Rheumatology Advance Access originally published online on May 10, 2007
Rheumatology 2007 46(7):1174-1179; doi:10.1093/rheumatology/kem088
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The role of MRI in the assessment of polymyositis and dermatomyositis
nková
ová
Institute of Rheumatology, Na Slupi 4, 12850 and 1Radiodiagnostic Department of the Military Hospital, Prague, Czech Republic.
Correspondence to: J. Vencovsk
, Institute of Rheumatology, Na Slupi 4, 12850 Praha 2, Czech Republic. E-mail: venc{at}revma.cz
| Abstract |
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Objectives. Acute inflammation in idiopathic inflammatory myopathies (IIM) causes oedema that can be visualized by magnetic resonance imaging (MRI). The inflammatory infiltrate in IIM is thought to be frequently in a focal distribution. The aim of this study is to better evaluate the relationship of MR image of thigh muscles to clinical and histological parameters in patients with IIM.
Methods. MRI-short tau inversion recovery (STIR) technique was used to distinguish between affected and non-affected muscles. Computer tomography (CT)-controlled targeted needle biopsy was used for sampling. The intensity of muscle oedema, its extent and total assessment on MRI were evaluated with 10 cm visual analogue scale. The intensity of inflammatory infiltrate was assessed using 5-point grading system. The second MRI and muscle biopsy were performed after the time interval of treatment.
Results. MR scans, muscle biopsy and clinical examination were performed in 29 patients with polymyositis (PM) and dermatomyositis (DM). Paired MRI-affected and MRI-non-affected biopsy samples were obtained from 17 cases. In six cases, the biopsy was available for comparison before and after period of treatment. At the initial examination, it was the intensity of oedema on MRI that was associated with clinical status. Mean intensity of MRI findings significantly decreased in 10 patients where the MRI was available also after treatment. The mean intensity of inflammatory infiltrate in PM/DM patients was 2.5 ± 0.7 for MRI-affected and 1.7 ± 0.6 for MRI-non-affected muscles (P < 0.001). Mean intensity of inflammatory infiltrate in the MRI-affected muscles in the first examination (n = 6) was 2.2 ± 0.8 and did not significantly decrease in the second examination in samples taken after the treatment (2.0 ± 0.9).
Conclusion. It is mainly the signal intensity in MR scan, which is associated with disease activity in the acute presentation of PM/DM. Muscle biopsy guided by positive MRI finding contains significantly more inflammatory cells than the biopsy taken from MRI non-affected sites. However, even in parts of muscles, which look unaffected on MR scan, the inflammatory cells can be found. The intensity on MR scans decreases significantly after the treatment, but the histologically detected inflammation does not change substantially.
KEY WORDS: Polymyositis, Dermatomyositis, Magnetic resonance imaging, Histopathology
| Introduction |
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Idiopathic inflammatory myopathies (IIM) are chronic systemic connective tissue diseases, which are clinically characterized by symmetrical proximal muscle weakness [13]. The hallmark and the basic histopathological criterion is the infiltrate with inflammatory cells. This inflammation of muscle may be unevenly distributed and not all of the muscles are affected at the same time in the same patient [1, 4]. Cases with persistent muscle weakness also exist, while at the same time the inflammatory infiltrate is only minimal or can no longer be found [1, 4]. It is assumed that selection technique should be used to guide for biopsy of the representative sample [57].
Magnetic resonance imaging (MRI) recognizes changes in soft tissues and can be used to examine muscles in IIM. Based on the presence of oedema, MRI can distinguish between muscles that are supposedly affected or non-affected [5, 6, 810]. Areas with inflammatory oedema are hyperintense, whereas less affected or non-affected muscles have low signal on T2 weighted images. Because fat can interfere with the interpretation of these changes, two techniques exist to eliminate signal of fateither T2-weighted images with fat suppression (T2W/FS) or short tau inversion recovery (STIR) sequence with long time to echo (TE). T1 weighted images, when fat has high signal and muscles (both affected and non-affected) are of medium signal intensity, are helpful to detect fatty degeneration of affected muscles [10, 11].
In the present study, we assessed the contribution of MRI examination to: clinical assessment of IIM, identification of the most appropriate site of the muscle biopsy and evaluation of the effect of treatment. Specifically, we compared the histological changes in the biopsies obtained from the muscle tissues distinguished as affected or non-affected by MRI scans. We also examined whether the global clinical status and muscle activity of polymyositis (PM) and dermatomyositis (DM) patients is associated with muscle evaluation by MRI.
| Methods |
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Patients
Twenty-nine patients with IIM, nine patients with PM and 20 patients with DM were examined. Twenty-three patients were female and six were male. Average age was 53.3 yrs (2478 yrs). Mean duration of the disease was 2.3 yrs (2 months11 yrs). This was defined as the time from the first symptoms of myositis as declared by physician. Twelve patients had not yet been treated at time of the first biopsy; while the others had been on treatment with prednisone (n = 17), methotrexate (n = 5), cyclosporine (n = 3) and azathioprine (n = 1). PM and DM were diagnosed with the use of valid diagnostic criteria and only those patients who fulfilled definite criteria either at the time of investigation or in their history were included [2, 3]. All the patients had active disease requiring new or intensified treatment. Patients with inclusion body myositis were excluded. The data were retrospectively analysed for the purpose of this study.
Methods
MRI technique was used in diagnostic protocol of IIM to distinguish between affected and non-affected muscles [5, 6, 1214]. In most of the patients, the first examination was performed for diagnostic purpose. In several of them, this was done because of other ongoing study [5]. Affected and non-affected muscles were differentiated according to presence of oedema in the skeletal muscle, which was identified on T2W/FS or on STIR sequence with long TE. Two assessors (J.T.S., J.V.) independently evaluated MRI muscle involvement and the mean of these two assessments has been taken as a final score. In all cases, the bilateral MR images of thighs were taken into account. Analysis of MR images was separately performed for the affected area (extent of MRI = EMRI), for the intensity of the signal (intensity of MRI = IMRI) and for the total MRI muscle affection (total MRI affection = TMRI). TMRI was not a simple arithmetical sum of EMRI and IMRI, but was rather separately assessed general impression of the total MRI affection. All this scoring was performed on 10 cm visual analogue scales (VAS) (Figs 1 and 2). In case that the difference between two evaluators was >2 cm on VAS (three cases), evaluation was repeated (without knowledge of the numerical value of the other evaluator's score). In case the second evaluation showed again difference >2 cm VAS (one case), the third evaluation was performed by both evaluators together and the consensual value was used. Both evaluators held the training session before the study started.
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Needle biopsy with the use of computer tomography (CT) control was employed for sampling using a bioptic needle (Quick Core Biopsy Needle, 14G, Cook, Denmark or Somatex, Germany) (Fig. 3). MRI examination always preceded this procedure and the muscle biopsy sites were identified. Separate samples were taken from MRI-affected and MRI-non-affected areas. First MRI examination with muscle biopsy was performed in the beginning of the study. In a subgroup of six patients, a second MRI examination with biopsy was done after 26 months. Five of these patients have improved and one remained stable according to the global clinical and muscle activity as assessed by VAS. Technical capacity did not allow investigating repeatedly more than six patients and no selection criteria have been employed besides the requirement for overall improvement on VAS and/or creatine kinase P (CPK). Best attempt was made to take the biopsy from the most affected muscle or, if there were no signs of oedema, from the same area as during the initial sampling. Only one specimen was taken in these cases and no biopsy from the non-affected areas was performed after the period of treatment. After removal, muscle samples were immediately covered with Tissue Tek embedding medium (Miles, Elkhart IN, USA) and frozen in propane-butane cooled in liquid nitrogen.
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The intensity of inflammatory infiltrate was assessed on haematoxylineosin (HE) stained samples and 5-point grading was used: 0 no inflammatory cells present, + (slight inflammation), ++ (moderate), +++ (obvious), ++++ (strong). Stained sections were coded and then evaluated independently by two observers (J.T.S., J.V.). Final results were the mean of the values from the two assessors. In case the score of two evaluators differed more than one degree (+) (four cases) evaluation was repeated (without knowledge of the other evaluator's score). In case the second evaluation showed again more than one degree difference (one case), the third evaluation was performed by both evaluators together and the consensual value was used. Samples were analysed using a light microscope (Olympus, Hamburg, Germany).
Global clinical activity (GA) and muscle disease activity (VAS-M) of PM/DM patients were evaluated semi-quantitatively using 10 cm VAS by one evaluator (J.T.S.) before the biopsies. Activity of disease in muscles in general was scored rather than only thigh muscle disease [15, 16].
CPK serum levels were measured using commercial kit (Boehringer Mannheim, Germany), and the upper normal limit was 2.84 µkat/l.
Statistics
For the paired test the plus signs were replaced with numbers (0 = 0, + = 1, ++ = 2, +++ = 3, ++++ = 4). Wilcoxon matched paired-test and Spearman's rank correlation test were used for statistical analysis. P-values <0.05 were considered significant.
The data for correlations were assumed to be sampled from Gaussian distribution and the correlations were made using Pearson's test.
Ethics Committee at the Institute of Rheumatology in Prague approved the tissue sampling and all patients had given an informed consent.
| Results |
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Patients and sampling
Twenty-four out of 29 patients had initial MRI examination when they were first seen by us (in five patients technical reasons did not allow to perform MRI initially). Twelve patients had the second MRI examination after a time interval of 26 months. In 10 cases, the initial and the second MR images were available. Seven out of these 10 patients improved clinically in both GA and the VAS-M, two patients improved in at least one of these parameters, and in one patient none of the clinical parameters was better, but the level of CPK dropped.
The initial biopsy was done in 25 patients with the needle under CT control. In one case, open biopsy was performed and one sample was taken during autopsy, and in two other patients the initial biopsy was not available for the analysis. From the 29 examined patients, we were able to receive paired affected and non-affected biopsy samples in 17 cases. In seven cases, the needle biopsy was done after the time interval of treatment. In one of these patients, only the second biopsy, not the one prior treatment, was available for the analysis.
The exact location of muscle biopsy was identified as the most affected part of thigh muscle as recognized by MRI and well accessible at the same time (mostly the front or lateral parts of thigh). MRI-non-affected muscles were taken from MRI recognized non-affected part in the maximum distance from where MRI affected sample was taken (mostly back part of thigh).
Correlation of MRI with clinical and laboratory parameters in PM/DM
In the first part of our study, we evaluated the correlation of MR images with the GA, VAS-M and CPK levels. At the time of the first examination, the clinical activity of muscles (1-VAS-M) was in good correlation with IMRI (r = 0.48; P = 0.018) and TMRI (r = 0.54; P = 0.006). The global clinical activity at the first examination (1-GA) correlated with IMRI (r = 0.41; P = 0.046). A good correlation of CPK levels with TMRI (r = 0.48; P = 0.018) was found during the first examination.
At the time of the second examination muscle activity (2-VAS-M) correlated both with the EMRI and TMRI. There was no correlation of any of the MRI assessments with GA of disease or CPK at the second examination (Tables 1 and 2).
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In the group of PM patients, 1-VAS-M correlated only with TMRI (r = 0.86; P = 0.028) and 1-GA with IMRI (r = 0.81; P = 0.049). There was no correlation of 1-CPK in PM with any MRI assessments.
In contrast to PM patients, 1-VAS-M in DM patients correlated with IMRI (r = 0.49; P = 0.038), EMRI (r = 0.48; P = 0.045) and also TMRI (r = 0.55; P = 0.018). GA of DM patients did not correlate with MR images in any of the investigated aspects. Levels of 1-CPK of DM patients correlated with TMRI (r = 0.6; P = 0.008).
There were no statistical significant differences in MRI (IMRI, EMRI, TMRI) between PM and DM patients.
MRI examination before and after treatment
In 10 patients, MRI examination was available both before and after treatment.
There was an improvement in the MRI parameters; however, only for IMRI this was significant (for IMRI it was 5.4 ± 2.2; 3.1 ± 1.6; P = 0.041; for EMRI 5.8 ± 2.5; 4.7 ± 2.4; for TMRI 5.2 ± 2.1; 2.9 ± 2.0) (Fig. 4).
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In those six patients who had the biopsy prior and after treatment, the significant improvement was seen only in TMRI (4.6 ± 1.7; 2.0 ± 1.32; P = 0.042) (Tables 1 and 2).
Intensity of inflammatory infiltrate in the muscle tissue
Intensity of inflammatory infiltrate, assessed as the number of inflammatory cells in muscle tissue, was evaluated by semi-quantitative scoring system. This was done in the muscle biopsy samples taken from MRI-affected and MRI-non-affected sites as well as in the samples from biopsies performed after a time interval of treatment. All biopsy samples that were available and examined have shown certain degree of infiltration with inflammatory cells (Tables 1 and 2).
The mean intensity of inflammatory infiltrate in all PM/DM patients (n = 17) was 2.53 ± 0.72 in MRI-affected muscles and this was significantly more than in MRI-non-affected muscles 1.71 ± 0.59 (P < 0.0001) (Tables 1 and 2).
In the group of DM patients (n = 12), the mean intensity of infiltrate was higher for MRI-affected (2.5 ± 0.8) than in MRI-non-affected tissues (1.75 ± 0.62) (P = 0.012). Numerically similar difference was seen in PM patients (n = 5) with the mean intensity of infiltrate 2.60 ± 0.55 in MRI-affected and 1.60 ± 0.55 in MRI-non-affected tissues; however, this was not statistically significant. Mean intensity of inflammatory infiltrate in MRI-affected muscles was similar in PM (n = 9) and DM (n = 18) patients (2.22 ± 0.67 and 2.33 ± 0.77, respectively).
Mean intensity of infiltrate in the MRI-affected muscles in the first examination (n = 6) was 2.17 ± 0.75 and did not significantly decrease in the second examination in samples taken after the treatment (2.00 ± 0.89) (Tables 1 and 2).
| Discussion |
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MRI is useful for demonstrating the soft tissue and musculature changes seen in patients with IIM. These changes include oedema within and around muscles, muscle calcification and fatty infiltration of muscles [11]. Inflammatory muscle tissue of PM/DM patients is oedematous, and although not specific for myositis, the increased signal on MRI due to oedema is a typical finding in acute IIM [5, 9, 1722]. The distribution of oedema in terms of localization and involved area as well as of signal intensity differs between individual patients [5, 9, 1214]. We have used MRI to assess several aspects of inflammation within the muscle tissue and differentiated the intensity, extent and total affection on MRI images. This was done in attempt to improve the precision of the MRI assessment in relation to clinical activity, histology assessment and response to treatment.
At the initial examination, the intensity of oedema on MRI was associated with clinical status, as assessed by muscle affection and GA of the disease. This could suggest that the intensity of oedema seen on MR scans is the major aspect, which determines the clinical presentation of the disease. In support of this might be the fact that it was the intensity of the MRI signal that diminished significantly in response to treatment. There was somewhat better correlation of muscle involvement assessed by MRI in patients with DM than in PM, and perhaps more frequent vascular changes usually seen in association with DM can be responsible for this observation. However, the difference between the MRI findings between PM and DM was not significant. The lack of correlation with global assessment in DM could be probably explained by the consideration of the cutaneous manifestations in DM in the global evaluation. The extent of MRI affection and the total MRI affection have been in relation to muscle activity after period of treatment in the subset of patients where MR was repeated. This shows that repeated use of MRI might be useful in the longitudinal follow-up of patient and in the assessment of ongoing activity. In this case, total evaluation or the assessment of the extent of affection may be preferable to signal intensity measurement.
Global evaluation of disease activity and muscle activity on VAS as well as levels of CPK have been used to estimate disease activity [15, 23]. Use of manual muscle test (MMT) would have probably helped in more precise correlation between the MRI findings and affected muscles, particularly if weakness and MRI-detected changes in individual muscles have been compared. However, MMT was performed only in part of the investigated patients, and therefore this could not be used for the evaluation in this study.
The very interesting aspect of this work was the evaluation of MRI-guided biopsy in selection of the most representative muscle sample for histology. Two biopsy sites, one from MRI-affected and one from MRI-non-affected muscles were selected and tissue removed with the biopsy needle under the CT control. PM and DM are often referred to as focal diseases [24, 25, 26]. Our approach enabled us to answer the question what could be expected on the histology assessment when the samples on both extremes of the oedematous scale are compared. The two biopsies showed significant difference in the intensity of the inflammatory infiltrate, with more inflammatory cells present in the sample taken from the MRI-affected site. The higher intensity found in the MRI-affected sites increases sensitivity of MRI-guided procedure in comparison to blind biopsy. This supports, in accord with previous studies, the current recommendations in using MRI-guided biopsy [5, 9, 13, 14, 20]. Some inflammatory changes have also been found in the MRI-non-affected sites and this could mean that there is a certain level of inflammation, which does not lead to oedema and cannot be depicted on MRI.
A somewhat surprising finding was the lack of improvement in the histology score in the six patients that were biopsied when first seen by us and then the biopsy was repeated after some clinical improvement has occurred. The second biopsy has been performed relatively early after the first biopsy and there might not have been sufficient time for inflammation to recede. The lack of correlation between the degree of histopathological features and the degree of muscle weakness has been reported previously [27, 28]. Recently it was shown that presence of inflammatory infiltrates, T cells and macrophages and expression of MHC class I and II antigens and of IL-1
on muscle fibres were independent of clinical symptoms, and were present to an equal degree in both proximal and distal muscles [28]. All these observations support the current view that various pathogenic mechanisms, and not only the presence of inflammatory infiltrate, may be responsible for clinical symptoms in patients with myositis [29].
Improvement in MRI score in our patients suggests that in clinical practice this can be a good parameter for short-term follow-up and clinical status assessment. It is not known whether patients who improve their MR scans significantly and quickly will do better in the further disease duration and this assumption needs to be confirmed in the long-term follow-up.
The lack of histopathological change in those patients who improved clinically and in MR scans suggests that improvement in number of cells infiltrating muscle might be a later event. We have not subtyped the cells in the inflammatory infiltrates, and therefore we cannot rule out that any changes in representation of different cell types could explain the clinical improvement. A contributing factor for the lack of improvement in the histopathological score could also be the fact that, for the repeated biopsy, MR scan helped us to identify the most affected sites which would still show the inflammation.
MRI evaluation of muscle in IIM has its limitations. In patients who remain weak after the treatment, it is usually not the active inflammation and oedema that cause symptoms. In such a situation, MRI evaluation, as used in this study, will not be helpful and other tools and investigations have to be performed to disclose the reason for persistence of symptoms.
In this study, we have investigated patients who were coming to our institute during the years 19982004 and who fulfilled definite diagnosis for PM and DM. In most of them we were able to perform MRI investigation and guided biopsies. There was a somewhat higher prevalence of DM patients in this cohort in comparison with what is usually seen in myositis patients. However, it was not too different from the proportion of DM in our total database of myositis patients, which includes about 60% of DM [30].
In summary, we have shown that MRI is a useful tool in evaluation of the disease activity in PM and DM. In the acute presentation, this is mainly the signal intensity that is associated with the disease activity; in the later stages the total evaluation and extent of affection may be more related to the disease process. Guiding the biopsy with MRI should be recommended because more inflammation has been found in such sites; however, inflammatory changes, although less intense, can also be seen in the biopsies that were negatively selected by MRI for inflammation. There is probably a certain level of inflammation that is necessary to cause oedema that can be seen on MRI. The histology score has not mirrored clinical improvement, whereas improvement in the MRI findings suggests that serial thigh muscle MR examination is a helpful non-invasive tool for follow-up of patients. Results of repeated biopsy, taken after a relatively short time after administration of new or intensified treatment, do not associate with clinical improvement. This supports the possibility of using histology also in patients who come for the diagnostic work-up late and are already treated with glucocorticoids and immunosuppressive drugs.
| Acknowledgement |
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This work received Institutional support No. 00023728 from the Czech Ministry of Health.
The authors have declared no conflicts of interest.
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2 on VAS), but almost all of the muscles are MRI-affected, that means extent of MRI affection was scored about 9.5 on VAS.

