Luca Ciprian

Improved detection of synovial boundaries in ultrasound examination by using a cascade of active-contours

Rheumatoid arthritis (RA) is a chronic multisystemic autoimmune disease, with an unclear etiopathogenesis. Its early diagnosis and activity assessment are essential to adjust the proper therapy. Among the different imaging techniques, ultrasonography (US) allows direct visualization of early inflammatory joint changes as synovitis, being also rapidly performed and easily accepted by patients. We propose an algorithm to semi-automatically detect synovial boundaries on US images, requiring minimal user interaction. In order to identify the synovia-bone and the synovia-soft tissues interfaces, and to tackle the morphological variability of diseased joints, a cascade of two different active contours is developed, whose composition corresponds to the whole synovial boundary. The algorithm was tested on US images acquired from proximal interphalangeal (PIP) and metacarpophalangeal (MCP) finger joints of 34 subjects. The results have been compared with a consensus manual segmentation. We obtained an overall mean sensitivity of 85±13%, and a mean Dices similarity index of 80±8%, with a mean Hausdorff distance from the manual segmentation of 28±10 pixels (approximately 1.4±0.5mm), that are a better performance than those obtained by the raters with respect to the consensus.

Evaluation of Finger Joint Synovial Vascularity in Patients with Rheumatoid Arthritis Using Contrast-Enhanced Ultrasound with Water Immersion and a Stabilized Probe

To assess synovial microvascularity in finger joints with rheumatoid arthritis (RA) by contrast‐enhanced ultrasound (CEUS), distinguishing between cases of active disease and those in remission; to standardize the technique for software analysis.

Effects of mud-bath therapy in psoriatic arthritis patients treated with TNF inhibitors. Clinical evaluation and assessment of synovial inflammation by contrast-enhanced ultrasound (CEUS).

OBJECTIVES Despite the efficacy of TNF inhibitors, most patients with psoriatic arthritis maintain a residual synovial inflammation. The main aim of the study was to evaluate the effects of mud-bath therapy on clinical picture of PsA patients treated with TNF inhibitors. The secondary outcome was to assess synovial inflammation in hand joints detected by contrast-enhanced ultrasound. Other aims were to verify the risk of arthritis flare and to evaluate the effects of spa treatment on functional ability and on quality of life. METHODS Thirty-six patients with psoriatic arthritis, treated in the last 6 months with TNF inhibitors, were enrolled. After 1:1 randomisation, 18 patients (group A) underwent mud-bath therapy (12 mudpacks and 12 thermal baths), maintaining treatment with TNF inhibitors; 18 patients (group B) continued pharmacological therapy alone. CRP, PASI, DAS28, swollen and tender joint count, VAS pain, HAQ and SF-36 were evaluated at baseline (T0) and after 45 days (T1). Synovial inflammation detected by contrast-enhanced ultrasound, analysed by a software system, was also assessed. RESULTS A significant improvement in PASI (P<0.005), DAS28 (P<0.05), swollen joint count and tender joint count (P<0.001), and HAQ (P<0.001) between T0 and T1 was observed in group A. No patient underwent a flare-up of arthritis. Ultrasound videos demonstrated a significant appearance delay (P<0.05) and faster washout (P<0.02) of contrast dye in group A patients with respect to group B. CONCLUSIONS These data suggest a decrease of residual synovial inflammation and a beneficial clinical effect of spa therapy in psoriatic arthritis patients treated with TNF inhibitors.

Pixel-based approach to assess contrast-enhanced ultrasound kinetics parameters for differential diagnosis of rheumatoid arthritis

Abstract. Inflammatory rheumatic diseases are the leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity, and increased mortality. The standard for diagnosing and differentiating arthritis is based on clinical examination, laboratory exams, and imaging findings, such as synovitis, bone edema, or joint erosions. Contrast-enhanced ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. Quantitative assessment is mostly performed at the region of interest level, where the mean intensity curve is fitted with an exponential function. We showed that using a more physiologically motivated perfusion curve, and by estimating the kinetic parameters separately pixel by pixel, the quantitative information gathered is able to more effectively characterize the different perfusion patterns. In particular, we demonstrated that a random forest classifier based on pixelwise quantification of the kinetic contrast agent perfusion features can discriminate rheumatoid arthritis from different arthritis forms (psoriatic arthritis, spondyloarthritis, and arthritis in connective tissue disease) with an average accuracy of 97%. On the contrary, clinical evaluation (DAS28), semiquantitative CEUS assessment, serological markers, or region-based parameters do not allow such a high diagnostic accuracy.

A comparison of region-based and pixel-based CEUS kinetics parameters in the assessment of arthritis

Inflammatory rheumatic diseases are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity and increased mortality. The gold-standard for diagnosing and differentiating arthritis is based on patient conditions and radiographic findings, as joint erosions or decalcification. However, early signs of arthritis are joint effusion, hypervascularization and synovial hypertrophy. In particular, vascularization has been shown to correlate with arthritis’ destructive behavior, more than clinical assessment. Contrast Enhanced Ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. The evaluation of perfusion pattern rely on subjective semi-quantitative scales, that are able to capture the macroscopic degree of vascularization, but are unable to detect the subtler differences in kinetics perfusion parameters that might lead to a deeper understanding of disease progression and a better management of patients. Quantitative assessment is mostly performed by means of the Qontrast software package, that requires the user to define a region of interest, whose mean intensity curve is fitted with an exponential function. We show that using a more physiologically motivated perfusion curve, and by estimating the kinetics parameters separately pixel per pixel, the quantitative information gathered is able to differentiate more effectively different perfusion patterns. In particular, we will show that a pixel-based analysis is able to provide significant markers differentiating rheumatoid arthritis from simil-rheumatoid psoriatic arthritis, that have non-significant differences in clinical evaluation (DAS28), serological markers, or region-based parameters.

Toward Early Detection and Differentiation of Arthritic diseases: Quantification of Haemodynamics Changes in Small Joints

Inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high co-morbidity and increased mortality; RA involves indirect expenses secondary to disability, loss of productivity and early retirement. The gold-standard for diagnosing RA is based on patient conditions and radiographic findings, as joint erosions or decalcification. Recently, it has been shown that development of microvessels in the synovia is the earliest sign of RA, so that identification of prognostic factors such as persistent synovial hyperaemia is fundamental. By using immersion contrast-enhanced ultrasound with a steady probe to analyse the perfusion of those joints that are the most important for early detection of RA, we propose a quantitative analysis of the contrast kinetics in the synovial and peri-synovial tissues. This analysis allows the identification and differentiation of rheumatoid arthritis from other diseases that involve synovial activity such as psoriatic arthritis. We show the results of the proposed immersion-CEUS with a semi-automatic quantification procedure of the contrast kinetics in the synovia on a set of 16 metacarpophalangeal (MCP) joints of consecutive patients affected either by RA or psoriatic arthritis. Estimated kinetics parameters allows an accurate separation of the two classes of patients, that can be further improved by using serologic data.

Dynamic automated synovial imaging (DASI) for differential diagnosis of rheumatoid arthritis

Inflammatory rheumatic diseases are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity and increased mortality. The gold-standard for diagnosing and differentiating arthritis is based on patient conditions and radiographic findings, as joint erosions or decalcification. However, early signs of arthritis are joint effusion, hypervascularization and synovial hypertrophy. In particular, vascularization has been shown to correlate with arthritis’ destructive behavior, more than clinical assessment. Contrast Enhanced Ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. The evaluation of perfusion pattern rely on subjective semiquantitative scales, that are able to capture the macroscopic degree of vascularization, but are unable to detect the subtler differences in kinetics perfusion parameters that might lead to a deeper understanding of disease progression and a better management of patients. We show that after a kinetic analysis of contrast agent appearance, providing the quantitative features characterizing the perfusion pattern of the joint, it is possible to accurately discriminate RA from PSA by building a random forest classifier on the computed features. We compare its accuracy with the assessment performed by expert radiologist blinded of the diagnosis.

FRI0478 Dynamic automated synovial imaging (DASI) For differentiating between rheumatoid arthritis and other forms of arthritis: automated versus manual interpretation in contrast-enhanced ultrasound

Background Rheumatoid arthritis (RA) is the most aggressive chronic arthritis and affects about 1% of population, impacting severely both the individual wellbeing and the health care system. Early diagnosis and effective treatment can avoid the devastating outcome of RA1, but the differential diagnosis is especially difficult at its onset. The diagnosis relies on conventional methods (clinical parameters, autoantibodies), even if distinct vascularization patterns have been identified in biopsy specimens2. Contrast-enhanced ultrasound (CEUS) allows a non-invasive dynamic study of synovial vascularisation and perfusion, although its capacity in differentiating among different arthritis forms has not yet been evaluated3,4. Objectives to investigate the performance of quantitative analysis of CEUS data versus manual semiquantitative assessment in differentiating RA from other arthritis (non-RA). Methods 78 outclinic patients with finger joints arthritis were recruited, 33 with RA and 45 with other arthritis. The most active joint was chosen for CEUS examination as previously described3, using a US device (MyLab25, Esaote) equipped with Contrast tuned Imaging (CnTI, Esaote), and as contrast agent sulfur hexafluoride microbubbles (SonoVue; Bracco International). Both the anatomical B-mode image and the CnTI cineloop video were digitally stored for subsequent quantiative analysis or manual review. Two in arthritis experienced radiologists manually assessed the examinations as consistent with RA or not. Quantitative image analysis was performed firstly applying a semi-automatic detection of synovial boundaries5. Then, the contrast time-activity curve of all pixels belonging to the synovial and perisynovial region was analysed fitting a gamma curve f(t)=A(t-t0)a×e(t-t0)/b on the data. The statistics summarizing the distribution of the estimated kinetics parameters in the synovial and in the perisynovial tissue were computed and their difference between the two groups (RA and non-RA) analyzed, so to study the existance of different vascularization or flow patterns. Finally, a supervised classifier (random forest) was trained to classify each patient through its CEUS-derived parameters, validating the classifier diagnostic power using a leave-one-out strategy. Results Manual assessment of CEUS examination consistent with RA or non-RA performed by radiologists showed high sensitivity (0,9), but indeed low specificity and accuracy (0,46 and 0,69, respectively). On the contrary, the classifier using CEUS quantitative parameters showed both good sensitivity (0,88) and specificitity (0,94), resulting in a diagnostic accuracy of 0,92. Conclusions The Dynamic Automated Synovial Imaging (DASI) proposed provided a high accuracy in discriminating RA from non-RA arthritis. DASI promises to be a powerful tool for the diagnosis and follow-up of arthritis, attributing to CEUS a new role in the field. References Smolen JS. Ann Rheum Dis 2010;69:965-75. Reece RJ. Arthritis Rheum 1999;42(7):1481-4. Stramare R. J Clin Ultrasound 2012;40(3):147-54. Klauser A. Eur Radiol 2005;15:2404. Veronese E. Med Eng Phys 2013; 35, 188–194. Disclosure of Interest None Declared

Balneotherapy in chronic inflammatory rheumatic diseases—a narrative review

Since ancient time, thermal baths and mudpacks have been used as treatments for rheumatic diseases and other musculoskeletal complaints. Despite basic researches suggest an anti-inflammatory effect of spa therapy, there is no consensus about the benefits of balneotherapy in patients with chronic inflammatory rheumatic diseases. The aim of this review is to summarize the currently available information on clinical effects of balneotherapy in these diseases. We did a literature search for articles considering the randomized controlled trials (RCTs) published until today. Although many selected studies do not have an elevated methodological quality, data from these RCTs support a beneficial effect of spa therapy. Balneotherapy highly improves the clinical course of the disease in patients with predominant axial involvement, such as with ankylosing and enteropathic spondylitis; the effects are less favorable in patients with predominant peripheral articular inflammation, such as rheumatoid arthritis. Good results have been observed in patients with psoriatic arthritis, but only few RCTs have been conducted on this disease. Spa therapy appears safe, and adverse events have been reported only in a few patients.

Unilateral psoriatic arthritis in hemiparesis

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