Screening for rheumatoid arthritis with finger joint power Doppler ultrasonography: quantification of conventional power Doppler ultrasonographic scoring

Power Doppler ultrasonography (PD-US) has proved to be a useful technique to measure synovial vascularity due to its capability to provide data that can be used to evaluate the level of joint inflammation and assess rheumatoid arthritis (RA). We have developed a novel PD-US finger joint scoring method that introduces quantitative measurements into the conventional PD-US assessment method. A comparison of the two methods revealed that our novel PD-US method strongly correlates with the conventional method in terms of RA assessment. We performed finger joint PD-US on 69 patients with RA and 70 patients who had multiple joint pain but showed no evidence of inflammatory diseases (non-inflammatory disease, NI) and measured the synovial vascularity of the metacarpophalangeal joints 1–5 and proximal interphalangeal (PIP) joints 1–5 for each patient. We analyzed the data with receiver operating characteristic analysis and, based on the results for the total vascularity of 20 finger joints, defined a cut-off value of 36% as discriminating between RA and NI. This cut-off value was found to be a valuable tool in screening for RA. We conclude that our finger joint PD-US scoring system is both useful and applicable for diagnosing RA.     

Screening for rheumatoid arthritis with finger joint power Doppler ultrasonography: quantification of conventional power Doppler ultrasonographic scoring

Abstract

Power Doppler ultrasonography (PD-US) has proved to be a useful technique to measure synovial vascularity due to its capability to provide data that can be used to evaluate the level of joint inflammation and assess rheumatoid arthritis (RA). We have developed a novel PD-US finger joint scoring method that introduces quantitative measurements into the conventional PD-US assessment method. A comparison of the two methods revealed that our novel PD-US method strongly correlates with the conventional method in terms of RA assessment. We performed finger joint PD-US on 69 patients with RA and 70 patients who had multiple joint pain but showed no evidence of inflammatory diseases (non-inflammatory disease, NI) and measured the synovial vascularity of the metacarpophalangeal joints 1–5 and proximal interphalangeal (PIP) joints 1–5 for each patient. We analyzed the data with receiver operating characteristic analysis and, based on the results for the total vascularity of 20 finger joints, defined a cut-off value of 36% as discriminating between RA and NI. This cut-off value was found to be a valuable tool in screening for RA. We conclude that our finger joint PD-US scoring system is both useful and applicable for diagnosing RA.     

Dichotomous versus semi-quantitative scoring of ultrasound joint inflammation in rheumatoid arthritis using novel individualized joint selection methods

The aim of the study is to compare the responsiveness of two joint inflammation scoring systems (dichotomous scoring (DS) versus semi-quantitative scoring (SQS)) using novel individualized ultrasound joint selection methods and existing ultrasound joint selection methods. Responsiveness measured by the standardized response means (SRMs) using the DS and the SQS system (for both the novel and existing ultrasound joint selection methods) was derived using the baseline and the 3-month total inflammatory scores from 20 rheumatoid arthritis patients. The relative SRM gain ratios (SRM-Gains) for both scoring system (DS and SQS) comparing the novel to the existing methods were computed. Both scoring systems (DS and SQS) demonstrated substantial SRM-Gains (ranged from 3.31 to 5.67 for the DS system and ranged from 1.82 to 3.26 for the SQS system). The SRMs using the novel methods ranged from 0.94 to 1.36 for the DS system and ranged from 0.89 to 1.11 for the SQS system. The SRMs using the existing methods ranged from 0.24 to 0.32 for the DS system and ranged from 0.34 to 0.49 for the SQS system. The DS system appears to achieve high responsiveness comparable to SQS for the novel individualized ultrasound joint selection methods.     

Standardising joint assessment in rheumatoid arthritis

Summary Evaluating joint involvement in rheumatoid arthritis in a key clinical assessment. We investigated the extent of variation in measurement of joint swelling and tenderness and evaluated the impact of training to standardise methods. Eight observers (medical and nursing staff) examined eight rheumatoid patients for joint swelling and tenderness before and after training in clinical methods. The EULAR handbook for joint evaluation was used for training and assessments were based on the 28 joint count. There was extensive variability in both numbers of swollen and tender joints. Coefficients of variation for articular indices recorded by the 8 observers in individual patients were often high (up to a maximum of 204%), indicating considerable differences between observers. Training had an impact on the assessment of the numbers of swollen joints which increased by a mean of 32% (P<0.05) and the number of tender joints which increased by 41% (p<0.01). Training had only a limited impact on the variation among observers in determining the number of swollen and number of tender joints. After training, the mean coefficients of variation were still 59% for swollen joints and 65% for tender joints. These results highlight the extent of variation in clinical assessment of rheumatoid arthritis and show the advantages of training. It leads to increased sensitivity of measurement. Standardisation appears essential for clinical studies.     

Contrast-enhanced power Doppler sonography of knee synovitis in rheumatoid arthritis: assessment of therapeutic response

The aim of this study was to evaluate the ability of power Doppler sonography (PDS) with ultrasound contrast agent to assess the synovial perfusion changes induced by intra-articular steroid injection therapy in the knee joints of patients with rheumatoid arthritis (RA). Eighteen RA patients (16 women, 2 men) with a history and signs of active knee synovitis were studied. Tenderness was evaluated using Thompsons modified index of synovitis activity. All patients underwent joint aspiration followed by intra-articular injection of 40 mg of triamcinolone hexacetonide. Gray-scale ultrasonography and PDS with an intravenous ultrasound contrast agent (Levovist) examinations were carried out before and 3 weeks after the intra-articular steroid injection. The calculation of the time–intensity curves provided a quantitative estimation of the synovial perfusion. The median values of the index of synovitis activity decreased significantly from 7.0 (95% confidence interval (CI) 6.0–8.0) to 3.0 (95% CI 2.0–4.0) (p<0.01) 3 weeks after the intra-articular steroid injection. All patients showed a reduction of PDS signal after intra-articular steroid therapy and the baseline and follow up median values of the area underlying time–intensity curves were 7.48 (95% CI 5.79–8.73) and 2.45 (95% CI 1.92–3.61), respectively. The comparison between baseline and follow-up median values of the area under the curves showed a statistically significant reduction of PDS findings (p<0.01). At follow-up examinations the changes in the index score of the synovitis activity were significantly correlated to the changes in the values of the area underlying time–intensity curves (r=0.785; p<0.01). A significant correlation was also observed between baseline values of the area underlying time–intensity curves and C-reactive protein (CRP) (r=0.548; p=0.023). In conclusion, PDS with an intravenous ultrasound contrast agent has been shown to be able to detect changes in synovial perfusion after intra-articular steroid injection and may be an additional useful method in the evaluation of synovial inflammation and in the assessment of the therapeutic response.Abbreviations DMARD Disease-modifying anti-rheumatic drugs - NSAID Non-steroidal anti-inflammatory drugs - PDS Power Doppler sonography - RA Rheumatoid arthritis - RF Rheumatoid factor - US Ultrasonography     

Predicting joint destruction in rheumatoid arthritis with power Doppler,anti-citrullinated peptide antibody,and joint swelling

Objective. To determine combined evaluation of musculoskeletal ultrasonography (MSUS) and power Doppler (PD) signals, anti-citrullinated peptide antibody (ACPA), and other clinical findings improve the prediction of joint destruction in rheumatoid arthritis (RA).

Methods. We performed a retrospective study of 331 RA patients (female n = 280 and male n = 51, mean age: 57.9 ± 13.2 years) who underwent MSUS from 2002 to 2012. Correlations with progression of joint destructions in 1,308 2nd and 3rd metacarpophalangeal (MCP) joints and various factors including PD signals of the same joints, clinical findings, age, disease duration at the study entry, gender, observation period, radiographic bone scores according to modified Sharp–van der Heijde methods, ACPA, and rheumatoid factor (RF) were analyzed in patient- and joint-based fashions, using univariate and multivariate logistic regression analyses and generalized linear mixed model.

Results. Patients’ characteristics were as follows: mean disease duration: 5.7 ± 7.5 years, observation period: 4.6 ± 2.6 years, RF positivity: 79.9%, and ACPA positivity: 77.5%. PD-positive 2nd and 3rd joints showed higher rate of joint destruction, especially in ACPA-positive patients. Moreover, PD-positive joints in ACPA-positive patients showed joint destruction even in joints without swelling. Multivariate analysis determined PD, swollen joint (SJ), observation period, basal radiographic bone scores, and ACPA as independent risks for joint destruction.

Conclusion. PD, SJ, basal radiographic bone scores, and ACPA are independent predictors for the joint destruction of 2nd and 3rd MCPs in RA; thus, considering these factors would be useful in daily practice.     

Longitudinal power Doppler ultrasonographic assessment of joint inflammatory activity in early rheumatoid arthritis: predictive value in disease activity and radiologic progression

OBJECTIVE: To evaluate the sensitivity to change of power Doppler ultrasound (PDUS) assessment of joint inflammation and the predictive value of PDUS parameters in disease activity and radiologic outcome in patients with early rheumatoid arthritis (RA). METHODS: Forty-two patients with early RA who started therapy with disease-modifying antirheumatic drugs underwent blinded sequential clinical, laboratory, and ultrasound assessment at baseline, 3 months, 6 months, and 1 year and radiographic assessment at baseline and 1 year. For each patient, 28-joint Disease Activity Score (DAS28) was recorded at each visit. The presence of synovitis was investigated in 28 joints using gray-scale ultrasonography and intraarticular power Doppler signal. Active synovitis was defined as intraarticular synovitis detected with power Doppler signal. The ultrasound joint count for active synovitis and an overall joint index for power Doppler signal were calculated. Sensitivity to change of PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. RESULTS: The SDD for ultrasound joint count for active synovitis and ultrasound joint index for power Doppler signal was lower than mean changes from baseline to 3 months, 6 months, and 1 year. Time-integrated values of PDUS parameters demonstrated a highly significant correlation with DAS28 after 1 year (r = 0.63, P < 0.001) and a stronger correlation with radiographic progression (r = 0.59-0.66, P < 0.001) than clinical and laboratory parameters (r < 0.5). CONCLUSION: PDUS is a sensitive and reliable method for longitudinal assessment of inflammatory activity in early RA. PDUS findings may have a predictive value in disease activity and radiographic outcome.     

Inter- and intra-observer agreement of high-resolution ultrasonography and power Doppler in assessment of joint inflammation and bone erosions in patients with rheumatoid arthritis

To assess the inter- and intra-observer reproducibility of musculoskeletal ultrasonography among rheumatologist in detecting inflammatory and morphostructural changes in small joints of the hands in patients with rheumatoid arthritis (RA). Five members of the “Escuela de Ecografía del Colegio Mexicano de Reumatología” tested their inter- and intra-observer reliabilities in the assessment of basic sonographic findings of joint inflammation and bone erosion. Their results were compared to those obtained by a group of international experts from European League Against Rheumatism. A clinical rheumatologist evaluated eight RA patients. Five Siemens Acuson Antares ultrasound machines (7–13 MHz linear probes) were used. The OMERACT preliminary definitions of joint effusion, synovial hypertrophy, bone erosions and tenosynovitis were adopted. Inter-observer and intra-observer agreement was calculated by overall agreement and kappa statistics. Mean kappa value for joint effusion was good, 0.654 (85%); synovial hypertrophy, 0.550 (77.2%); power Doppler signal, 0.550 (82.5%); bone erosions, 0.549 (81%); and tenosynovitis, 0.500 (91.5%). Mean and overall intra-observer agreement for semiquantitative score was good for joint effusion, 0.630 (77.2%) and bone erosions, 0.605 (56.25%); and moderate to synovial hypertrophy, 0.476 (65%) and power Doppler signal, 0.471 (80%). Mean kappa value for joint effusion was 0.381 (95%), synovial hypertrophy, 0.447 (72%); power Doppler signal, 0.496 (81%); bone erosions, 0.294 (81%); and tenosynovitis, 0.030 (66%). Mean and overall inter-observer agreement for semiquantitative score was poor for joint effusion, 0.325 (57%) and bone erosions, 0.360 (43%); and moderate to synovial hypertrophy, 0.431 (55%) and power Doppler signal, 0.496 (81%). Intra-observer variability reached the highest levels of agreement. Factors related to the experience of the rheumatologist, the time spent in each examination and knowledge of the software ultrasound equipment could influence the lower level of inter-observer agreement in this study.     

Performance of an automated computer-based scoring method to assess joint space narrowing in rheumatoid arthritis: a longitudinal study

OBJECTIVE: To compare the diagnostic performance of a computer-based method for measuring joint space width with the Sharp joint space narrowing (JSN) scoring method in patients with rheumatoid arthritis (RA). METHODS: A random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases. Hand joint space width was measured using an automated, computer-based method in random order and with blinding for clinical information. We constructed a receiver operating characteristic curve and compared the diagnostic performance of the computer-based and Sharp methods based on the areas under the curve. RESULTS: One hundred twenty-nine patients with early RA who underwent serial radiography were included. Changes in the computer-based and Sharp methods were highly correlated (r = 0.75, P < 0.001). The computer-based method was significantly more discriminant than the Sharp JSN subscale. The area under the curve of the computer-based method was 0.96 (95% confidence interval [95% CI] 0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P = 0.024). At the most discriminant cutoff, specificity of the computer-based method was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was 87.6% for the computer-based method compared with 82.2% for Sharp subscale (P = 0.19). The signal-to-noise ratio for the computer-based method was 83% compared with 70% for the Sharp subscale (P = 0.013). CONCLUSION: The computer-based method for measuring joint space width is more discriminant than the semiquantitative Sharp JSN subscale.     

Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience

OBJECTIVE: To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity. METHOD: Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health-visual analogue scale, disability index-Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves. RESULTS: The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables. CONCLUSION: PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.     

A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis

OBJECTIVE: To develop an ultrasonographic (US) synovitis scoring system suitable for evaluation of finger joint inflammation in patients with active rheumatoid arthritis (RA) and to compare semiquantitative US scoring with quantitative US measurements. METHODS: US was performed at the palmar and dorsal sides of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in 10 healthy subjects and in the clinically more affected hand in 46 RA patients. Ten patients additionally underwent magnetic resonance imaging (MRI). Synovitis was measured, standardized, and scored according to a semiquantitative method. The 2 methods (semiquantitative US scoring, quantitative US) were compared and statistical cutoffs were identified using receiver operating characteristic (ROC) curve analysis. MRI results were compared with semiquantitative US scoring and quantitative US results. The optimal US scoring method from 6 joint combinations was identified (ROC curve analysis). RESULTS: Synovitis was most frequently detected in the palmar proximal area (86% of affected joints). We found no significant differences between individual PIP joints or between individual MCP joints, indicating that all fingers within each of these joint groups should be treated equally for statistical calculations, although each joint group as a whole should be treated separately. The optimal cutoff point to distinguish between "health" and "pathology" was 0.6 mm both for MCP joints (sensitivity 94%, specificity 89%) and for PIP joints (sensitivity 90%, specificity 88%). There was no significant difference between semiquantitative US scores and quantitative US measurements. The best results for joint combinations were achieved using the "sum of 4 fingers" (second through fifth MCP and PIP joints) and "sum of 3 fingers" (second through fourth MCP and PIP joints) methods. Comparison of MRI results with semiquantitative US scores revealed high concordance. CONCLUSION: US evaluation of finger joint synovitis can be considerably simplified by focusing on the palmar side and by applying semiquantitative grading instead of quantitative measurements. For evaluation of treatment efficacy based on synovitis in RA patients, we recommend using the "sum of 3 fingers" method in longitudinal trials.     

Finger joint synovitis in rheumatoid arthritis: quantitative assessment by magnetic resonance imaging.

OBJECTIVE: To assess quantitatively, by magnetic resonance imaging (MRI), the synovial membrane volume in second to fifth metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis and healthy controls, and to compare the synovial membrane volumes with a more easily obtained semi-quantitative score for hypertrophic synovial membrane. PATIENTS AND METHODS: MCP joints of the dominant hand of 37 patients and five controls were examined clinically and by MRI. Laboratory assessments were performed. RESULTS: Median synovial membrane volumes were considerably larger in clinically active rheumatoid arthritis (RA) joints (e.g. 0.97 ml in the second MCP joint) than in clinically inactive joints (0.54 ml) and control joints (0.04 ml). Nevertheless, group distributions overlapped and marked volume differences were found within clinically uniform groups. The semi-quantitative score was highly correlated with the synovial volumes (Spearman rho = 0.79; P < 0.00001). Synovial membrane volumes were poorly related to the presence of rheumatoid factor and to laboratory markers of inflammation. CONCLUSION: These findings suggest that synovial membrane volumes, as determined by MRI, in finger joints are related to clinical signs of synovitis, but also that the volumes may vary more than what can be accounted for by the clinical appearances. A semi-quantitative score may be sufficient for more routine purposes.     

Performance of an automated computer‐based scoring method to assess joint space narrowing in rheumatoid arthritis: A longitudinal study

Objective

To compare the diagnostic performance of a computer‐based method for measuring joint space width with the Sharp joint space narrowing (JSN) scoring method in patients with rheumatoid arthritis (RA).

Methods

A random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases. Hand joint space width was measured using an automated, computer‐based method in random order and with blinding for clinical information. We constructed a receiver operating characteristic curve and compared the diagnostic performance of the computer‐based and Sharp methods based on the areas under the curve.

Results

One hundred twenty‐nine patients with early RA who underwent serial radiography were included. Changes in the computer‐based and Sharp methods were highly correlated (r = 0.75, P < 0.001). The computer‐based method was significantly more discriminant than the Sharp JSN subscale. The area under the curve of the computer‐based method was 0.96 (95% confidence interval [95% CI] 0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P = 0.024). At the most discriminant cutoff, specificity of the computer‐based method was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was 87.6% for the computer‐based method compared with 82.2% for Sharp subscale (P = 0.19). The signal‐to‐noise ratio for the computer‐based method was 83% compared with 70% for the Sharp subscale (P = 0.013).

Conclusion

The computer‐based method for measuring joint space width is more discriminant than the semiquantitative Sharp JSN subscale.

     

Anti-CCP status determines the power Doppler oscillation pattern in rheumatoid arthritis: a prospective study

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Serologically, it can be differentiated according to rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), or both. This differentiation is prognostically and therapeutically relevant. No method has been described to separate the two forms phenotypically. We hypothesize that a differentiation is possible by evaluating oscillation patterns in power Doppler sonography (PDS). In a prospective study, 20 patients with anti-CCP-positive RA and 20 patients with anti-CCP-negative RA with active wrist synovitis were examined. A PDS scan was performed, and perfusion maxima (P _max) and minima (P _min) as well as the amplitude (ΔP) were determined by a blinded study member. The amplitude was standardized (sΔP) by dividing by P _max, and the anti-CCP-positive and anti-CCP-negative patients as well as the RF-positive and RF-negative were compared to each other. In the ultrasonographic evaluation, we found a highly significant difference in sΔP between CCPp and CCPn patients (median 19.0 vs. 42.9 %, p < 0.0001). sΔP is independent of disease activity. The absolute amplitude ΔP did not differ between the groups. Also, in anti-CCP-positive patients there was a completely linear correlation between P _max and P _min, and this was far less marked in anti-CCP-negative patients. Anti-CCP-positive and anti-CCP-negative RA display different PDS oscillation patterns. This constitutes a nonserological parameter to differentiate between the two forms. The difference in PDS oscillation patterns suggests that the underlying pathological process differs between the forms.