Imaging techniques
Before discussing the diagnostic value of different imaging techniques in the detection of muscle abnormalities in patients with inherited muscle disorders, we have to be aware that striated muscle is a dynamic tissue that is influenced by many factors such as exercise, age and gender [5]. These physiological changes can be observed across all imaging techniques and have to be distinguished from pathological changes.
Age is one of the most important factors influencing muscle tissue appearance [6]. During childhood, muscle thickness increases rapidly and is not relevantly influenced by gender. After puberty, the gender-specific muscle development starts (men develop thicker muscles after puberty than women), reaching a peak of muscle volume between 25 and 40 years of age, followed by a subsequent decrease in muscle volume. The influence of age and gender is, however, not constant and differs slightly for each muscle group [6–9].

Ultrasound
Ultrasound (US) is a well-established and validated diagnostic imaging method in the evaluation of patients with suspected muscle disorders [10]. It is a relatively cheap and easily applicable method, allowing the visualisation of striated muscle with a high temporal resolution (>0.1 mm). The major advantage of US is the lack of any radiation exposure, which makes it the perfect imaging method for the evaluation of children. It even allows dynamic imaging of contracting muscles and can visualise pathological muscle activity such as fasciculation [11–13].
A major drawback of US is that its application is limited to superficial muscle groups. Sound wave reflection and absorption lead to difficulties in displaying the deeper structures. This effect becomes even more pronounced when multiple muscle groups overlap. Another disadvantage is the relatively low inter-observer agreement and intra-observer agreement (depending on the level of experience), which makes a strictly standardised examination (e.g. according to certain anatomical landmarks) crucial [2, 14]. However, ultrasound is a reliable method concerning the measurement of muscle thickness and muscle echo intensity. In addition, by measuring muscle echo intensity it is possible to further characterise age-related or pathological changes of the striated muscles with special regard to dystrophic changes in terms of fatty degeneration and replacement of muscle by connective tissue (Fig. 1). In order to quantify the degree of fat deposition there are several ratings scales available (e.g. the Heckmatt score) as well as computed-assisted quantification methods of muscle echo intensity [15–19].
Fig. 1 Ultrasound images of the quadriceps muscle in normal control (a) and a patient with Duchenne muscular dystrophy (b). In the healthy subject (a), muscle appears largely black with few perimysial septa. Note the increased homogeneous fine granular echogenicity of muscle due to increased replacement of normal muscle by connective and fatty tissue in the patient with muscular dystrophy (b)
Ultrasound applications are widely and routinely used in neuromuscular disorders in terms of assessment of changes in muscle morphology (atrophy, hypertrophy, changes in muscle architecture). In particular it is a useful screening tool during the initial diagnostic phase, especially in children. Depending on the disease entity, the sensitivity of detecting dystrophic changes ranges from 25% in non-dystrophic myopathies up to 100% in dystrophic myopathies (Duchenne muscular dystrophy) [10, 19, 20]. The detection of pathological changes can be helpful in guiding muscle biopsy, and the description of the muscle involvement pattern might help in the differential diagnosis [10, 21].

Computed tomography
Computed tomography (CT) has been widely used in the past in order to evaluate the presence and extent of change in the striated muscles in patients with hereditary neuromuscular disorders [2, 22–24]. CT is a fast imaging method that is easy to apply and allows a good and standardised assessment of the aspect and shape of the muscles as well as dystrophic changes (in particular fatty degeneration). CT is also relatively operator-independent and allows the evaluation of deeper muscle groups, and newer CT methods using multi-detector rows provide improved imaging possibilities in terms of spatial resolution and multi-planar reconstructions. However, CT has substantial drawbacks leading to an almost complete replacement of this imaging technique by US and MRI. One of the most relevant disadvantages of CT compared with US and MRI is the relatively high radiation dose, which makes the application obsolete, especially in children. Because of the high radiation dose, whole-body applications in order to describe the pattern of muscle involvement are not desired. Another drawback of CT is the limited soft tissue contrast, which substantially impairs the sensitivity in the detection of inflammatory changes (e.g. oedema) that can precede muscle dystrophy.

Magnetic resonance imaging
MRI is increasingly being used in the evaluation of patients with suspected or proven inherited or metabolic neuromuscular disorders. MRI provides a high soft tissue contrast allowing excellent assessment of striated muscles concerning shape, volume (hypotrophy, hypertrophy) and tissue architecture [1, 2]. Because of the lack of ionising radiation, MRI has become a valuable imaging method in children, although sometimes sedation might be necessary. Basically, MRI is performed as a multi-sequence imaging protocol including T1-weighted (T1W) and T2-weighted (T2W) (turbo) spin echo as well as fat-suppressed (short tau inversion recovery or spectral fat suppression techniques) T2-weighted sequences (T2WFS). The image acquisition is performed in the axial plane with a slice thickness of 5-7 mm. If necessary, additional images in other anatomical planes (coronal, sagittal) can be easily acquired.
Dystrophic changes such as fatty degeneration can be easily and sensitively detected using the T1W and T2W sequences. In addition, inflammatory changes such as muscle oedema can be depicted on the T2WFS sequences (Fig. 2). It has been conclusively shown that MRI has a higher sensitivity in the detection of dystrophic changes compared with CT [22, 23]. MRI can be performed and rated in a standardised manner suggesting a good inter-rater agreement and intra-rater (during follow-up) agreement. The degree of muscular dystrophy in inherited muscle diseases is rated according to rating scales [25–27]. Most of the established rating scales are based on the amount of fatty degeneration ranging from normal appearance to complete fatty degeneration (Table 1). The evaluation of the muscle MRI using standardised rating scales allows a fast and reproducible assessment of the degree of involvement of each muscle. Initially, muscle MRI protocols were developed to evaluate certain anatomical areas such as the lower extremities and pelvis. More recent whole-body imaging protocols have been established allowing the evaluation of almost all relevant striated muscle groups. Pattern recognition of muscle involvement is sometimes helpful in narrowing the differential diagnosis and leading to the most probable diagnosis before muscle biopsy. Because of the lack of any radiation exposure, muscle MRI has become an important diagnostic technique for the evaluation of children [3]. In addition, whole-body MR imaging protocols allow evaluation of tissues and organs beyond the striated muscle such as the parenchymatous organs in the abdomen, the oesophagus and heart, all of which can be affected in patients with inherited neuromuscular diseases [28, 29] (Fig. 3).
Fig. 2 Transverse T1-weighted (upper row) and spectral fat-suppressed T2-weighted MR image (bottom row) of the thighs of a 48-year-old woman presenting with myotonic dystrophy type 1. Note the different degrees of fatty degeneration within the gastrocnemius muscle. The medial head shows an end-stage fatty degeneration (grade 4 according to the Mercuri and Fischer scale, grade 3 according to the Kornblum scale, Table 1). The muscle tissue is completely replaced by fat. The lateral head shows a moth-eaten appearance with scattered small areas of increased signal (fatty degeneration grade 2 according to the rating scales established by Mercuri et al., Kornblum et al. and Fischer et al., Table 1). The fat-suppressed T2-weighted image shows a high signal in the medial head of the gastrocnemius muscle indicating oedema because of inflammatory changes before and during the degenerative disease stages
Table 1 Summary of the well-established rating scales on MRI concerning the visual rating of dystrophic change of striated muscle tissue
Grade Mercuri et al. 2002 [25] Kornblum et al. 2006 [27] Fischer et a. 2008 [26]
0 Normal appearance Normal appearance
1 Normal appearance Discrete moth-eaten appearance with sporadic T1 hyperintense areas Mild: traces of increased signal intensity on the T1-weighted MR sequences
2 Mild involvement: Early moth-eaten appearance with scattered small areas of increased signal or with numerous discrete areas of increased signal with beginning confluence, comprising less than 30% of the volume of the individual muscle a. Moderate moth-eaten appearance with numerous scattered T1 hyperintense areas Moderate: increased T1-weighted signal intensity with beginning confluence in less than 50% of the muscle
b. Late moth-eaten appearance with numerous confluent T1 hyper-intense areas
3 Moderate involvement: Late moth-eaten appearance with numerous discrete areas of increased signal with beginning confluence, comprising 30-60% of the volume of the individual muscle Complete fatty degeneration, replacement of muscle by connective tissue and fat Severe: increased T1-weighted signal intensity with beginning confluence in more than 50% of the muscle
4 Severe involvement: Washed-out appearance, fuzzy appearance due to confluent areas of increased signal or an end-stage appearance, with muscle replaced by increased density connective tissue and fat, and only a rim of fascia and neurovascular structures distinguishable End-stage appearance, entire muscle replaced by increased density of connective tissue and fat
Fig. 3 Transverse spectral fat-suppressed T2-weighted images obtained from two patients presenting with a myotonic dystrophy type 1 (A: 37-year-old woman; B: 16-year-old boy). The images were obtained during a multi-sequence whole-body muscle MRI protocol. In both patients, dilatation of the oesophagus in the proximal segment with the air-fluid level could be diagnosed, which was clinically reflected by dysphagia
Using T2WFS sequences, MRI can sensitively detect discrete toxic, metabolic and inflammatory changes that are reflected by muscle oedema, which normally precedes dystrophic changes in terms of fatty degeneration. Therefore, MRI is able to detect ongoing disease activity in the muscle tissue and can be helpful in guiding muscle biopsy (Fig. 2).
The diagnostic value of contrast-enhanced (CE) MR imaging protocols has not been investigated so far. Late contrast enhancement may be a valuable option for the assessment of connective tissue that replaces normal muscle tissue in degenerative myopathies. However, this assessment is associated with a substantial increase in examination time. Therefore, CE MR imaging should not been performed on a regular basis. Recently performed animal studies with more specific contrast agents entering affected muscle tissue have shown that CE MRI might be helpful in distinguishing normal non-affected muscles from damaged muscles and further describe the extension and mechanism of muscular damage in dystrophic disorders [30, 31]. However, more prospective studies are necessary before the clinical application of such imaging protocols in humans during the diagnostic workup.
Quantitative MRI methods such as T2 relaxation time measurements, muscle fat quantification using the 3-point Dixon technique, magnetic resonance spectroscopy and perfusion imaging might be helpful to further analyse the degree of pathological changes in the striated muscles [32–34]. In particular blood flow measurements in the striated muscle based on either dynamic contrast-enhanced T1-weighted MRI, arterial spin labelling or blood oxygen-dependent MRI can be helpful to distinguish between inflammatory (increase of microvascular perfusion) and degenerative/dystrophic changes [4, 35]. However, there have been only a limited number of studies with low numbers of included subjects available up to now. Therefore, these techniques remain experimental for this purpose and should not be considered a standard imaging tool in the clinical routine setting.