Introduction: Traditionally, muscular dystrophies are evaluated clinically with history and examination; electro-diagnostic testing (nerve conduction testing and electromyography); genetic testing; and muscle biopsy. Recently, there has been increasing interest in non-invasive imaging modalities, particularly muscle magnetic resonance imaging (MRI), for the diagnosis and assessment of disease progression for various neuromuscular diseases. In this article we shall discuss the various roles imaging (especially MRI) can play in patients with muscular dystrophies.
Imaging Modalities: Various imaging modalities have been used to assess muscular dystrophies.
1) Muscle USG - initially there was lot of interest regarding the use of ultrasonography (USG) in muscle diseases due to its ready availability and low cost. However, it did not gain much clinical acceptance because it was operator dependent and not all muscles could be adequately assessed. Moreover, it is difficult to do comparative follow up studies over time. It is still occasionally used to target the site of muscle biopsy.
2) Computed tomography - CT scan does provide a more reliable evaluation of all the muscle groups as compared to USG and is less operator dependent. However, it uses ionising radiation and hence it is not suited for repeated assessments of entire musculoskeletal system in these patients.
3) MRI - The advent of muscle MRI has completely replaced the use of CT. The main advantage of MRI compared to CT is that it does not require ionizing radiation and also allows the use of multiplanar scanning, which is particularly useful for patients with severe limb contractures who are unable to lie in the correct position during the examination. Furthermore, comparative studies using both CT and MRI techniques have shown that MRI has a higher sensitivity than CT for identifying early fatty replacement in muscles and provides better anatomical details (1,2).
MRI in Muscular Disorders: Imaging protocol and muscle assessment:
A musculoskeletal (MSK) MRI study involves scanning of the upper and lower limbs in axial and coronal planes. The axial plane is more useful since it allows better assessment of individual muscles. 5 mm thick slices are taken and multiple sequences are used. The most commonly employed sequences are T1 and STIR (Short Tau Inversion Recovery). The T1 weighted images are very sensitive to detect fatty infiltration (fat appears bright as compared to the muscle fibres which appear dark grey). STIR images, on the other hand, are very sensitive to detect muscle edemawhich indicates active inflammation. Children may require sedation during the scan.
Scans are assessed for normal and abnormal (atrophy/hypertrophy) muscle bulk and for normal and abnormal signal intensity within the different muscles. Each muscle group can be staged as follows using the T1 weighted images:
1. Normal appearance
2. Mild involvement: An early moth-eaten / feathery 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.
3. Moderate involvement: A late moth-eaten appearance, with numerous discrete areas of increased signal with beginning confluence, comprising 30% to 60% of the volume of the individual muscle.
4. Severe involvement: A washed-out appearance, a fuzzy appearance due to confluent areas of increased signal, or an end-stage appearance, with muscle replaced by increased signal intensity connective tissue and fat, and only a rim of fascia and neurovascular structures distinguishable.
Role of MSK MRI in muscular dystrophies:
1) Diagnosis: Although the diagnosis is generally made by clinical history, examination, electro-diagnostic and genetic tests and muscle biopsy, MRI can also demonstrate the classical changes of muscular atrophy and fatty replacement and thus suggest the diagnosis. The patterns of muscle involvement seen on MRI may even indicate the specific dystrophy. For example, in Duchenne Muscular Dystrophy (DMD), there is early involvement of the gluteus maximus and adductor magnus, followed later by the involvement of the quadriceps, rectus femoris, and biceps femoris, with selective sparing of the sartorius, gracilis, semitendinosus, and semimembranosus muscles till late in the disease (fig 2). On the other hand, patients with Limb Girdle Muscle Dystrophy (LGMD) show a striking and early involvement of the adductor magnus and posterior thigh muscles.
2) Disease Progression and activity: Follow up comparative MSK MRI studies can demonstrate the progressive fatty infiltration and atrophy of the muscles and thus can be used to monitor the disease progression / treatment response. Studies have shown that the degree of fatty infiltration correlates with the functional decline (3). Also, as mentioned above, STIR images can detect active muscle edema (fig 3). This may be a particularly useful technique inyounger boys with DMD in whom inflammatory changes with edema may be bettermarkers of disease activity than fatty infiltration because the latter change occurs later in the diseaseprocess.
3) MRI as a biomarker in clinical studies: Because of its ability to noninvasively monitor the disease progression, MRI is being used in clinical research studies to evaluate the efficacy of various interventions in Muscular dystrophy. There are several concerns with the use of muscle biopsy in clinical trials. First, it is an invasive procedure that involves taking repeated samples from individuals who may already have limited muscle mass. Furthermore, recent studies have suggested considerable variability of muscle involvement in DMD, even within a single muscle (eg. rectus femoris), and a focal muscle biopsy may not provide a true representation of the overall disease progression or therapeutic response. A recent study by Kinali and colleagues (4) showed a good correlation between MRI severity score and a categorical assessment of muscle involvement on standard histologic staining.
Recent Advances and future trends: Currently we rely on subjective or semi-quantitative assessment of the muscular atrophy and fatty infiltration. Various novel MRI techniques are being tried so as to provide a more robust quantitative assessment of the muscle changes to monitor the disease progression in muscular dystrophies. These include:
1) MSK MR Spectroscopy: This is an MRI technique which quantifies the muscle metabolites within a selected voxel of the muscle. The result is presented as a graph (spectrum) which shows the relative concentrations of the muscle metabolitesin that selected voxel. In the involved muscles, there is increase in the intramyocellular and extramyocellular lipids with reduced other active muscle metabolites like trimethylamines and total creatine
2) MR Diffusion Tensor Imaging (DTI): This allows us to assess the structural integrity of the muscle fibres and provides a colour coded image of the preserved muscle bulk.
3) The three-point Dixon technique: In standard MRI sequences, the signal intensity for each voxel is determined based on the fat and water signal intensities within that voxel.The three-point Dixon technique allows separation of MRI signal intensity into separate values for the individual contributions of fat and water in each voxel of tissue (5). This results in high-resolution water and fat maps and enables quantifying the fat fractions of individual muscles.
Conclusion: Skeletal muscle MRI is a powerful and sensitive technique in the evaluation of muscle disease. MR imaging enables the radiologist to assess the distribution and severity of the diseased muscles and thereby provides a powerful tool for guiding tissue diagnosis and monitoring disease progression / treatment response.