/2
Vasti intermedius/medialis
1/9
1/4
7/11
1/2
desmin
myotilin
Straub et al., Neuromuscul Disord 2012
Titin associated myopathy
62 year old male
40 year old male
Muscle imaging findings in GNE-myopathy
G. Tasca et al., J Neurol (2012)
Muscle imaging findings in GNE-myopathy
muscles prominently and invariably involved from
the early stages of GNE myopathy include:
• the gluteus minimus (a red)
• the biceps femoris short head (b green)
• the tibialis anterior (c blue)
• the extens. hallucis/digitorum longus (c yellow)
• the soleus (c violet)
• the gastrocnemius medialis (c orange)
the femoral quadriceps muscle is
normally well preserved
G. Tasca et al., J Neurol (2012)
51 year old female with an axial,
non-progressive myopathy
RYR1-associated myopathies
Arch Neurol 2011
MTM1,
manifesting
carrier
SEPN1 associated myopathy (RSS)
Mercuri et al., Ann Neurol 2010
SEPN1 associated myopathy (RSS)
Bethlem Myopathy
Collagen VI-related disorder
Bethlem Myopathy
Ullrich CMD
Mercuri et al., Ann Neurol 2010
Bethlem Myopathy
STIR images have very low signals from fat
but high signal from fluid
45 year-old woman with thigh pain and swelling
This is a case of pyomyositits
Coronal STIR image reveals a fluid collection in the mid right thigh, with extensive soft
tissue edema. (A) Axial T1 and (B) Axial STIR images show that the fluid collection is
associated with the vastus intermedius muscle. (http://musculoskeletalmri.blogspot.co.uk/)
FSHD
T1w
T2-STIR
Tasca G et al. PLoS One. 2012
Frisullo G et al. J Clin Immunol. 2011
A diagnostic algorithm for LGMD using muscle MRI
Myofibrillar myopathies
Applications of MR imaging and spectroscopy techniques in neuromuscular disease: collaboration
on outcome measures and pattern recognition for diagnostics and therapy development
DICOM sharing:
Web-based online atlas:
Users can access and
search all uploaded scans
curated images with
descriptions and annotations,
linked back to DICOM source
Central online PACS
Scans from all collaborating centres
Anonymization
Stage 1: Better image sharing
Stage 2: Development of curated public resource
Stage 3: Future-proofing
Pattern recognition – the quiz
Titinopathy
LGMD2A
RYR1
Pompe
LGMD2L
desminopathy
Myotilinopathy
SEPN1 (RSS)
Bethlem
Thank You
Institute of Genetic Medicine, Newcastle upon Tyne, UK