Diagnostic Accuracy of Ultrasonography in Detection of ... - JAPI

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Journal of The Association of Physicians of India ■ Vol. 64 ■ November 2016

Original Article

Diagnostic Accuracy of Ultrasonography in Detection of Destructive Changes in Small Joints of Hands in Patients of Rheumatoid Arthritis: A Comparison with Magnetic Resonance Imaging Sonal Saran1, Meenu Bagarhatta2, Renu Saigal3

Abstract

Editorial Viewpoint

Background: Ultrasonography can be used in early Rheumatoid Arthritis to determine and to follow parameters of joint inflammation, such as effusion, synovitis, and marginal erosion that can be radiologically occult. We therefore planned a study to investigate whether Ultrasonography could provide information on signs of inflammation and destruction in Rheumatoid Arthritis affected finger joints that was not available with Radiography and compared it to the information provided by Magnetic resonance imaging.

• Detecting early affection of joints is very important in treatment of early RA.

Study Design: Hospital Based Descriptive Study. Methods: The study included 30 patients fulfilling American College of Rheumatology 2010 criteria of Rheumatoid Arthritis with no erosions present on radiographs of hands. Erosion, Synovial thickening/vascularity, effusion and Tenosynovitis of Flexor tendon sheath / Extensor tendon sheath were assessed on both Ultrasonography and Magnetic resonance imaging. Statistical Analysis: Considering Magnetic resonance imaging as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of Ultrasonography were calculated. Kappa value was calculated by kappa statistics to show agreement between the two modalities Results: Ultrasonography and Magnetic resonance imaging had near perfect agreement for detecting synovial thickening and vascularity, substantial agreement for detecting effusion, Flexor tendon sheath / Extensor tendon sheath inflammation, and only moderate agreement for detecting erosions in Metacarpophalangeal and Proximal interphalangeal joints. Conclusion: Th e e a r l y d i a gn o s i s o f R h e u m ato i d A r t h r i t i s by Ultrasonography and MRI is very important to early treatment of Rheumatoid Arthritis. Ultrasonography is a reliable method for assessing inflammatory activity and destructive changes in small joints of hand as the Ultrasonographic findings are comparable to those of MRI.

• USG is a reliable and costeffective tool to determine inflammatory changes in synorium in early RA. • This study finds USG and MRI have near perfect agreement for detecting synovial thickening and vascularity in RA.

Introduction

E

arly diagnosis of Rheumatoid a r t h r i t i s ( R A) i s i m p o r t a n t because early aggressive treatment reduce the long term disability. For early detection of synovitis conventional radiography, clinical examination and laboratory tests are limited in their usefulness. 1 Musculoskeletal ultrasound has become an essential tool in routine clinical practice for early detection of joint inflammation, assessing ongoing disease activity and monitoring therapeutic responses.2 Ultrasonography (USG) has been shown to be more sensitive than clinical examination in determining synovitis. USG can be used in early

1 Senior Resident, Department of Radio-diagnosis, All Indian Institute of Medical Science, Jodhpur, Rajasthan; 2Professor, Department of Radio-diagnosis, Sawai Man Singh Medical College and Attached Group of Hospitals, Jaipur, Rajasthan; 3Professor, Department of Medicine, Mahatma Gandhi Medical College, Jaipur, Rajasthan Received: 30.10.2015; Revised: 15.03.2016; Accepted: 29.03.2016


RA to determine and to follow, more objective parameters of joint inflammation, such as effusion, synovitis, and marginal erosion that can be radiologically occult. 3 Magnetic resonance imaging (MRI) of small joints of hands and wrists can directly visualize the bone and soft tissues in three dimensions, and has the potential to measure inflammatory activity and joint destruction. 3 Since early changes are nonosseous in nature, USG and MRI are superior to conventional radiography in terms of disease detection and therefore are the imaging methods of choice to evaluate synovium directly and to assess inflammation and joint damage. 4

Methods Study Design

This hospital based descriptive s t u d y wa s c a r r i e d o u t i n t h e Department of Radio-diagnosis of our institute, between April 2012 and October 2013. Institutional ethical clearance was taken and all patients gave written consent. Aims and objectives of the study were : A. E va l u a t i o n o f s m a l l j o i n t s of hands in cases of RA by USG (power Doppler and high frequency gray scale) and MRI. B. To investigate whether USG can provide information on signs of inflammation and destruction in RA finger joints (that are not available with conventional radiography), and compare it to the information provided by MRI. Subjects

Consecutive patients with Rheumatoid arthritis, attending the outpatient rheumatology clinic, and who gave consent were recruited. Thirty patients fulfilling American College of Rheumatology (ACR) 2010 criteria of rheumatoid arthritis 5 with no erosions present on conventional radiography of hands were selected. This selection

wa s m a d e i n o r d e r t o i n c l u d e only patients whose joints were not damaged on radiographs, that is, the patients in which MRI and USG would be expected to have the greatest clinical value. All patients in whom MRI was contraindicated due to implanted medical devices, uncooperative patients, and patients showing e r o s i o n s o n r a d i o g r a p h s we r e excluded. Disease activity score in 28 joints (DAS28) was calculated at the time of patient’s visit to the rheumatology clinic by counting swollen and tender joints, recording ESR and assessing patient’s global health. Ultrasound Assessment

USG was done using ultrasound machine (Hitachi Color/power Doppler Ultrasound system) with high frequency 6-13 MHz 25-mm broadband linear array transducer. Patients were comfortably seated with both hands placed on a pillow. USG was done on the second to fifth metacarpophalangeal (MCP) joints and the second to fifth proximal interphalangeal (PIP) joints of both hands. Gray scale images of MCP and PIP joints of both hands were obtained in longitudinal and transverse planes followed by power doppler study to assess vascularity. The lowest wall filter was set for the power Doppler to detect any minimal flow. The most prominent power Doppler activity was identified and the images were frozen. Generous amounts of scanning gel was used to obtain acoustic contact and minimum pressure was exerted with the transducer. MRI Assessment

Later in the day on which USG was performed, MRI (3 Tesla Philips) of both hands was done. Patients were placed in a prone position with the hands above the head. Sand bags were used to avoid any movement. We used conventional T1-weighted sequences, SE images of repetition time (TR) 600 m-sec, echo time (TE) 15 m-sec. T2-weighted sequences,

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TSE: TR = 2000–4000 m-sec, TE = 90– 130 m-sec. Conventional short time inversion recovery (STIR) sequences. Fluid and pathologic tissues have high signal intensity in comparison to suppressed marrow and fat signal. To increase image quality we require a small field of view (FOV), we typically used an 16 to 18cm FOV for examinations of both hand. Coronal, sagittal and axial views in T2 and fat suppressed short tau inversion recovery (STIR) weighted spin-echo magnetic resonance sequences were performed. Continuous axial and coronal pre-Gadolinium (Gd) and post-Gadolinium T1- weighted spin-echo magnetic resonance sequences of b ot h h a n d s were performed. While the patient remained motionless in the MRI unit, 0.1 m-moles/kg body weight of gadodiamide (Omniscan) was injected into a vein in one of the arms via a cannula that had been inserted before the examination. Tw o d i f f e r e n t o b s e r v e r s interpreted the ultrasound and MRI findings to ovoid bias in the interpretation. Total 240 MCP and 240 PIP joints (2nd to 5th MCP and PIP joints of both hands in 30 patients) were assessed. Assessment of the 6 parameters- Erosion, Synovial thickening, Synovial effusion, Tenosynovitis of flexor tendon sheath (FTS), Tenosynovitis of extensor tendon sheath (ETS), a n d Va s c u l a r i t y o f s y n o v i u m were done on both USG and MRI on the basis of sonographic and MRI definitions of the above pathologies given by Outcome measures in rheumatology clinical trials (OMERACT) Rheumatoid Arthritis Imaging Studies system. 6,7 Parameters were graded binarily as present or absent. Statistical Analysis

Considering MRI as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of USG were calculated. Kappa value was calculated by kappa statistics to show agreement between the

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Table 1: Total number of MCP and PIP joints showing erosion, effusion, synovial thickening and synovial vascularity on USG and MRI (n=240) Criteria Erosion Effusion Synovial thickening Synovial vascularity

USG MCP 35 (14.5%) 59 (24.5%) 73 (30.4%) 60 (25%)

MRI PIP 24 (10%) 63 (26.2%) 61 (25.4%) 56 (23.3%)

MCP 45 (18.7%) 74 (30.8%) 75 (31.2%) 63 (26.2%)

PIP 26 (10.8%) 69 (28.7%) 61 (25.4%) 55 (22.9%)

Table 3: Diagnostic accuracy of USG as compared to MRI Criteria MCP Erosion Effusion Synovial thickening Synovial vascularity Erosion PIP Effusion Synovial thickening Synovial vascularity Flexor tenosynovitis Extensor tenosynovitis

Sensitiviy 55.5 74.3 93.3 95.2 57.6 79.7 95.0 90.9 81.8 64.4

two modalities. Our main aim was to determine presence or absence of pathology without quantifying its severity and so scoring for synovitis, erosions, effusion and synovial vascularity according to the OMERACT Rheumatoid Arthritis Imaging Studies system was not performed. 6,7

Results The study included 30 patients (F: M - 4:1) of Rheumatoid arthritis with mean age 42.333±24.92 years. Mean duration of illness in our study was 3.933±2.514 months. Rheumatoid factor (RF) was elevated (>20 IU/ml) in 16 patients (53.3%) with mean titer of 37.85±17.54 IU/ml. Mean ESR(mm/hr), CRP level (mg/L) and ACPA(EU) of the patients in our study were 36.73±30.95, 8.79±10.09 and 45.12±24.32 respectively. DAS28 values ranged from 0 to less than 3.2 in 4 patients, 3.2 to 5.1 in 23 patients and more than 5.1 in 3 patients. On ultrasound and MRI assessment, out of 240 MCP and P I P j o i n t s ( 2 nd t o 5 th M C P a n d PIP joints of both hands in 30 patients) erosion, effusion, synovial thickening and synovial vascularity were present in various number of

Specificity 94.8 97.5 98.2 100 95.7 95.3 98.3 96.7 94.0 93.2

PPV 71.4 93.2 95.8 100 62.5 87.3 95.0 89.2 88.8 81.6

NPV 90.2 89.5 97.0 98.3 94.9 92.0 98.3 97.3 89.9 85.0

Kappa value 0.55 0.76 0.92 0.93 0.55 0.77 0.93 0.87 0.77 0.61

joints as summarized in Table 1. Similarly out of 240 FTS and ETS (2nd to 5th FTS and ETS of both hands in 30 patients) tenosynovitis was present in the tendon sheaths as described in Table 2. Considering MRI as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of USG were calculated which are shown in Table 3. There was an increase in the average number of joints having erosions (detected on MRI) with increase in the duration of disease as described in Table 4.

Discussion This study found lower sensitivity of USG in detecting erosions in MCP and PIP joints. There was only moderate agreement between USG and MRI for detection of erosions. This is similar to the study conducted by Hoving et al. 8 They reported that MRI has significantly increased sensitivity compared with ultrasound for detection of erosions in the hand and wrist. Dohn et al 9 reported sensitivities of only 68% and 42% for MRI and USG in detecting erosions, respectively, although only 17 patients with RA were

Table 2: Total number of FTS and ETS showing inflammation (tenosynovitis) on USG and MRI (n=240) Criteria FTS inflammation ETS inflammation

USG 81 (33.75%)

MRI 88 (36.6%)

60 (25.0%)

76 (31.6%)

Table 4: Total no. of joints having erosions on MRI and duration of disease Duration in Average no. of joints having months erosions detected on MRI 2 0 3 1.5 4 2.5 5 3.6 6 4.3

included in the study, however specificity for erosion were high indicating proportion of negatives which were correctly identified as such. Sensitivity of USG for detecting FTS inflammation was higher than that for detecting ETS inflammation however specificity for these criteria were comparable and high. For detection of effusion, FTS and ETS inflammation USG and MRI s h o we d s u b s t a n t i a l a g r e e m e n t (Figure 1). Backhaus et al 10 found significant correlation between tenosynovitis detected by USG and MRI which agrees with our results. In this study highest sensitivity of USG was found for detecting synovial vascularity in MCP joints. Sensitivity and specificity for detecting synovial thickening in MCP and PIP, and synovial vascularity in PIP were also high indicating that USG can detect synovial inflammatory activity with high sensitivity and specificity. There was near perfect agreement between USG and MRI for detection of synovial thickening and vascularity in MCP and PIP joints (Figure 2). This is important, because in the early stages of RA, the synovitis is the primary pathology and seems to be the best predictive marker of joint damage. 3 Szkudlarek et al. 2004 11 also compared USG and MRI, with


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Fig. 1: (a and b) USG demonstrates hypo-echoic thickened tissue within the flexor tendon sheath, which is seen in two perpendicular planes (a) longitudinal plane (b) transverse plane suggestive of flexor tendon sheath inflammation (Fts infl) (arrow). (c) MRI demonstrates an area adjacent to flexor tendons with an above-normal Gd enhancement and abnormal thickening of the tendon sheath suggestive of flexor tendon sheath Inflammation (arrow) ETS

Fig. 2: USG demonstrates (a) an abnormal hypo-echoic intra-articular tissue that is non-displaceable and poorly compressible and (b) exhibit power Doppler signal suggestive of synovial thickening with increased vascularity. (c) MRI demonstrates an area in the synovial compartment which shows thickness greater than the width of the normal synovium and above normal post-Gd enhancement suggestive of synovial thickening with increased vascularity (arrow). ETS : extensor tendon sheath

MRI as the reference method, the sensitivity, specificity, and accuracy of USG in detection of synovitis were 87%, 74% and 79%. Farrant et al., 2007 12 found that Doppler USG and early MRI enhancement in rheumatoid joints have been closely correlated; the sensitivity and specificity of Doppler USG, with MRI as a reference, were 89% and 98 % respectively. Above findings indicate that USG is more sensitive in detecting soft tissue changes than bony changes (erosions) when MRI was used as reference method. Our study cohort included only patients having no erosion on hand radiographs this automatically concluded that USG and MRI can detect erosions earlier than radiography. This matched with many of the previous studies. Wakefield, et al 13 reported the superior sensitivity of ultrasound over radiography for the detection of bone erosions in patients with rheumatoid arthritis. McQueen et al 14 reported carpal erosions in 45% of patients on MR images 4 months after the onset of symptoms, while only 15% of patients had erosions on plain radiographs.

Conclusion RA is a potentially devastating condition affecting a large proportion of the population. Treatment has significantly progressed in recent years and outcome is significantly improved when disease is diagnosed and treated at an early stage. The early diagnosis of RA by USG and MRI is very important to early treat ment and modificat ion of treatment according to activity and severity of RA disease. There are only few published studies directly comparing the sensitivity and specificity of these two modalities, particularly where a valid reference standard has been used. USG is a reliable method for assessing inflammatory activity and destructive changes in small joints of hand as the USG findings are comparable to those of MRI. Clearly defined quantitative measures of synovitis will provide increased accuracy in monitoring disease changes in patients and will also provide a reference standard for clinical trials to compare results in a formal reproducible manner. Future studies are required with

increased patient number to determine which one of these two modalities is more appropriate as the imaging modality of choice. Both have advantages and disadvantages and as technology and skills develop they may continue to evolve in terms of sensitivity and availability. The availability is often determining factor for the choice of modality in a given center. In developing countries like India, where there are constraints of finances and availability of MRI centers, USG examinations offering reliable and early diagnosis of disease activity in patients of RA would be very beneficial. This would help the clinicians to monitor the treatment and prevent the debilitation due to this disease.

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metatarsophalangeal joints in rheumatoid ar thritis, compared with magnetic re s o n a n ce i m a gi n g, co nve nt i o n a l radiography and clinical examination. Arthritis Res Ther 2006; 8:2103-2112. 12. Farrant JM, O’Connor PJ, Grainger AJ. Advanced imaging in rheumatoid arthritis Part 1: synovitis. Skeletal Radiol 2007; 36:269–279. 13. Wakefield RJ, Gibbon WW, Conaghan PG, et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis and Rheumatism 2001; 43:2762-70. 14. McQueen FM, Stewart N, Crabbe J, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis 1998; 57:350–356.

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