MRI-guided biopsy in inflammatory myopathy: Initial results

II, pp.1093-1099,

Magnrrrc Resonance Imagmg, Vol. Prmted in the USA. All rights reserved.

l

1993 Copyright 0

0730-725X/93 $6.00 + .oO 1993 Pergamon Press Ltd.

Original Contribution MRI-GUIDED

BIOPSY IN INFLAMMATORY INITIAL RESULTS

MYOPATHY:

ALAN M. PITT,* JAMES L. FLECKENSTEIN,* RALPH G. GREENLEE, JR.,? DENNIS K. BURNS, $ WILSON W. BRYAN,? AND RONALD HALLERJ~ Departments of *Radiology, tNeurology, and $Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA. The purpose of thi:s report is to describe our initial experience with techniques employing magnetic resonance imaging (MRI) to gubde the choice of muscle to be biopsied in patients suspected of having inflammatory myopathy. Five patients with a clinical diagnosis of inflammatory myopathy (IM) were studied. Four were imaged prior to biopsy. Four had repeated examinations, either immediately following biopsy or to evaluate disease progression. Use of MRI to localize muscle lesions was associated with abnormal pathologic findings in all cases, including histopathologic demonstration of lymphocyte infiltration in three cases of idiopathic polymyositis; nonspecific myopathic changes were seen in one patient with probable dermatomyositis and in one patient with chronic inflammatory polyneuropathy and high serum creatine kinase levels (>45,000 W/ml). The precise location of the area sampled by biopsy was visible in only one of four postbiopsy images. MRI shows promise in identifying pathologic muscle in patients suspected of having one of the inflammatory myopathies; however, further refinement of localization techniques may be needed to optimize histopathologic diagnoses.

Keywords: Muscles; MRI; Myositis; Biopsy; Myopathy

abnormalities, especially edema and fatty deposition, MRI has been suggested to be a valuable tool in the selection of tissue for biopsy. This report details our initial experience with this approach in five cases with clinical evidence of IM.

INTRODUCTION Inflammatory myopathy (IM) includes both infective and autoimmune myositides. Of the autoimmune diseases the most common are polymyositis, dermatomyositis, inclusion body myositis and granulomatous myositis. The diagnosis of inflammatory myopathy (IM) often is a clinical challenge. Other muscle disorders can be mistaken for IM, leading to unnecessary immunosuppressive therapy. Alternatively, for patients with a certain diagnosis of IM, drug regiments involving multiple toxic therapies are frequently used with limited information. In some cases, altering medications according to laboratory values and clinical response may not be appropriate.‘,2 The application of magnetic resonance imaging (MRI) has expanded the ability to evaluate patients with IM.3-1’ The technique provides information regarding muscle anatomy3 and distinguishes mesenchyma1 alterations, such as fatty change and fibrosis from edema.6s7 Because of its high sensitivity to muscle

METHODS Magnetic resonance imaging was performed using either a Toshiba America, MRI Inc. 0.35 T or a 0.064 T system (South San Francisco, CA). Contiguous axial images were obtained through the pelvis and shoulder girdle. Sequences for the 0.35 T images were moderately T, -weighted (500/30, TR/TE), spin density (2000/30, TR/TE), T,-weighted (2000/60, TR/TE), and short inversion time inversion recovery (STIR: 1500/30/100, TR/TE/TI). A quadrature detection body coil, 128 x 256 matrix, 1.7 x 1.7 x 10 mm voxel dimensions, and 2 acquisitions were used. The 0.064 T system was used with a quadrature detection body coil for needle biopsy in Case 3. Prior to

RECEIVED 3/16/93; A~ZCEPTED5/10/93. Address correspondence to James L. Fleckenstein, MD, Algur H. Meadows Diagnostic Imaging Center, University

of Texas Southwestern Medical Center, Blvd., Dallas, TX 752354896. 1093

5171 Harry Hines

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biopsy, a gradient-echo sequence (145/53/35, TR/TE/ flip angle) with a 248 x 256 matrix, 1.25 x 1.25 x 7.55 mm voxel dimensions, and 1 acquisition was used to identify edematous tissue. An area suitable for biopsy was marked on the skin by placement of a MRIvisible marker. The patient was moved away from the magnet, but kept on the table after marking. An 18gauge ASAP biopsy system (Boston Scientific Corp., Watertown, MA) was used to obtain a needle core of tissue. After biopsy, T, -weighted (100/26 TR/TE) spin density and Tz-weighted images (1568/30,105 TR/TE) were acquired using a 128 x 256 matrix, I .7 x 1.7 x 5mm voxels and 2 acquisitions. The remaining four patients underwent open biopsy after MR imaging at 0.35 T. The area for biopsy was selected based on local changes in muscle signal characteristics in three of the cases. The fourth case was imaged after biopsy to evaluate muscle abnormalities in the area sampled. These data are summarized in Table 1. All muscle specimens were received in formalin and examined with adenosine triphosphate, Gomori, and glycogen stains. The presence of bacteria and acid fast bacilli was also assessed. RESULTS The clinical data from the five patients studied is summarized in Table 1. All met criteria for at least a provisional diagnosis of IM, as described above.’ On MRI, all patients demonstrated patchy, edema-like changes in a variety of muscles, with normal muscles appearing in close proximity to abnormal muscles (Figs. l-5). Of the four tissue samples selected based on MRI, each showed myofiber degeneration, regeneration and endomesial fibrosis. However, only two showed lymphocytic infiltration. Both patients lacking lymphocytic infiltration had been treated with glucocorticoids. One of these (Case 1) showed marked improvement both clinically and on MRI after therapy (Figs. 1,2). In Case 4, MRI lead to choice of a muscle not usually biopsied, the subscapularis. Muscle in that case was positive for lymphocytic infiltration. Immediate postbiopsy MRI was done in four cases. In only one instance could a definite biopsy track be identified (Figs. 3,4). In Case 5, the only imaging study was performed after biopsy to evaluate signal characteristics of the muscle sampled. However, extensive bleeding prevented visualization of the precise muscle sampled. Additional follow-up imaging examinations were done in 2 cases, one at 6 mo and the other at 2 mo. In contrast to Case 1, who improved, Case 2 had only limited clinical or MRI improvement (Fig. 5).

DISCUSSION Commonly used criteria for the clinical diagnosis of inflammatory myopathy include: (1) symmetrical proximal muscle weakness; (2) elevation of serum muscle enzymes; (3) EMG findings; and (4) muscle biopsy.’ However, IM still may be difficult to distinguish from other disorders affecting muscle. For example, muscular dystrophy, amyotrophic lateral sclerosis, hypothyroidism, and McArdle’s disease may each clinically mimic the pattern of weakness expected with IM.’ Glucocorticoids, often used empirically in IM, will lower creatine kinase (CK) in all of these noninflammatory disorders and so an apparent clinical response of the patient is nonspecific. EMG results may be normal, as seen in Case 4. Even after reaching a definitive diagnosis of IM, management can be complicated. Combinations of muscle atrophy, fibrosis and steroidinduced effects may each contribute to progressive weakness in the face of diminishing inflammation, thereby confusing the assessment of the clinical response. Faced with these uncertainties, many physicians obtain a muscle biopsy of an easily accessible muscle before committing patients to long term glucocorticoids or other potentially toxic drugs. However, up to 25% of autoimmune IM cases lack one major criterion for a definitive pathologic diagnosis of IM, namely, lymphocytic infiltration on biopsy.’ This leads to a nonspecific pathologic diagnosis of “myopathic change,” usually reflecting myofiber degeneration, regeneration, myophagocytosis, and endomesial fibrosis. A review of 16 such cases suggested that the patchy, multifocal nature of the inflammatory change may be responsible for this finding.12 MRI offers a new approach to evaluate IM. It is highly sensitive to skeletal muscle alterations such as inflammation, necrosis, denervation and fatty change in neuromuscular disease.3 Compared with muscles selected because of easy access, tissue selected for biopsy based on MRI signal characteristics might be presumed to be more likely to have histopathologic evidence of IM. This is supported in Case 4, in whom MRI detected abnormalities proved to be associated with lymphocyte inflammation. In two of our cases, contrary to expectations based on recent reports,4-6*9-” the use of prebiopsy STIR images for guidance of biopsy site did not reliably yield an inflammatory infiltrate. This result has multiple possible explanations. First, in both patients lacking muscle lymphocytes, glucocorticoids were administered days before biopsy. This therapy may have altered the original infiltration. Nevertheless, after the tissue was sampled, clinical, laboratory and MRI signal alterations persisted in both patients. Furthermore, the institution of therapy does not

s z

Normal

Myopathic

6,500

3,380

Case 4: 39-yr-old with months of proximal weakness

Case 5: 58-yr-old with 2 yr of fatigue and 8 wk of progressive weakness and dysphagia

None

None

High dose immunoglobulin

High dose glucocorticoids, immunopharesis

High dose glucocorticoids

Treatment prior to biopsy

Needle; gastrocnemius

Open; subscapularis Open; quadriceps

Identified abnormal subscapularis None

Open; gluteus maximus

Open; vastus lateralis

Type and site of biopsy

Identified lateral gastrocnemius muscles

Identified gluteus maximus to be abnormal

Identified left vastus lateralis to be appropriate muscle to biopsy

Pre-biopsy MRI

Myopathic EMG: Small amplitude motor units, insertional activity, fibrillations. Myopathic biopsy: Nonspecific muscle fiber degeneration, regeneration, and endomesial fibrosis.

Myopathic

Myopathic; Mildly decreased nerve conduction velocity

Myopathic

Electrophysiology

9,800

40,050

2,281

Peak CK

Case 3: 50-yr-old with 10 wk of progressive proximal weakness. HIV positive

Case 2: 36-yr-old with rapidly progressing, marked proximal weakness. Elevated cerebrospinal fluid protein

Case 1: 58-yr-old with proximal weakness and dysphagia

Patients

Table 1. Patient data

None

Extensive bleeding obscured site of tissue sampling

Muscle infiltration by lymphocytes

Immediate postbiopsy MRI did not identify sampled muscle.

Persistent signal abnormalities; biopsy site not detectable.

Improved; postbiopsy MRI confirmed correct sampling.

Follow-up MRI

Muscle infiltration by lymphocytes

Muscle infiltration by lymphocytes

Nonspecific changes, including denervation

Myopathic

Histopathology

Fig. 1. MRI of inflammatory myopathy (IM) in Case 1 prior to therapy. 2000/30 (a), 2000/60 (b), 500/30 (c), and short inversion time inversion recovery (STIR) (d) images of the thighs are presented. Each of the quadriceps muscles are abnormal, with the right rectus femoris less involved (arrowhead). The adductor magnus (arrow) shows patchy increased signal intensity.

Fig. 2. MRI support of improvement in inflammatory myopathy (IM). 2000/30(a), 2000/60 (b), 500/30 (c), and short inversion time inversion recovery (STIR) (d) images of the thighs of Case 1 at approximately the same level as in Fig. 1 show minor atrophy bilaterally. Only mildly increased signal intensity remains in the quadriceps. High signal intensity in the lateral aspect of the subcutaneous (SC) fat is due to radiofrequency field inhomogeneity, a well-recognized artifact using STIR (d, arrowhead).”

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Fig. 3. MRI confirmation of muscle biopsy site in Case 1. 500130 image of the left thigh shows deformation of subcutaneous (SC) tissue along the biopsy track (arrow), leading to a focal defect in the vastus lateralis (V) indicating where the biopsy was obtained.

necessarily preclude a positive pathologic result.‘*2~‘2 Second, in a subset of IM cases, lymphocyte infiltration of muscle apparently does not occur. This hypoth-

esis is supported by the observation that nondiagnostic

biopsies occur in up to 25% of patients with clear clinical and laboratory evidence of polymyositis.‘*2 A dif-

fusible cytotoxin has been proposed as an etiology in such cases.12 A third possibility relates to the nonspec-

Fig. 4. Short inversion time inversion recovery (STIR) image of the prone pelvis from Case 2, 1 hr after biopsy. Muscle of normal signal intensity (arrowhead) lies in close proximity to muscle with abnormal signal intensity (arrow). No biopsy track or muscle deformation could be identified on this or adjacent contiguous slices so that the precise tissue sampled is unknown.

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Fig. 5. Sequential short inversion time inversion recovery (STIR) images of Case 2 at the level of the mid-thighs demonstrate the patchy nature of muscle lesions in patients with clinical evidence of inflammatory myopathy (IM). An initial (a) and follow-up image 60 days later (b) demonstrate that the distribution of edema-like signal intensity changes is not only spatially heterogenous, but also varies over time.

ificity of the MRI appearance of “edema.” In fact, denervation of muscle, which was coexistent with IM in Case 2, may have an MRI appearance that is indistinguishable from edema, thus mimicking inflammation and/or necrosis.3 Small patches of muscle necrosis, such as might be seen as a result of vasculitis and microinfarction would also have an edematous appearance.13 Furthermore, exertion-induced muscle injury also has this appearance.3 Hence, the MRI appearance of muscles in IM is nonspecific; one should not assume that well-directed biopsies will always demonstrate lymphocytes histopathologically. We acknowledge a lack of a rigorous localizing technique to guide muscle biopsy in this study and that it may be insufficient to identify a given muscle as abnormal when only a portion of it is abnormal. In these cases, nearby normal muscle may be accidentally biopsied. We also found that needle biopsies may not cause sufficient disruption to provide a visible track on postbiopsy MRI (Fig. 4). On the other hand, postsurgical change may be so extensive so as to obscure the precise muscle sampled. Development of needles designed for use in the MRI device, use of external markers and/or a stereotactic approach may allow for more precision in tissue sampling. By guaranteeing a specific area has been sampled, repeat biopsies may be avoidable.

An association of acquired immunodeficiency syndrome (AIDS) and polymyositis (PM) has been well established.14 As in Case 3, PM may be the presenting manifestation of AIDS. The precise mechanism for this association has not been fully elucidated. However, as radiologists become more integrated into the management of patients with IM, including biopsy, it will be prudent to remember this association with AIDS so that safety can be assured. This preliminary series illustrates some of the benefits and limitations of prebiopsy, postbiopsy and follow-up MRI studies in assessing patients suspected of having IM. MRI may identify areas of abnormal signal intensity, suggesting unusual biopsy locations and help support clinical impressions during therapy. However, current methodology may cause too much or too little distortion of subcutaneous tissue and muscle to allow precise localization of the volume of muscle sampled. This lack of precision highlights the need for improved MRI-guided sampling techniques.

Acknowledgmenls-This work was supported in part by a grant from Toshiba America MRI, Inc. We thank Kevin Baker, Joe Reyes, Allison Russell, Dorothy Gutekunst, Virginia Reed Vaughn, Mia Hale, and Marilyn Taylor for their technical

expertise.

MRI-guided biopsy in inflammatory myopathy 0 A.M. PITT ETAL.

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