Tomosynthesis of the Wrist and Hand in Patients With Rheumatoid Arthritis: Comparison With Radiography and MRI

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1 Musculoskeletal Imaging Original Research Aoki et al. Imaging of the Wrist and Hand in Rheumatoid Arthritis Musculoskeletal Imaging Original Research Takatoshi Aoki 1 Masami Fujii 1 Yoshiko Yamashita 1 Hiroyuki Takahashi 1 Hodaka Oki 1 Yoshiko Hayashida 1 Kazuyoshi Saito 2 Yoshiya Tanaka 2 Yukunori Korogi 1 Aoki T, Fujii M, Yamashita Y, et al. Keywords: hand, rheumatoid arthritis, tomosynthesis, wrist DOI: /AJR Received September 29, 2012; accepted after revision June 17, Department of Radiology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu , Japan. Address correspondence to T. Aoki (a-taka@med.uoeh-u.ac.jp). 2 First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. AJR 2014; 202: X/14/ American Roentgen Ray Society Tomosynthesis of the Wrist and Hand in Patients With Rheumatoid Arthritis: Comparison With Radiography and MRI OBJECTIVE. The purpose of this article is to compare tomosynthesis with radiography and MRI of the wrist and hand for evaluating bone erosion in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS. Twenty consecutive patients with an established diagnosis of RA and five control patients were included in this study. They underwent radiography, tomosynthesis, and MRI of the bilateral hand and wrist within a week. The mean total dose of radiography and tomosynthesis was 0.13 and 0.25 mgy, respectively. MRI evaluation was performed according to the Outcome Measures in Rheumatology Clinical Trials recommendations. Bone erosion on images from the three modalities was independently reviewed by two certificated radiologists with a 4-point scale (0, normal; 1, discrete erosion; 2, < 50% of the joint surface; and 3, 50% of the joint surface). RESULTS. The detection rates of bone erosion for radiography, tomosynthesis, and MRI were 26.5%, 36.1%, and 36.7%, respectively. Significantly more bone erosions were revealed with tomosynthesis and MRI than with radiography (p < 0.01). When MRI was used as the reference standard, the sensitivity, specificity, and accuracy were 68.1%, 97.5%, and 86.7%, respectively, for radiography and 94.8%, 97.8%, and 96.7%, respectively, for tomosynthesis. Interobserver agreement (kappa value) for bone erosion was good to excellent on tomosynthesis and MRI for all joints ( and , respectively), whereas it was slight to fair on radiography for some carpal bones and bases of metacarpal bones ( ). CONCLUSION. Tomosynthesis is superior to radiography and almost comparable to MRI for the detection of bone erosion in patients with RA. R adiography of the wrist and hand is traditionally used for the clinical assessment of patients with rheumatoid arthritis (RA). According to the international recommendations of the American College of Rheumatology and the European League Against Rheumatism, radiography remains the reference method for the diagnosis and follow-up of patients with RA. However, there is a disadvantage of low sensitivity for the detection of bone erosions in patients with RA. Several studies have shown that MRI has enabled clinicians to visually detect bone erosion before the changes are visible on conventional radiographs [1, 2]. Tomosynthesis is a new technology that obtains images on arbitrary parallel cross-sections through image reconstruction of multiple projected images taken by a single exposure [3]. The image reconstruction is based on that for cone-beam CT, with additional correction for differences between CT rotation and to- mosynthesis parallel-plane scanning, and 3D filtered projection to remedy artifacts due to angular restrictions. Regions with significant overlapping of anatomic structures can be difficult to evaluate on radiography, whereas tomosynthesis may offer clear images for these regions [4]. Tomosynthesis is already used in routine clinical practice to image for musculoskeletal indications, as well as for the chest and breast. In musculoskeletal imaging, tomosynthesis has been shown to be useful for the evaluation of subtle fractures [5] and joint surface [6, 7] and for imaging of metallic implants, in which beam-hardening and metallic artifact make visualization on CT difficult [8]. To the best of our knowledge, however, only one article in the literature has considered the use of this new technology in the diagnosis of RA, but it did not assess its diagnostic value compared with that of MRI [9]. Our purpose in this study is to compare tomosynthesis with radiography and MRI of 386 AJR:202, February 2014

2 Imaging of the Wrist and Hand in Rheumatoid Arthritis TABLE 1: Comparison of Interobserver Variability for Bone Erosions in Metacarpophalangeal s Metacarpophalangeal I Proximal Distal Metacarpophalangeal II Proximal Distal Metacarpophalangeal III Proximal Distal Metacarpophalangeal IV Proximal Distal Metacarpophalangeal V Proximal Distal the wrist and hand for evaluating bone erosion in patients with RA. Materials and Methods Our institutional review board approved this study and informed consent was waived. Study Population We retrospectively reviewed 20 consecutive patients with an established diagnosis of RA (five men and 15 women; age range, years; disease duration, 2 months to 4 years and 4 months) from April 2010 to February All patients with RA met the 2010 American College of Rheumatology and European League Against Rheumatism diagnostic criteria [10]. Nine patients (45%) had early RA at presentation, defined by the presence of the disease for less than 6 months since the first episode of clinically detectable joint inflammation. In addition, five patients with unclassified self-limited arthritis who had polyarthralgia including the wrist joint (two men and three women; age range, years) were enrolled as a control group. All these patients underwent radiography, tomosynthesis, and MRI of the bilateral hand and wrist within a week of enrollment. Conventional Radiography The digital radiographic examination (FCR, Fuji Photo Film) including posteroanterior and oblique views of the hand and wrist was obtained at a tube voltage of 42 kvp and a tube current of 200 ma, according to the standard protocol of our department. The mean total radiation dose was 0.13 mgy per patient. Tomosynthesis Tomosynthesis examinations were performed with a commercially available direct-conversion flat-panel detector device (Sonialvision safire II, Shimadzu). Thirty-six low-dose projection images were collected at a tube voltage of 47 kv and TABLE 2: Comparison of Interobserver Variability for Bone Erosions in Base of Metacarpal Bones Base of metacarpal I Base of metacarpal II Base of metacarpal III Base of metacarpal IV Base of metacarpal V tube current of 1.25 ma within 2.5 seconds. The data acquisition rate was 15 frames per second. The FOV was 12 inches (30.48 cm) with matrix. The x-ray tube performed a continuous horizontal movement from 20 to 20 around the standard orthogonal posteroanterior position while the flat-panel detector, located under the patient table, moved in the opposite direction of the x-ray tube. The examination resulted in 21 reconstructed coronal section images with a 2-mm pitch. The mean total radiation dose of tomosynthesis was 0.25 mgy. MRI Protocol MRI was performed with a 3-T MRI unit (Signa 3 T, GE Healthcare). In accordance with the Outcome Measures in Rheumatology Clinical Trials 2002 RA MRI scoring system recommendations [11], unenhanced coronal gradientecho T1-weighted images, contrast-enhanced fat-suppressed coronal and axial gradient-echo T1-weighted images (3D; 3-point Dixon; TR/TE, 6.8/2.9; matrix size, ; FOV, 24 cm), and coronal fat-suppressed fast spin-echo T2-weighted sequences (TR/TE, 3000/86; echo-train length, 12; matrix size, ; FOV, 24 cm) were included. The MRI section thickness was 3 mm for coronal images and 5 mm for axial images. Contrast-enhanced images were obtained after bolus injection of 0.1 mmol/kg gadoteridol (ProHance, Eisai) into a vein in the contralateral arm. Image Assessment Two certificated radiologists with 23 and 16 years of experience separately assigned the images for the presence of bone erosion. Bone erosion was considered to be a sharply delineated juxtaarticular lesion with a cortical defect. If each observer arrived at a decision that the patient had bone erosion, they analyzed the erosion by using a 4-point scale (0, normal; 1, discrete erosion; 2, < 50% of the joint surface; 3, 50% of the joint surface). The images were evaluated for bone erosion uptake in 25 sites in each finger and wrist, including the distal radius, the distal ulna, the eight carpal bones, the first through fifth bases of metacarpal bones, and the proximal and distal aspects of the first through fifth metacarpophalangeal joints. For assessment of the detection rate between modalities, when at least one observer detected a bone erosion, the other observer interpreted whether the bone erosion was present, and any disagreement was resolved by consensus. Statistical Method Statistical analysis of the detection rate of bone erosions in patients with RA was performed by using the Fisher exact test. Comparison of detectabil- AJR:202, February

3 Aoki et al. TABLE 3: Comparison of Interobserver Variability for Bone Erosions in Wrist s Trapezium Trapezoid Capitate Hamate Scaphoid Lunate Triquetrum Pisiform Distal radius Distal ulna ity for bone erosions between radiography and tomosynthesis was analyzed by using the two-sided paired Student t test. All statistical analyses were performed with StatView 5.0 (SAS Institute). p Values less than 0.01 were considered significant in all analyses. Interobserver variability for bone erosions was calculated as a weighted kappa value. The strength of agreement was considered slight for kappa values of 0.40 or less, fair for kappa values of , good for kappa values of , and excellent for kappa values of 0.81 or greater. Results The detection rate of bone erosion for radiography, tomosynthesis, and MRI was 26.5%, 36.1%, and 36.7%, respectively. Significantly more bone erosions were revealed Fig year-old woman with rheumatoid arthritis. A D, Bone erosions (arrows) in second through fourth metacarpophalangeal joints are visible on both radiography (A) and tomosynthesis (B D) but they are more clearly depicted on tomosynthesis than on radiography. with tomosynthesis and MRI than with radiography (p < 0.01). When MRI was used as the reference standard, the sensitivity, specificity, and accuracy were 68.1%, 97.5%, and 86.7%, respectively, for radiography and 94.8%, 97.8%, and 96.7%, respectively, for tomosynthesis. Sensitivity of bone erosions was increased by 26.7% when using tomosynthesis compared with radiography (p < 0.01). Accuracy was also increased by 10.0% when using tomosynthesis (p < 0.01). Comparisons of interobserver variability for bone erosions are summarized in Tables 1 3. Interobserver agreement for bone erosion was good to excellent on all modalities for the metacarpophalangeal joints ( ) (Fig. 1). In the base of the metacarpal bone, interobserver agreement for bone erosion was fair on radiography for the bases of metacarpals II and III (0.56 and 0.45, respectively), whereas it was good to excellent on tomosynthesis ( ) and MRI ( ) for all sites. In the carpal bones, interobserver variability for bone erosion was good to excellent on tomosynthesis ( ) and MRI ( ) for all sites, whereas it was slight to fair on radiography for the capitate (0.27), hamate (0.52), triquetrum (0.22), and pisiform (0.26) bones (Fig. 2). Discussion Recognition of RA as early as possible is crucial, because a significant proportion of patients develop irreversible joint damage shortly after disease onset [12, 13]. Early intervention with nonbiological or biologic disease-modifying antirheumatic drugs is important for the control of bone destruction. The presence of bone erosions suggests highly ac- A B C D 388 AJR:202, February 2014

4 Imaging of the Wrist and Hand in Rheumatoid Arthritis tive RA, and the progression of the erosive process after treatment would require therapeutic changes. Thus, assessment for bone erosions is very important for the early diagnosis and management of patients with RA. Radiography remains the reference method for the diagnosis and follow-up of patients A D G with RA because of the advantages of short examination time, low radiation dose, and low cost. The consensus among researchers is that MDCT represents the best imaging modality for recognizing bone erosions in patients with RA because of its multiplanar capacity and the enhanced cortical definition [14 16]. However, CT is not routinely used in patients with RA because of some drawbacks, including higher costs, more limited access, and higher radiation dose than with radiography [4, 17]. Tomosynthesis can provide thin coronal sections and improve the detectability of bone erosion with a small increase in radiation dose compared with radiography. Although interobserver variability for bone erosion within wrist and carpometacarpal joints was slight to fair with radiography, it was good to excellent for all joints with tomosynthesis. Tomosynthesis may B E Fig year-old man with rheumatoid arthritis. A G, Erosions with significant overlapping of bones (arrows) can be difficult to evaluate on radiography (A), whereas tomosynthesis (B D) offers clear images, almost like T1-weighted MRI (E G), for these regions. represent an alternative for the evaluation of bone erosions in the wrist and hand and would provide useful clues for therapeutic strategies in patients with RA. Tomosynthesis detected more bone erosion than did radiography but not all the erosions were detected by MRI. These falsenegative findings were mostly located in the volar or dorsal aspect of wrist joints and base of metacarpal bones. Tomosynthesis cannot obtain sagittal and axial images, which may explain the locations of false-negative findings. There were also some false-positive findings on tomosynthesis when MRI was used as the reference standard. Some of them were located in the metacarpophalangeal joints, which are inclined to display microdamage in healthy elderly patients [18]. On the other hand, because tomosynthesis provides far superior spatial resolution on ar- C F AJR:202, February

5 Aoki et al. bitrary parallel cross-sections and fine bone detail, there is some possibility that the falsepositive findings when MRI was used as the reference standard may reflect true pathologic erosion. Further study with pathologic correlation is needed to confirm this point. MRI has been increasingly recognized as a useful method for the diagnosis and monitoring of therapeutic response in patients with RA, because it enables clinicians to visually detect bone erosion and active synovitis in early RA before the changes are visible on radiography. Although there was no significant difference between tomosynthesis and MRI for the detection of bone erosion, tomosynthesis cannot depict synovitis and bone marrow edema the same way as MRI, which may limit its clinical usage. However, the use of MRI in screening potential subjects and in frequent follow-up is difficult because of practicability and cost issues. The costs of MRI, tomosynthesis, and radiography (posteroanterior and oblique views of the hand and wrist) are approximately $200 (without contrast media), $50, and $30, respectively, in our country. Although tomosynthesis is 1.7 times more expensive than radiography, it is still much cheaper than MRI. The use of tomosynthesis may be practical in screening potential subjects or in follow-up study for patients with RA with bone erosion. Our study has several limitations. First, this study included a rather small number of cases. Second, we analyzed bone erosions of the hands alone, although RA is a systemic disease. We consider, however, that it is practical because the hands are the earliest and most common site of disease in patients with RA. Third, reading time between modalities was not assessed for comparison in this study. Comparison of the reviewing time in the interpretation may also be important to evaluate the usefulness of the modalities. In our impression, the reading time was shortest using radiography and nearly equal between tomosynthesis and MRI. Fourth, our results cannot be compared with ultrasound. Because ultrasound is increasingly being used to detect early soft-tissue and joint changes in RA, a comparative study with ultrasound would be needed to validate the utility of tomosynthesis. Finally, intraobserver reproducibility was not assessed. An additional prospective study with a larger number of cases may be necessary to confirm the clinical usefulness of tomosynthesis. In conclusion, tomosynthesis is far superior to radiography and is comparable to MRI for the detection of bone erosion in patients with RA and would provide useful clues for therapeutic strategies in patients with RA. References 1. McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at 4 months after symptom onset. 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