Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI.

OBJECTIVES: To evaluate contrast-enhanced ultrasound (CE-US) as a monitoring tool to assess hypervascularisation of synovial processes in knee osteoarthritis (OA) treated with intra-articular injections of the bradykinin-receptor 2 antagonist icatibant compared to contrast-enhanced magnetic resonance imaging (CE-MRI). PATIENTS AND METHODS: In a randomised, double-blind, placebo-controlled trial, 41 patients with painful knee OA underwent US (12.5 MHz for B-mode and 3-8 MHz for CE-US), and 36 of the patients underwent additional MRI (0.2T) at baseline and after 3 injections of the study drug (after a mean of 22.2 days). A total of 15 patients received placebo (group A), 12 patients 500 microg icatibant (group B) and 14 patients 2000 microg icatibant (group C). Pain and the synovial process (B-mode, power Doppler US (PD-US), CE-US, CE-MRI) were assessed at both time points. RESULTS: At baseline, the placebo group showed more activity in terms of effusion in the superior and lateral recess in ultrasound as well as in PD-US in the lateral recess. Pain improved significantly in all subgroups. Effect sizes were 0.43 (pain at rest) and 0.52 (pain during activity) in group B vs 0.48 and 1.11 in group C. There was no change of US and MRI parameters. We found moderate to good correlation (r) and kappa values (kappa) for effusion in the superior recess (r = 0.591, k = 0.453), effusion in the lateral recess (r = 0.304, k = 0.440) and contrast enhancement (r = 0.601, k = 0.242) between US and MRI. CONCLUSIONS: Our results show that CE-US and CE-MRI have good agreement in assessing inflammatory changes in knee OA. For the 41 patients with OA, an analgesic effect of icatibant could clearly be shown, especially for pain during activity in the high dose icatibant group. However, we could not find an anti-inflammatory effect of icatibant by CE-US compared to CE-MRI.

Knee osteoarthritis. Efficacy of a new method of contrast-enhanced musculoskeletal ultrasonography in detection of synovitis in patients with knee osteoarthritis in comparison with magnetic resonance imaging.

OBJECTIVE: To develop a new method of digital synovial vascularisation quantification by using contrast-enhanced musculoskeletal ultrasonography (MUS) in detecting synovitis in patients with knee osteoarthritis (OA) compared with healthy subjects and MRI. METHODS: Evaluation of 41 patients with painful knee OA and 6 healthy subjects. The severity of knee pain was evaluated. All patients and all 6 healthy subjects underwent contrast medium-enhanced (CE)-MUS with SonoVue, and 36 patients additionally underwent CEMRI with Magnevist. Joint effusion, synovial thickening and pain were assessed and compared with B-mode and Power Doppler sonography (PDS) as well as contrast medium enhancement. RESULTS: Pain evaluated by the visual analogue scale(VAS) hardly correlated with other markers of disease activity measured by ultrasound (US) in B-mode or MRI. US of the superior recess revealed an effusion or synovial thickening in 58%. PDS findings were positive in 63%, and CE-MUS in the superior knee recess was positive in 95%. MRI showed effusion in the superior recess in 61% and showed positive findings in 82% when using contrast medium. The kappa value was 0.48 between US and MRI with regard to the effusion in the superior recess, and 0.53 between PD signal in the superior recess and effusion in the superior recess by US. Using MRI as the reference standard, there was a sensitivity of 72% for assessing effusion in the superior recess and 81% for assessing effusion in the lateral recess. CONCLUSION: Assessment of disease activity (synovitis) in knee OA by VAS is not sufficient. US PDS was more sensitive than B-mode, and CE-MUS was more sensitive than PDS and CE-MRI in detecting synovitis in patients with painful knee OA. Also, CE-MRI was more sensitive in detecting inflammatory changes in the superior recess than without contrast medium. Using CE-MUS and performing time/intensity analysis has shown to be a good model for evaluation of an inflammatory process in the setting of knee OA in the superior recess.

[New developments in joint ultrasonography]. / Neue Entwicklungen in der Gelenksonographie.

Musculoskeletal ultrasonography has become an established imaging technique in rheumatology. The ability of ultrasonography to visualize soft tissue changes provides a possibility for differentiating between exudative and proliferative synovial tissue changes. Superficial cartilage and bone lesions can be detected earlier by ultrasonography than by conventional radiography. The application of Doppler and power Doppler ultrasonography is helpful for the detection of early inflammation. Current studies with ultrasound contrast media demonstrate its benefit in the differentiation of inflammatory processes. Musculoskeletal ultrasonography is helpful in the diagnosis of early arthritis, especially in patients with inconspicuous conventional radiography or suspicious clinical findings. It is a convenient method for follow-up analysis, and therefore has an impact on the monitoring of therapy. It is patient-friendly and is an important tool for the diagnostic work-up of arthritis.

Bioimpedance analysis and intradialytic hypotension in intermittent hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is one of the most severe complications during hemodialysis. Its appearance is caused in part by rapid fluid removal with concomitant failure in blood pressure regulation but also by other dialytic-dependent and independent factors. PATIENTS AND METHODS: We investigated total (TBW), extracellular (ECW) and intracellular water (ICW) in chronic intermittent hemodialysis dialysis hypotension-prone (CRF-HP, n = 11) and nonhypotension-prone (CRF-NHP, n = 10) patients with end-stage renal disease before, every 30 minutes during, as well as after dialysis and within onset of intradialytic hypotension by multifrequent bioimpedance analysis (BIA). Additionally, intradialytic time course of BIA in patients with acute renal failure (ARF) and septic shock (n = 10) was observed. RESULTS: IDH occurred in 72.1% of CRF-HP and in 80% of ARF patients. In CRF-HP and CRF-NHP, ECW significantly decreased by -12.44 +/- 4.22% in CRF-HP and -9.0 +/- 6.2% in CRF-NHP comparing pre- and post-dialysis values (each p < 0.01). Conversely, ICW increased by +11.5 +/- 11.3% in CRF-HP and +18.4 +/- 25.2% in CRF-NHP (each p < 0.05). In patients with ARF no significant changes could be detected. Calculated ECW/ICW and ECW/TBW ratio significantly decreased in CRF patients with a higher rate in CRF-HP patients (p < 0.05). Neither ECW/ICW nor ECW/TBW ratio correlated with mean arterial pressure. The onset of intradialytic hypotension (n = 35) did not differ intraindividually compared to normotensive periods (n = 411). Fluid removal in CRF patients seems to be mainly from the extracellular space. The reduced decreases in ECW/ICW and ECW/TBW ratios in CRF-HP compared to CRF-NHP may indicate an insufficient refilling from intra- to extracellular compartment in CRF-HP. CONCLUSION: In conclusion, multifrequent BIA is not capable to predict hypotension in the individual patient during a particular dialysis session.

Low-field MRI for assessing synovitis in patients with rheumatoid arthritis. Impact of Gd-DTPA dose on synovitis scoring.

OBJECTIVE: To investigate the impact of a double dose compared to a single dose of contrast material in low-field magnetic resonance imaging (MRI) on semi-quantitative scoring of synovitis in patients with rheumatoid arthritis (RA). METHODS: This prospective study included 38 RA patients (23 women and 15 men, mean age 51 years). All patients underwent low-field MRI of the hand before administration of contrast medium, after intravenous injection of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), and after another dose of 0.1 mmol/kg Gd-DTPA. Two readers (A and B) blinded to dosage independently scored the single dose and double dose image sets for synovitis according to outcome measures in rheumatology (OMERACT) recommendations. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were also calculated for each set. RESULTS: 149 metacarpophalangeal (MCP) joints were evaluated. There was good inter-reader agreement for each of the two sets (intra-class correlation coefficient of 0.75 for the single dose set and 0.83 for the double dose). Median CNR and SNR values were 5.4 and 15.9, respectively, for the single dose set and 8.5 and 16.6, respectively, for the double dose set (p<0.0001). Single dose set mean synovitis scores were 1.7 and 1.6 for readers A and B, respectively. Double dose set scores were 1.9 and 2.0, respectively. Thus, higher synovitis scores were recorded for the double dose sets than the single dose sets (p<0.005). CONCLUSION: In low-field MRI, when evaluating RA, the dose of the contrast material influences synovitis scoring. Therefore, dosage of contrast material should be taken into consideration when using extremity dedicated low-field MRI.

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

[Role of imaging methods in the early diagnosis of rheumatoid arthritis]. / Frühdiagnostik der rheumatoiden Arthritis: Sono und MRT dem Röntgen übberlegen.

Because of the good contrast obtained in soft tissues, ultrasound permits differentiation of the exudative and proliferative synovial tissue changes, as well as tenosynovitis. Superficial cartilage and bone lesions or erosions can be detected through ultrasound earlier than with conventional radiodiagnostics. The use of power Doppler sonography with ultrasound contrast agents is especially helpful in the further differentiation of the synovial inflammatory process and hence, progression of the destructive processes in the joint can be more clearly evaluated. Arthrosonography aids in the diagnosis of early arthritis, particularly in patients without pathological radiological findings and suspicious clinical results. Moreover, it permits sound assessment of the disease progression and hence, therapeutic monitoring. The method is patient friendly, has high diagnostic value and is an integral component in the clarification of arthritic symptoms.

Interobserver reliability in musculoskeletal ultrasonography: results from a "Teach the Teachers" rheumatologist course.

OBJECTIVE: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. METHODS: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients' clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. RESULTS: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; kappa values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. CONCLUSIONS: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

Prospective 7 year follow up imaging study comparing radiography, ultrasonography, and magnetic resonance imaging in rheumatoid arthritis finger joints.

OBJECTIVE: To perform a prospective long term follow up study comparing conventional radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI) in the detection of bone erosions and synovitis in rheumatoid arthritis (RA) finger joints. METHODS: The metacarpophalangeal and proximal interphalangeal joints II-V (128 joints) of the clinically dominant hand of 16 patients with RA were included. Follow up joint by joint comparisons for erosions and synovitis were made. RESULTS: At baseline, CR detected erosions in 5/128 (4%) of all joints, US in 12/128 (9%), and MRI in 34/128 (27%). Seven years later, an increase of joints with erosions was found with CR (26%), US (49%) (p<0.001 each), and MRI (32%, NS). In contrast, joint swelling and tenderness assessed by clinical examination were decreased at follow up (p = 0.2, p<0.001). A significant reduction in synovitis with US and MRI (p<0.001 each) was seen. In CR, 12 patients did not have any erosions at baseline, while in 10/12 patients erosions were detected in 25/96 (26%) joints after 7 years. US initially detected erosions in 9 joints, of which two of these joints with erosions were seen by CR at follow up. MRI initially found 34 erosions, of which 14 (41%) were then detected by CR. CONCLUSION: After 7 years, an increase of bone erosions was detected by all imaging modalities. In contrast, clinical improvement and regression of synovitis were seen only with US and MRI. More than one third of erosions previously detected by MRI were seen by CR 7 years later.

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course.

OBJECTIVE: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging "gold standard". METHODS: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. RESULTS: Taking an agreement in US examination of 10 out of 14 experts into account, the overall kappa for all examined joints was 0.76. Calculations for each joint region showed high kappa values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). kappa Values for bone lesions, bursitis, and tendon tears were high (kappa = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). CONCLUSION: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

[Erdheim-Chester disease]. / Erdheim-Chester-Krankheit.

HISTORY AND CLINICAL FINDINGS: A 55-year-old female was admitted complaining of musculoskeletal pain and weakness of both lower extremities for a number of years. Due to a hypothalamic mass of unknown aetiology a diabetes insipidus, a gonadotrophic, somatotrophic and a partially corticotrophic insufficiency had developed. INVESTIGATIONS: Laboratory investigations yielded elevated levels of several inflammatory parameters (C-reactive protein, blood sedimentation rate, fibrinogen and thrombocytes). Serological parameters indicating a systemic rheumatic disorder were absent. X-ray examination revealed combined osteolytic and osteoblastic lesions within the distal parts of both femora and within the proximal portions of both tibiae. MRI showed signal alterations and (99m)Technetium bone scan exhibited a considerably increased uptake. Histopathologically, a biopsy of the left tibia showed multifocal small infiltrates of foamy histiocytes indicating Erdheim-Chester disease (ECD). TREATMENT AND COURSE: Under treatment with glucocorticosteroids musculoskeletal complaints improved, but re-appeared following dose reduction. A therapeutic trial using methotrexat did not affect the complaints. CONCLUSION: The Erdheim-Chester syndrome is considered to belong to diseases with a proliferation of the monocytic-histiocytic and dendritic cellular system. In the presence of symmetric musculoskeletal symptoms associated with osteosclerotic and osteolytic lesions particularly occurring in the long bones of the lower extremities and concomitant with elevated serum markers of inflammation, the Erdheim-Chester disease should be taken into account. To date, no validated therapy exists.

First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints.

OBJECTIVE: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. METHODS: 78 SLOT images of proximal interphalangeal joints II-IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. RESULTS: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. CONCLUSION: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.

Diagnosis and follow up of aortitis in the elderly.

OBJECTIVES: To evaluate the correlation of MRI and [(18)F]FDG-PET scans with the clinical course and inflammatory markers in patients with aortitis. METHODS: Eight patients with aortitis presenting with unspecific GCA-like symptoms were examined. Aortitis was diagnosed and followed up by [(18)F]FDG-PET and MRI. The aorta was divided into three vascular regions (ascending aorta, aortic arch, and descending aorta) to localise the aortic inflammation and compare both imaging techniques. RESULTS: were correlated with clinical and laboratory examinations. RESULTS: At diagnosis, 20/24 vascular regions from eight patients were positive by [(18)F]FDG-PET scan and 15/21 aortic regions by MRI. Patients were treated with corticosteroids and followed up for a mean (SD) of 13.3 (4.7) months. In [(18)F]FDG-PET, 11/20 (55%) initially pathological aortic regions returned to normal in the follow up examination, which correlated closely with the clinical and laboratory follow up examination. Conversely, in MRI, 14/15 initially affected vascular regions were unchanged. CONCLUSIONS: [(18)F]FDG-PET and MRI are both effective techniques for detecting early aortitis and have a high correlation with laboratory inflammatory measures. However, during the follow up examination, [(18)F]FDG-PET uptake decreased in line with the clinical symptoms and inflammatory serum markers, whereas MRI scans gave more static results.

[Detection of fasciculations and other types of muscular hyperkinesias with ultrasound]. / Sonographische Darstellung von Faszikulationen und anderen Formen muskulärer Hyperkinesen.

Muscular hyperkinesias can be visualized by means of ultrasound (US): Ultrasonographic detection of fasciculations has been best evaluated. However, so-called ripplings, myoclonias and choreatic hyperkinesias as well as tremores can also be visualized by US. Muscular US has proven as a precise imaging technique for the detection of fasciculations. Fasciculations are brief, localized muscle twitches, usually lasting for 0.2 - 0.5 seconds. Some myoklonias may present similar in US, others present with a longer duration. In addition, muscle US allows a very easy and reliable detection of tremor frequency. This article reviews the present ultrasonographic facilities in the detection of muscular hyperkinesias and gives future perspectives.

Benign prostatic hyperplasia (BPH) requiring transurethral resection in freshly transplanted renal allograft recipients.

With recent progress in surgery and immunosuppression, more and more older men receive a kidney transplant. Thus, it is likely that the incidence of BPH in male transplant recipients is growing in parallel with age. Nonetheless, no data exist about diagnostic parameters for BPH in freshly transplanted male kidney allograft recipients. We evaluated whether established diagnostic and therapeutic criteria for BPH are valid for the evaluation of renal transplant recipients. BPH was diagnosed in 8 of 11 recipients older than 55 years. In all freshly transplanted renal allograft recipients, lower urinary tract symptoms (LUTS) were detected using an international prostate symptoms score (IPSS). This score was 9.6 +/- 7.1 in patients without BPH, and significantly higher with 21.1 +/- 4.3 in patients with BPH. In receiver-operating characteristics (ROC) curve analysis a cut-off of 15.5 was calculated to distinguish best between BPH and non-BPH giving an accuracy of 90.2%. Acute urinary retention (AUR) was the predominant sign, which occurred in all BPH patients but only in 6.9% in non-BPH patients. Bladder outlet obstruction (BOO) was also common with a reduced uroflow with 9.5 +/- 2.2 ml/sec in non-BPH and 3.0 +/- 1.8 ml/sec in BPH (8/11 BPH-patients developed AUR prior to measurement). By digital rectal examinations, benign prostate enlargement was estimated as minimal in 10 of 11 cases of BPH. In urethrocystoscopy kissing lobes were detected in all cases of BPH. Since medical treatment with alpha-receptor antagonists was not successful, a surgical procedure using a transurethral resection was performed without any complications in all cases. Symptoms did not recur after resection, and BOO improved with increased uroflow measurements with 12.3 +/- 4.8 ml/sec 8 days after resection. We conclude that LUTS and BOO are common in freshly transplanted renal allograft recipients. The sudden onset of outlet obstruction without the potentiality of adaptation of urinary bladder may effect lower urinary tract symptoms and bladder outlet obstruction. We conclude that an elevated IPSS over 15.5 in combination with AUR and typical urethrocystoscopy results are the best methods to diagnose BPH. Conversely, our results indicate that uroflowmetry and digital rectal examination are neither sensitive nor specific. In addition, once BPH has been diagnosed and treatment with receptor antagonists does not relieve urinary tract symptoms, surgical resection should be considered.

Ultrasonographic assessment of the prevalence of fasciculations in lesions of the peripheral nervous system.

In previous studies, ultrasonography was a very sensitive method in detecting fasciculations. The present study was intended to examine the prevalence of ultrasonographically visible fasciculations in patients with neuromuscular diseases affecting the lower extremities. Ultrasonography of 9 muscles (rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, semitendinosus, tibialis anterior, gastrocnemius, and soleus muscles) was performed bilaterally in 70 adult healthy subjects and 172 patients with various neuromuscular diseases. Fasciculations were detected in 109 (63%) of 172 patients. The median value of affected muscles was 10 (range 1-18). Patients with spinal muscular atrophy (37/38, p < 0.001), hereditary motor and sensory neuropathy (24/25, p < 0.001), and lumbosacral radiculopathy with motor deficits (24/29, p < 0.001) exhibited fasciculations more frequently than did healthy volunteers. Radiculopathy with sensory deficits, lesions of either plexus or peripheral nerves, compartment syndrome, and myopathy were not associated with a significantly enhanced prevalence of fasciculations in the patient group compared to the control group. In summary, fasciculations are a frequent ultrasonographic sign in neuromuscular diseases. They are almost regularly found in patients with spinal muscular atrophy and those with hereditary motor and sensory neuropathy. Thus, the absence of fasciculations in ultrasonographic assessment should give cause for reconsidering these diagnoses.