Magnetic Resonance Imaging of Inflammatory Myopathies : Topics in Magnetic Resonance Imaging

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Original Article

Magnetic Resonance Imaging of Inflammatory Myopathies

Del Grande, Filippo MD, MBA, MHEM*; Carrino, John A. MD, MPH*; Del Grande, Maria MD; Mammen, Andrew L. MD, PhD; Stine, Lisa Christopher MD, MPH

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Topics in Magnetic Resonance Imaging 22(2):p 39-43, April 2011. | DOI: 10.1097/RMR.0b013e31825b2c35
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Abstract

Idiopathic inflammatory myopathies (IIMs) are a spectrum of heterogeneous muscle diseases in which polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM) are the most common forms. Necrotizing myopathy, giant cell myositis, eosinophilic myositis, granulomatous myositis, macrophagic myofasciitis, pipestem capillary disease, and myositis related to other connective tissue diseases are believed to be much rarer entities and will not be directly discussed in this review.1

Idiopathic inflammatory myopathies present with different clinical, histological, and laboratory findings, but they share several key characteristics. First, muscle weakness is generally a prominent clinical manifestation. Second, muscle biopsies typically reveal collections of inflammatory cells. Third, electromyography demonstrates features of an irritable myopathy. And fourth, muscle enzymes are frequently elevated.1–3

Polymyositis was previously thought to be the most common manifestation of the disease group with the other types of IIM considered only variations of PM. It is now appreciated that PM, DM, and IBM are distinct diseases. Polymyositis is considered probably the least common of the IIMs,4 and IBM is probably the most common IIM, particularly in men older than 50 years.1

Polymyositis affects mainly the adult population and is very rare in children. It presents with predominantly symmetric proximal muscle weakness. Until recently, it was generally accepted that the only difference between PM and DM were the dermatological manifestations of DM. These include the classic heliotrope eruption around the eyes and erythematous papules around the knuckles known as the Gottron sign. However, each of these diseases has distinct histological features.5 For example, the inflammation in PM is predominantly endomysial and includes large numbers of CD8+ cytotoxic cells. In contrast, CD4+ T helper cells and plasmacytoid dendritic cells predominate in DM and are preferentially located in the perimysial and perivascular spaces.6,7 Nevertheless, DM shares several characteristics with PM such as a female preponderance in prevalence, the absence of family history for myositis, a potential association with malignancy, the symmetric proximal muscle weakness distribution, and the increase in creatine kinase (CK) up to 50-fold greater than normal.4

Inclusion-body myositis affects more men than women, usually those who are older than 50 years. The muscle weakness pattern in IBM is distinct from that in PM or DM, and it presents typically including quadriceps weakness and distal muscle weakness (especially the wrist flexors, finger flexors, and ankle dorsiflexors). Unlike in DM or PM, muscle involvement may be markedly asymmetric. Furthermore, dysphagia may be an early and prominent manifestation of IBM, whereas this is typically only found in patients with severe DM or PM. The presence of rash and the association with malignancy are not characteristics of IBM.4 Finally, unlike DM and PM, which typically respond well to medical therapy, IBM responds poorly, if at all, to immunosuppressive medications. Indeed, growing evidence suggests that IBM may be a myodegenerative disease with secondary inflammation rather than a primary autoimmune disease.8

Some general and helpful attributes that lead toward the diagnosis of DM or PM include a characteristic DM rash, gradual onset of muscle weakness over weeks and month, symmetric distribution, proximal limb and truncal involvement, other connective tissue disease features, and lung involvement. Conversely, a family history of similar disease, weakness related to fasting, eating or exercise, sensory disturbances, abnormal reflexes, fasciculations, cranial nerve involvement, muscle cramping, myasthenia, myotonia, and CK level less than 2 times the normal or more than 100 times the normal are features that speak against the diagnosis of myositis.1

Even if the diagnosis of myositis is strongly suspected based on clinical presentation, laboratory tests, and electromyography, technically, the final diagnosis requires histopathologic confirmation with a muscle biopsy.1,9

WHAT IS THE ROLE OF MRI IN INFLAMMATORY MYOPATHIES?

It is well known that MRI is the best imaging technique to investigate soft tissue abnormalities and can detect, depending on the stage of the myositis, muscle edema (Figs. 1 and 2), fatty replacement, and muscle atrophy (Figs. 3 to 4–5).10

F1-1
FIGURE 1:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Acute asymmetric bilateral myopathy with mild to moderate muscle edema of the anterior compartment in a patient with dermatomyositis is shown.
F2-1
FIGURE 2:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Moderate acute bilateral myopathy with muscle edema more pronounced in the anterior compartment and in the adductor magnus muscle is shown.
F3-1
FIGURE 3:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Mild diffuse atrophy and fatty replacement and bilateral asymmetric edema in a patient with inclusion body myositis is shown.
F4-1
FIGURE 4:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Moderate to severe acute on chronic myopathy more pronounced in the posterior compartment with moderate bilateral fatty replacement and moderate to severe bilateral edema.
F5-1
FIGURE 5:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Severe chronic myopathy with bilateral complete fatty replacement of the anterior compartment is shown.

Routinely, an MRI protocol of both thighs is generally performed with axial T1-weighted images and axial fluid-sensitive sequences such as short tau inversion recovery (STIR) or fat-suppressed T2-weighted sequences. STIR sequences are preferred to T2 fat-saturated sequences owing to the more homogenous signal on both thighs. Short tau inversion recovery sequences, T2 fat-saturated sequences, and T1 fat-saturated sequences after administration of gadolinium are reported to be similar in detecting the muscle inflammation.11 Imaging of the thighs is usually performed for several practical reasons: thigh muscle are generally the most affected ones, they can be an easy target for a potential muscle biopsy, and thigh MRI is generally an easy examination to perform in 1 session. However, this approach does not allow assessing the extent of the disease in other muscle groups.

Several reasons support the use of MRI for diagnostic and therapeutic monitoring purposes. First, it can confirm the diagnosis and can rule out other potential pathologic myositis mimics. Second, it can help refine the myositis phenotype. Third, it can be important in directing the muscle biopsy reducing the false-negative rate and, consequently, reducing the risk of repeat biopsy. Fourth, it is important in the follow-up of the disease progression. Fifth, it gives information about the response to therapy and can assess when immunosuppressive therapy may be no longer warranted. Sixth, it can also decrease the cost of care.12

As previously mentioned, MRI allows the assessment of different stage of the disease (Figs. 1–5).13–17 In the acute stage, the muscle will show diffuse edema with high signal intensity on STIR sequences and sometimes an increase in volume of the affected muscle. Muscle edema is a highly nonspecific sign and can be seen in several muscle abnormalities such as injuries (strain/contusion), in acute and subacute denervation, in inflammation, and in cases of interstitial fluid overload. In the chronic stage of damage, muscle undergoes progressive fatty replacements and atrophy depending mainly of the duration of the disease.

Some other important entities can show muscle edema and involvement of the fascia and have to be differentiated from IIM in MRI even if they usually present with different clinical manifestations. Infectious myositis is generally the consequence of open traumata or of hematogenous spread of the infection in immune-suppressed patients and drug abusers.18 Nonnecrotizing and necrotizing fasciitis are clinically sometime difficult to differentiate and MRI plays an important role in the diagnosis.19 Necrotizing fasciitis is a bacterial infection that can be life-threatening if not recognized in the early stage. Magnetic resonance imaging can differentiate necrotizing fasciitis showing thickness of more than 3 mm of the fascia in fluid-sensitive sequences and extensive involvement of the deep fascia with low signal intensity along the deep fascia corresponding to gas inclusions.19

Other myopathies to consider are drug-induced myopathies such as statin-induced rhabdomyolysis and myonecrosis. To our knowledge, there are no article describing the MRI lesions of statin-induced myopathy aside from isolated reports of focal myositis attributed to statin therapy.20,21

Several studies analyzed the MRI patterns of PM, DM, and IBM, suggesting some specific lesions for different myopathies.11,22 An isolated muscle inflammation and the absence of fatty infiltration or atrophy are more predictive of PM or DM than of IBM.11 The MRI pattern of DM is similar to that of PM with symmetric proximal involvement, but an edema-like reaction is seen along the fascia more frequently in DM than in PM (Fig. 6).23

F6-1
FIGURE 6:
Axial STIR sequences of the thighs. Severe fascial edema of semimembranousus muscle is shown.

Cox et al22 studied the MRI pattern in 32 patients with IBM and found that the anterior compartment muscles of the upper leg was the most involved one with exception of the rectus femoris muscle. This study confirmed that fatty infiltration is more common than edema and is the main MRI pattern of IBM that correlates with weakness (Fig. 7).

F7-1
FIGURE 7:
Axial T1-weighted sequences (A) and STIR sequences (B) of the thighs. Moderate to severe acute chronic myopathy in a patient with inclusion body myositis is shown.

Moreover, 1 study shows that all patients with adult-onset DM (14 in total) show higher total inflammation score around the fascia, suggesting that the microvasculature around the fascia is the primary target of the inflammation.24

Another study with 220 patients addressed the topic of specific MRI findings in IIM. Of 220 patients, 25 had biopsy-proven PM and 25 had biopsy-proven IBM. Patients with IBM turned out to have more asymmetric and distal involvement, anterior group muscle involvement (rectus femoris muscle, vastus medialis, intermedius, and lateralis muscle), more fatty replacement lesions, and more heterogeneous presence of muscle edema compared to patients with PM and DM. On the other hand, patients with PM showed more asymmetric proximal involvement and isolated inflammatory lesions mainly affecting the posterior muscle group. Interestingly when the duration of the disease was taken into account, the degree of fatty infiltration was the same in the 2 groups.11

In our experience, owing to the patchy nature of myositis, the false-negative rate of muscle biopsy could be significant. Therefore, MRI can have an important role in guiding the biopsy site and in reducing the false-negative rate and the potential repetition of muscle biopsy.25

In a recent study, Tomasova Studynkova et al26 studied 58 patients with PM, DM, and IBM. The patients underwent muscle biopsy on the affected (edema) muscle and the unaffected muscle under MRI. As a result, the muscles that showed edema on MRI contained more inflammatory cells than the sample without edema on MRI. Interestingly, inflammatory cells were found even in muscles without MRI signs of inflammation but in different amounts.

Monitoring the disease activity during therapy is another important role of MRI. In the short-term follow-up, muscle edema decreases on MRI during therapy (Fig. 8), but interestingly, the histological grade of infiltration remains unchanged.26 In the case of complete fatty replacement of the muscle, MRI can provide important information on avoiding further therapy that would be futile and would expose the patient to unnecessary untoward adverse effects (Fig. 9).

F8-1
FIGURE 8:
Axial T1-weighted sequences before (A) and after (C) and STIR sequences before (B) and after (D) therapy. One year of follow-up between MRI procedures in a patient with myositis under biological treatment is shown. Note on STIR sequences (B and C) the significant improvement of the bilateral muscle edema under therapy.
F9-1
FIGURE 9:
Axial T1-weighted sequences of the thighs: complete fatty replacement. In this situation, therapy will be futile and will expose the patient to potential unnecessary adverse effects.

MUSCLE MRI ADVANCES TECHNIQUES

Several advanced MRI techniques emphasize the physiological and functional aspects of the muscle such as proton MRI spectroscopy, T2 mapping, diffusion-weighted imaging, blood oxygenation level-dependent imaging, and magnetic resonance elastography.

Proton MRI spectroscopy is an imaging technique that can benefit greatly from the advent of 3-T MRI scanners that improve the SNR and the spectral resolution.27 Fayad et al28 studied the choline concentration in phantoms and healthy individuals with proton MRI spectroscopy on 3-T MRI and found that the measurement of choline concentration is feasible using water as the internal reference. These data suggest some future directions on the research of proton MRI spectroscopy, such as exploring the possibility of phenotyping the myopathy and predicting the response to therapies.

T2 mapping is a semiquantitative imaging technique to measure the T2 relaxation time of water in the muscle, which increases during exercise. These measurements could carry potential application in the assessment of muscle activation of pathologic or physiological conditions.10,29

Diffusion-weighted imaging is based on the principle of the random motion of water molecules in tissue. Muscular diffusion value depends from muscle activity, muscle edema, and the orientation of muscle fibers. The diffusion coefficient parallel to muscle fibers (z axis) is higher than that in the x or y axis. In patients with myositis, unaffected muscles show the same diffusion parameters in the z, y, and x axis as those of the healthy population, whereas the diffusion coefficient in the z axis is 24% higher in the affected muscle compared with healthy individuals or unaffected patient muscle. Moreover, diffusion-weighted imaging could play an important role in monitoring the response to therapy. In fact, the patient with DM in the study showed reduction in the diffusion coefficient after 4 months of treatment.30

Blood oxygenation level-dependent imaging is a functional imaging technique that can functionally evaluate the microcirculation of the muscle. This technique is well known in neuroimaging as functional MRI and is based on the ratio of the microcirculation of oxy-hemoglobin and desoxy-hemoglobin. The first is diamagnetic; the latter is paramagnetic and produces a susceptibility effect and then an MRI signal.31 Blood oxygenation level-dependent imaging is a technique that does not require the intravenous injection of a contrast medium, and with a high temporal resolution, it could thus play a role in assessing the tissue perfusion such as distinguishing vasculitis from myositis.10,31

Magnetic resonance elastography is a noninvasive imaging technique that allows us to draw information about the mechanical properties of a tissue. Compared with muscle in healthy individuals, muscle of patients with myositis shows higher stiffness grades in magnetic resonance elastography.32

CONCLUSIONS

Muscle edema, fatty replacement, and muscle atrophy are not specific MRI findings in patients with myositis. Nevertheless, these patterns associated with the clinical manifestations and laboratory findings of IIM play an important role in the diagnosis and monitoring of therapy for these patients. Therefore, MRI should be included in the diagnostic workup and therapeutic assessment and management of patients with IIM.

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Keywords:

magnetic resonance imaging; inflammatory myopathy

© 2011 Lippincott Williams & Wilkins, Inc.