What structural pathologies can MRI detect?

The use of MRI has undoubtedly enhanced our understanding of the pathophysiology of inflammatory joint diseases. MRI is superior to conventional CR as it allows a three- dimensional perspective and precise assessment of the bony and surrounding soft tissue structures within a targeted joint. MRI has been used increasingly in RA clinical trials typically in assessing peripheral joints (mostly the hands and wrists, and to a lesser extent knees and feet) although it has also been used to study relevant axial joints such as the cervical spine. The main ‘activity’ findings detected by MRI include synovitis, tenosynovitis and bone marrow oedema (BME) while the ‘damage’ findings include bony erosions and JSN. In 2003, the Outcome Measures in Rheumatology (OMERACT) MRI work group provided some important definitions for the various structural abnormalities detected on MRI .

Synovial inflammation is the hallmark of RA. The OMERACT group defines this as an area in the synovium with increased contrast enhancement whose thickness exceeds the width of the normal synovium . The use of MRI for synovial assessment is invaluable as it is sensitive to early pathology and change . Synovial inflammation is detected on MRI as an increase in synovial thickening, volume and/or enhancement post intravenous (IV) contrast use (e.g., gadolinium) . The latter is useful as enhancement allows easier recognition of inflamed synovial tissue; Østergaard et al. demonstrated that the addition of IV gadolinium allows a more reliable assessment of synovial inflammation . This should be weighed against the increase in cost, invasiveness and potential side effects of IV gadolinium use (such as rare nephrogenic systemic fibrosis) . MRI synovial inflammatory findings also correlate well with histopathological features of inflammation: increase in synovial volume detected on MRI has been correlated with overall synovial inflammatory activity on histological assessment . The extent of synovitis in the metacarpophalangeal joint (MCPJ) of RA subjects not only correlated well between MRI and macroscopic findings on miniathroscopy but also with clinical disease activity . Recently, increased synovium vascularity assessed by MR angiography has been shown to correlate well with both MRI and US-detected synovitis in a pilot study involving 30 patients with early IA .

BME is a unique but nonspecific MRI finding and it can occur in various traumatic, degenerative and inflammatory joint disorders including RA. This finding has been an important unique contribution from MRI, as BME is not visualised by other imaging modalities. The OMERACT group has defined BME on MRI as a lesion within the trabecular bone with ill-defined margins and signal characteristics consistent with increased water content . In early RA, its prevalence is estimated to be between 39% and 75% and histopathologic studies on BME lesions in RA subjects scheduled for orthopaedic surgery have demonstrated this to be an area of cellular infiltrates in the subchondral bone, or osteitis . This was initially postulated to be a precursor of bone damage/erosion, and this has been borne out in subsequent studies of its strong ability to predict subsequent bone erosion .

Bone erosions are a reflection of bone damage in RA. According to the OMERACT definition, bone erosion needs to be visible on MRI in two planes, with a cortical break seen in at least one, and with correct juxta-articular localisation . MRI (like computed tomography, CT) is more sensitive in detecting bone erosions when compared with CR, due to its tomographic properties. McQueen et al. studied 42 patients with early RA and reported MRI detected bone erosions in 45% of scans versus 15% of scans using CR . A more recent study reported the sensitivity of CR compared with MRI in detecting bone erosion in early RA to be 0.13. Specifically, amongst 216 finger joints, CR detected five joints with erosions while MRI detected 38 joints with erosions . In terms of criterion validity, MRI has been shown to have a high concordance rate when compared with CT, which is the current gold standard modality for imaging cortical bone abnormalities .

The OMERACT MRI group has devised a validated method for scoring joint abnormalities that has both good inter-/intra-reader reliability and high sensitivity to change over time . This is known as the RA MRI Score (RAMRIS) and it represents an international collaborative effort to standardise evaluation and reporting of inflammatory and destructive joint abnormalities in RA using semiquantitative scoring to grade synovium inflammation, bone erosion and BME. Tendon sheath inflammation is common in RA and recently an MRI scoring system for tenosynovitis with good reliability has been introduced as a proposed adjunct to the current RAMRIS . Cartilage assessment (via JSN assessment) was initially excluded in RAMRIS due to poor inter-reader reliability. This problem has been overcome with advances in MRI technology and better image resolution, especially with higher magnet strengths (e.g., 3 T machines). An MRI JSN scoring system subsequently proposed by McQueen et al. demonstrated excellent inter- and intra-reader reliability. However, perhaps not surprisingly, it was not capable of distinguishing JSN in those with early RA from healthy subjects . Most recently, the OMERACT MRI group has commenced development of a JSN MRI score as a potential RAMRIS addendum for cartilage assessment . Preliminary use of this scoring method on a small cohort of RA patients and controls demonstrated construct validity and good intra-/inter-reader agreements .

Does MRI help in diagnosis?

The emphasis on early RA diagnosis means MRI may be better suited than CR for diagnostic workup in early disease. A few authors have devised a scoring system/prediction model combining MRI findings with various clinical and/or laboratory parameters for RA diagnosis with rather encouraging results. Tamai et al. reported a scoring system, using baseline anti-cyclic citrullinated peptide antibody (anti-CCP) and/or rheumatoid factor (RF), MRI findings of symmetrical synovitis and MRI BME and/or bone erosion, which could predict early RA with 82.5% sensitivity and 84.8% specificity . In a separate study involving 99 participants with undifferentiated arthritis/suspected RA, a combined positive anti-CCP or RF with MRI flexor tenosynovitis was found to enhance the predictive value in the diagnosis of early RA . Duer-Jensen and colleagues prospectively followed up 116 patients with undifferentiated arthritis for more than 12 months and derived an RA prediction model that combined clinical findings (hand arthritis, morning stiffness greater than 1 h), laboratory findings (positive RF) and MRI findings (BME score in the metatarsophalangeal joints (MTPJs) or wrist). This correctly identified the RA status in 82% of patients .

A recent systemic review performed by Suter et al. specifically addressed the question of diagnostic utility of MRI in RA . Eleven studies (with 606 subjects) were analysed with sensitivity and specificity for the diagnostic use of MRI reported to range widely between 20–100% and 0–100%, respectively. The diagnostic utility of MRI therefore varies depending on the study: MRI was found to be useful in predicting the diagnosis of RA in one small cohort of anti-CCP negative subjects while it was unable to reliably discriminate IA in RA from those occurring in other inflammatory arthritides . When multiple MRI findings in various combination with clinical and/or laboratory findings are used, this resulted in better specificity at the expense of sensitivity. The main difficulty in interpreting results across studies was related to non-uniformity in the use of MRI RA criteria, OMERACT MRI definitions and cut-off values in MRI scoring systems; clearly, well-designed studies are needed in this area.

Does MRI help in disease prognostication?

Information on RA prognosis is highly important as this can impact on the choice of therapy. Traditionally, the contribution of imaging to disease prognosis in RA has been the identification of damage (CR erosions). Given its ability to study soft tissues as well as bone, MRI is well placed to provide unique information on prognosis. In a study involving 42 subjects with early RA, a global score of the carpus (including synovitis, BME, erosions and tendonitis) at baseline was shown to be predictive of subsequent CR erosions at 2 years . Studies that looked at scoring of individual MRI pathologies in RA have consistently reported subchondral BME as a reliable predictor of CR erosive progression . The CIMESTRA study was a 2-year randomised controlled trial involving 130 patients with early RA. Various baseline clinical, laboratory and imaging parameters were analysed and the results demonstrated MRI BME to be the strongest predictor of subsequent CR erosions . Thereafter, BME continued to predict CR erosions up to 5 years . The previously mentioned systematic review by Suter et al. identified 17 studies (with a total of 710 RA patients) that looked at the prognostic use of MRI in RA . The sensitivity (18–100%) and specificity (5.9–97%) reported for the use of various predetermined MRI findings in predicting CR erosive progression again was highly variable, although BME was highlighted as potentially useful. The main limitations were again a lack of uniformity in the use of MRI prognostic criteria and a wide variability in methodologic quality across studies. The heterogeneity of study inclusion therefore makes it difficult to understand any health economic model based on this data , and better designed studies reflecting clinical practice are required.

However, not all baseline MRI findings have been shown to be consistently predictive of CR erosions. For example, although synovitis detected on baseline MRI have been reported to predict CR progression in the study by Bøyesen et al. , this association has not been reproduced in another study with longer patient follow-up . This could possibly relate to synovitis not being a time-integrated measure and hence single time measurement is unlikely to truly reflect the degree of cumulative joint inflammation over time. Indeed, the same study by Bøyesen et al. revealed that a 1-year cumulative measure of MRI synovitis was predictive of CR progression. This contrasts with BME that probably represents a sustained inflammatory process and is therefore likely to be informative with a single time point measurement.

Role of MRI in clinical remission

Recent evidence has demonstrated that MRI inflammatory features are a frequent finding in RA clinical remission/low disease activity state (LDS) . Gandjbakhch et al. have subsequently published pooled data from six patient cohorts from five international centres ( n = 81) confirming this important observation . Patients were in either RA clinical remission (DAS28-CRP < 2.6) or LDS (DAS28-CRP between 2.6 and 3.2). By MRI (wrists and/or MCPJs), synovitis and BME were found to be present in 95% and 35% of the patients, respectively. In a separate study involving 102 RA patients judged by rheumatologists to be in clinical remission (receiving stable therapy and without any flare-ups in the preceding 6 months), progressive CR changes occurred in about one-fifth of the subjects. Baseline MRI synovitis was predictive of the CR deterioration .

Using MRI as an outcome measure

Besides being more sensitive than conventional imaging in detecting structural changes, MRI is also a highly responsive imaging modality to measure joint inflammation. A recent study conducted with RA patients on an anti-tumour necrosis factor (anti-TNF) agent over a 12-month period demonstrated that an MRI composite measure of synovitis, tenosynovitis and BME was the most responsive measure of joint inflammation (when compared with US and CR) with a standardised response mean of between −1.05 and −1.24 . With these superior attributes, MRI is not surprisingly used increasingly as an outcome measure in RA clinical trials.

Several authors have reviewed the usefulness of MRI in evaluating different DMARDs or therapeutic interventions in RA. This included intra-articular corticosteroids, conventional and biological DMARDs and other therapies such as bisphosphonates, either used alone or in combination . Table 1 shows an overview of the randomised placebo-controlled trials to date in RA using high-field MRI as an outcome measure. Other randomised MRI studies where placebo was not used were not included. Preliminary data from other trials have been presented and many more randomised controlled trials are under way. The first two studies described below are smaller observational studies followed by a few examples of recently conducted randomised placebo-controlled trials. Rituximab (a monoclonal antibody against B-cells) has been used in 10 RA subjects with MRI of the wrist/2nd to 4th MCPJs performed at baseline, 6 and 12 months and scored with RAMRIS. There was no mean progressive joint damage at the end of the study. The MRI synovitis/BME scores were reduced and MRI erosive changes trended towards regression, although all these did not achieve statistical significance . In a separate uncontrolled study, 29 RA patients were treated with the anti-interleukin 6 receptor antibody tocilizumab. At 5 months, the MRI (one hand and wrist) RAMRIS bone erosion score and synovitis score showed moderate and small responsiveness, respectively. The lack of good responsiveness may be partly explained by the small sample size and the use of a relatively large field of study for MRI image acquisition, thereby compromising spatial resolution . Abatacept (a T-cell costimulation modulator) has been studied in 56 anti-CCP-positive patients with undifferentiated or very early RA. Active treatment was ceased after 6 months. Beneficial effects seen on MRI hand/wrist RAMRIS synovitis, erosion and BME scores persisted for 1 year in the abatacept group, providing evidence that early T-cell modulation could favourably alter the course of RA . A separate MRI RA study reported significant improvement from baseline in both MRI (hand/wrist) RAMRIS synovitis and BME score (but not the erosion scores) at 3 and 6 months after the use of anti-TNF golimumab plus MTX when compared with placebo plus MTX in a cohort ( n = 240) of active RA patients despite MTX use . In this study, less than 10% of patients had significant erosion progression which did not allow an adequate assessment of the impact that golimumab may have on bone erosions. This may have been due to the baseline low disease activity of the study subjects (assessed by CRP measurements) which could account for the minimal CR progression, or to the degree of damage present at inclusion reflecting a ‘ceiling’ effect of the scoring system. A parallel study in early RA patients did demonstrate a beneficial effect of the new therapy on progression of MRI bone erosions . Denosumab, a fully human monoclonal antibody that suppresses bone resorption through inhibition of RANKL (receptor activator of NF-kappaB ligand), has recently been studied in a randomised double blinded placebo-controlled phase II trial involving 227 RA patients . A variation of MRI RAMRIS was used to image both hands and wrists. At 6 months, the percentages of patient without an increase in the MRI erosion scores were reported as 39%, 51% and 64% in the placebo, 60 and 180 mg of denosumab groups, respectively. The increase in the MRI erosion score from baseline to 6 months was significantly lower with 180 mg of denosumab when compared with placebo. Fostamatinib (an inhibitor of spleen tyrosine kinase) is another immune modulator used recently in a cohort of RA patients ( n = 219) whose disease was refractory to biological DMARDs. Inconsistent results were reported using American College of Rheumatology (ACR) response criteria and MRI (hand/wrist) RAMRIS scores, perhaps related to study design issues, important baseline differences between treatment groups and a high placebo response rate .

What structural pathologies can US detect?

Like MRI, musculoskeletal US allows an in-depth analysis of soft-tissue structures but it cannot provide information on osteitis. It can however be used in real time to examine multiple joint sites. In the past, there has been a lack of standardised definition of US-detected pathological findings in inflammatory joint disease and hence interpreting results and comparing between studies was often not easy. In 2005, the OMERACT US group addressed this problem and published consensus US definitions for common pathological lesions in IA .

According to the OMERACT definition, synovial fluid is an abnormal hypoechoic or anechoic intra-articular material that can be displaced and compressed, but without Doppler signal. This can be distinguished from synovial hypertrophy that is represented by a hypoechoeic (most often) material that is non-displaceable, poorly compressible and may exhibit Doppler signal . The use of power Doppler (PD) has made it possible for US to determine the degree of synovial vascularity. This can be assessed semi-quantitatively by scoring the amount of PD signals within the joint capsule on a 0–3 scale or quantitatively by counting the number of vascular flow pixels in the region of interest with an automated analysis system. Power Doppler ultrasound (PDUS) is shown to correlate well with histologically detected synovitis in inflamed joints and is reliable in qualitative grading of the synovium vascularity . US has been demonstrated to be a valid and reproducible tool in detecting synovitis. Using knee arthroscopic findings of synovitis as a gold standard reference method, US has been reported to be highly sensitive, specific and accurate in detecting synovitis in a cohort of 60 patients with knee pain due to various arthritides. In this study, US reliably discriminated between the presence and absence of synovitis .

Joint erosion seen on US is defined by OMERACT as an intra-articular discontinuity of the bone surface that is visible in two perpendicular planes . US detects more RA joint erosions than CR especially in the context of early disease ; its limitations arise in areas where there is a poor acoustic window, such as in the mid-carpus. When compared with gold standard CT, US has a moderate sensitivity but a high specificity and accuracy in detecting MCPJ erosions in RA . Both synovitis and bone erosions detected by US in the finger joints have also been studied in RA subjects using post-contrast MRI as a reference method and this yielded a sensitivity, specificity and accuracy of 0.70, 0.78 and 0.76, respectively, for US synovitis, and 0.59, 0.98 and 0.96, respectively, for US erosions .

The OMERACT group defines tenosynovitis on US as a hypoechoic or anechoic thickened tissue seen in two perpendicular planes with or without tendon sheath fluid and Doppler signal . Current literature on US-detected tenosynovitis in RA is still limited. A recent study found that approximately half of the patients with early IA ( n = 33) had tenosynovitis on US of their MCPJs. This was most commonly seen in the second and third MCPJs. US was also reported to be useful in detecting tenosynovitis in the context of a negative clinical examination in this study . Use of grey scale (GS) US to detect tenosynovitis in RA was however a less sensitive modality when compared with contrast-enhanced MRI . In a study involving 50 early, untreated RA patients, the former modality detected flexor tenosynovitis in 28.5% joints and 48% patients while this was reported to be 64% joints and 82% patients for the latter modality. Important differences in such comparative studies include at what sites the tendons were imaged, for example, at the joint level or along the tendon length.

Determining cartilage loss or JSN on US has not been well studied, nor has there been a formal definition by the OMERACT US group. Preliminary work has demonstrated that directly measuring cartilage thickness on US in the MCPJs and PIPJs is correlated with CR finding of JSN . Direct cartilage measurement, however, may not always be possible, for example, in the presence of synovitis and absence of the interface artefact on the cartilage surface which represents the upper limit of cartilage measurement from the subchondral bone surface. More recently, a study using a semiquantitative cartilage damage scoring method (scale of 0–4) was shown to have a moderate to good inter-observer reliability when used in RA subjects . In that study, cartilage damage scoring is based on the qualititative morphological changes seen on US that range from normal cartilage (score of 0) to complete loss of cartilage with subchondral bone involvement (score of 4). Overall, cartilage assessment by US holds promise but at present requires more extensive evaluation.

Does US help in diagnosis?

There is evidence supporting the use of US for diagnostic evaluation in routine rheumatology practice . A study involving patients from an early arthritis clinic found the use of US to be valuable. When available, US findings changed the overall patient diagnosis in only a small percentage of patients but changed the site-specific diagnosis (e.g., tenosynovitis vs. synovitis) in about half of the patients . More recently, Agrawal et al. looked into the usefulness of a rheumatology clinic-based US service in 237 patients with musculoskeletal conditions and found that US was useful in confirming/changing the diagnosis in 76.3% of newly referred patients and in revising the diagnosis in 7.2% of follow-up patients .

Being more sensitive than clinical examination in detecting joint inflammation, US can be useful when clinical features of synovitis and/or tenosynovitis is equivocal or when sub-clinical disease is suspected, especially in the context of early disease. Wakefield et al. studied the use of GS US in a cohort of 80 patients with early (<12 months’ symptoms) untreated oligoarthritis. Conventional methods of joint assessment including clinical examination detected clinical synovitis in 185 out of 1470 (12.6%) joints. Of these joints, GS US confirmed synovitis in 79% while the remaining joints in this subgroup either had tenosynovitis, possible synovitis or were normal on US. The superiority of US over conventional examination was further seen in two subgroups: the first subgroup without clinical synovitis had inflammatory findings present on US in one-third of the joints. The second subgroup with clinically detected monoarthritis had more than half reclassified to either oligoarthritis or polyarthritis with the use of US . In a separate study involving 58 patients presenting with very early (<3 months) inflammatory joint symptoms, half of them had a final diagnosis of RA. Out of these 29 patients who were diagnosed as RA, 24 (83%) fulfilled the 2010 RA diagnostic criteria at baseline while the additional use of an extended 38 joint GS and PDUS at baseline helped identify three more RA patients (93%) . US was also shown to have added value to standard clinical evaluation in the assessment of a subset of patients (presenting within 3 months of inflammatory hand symptoms) who were seronegative (negative RF and anti-CCP). GS and PDUS were used to evaluate bilateral MCPJs, wrists and flexor tendons in 50 subjects with 1-year follow-up. US helped to increase the overall diagnostic ability when used with other conventional methods of assessment . Recently, quantitative PDUS has also been used as an RA screening tool in a small cohort of patients ( n = 50) with undifferentiated polyarthralgia (about half eventually developed RA). The values for the sensitivity, specificity and positive likelihood ratio were high and reported as 92.3%, 91.7% and 11, respectively, when a novel scoring system was used for RA diagnosis .

A further scenario that US may be useful is in the prediction of which patients will go on to develop IA. A recent study has shown that a positive anti-CCP status places a patient with joint pain at a higher risk of developing IA , but presently it is not known with certainty which of these patients will go on to develop IA. Van de Stadt et al. evaluated the use of GS and PD US in 192 seropositive patients with arthralgia and reported findings at both the patient and the joint level . Various painful/tender joints and their adjacent joints were identified and scanned (predominantly wrist, MCPJs, proximal interphalangeal joints (PIPJs) and MTPJs). At the patient level, a positive trend was seen using US findings to predict IA although this did not attain statistical significance. At the joint level, US inflammatory findings did however predict the development of IA in that joint and the positive predictive value was further enhanced when both GS and PD findings were used.

Does US help in disease prognostication?

There have been conflicting data on the usefulness of US-detected synovitis in predicting poor disease outcome in RA. Using the degree of CR joint damage as a final measure of disease outcome, baseline US-detected synovitis was correlated with a worse prognosis in the placebo/MTX arm of a randomised controlled trial by Taylor et al. (primarily designed to evaluate the use of infliximab in early RA) and in another cohort study involving active RA patients by Fukae et al. Similar results were not seen in two other studies which showed that baseline US findings do not predict progressive erosive disease . One of these studies did demonstrate a correlation between time-integrated values of PDUS findings and CR damage at 1 year, once again supporting (as with the MRI data discussed above) the observation that measuring cumulative synovial inflammation is more informative compared with single time point measurements. The reasons for the disparate results from the above studies may also relate to important differences in baseline patient characteristics, therapeutic regimens used and the method of US assessment. For example, the positive study by Taylor et al. recruited patients with a much stricter inclusion criteria (positive RF, active disease despite MTX and presence of CR erosion) and has a well-defined treatment protocol (which allowed rigorous stepping up of MTX after week 18) when compared with the other two negative studies. The two positive studies also employed quantitative PDUS scoring which may be more reliable than the semiquantitative scoring used in the two negative studies. A recent study by Bøyesen et al. compared the use of various imaging modalities in a cohort of early (disease duration less than 1 year) RA patients. Baseline GS US of the wrist was identified as an independent predictor of 1-year MRI erosive progression with a high likelihood ratio (1.75) and accuracy (0.70) in predicting which patient is at risk of MRI erosive progression .

Role of US in clinical remission

Inflammatory findings on US are commonly seen in RA patients in clinical remission , and both GS findings of synovial hypertrophy and PD synovitis have been demonstrated to be independent predictors of CR structural progression . More recently, PDUS findings have been reported to be useful in predicting risk of subsequent relapse after achieving clinical remission. For example, in a cohort of early RA patients who achieved clinical remission state defined by disease activity score (DAS) less than 1.6 at two consecutive visits 3 months apart, an extended 44 joint US examination demonstrated that a positive PD signal in at least one joint site was able to predict disease relapse within 6 months . Another study involving 94 RA patients (with both early and chronic disease) in clinical remission (DAS less than 1.6) had a similar finding. Specifically, nearly half the patients with a positive PD signal had a flare within 12 months compared with only one-fifth of those with a negative PD signal . In a separate study that looked at the effect of cessation of anti-TNF therapy in a cohort of 47 RA patients, there were however no significant differences reported in the percentage of patients with US-detected inflammation (GS > 0 and PD > 0) between both the remission (DAS < 2.6) and the relapse group . The use of PDUS in disease prognostication will need further exploration.

Using US as an outcome measure

Musculoskeletal US offers good sensitivity in detecting structural abnormalities, avoids ionising radiation and can allow multiple joints to be assessed in real time in a multiplanar, dynamic and interactive manner. In the RA research setting, US has been used increasingly as an outcome measure in clinical trials. For results to be interpreted and compared meaningfully across studies, standardised US scanning and scoring are important. For the past few years, the OMERACT US workgroup has been focussing on the development of a reliable, standardised semiquantitative (0–3 scale) scoring system for synovitis in RA that uses both GS US and PD findings. When used with the OMERACT consensus definition and standardised acquisition protocol, such a scoring system yielded good inter-/intra-observer reliability . The OMERACT US taskforce has plans to develop and validate an ultrasound global synovitis score (GLOSS) that aims to unify the components of synovitis (synovial hypertrophy, effusion and vascularity) into a semiquantitative global score . The minimal number of joints to be scanned in such a global scoring system has yet to be defined. An extended US scanning involving multiple joints is unlikely to be ideal as this can be highly time consuming and hence less feasible for routine use. Some authors have looked into the use of reduced joint counts for US assessment and have published encouraging results. Mandl et al. systematically reviewed various published studies ( n = 14) on US joint counts and scoring systems for RA synovitis and reported a wide variability in the joint counts used (ranging from 5 to 60) across studies . Two studies with seemingly good validity issues were highlighted: the 12 joints’ count and the seven joints’ count PDUS proposed by Naredo et al. and Backhaus et al., respectively . The latter, when applied on the data set of Naredo et al., did demonstrate good sensitivity for GS and PD inflammatory changes and this was further enhanced by applying the seven joints’ counts bilaterally (14 joints’ count). Two recent studies (not included in the above systematic review) further support the use of reduced US joints’ count RA assessment. Hammer et al. showed that a reduced US seven joints’ count score was highly correlated with a much more comprehensive 78 joints’ count and still retained sensitivity to therapeutic changes when used in RA patients treated with adalimumab plus MTX . Filer et al. evaluated the use of an extended 38 joint GS and PDUS on a cohort of patients with very early (<3 months) inflammatory joint symptoms . Wrist and MCPJ GS findings and MTPJ PD findings were reported as independent RA predictors. US scanning consisting minimally of these three joint sites was recommended to obtain important data required for RA prediction.

There is currently a need to develop validated and reliable systems for US scoring of tenosynovitis. Recently, Hammer et al. examined the use of GS and PDUS at multiple wrist and ankle tendon sites in a cohort of RA patients on adalimumab and found tenosynovitis most frequently in three tendon sites (extensor carpi ulnaris in the wrists, tibialis posterior and flexor digitorum longus in the ankles). Bilateral assessment of these three tendons was sensitive to therapeutic changes when compared with scoring at all tendon sites .

Table 2 shows an overview of the studies using US to measure therapeutic effects. A few illustrative examples will be mentioned. Earlier studies used US to measure the therapeutic efficacy of steroids when administered via various routes (oral/IV/intra-articular). Naredo et al. studied the use of PDUS in 42 early RA patients treated with various conventional DMARDs (MTX, leflunomide, sulphasalazine, etc.) and reported a mean reduction of 2.1 ± 2.3(standard deviation) for US-detected active synovitis joint count .

Table 2

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