E. Qvistgaard

Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Doppler technique

OBJECTIVE To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis. METHODS Ultrasonography was performed with a high frequency transducer (13 MHz).  Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI). RESULTS The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82–0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow—that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) (r s=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR (r s=−0.557, p<0.05) and Health Assessment Questionnaire score (r s=−0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. CONCLUSION Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis.

Estimation of inflammation by Doppler ultrasound: quantitative changes after intra-articular treatment in rheumatoid arthritis

Objective: To evaluate the use of ultrasound, including quantitative Doppler analysis of synovial vascularisation, before and after intra-articular treatment with glucocorticosteroids in patients with rheumatoid arthritis (RA). Methods: 51 patients with RA were followed prospectively after an intra-articular glucocorticosteroid injection. Disease modifying antirheumatic drug treatment was kept unchanged and no further injections given in this observation period. At baseline, disease activity was estimated clinically by target join pain on a 100 mm visual analogue scale, on which the target joint was scored 0–3 for swelling and tenderness, and by ultrasound measurements of grey scale pixels, colour Doppler pixels, and the spectral Doppler resistive index (RI) as indicators of synovial swelling and inflammation. After four weeks, the measurements were repeated on the same joint. An observer unaware of the sequence and patient number evaluated the ultrasound images. Results: At one month follow up after the glucocorticosteroid injection, a marked decrease in the fraction of colour pixels was seen in 41/51 patients (Student’s t test p<0.001). Correspondingly, the RI increased indicating a diminished flow to the synovium (Student’s t test p<0.01). Both the fraction of colour pixels and the RI values corresponded with the clinical evaluation and with the subjective effect of the treatment. The synovial membrane volume estimated by total amount of pixels showed a significant decrease by 31% after treatment. Conclusion: Ultrasound-Doppler seems to be a promising tool for the estimation of synovial activity in arthritis. After intra-articular glucocorticosteroid, changes in RI and fraction of colour pixels may both be used as quantitative measurements of the blood flow.

Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography

Objective: to estimate and visualise the efficacy of treatment with etanercept (Enbrel) in patients with rheumatoid arthritis (RA) using colour Doppler and spectral Doppler ultrasonography to determine the possible changes in synovial perfusion during a one year observation period. Methods: Eleven patients from the European multicentre trial of the efficacy and safety of etanercept were included in this study when transferred into the open label, long term safety, and efficacy study. Before a scheduled dosage increase to 50 mg/week they were examined clinically, serologically, and by ultrasonography using the colour Doppler pixels and the spectral Doppler resistance index (RI) as indicators of inflammation. The patients were re-examined at two weeks and at one year follow up Results: The clinical activity decreased significantly from baseline to week 2, but no significant changes were seen from baseline to one year. The number of coloured pixels in each region of interest decreased from baseline to week 2 with a median reduction of 60% (p=0.005). This effect on the perfusion in the synovium could not be found after one year of treatment. During the initial treatment we detected an increase in synovial RI by spectral Doppler. The median increase in peripheral resistance from baseline to week 2 as estimated by the mean RI was 22.6% (p=0.005). The increase in peripheral resistance was maintained to some extent after one year (mean RI increased by 18.8% p=0.074). Conclusion: Ultrasonography seems to be a promising tool for the detection of treatment response using spectral Doppler and pixel estimation.

Ultrasound and Power Doppler findings in jumper's knee - preliminary observations.

OBJECTIVE to examine a group of high risk athletes, for signs of inflammation in jumpers knee (JK) by gray-scale ultrasonography (US) and color/Power Doppler findings in JK. SUBJECTS AND METHODS eighteen high-elite basketball players participated in the investigation after a match. Seven players were examined by ultrasound before the match as well. The players were clinically examined for signs of JK and filled in a questionnaire concerning previous and present knee symptoms. RESULTS clinical signs of JK were found in 13 knees. Of these knees, ten had hypoechoic areas and six had Power Doppler flow. Four players reported symptoms of JK and clinical examination suspected the same. Three of them had both hypoechoic areas and Power Doppler flow. Fourteen players were asymptomatic at the time of examination but both hypoechoic areas and Power Doppler flow was found in the patellar tendons of four players. No correlation was found between clinical findings, symptoms of JK and US findings - including Power Doppler. The risk of type II error in this material is considerable. CONCLUSION an association between gray-scale US and color/Power Doppler was found in JK which may suggest an inflammatory component to be a part of the pathogenesis of JK.

A randomized, controlled study of a single intra-articular injection of etanercept or glucocorticosteroids in patients with rheumatoid arthritis.

Objective: Glucocorticosteroids are used successfully for both systemic and intra‐articular treatment of arthritis. Inhibitors of tumour necrosis factor alpha (TNF‐α) are effective when administered systemically and this study was performed to compare the effect of intra‐articular injection of these two substances. Design: A randomized, parallel‐group, double‐blind study with an independent observer. Thirty‐eight patients with flare of arthritis in a single joint (wrist, elbow, or knee) were given intra‐articular 25 mg etanercept or 40 mg methylprednisolone guided by ultrasound. The primary end‐point was the 4‐week change in pain in the target joint. The study complied with Good Clinical Practice (GCP) and the Consolidated Standards for Reporting of Trials (CONSORT) statement. Results: At 4 weeks no difference in pain outcome between treatment groups was demonstrated by analysis of covariance (ANCOVA). Pain on the Visual Analogue Scale (VAS) for etanercept was baseline mean 40.9 (SD 19.6) mm, follow‐up 32.7 (29.1) mm (p = 0.29), methylprednisolone baseline mean 47.1 (29.6) mm, follow‐up 25.3 (24.7) mm (p<0.001). The investigators evaluation was for etanercept baseline 30.6 (21.2) mm, follow‐up 17.1 (15.5) mm (p = 0.054) and for methylprednisolone baseline 35.4 (26.4) mm, follow‐up 11.9 (14.6) mm (p = 0.012). Joint swelling was for etanercept baseline 1.78 (0.73), follow‐up 1.25 (0.77) (p = 0.015) and for methylprednisolone baseline 1.74 (0.73), follow‐up 0.71 (0.77) (p<0.001). One serious adverse event was seen in a patient treated with methylprednisolone injection. Conclusion: Although no difference between groups was demonstrated, the within‐group effect of methylprednisolone was more marked than that of etanercept. Injections with 25 mg etanercept were well tolerated. However, the cost of etanercept will presumably limit its use to patients with adverse reactions to steroid.

Preliminary results of colour Doppler-guided intratendinous glucocorticoid injection for Achilles tendonitis in five patients.

Background: It is debated as to whether Achilles tendonitis (AT) has an inflammatory component. The intratendinous hyperaemia demonstrated with colour Doppler has been interpreted as neovascularisation. Glucocorticoid injection around the tendon is a common therapeutic procedure.

Reproducibility and inter-reader agreement of a scoring system for ultrasound evaluation of hip osteoarthritis

Objective: To evaluate the intra-reader and inter-reader agreements of ultrasonographic assessments of hip joints in patients with hip osteoarthritis. Design: Ultrasonography was performed on 100 patients with hip osteoarthritis at 14 MHz using a 8–15 MHz linear probe. Dynamic sweeps of the hip and representative still images were used for the analysis. A semiquantitative grading score was introduced in the evaluation of the ultrasound pictures and compared with an overall ultrasound evaluation. The evaluation was performed by a specialist in ultrasonography and a rheumatologist trained in musculoskeletal ultrasound examination. Clinical pain assessment and joint aspiration were obtained in parallel with the ultrasonography. Results: Intraobserver agreement represented by intraclass correlation coefficients (ICC) (exact agreement in percentage; unweighted κ values) showed good to excellent correlation, 0.8 with regard to the osteophyte score, 0.78 with regard to the femoral head score, 0.71 with regard to the fluid score and 0.69 with regard to the synovial profile score. Interobserver agreement was fair to good with corresponding ICC 0.65, 0.63, 0.45 and 0.6, respectively. In comparison, the ICC for the global osteoarthritis and synovial assessments were 0.7 and 0.72, respectively, for the intraobserver rating and 0.56 and 0.58, respectively, for the interobserver rating. Conclusions: This study suggests that ultrasound is a reproducible method for the assessment of changes in the osseous surface and synovium-related inflammation. The semiquantitative scoring system presented seemed to match the global assessment of a trained ultrasound investigator and might be used by less-trained investigators.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging (dGEMRIC) of Hip Joint Cartilage: Better Cartilage Delineation after Intra-Articular than Intravenous Gadolinium Injection

Purpose: To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. Material and Methods: In 10 patients (50% males, mean age 58 years) with clinical and radiographic hip osteoarthritis (OA; Kellgren score II–III), MRI of the hip was performed twice on a clinical 1.5T MR scanner: On day 1, before and 90–180 min after 0.3 mmol/kg body weight i.v. Gd-DTPA and, on day 8, 90–180 min after ultrasound-guided i.a. injection of a 4 mmol/l Gd-DTPA solution. Coronal STIR, coronal T1 fat-saturated spin-echo, and a cartilage-sensitive gradient-echo sequence (3D T1 SPGR) in the sagittal plane were applied. Results: Both the post-i.v. and post-i.a. Gd-DTPA images showed significantly higher signal-to-noise (SNR) and contrast-to-noise (CNR) in the joint cartilage compared to the non-enhanced images (P<0.002). I.a. Gd-DTPA provided significantly higher SNR and CNR compared to i.v. Gd-DTPA (P<0.01). Furthermore, a better delineation of the cartilage in the synovial/cartilage zone and of the chondral/subchondral border was observed. Conclusion: The dGEMRIC MRI method markedly improved delineation of hip joint cartilage compared to non-enhanced MRI. The i.a. Gd-DTPA provided the best cartilage delineation. dGEMRIC is a clinically applicable MRI method that may improve identification of early subtle cartilage damage and the accuracy of volume measurements of hip joint cartilage.

Spectral Doppler and resistive index: A promising tool in ultrasonographic evaluation of inflammation in rheumatoid arthritis

Purpose: To evaluate the use of spectral Doppler in the longitudinal follow-up of inflammatory joint involvement in rheumatoid arthritis (RA) by comparing resistive index (RI) findings with color fraction and pain on a visual analog scale (VAS). Material and Methods: Five patients on unchanged disease modifying anti-rheumatic drugs (DMARD) treatment were followed after an intra-articular corticosteroids injection and received no further injections in the observation period. They were followed clinically and by ultrasound using color Doppler pixels and the spectral Doppler RI as indicators of inflammation. At 1, 6 and 12 months the measurements were repeated on the same joint. Results: At 1-month follow-up after the corticosteroids injection, a marked decrease in the color fraction was seen in 4 out of 5 patients, while the fifth patient had a moderate decrease (Wilcoxon p < 0.05). The changes in RI showed correspondingly a marked increase in 4 out of 5 patients indicating a diminished flow to the synovium (Wilcoxon p < 0.05). The effect of the corticosteroid injection could still be seen after 1 year in 4 out of 5 patients. In RI, pixel fraction and VAS there was improvement compared with the baseline values; however, only the pixel fraction was statistically significant (Wilcoxon p < 0.05). Conclusion: RI seems to be an objective alternative to pixel estimation of the degree of inflammation and treatment response in RA.

Effect of glucocorticosteroid injections in tennis elbow verified on colour Doppler ultrasonography: evidence of inflammation

Objectives: It has previously been reported that lateral epicondylitis may be diagnosed with colour Doppler ultrasonography (US) by detecting hyperaemia inside the common extensor origin (CEO).This study reports on the association between Doppler US findings and the short-term response of US-guided corticosteroid injection in patients with LE. Design: Case-only, blinded intervention study. Setting: Secondary care at a government hospital. Patients: 62 patients with LE verified by colour Doppler US. Intervention: One US-guided corticosteroid injection was given into the CEO. Main outcome measures: Patients were evaluated at baseline before the injection and at 2 weeks of follow-up. Outcome measures were changes in pain score and US parameters (resistive index (RI) and the amount of colour within the CEO). Prognosticators for outcome were: use of computer mouse, symptom duration, elbow strain, RI, colour fraction, Likert pain score, pain at rest, pain during activity, age, height, weight, disease in dominant versus nondominant arm. Results: All but one patient experienced improvement of general elbow pain perception at follow-up at 2 weeks. In parallel, Doppler US showed significant reduction in colour fraction (mean (standard deviation) with 95% confidence limits: baseline 0.14 (0.10), at follow-up 0.02 (0.02), p<0.0001). All but five patients showed a decrease in colour fraction; 74% decreased to 0. No clinical or US parameter could distinguish responders from non-responders. Conclusion: Corticosteroid injection has a marked short-term effect on pain and Doppler parameters. The reduction in hyperaemia mediated by an anti-inflammatory drug can be interpreted as evidence of an inflammatory component in LE.