Value of Contrast-Enhanced Ultrasonography for the Detection and Quantification of Enthesitis Vascularization in Patients With Spondyloarthritis GAE ¨ L MOUTERDE, 1 PHILIPPE AEGERTER, 2 JEAN-MICHEL CORREAS, 3 MAXIME BREBAN, 4 AND MARIA-ANTONIETTA D’AGOSTINO 2 Objective. To evaluate if contrast-enhanced ultrasound (CEUS) can improve the detection and quantification of the vascularization of mild enthesitis in spondyloarthritis (SpA) and to evaluate the influence of nonsteroidal antiinflam- matory drugs (NSAIDs) on such detection. Methods. Fourteen patients with mildly active SpA were evaluated at 3 consecutive visits: at baseline while undergoing NSAID treatment (V1), after 1 week of stopping NSAIDs (V2), and after 1 week of resuming NSAIDs (V3). At each visit, enthesitis was evaluated clinically and by power Doppler US (PDUS). A selected enthesis with a doubtful PDUS vascularization signal was studied by CEUS in 2 steps: 1) using a dedicated technology that preserves microbubbles (Contrast Tuned Imaging technology [CEUS-CnTI]) and 2) using high PD (CEUS-PD) to destroy microbubbles. A linear mixed model statistical analysis, taking visits and contrast agent as fixed factors and the patient as a random factor, was used. Results. Disease activity and PDUS findings increased between V1 and V2 and then decreased between V2 and V3. As compared with PDUS alone, CEUS-PD and CEUS-CnTI each detected 1 supplementary vascularized enthesis at V1, CEUS-PD detected 1 vascularized enthesis and CEUS-CnTI detected 3 vascularized entheses at V2, and CEUS-PD and CEUS-CnTI each detected 2 vascularized entheses at V3. The mean inflammation score was increased by the use of CEUS (P  0.04). This score increased between V1 and V2 (P  0.03 by CEUS-PD and P  0.01 by CEUS-CnTI) and decreased between V2 and V3. Conclusion. CEUS improved the detection of enthesitis in SpA patients by confirming all doubtful enthesitis signals and confirming the absence of enthesis vascularization. The use of NSAIDs influenced the detection of vascularization. INTRODUCTION Enthesitis, inflammation at the origin and insertion of lig- aments, tendons, aponeuroses, and joint capsules to bone, is a widely accepted clinical, histopathologic, and imaging feature of spondyloarthritis (SpA) (1,2). Enthesitis is the result of focal, destructive microscopic inflammatory le- sions that evolve toward fibrous scarring and new bone formation (3). Enthesitis may involve synovial and carti- laginous joints, syndesmoses, and extraarticular entheses (4). Several studies have pointed out enthesitis as a pri- mary lesion in SpA (5). In enthesitis, conventional radiog- raphy shows only structural bone changes, such as prolif- eration or erosions. In contrast, magnetic resonance imaging (MRI) and power Doppler ultrasound (PDUS) de- tect a spectrum of early and late changes, some of which are related to inflammation (i.e., adjacent bone marrow edema and abnormal vascularization at the bone– enthesis junction, respectively) (5–9). Unlike MRI, US enables the examination of several en- theses during the same examination session. Over the past few years, numerous studies have proven the ability of B-mode US to detect enthesitis in SpA (10 –15). The pres- ence of a PD signal at the cortical bone insertion, reflecting an abnormal vascularization and hyperemia of enthesitis, 1 Gae ¨l Mouterde, MD: AP-HP, Ho ˆ pital Ambroise Pare ´, Boulogne-Billancourt, France (current address: Lapeyronie Hospital, Montpellier 1 University, UMR 5535, Mont- pellier, France); 2 Philippe Aegerter, MD, PhD, Maria- Antonietta D’Agostino, MD, PhD: AP-HP, Ho ˆ pital Ambroise Pare ´, Boulogne-Billancourt, and Universite ´ Versailles St- Quentin, UPRES EA 2506, Paris, France; 3 Jean-Michel Correas, MD, PhD: AP-HP, Ho ˆ pital Necker, Paris, France; 4 Maxime Breban, MD, PhD: AP-HP, Ho ˆ pital Ambroise Pare ´, Boulogne-Billancourt, and Universite ´ Versailles St-Quentin et Institut Cochin, INSERM U1016, CNRS UMR 8104, Uni- versite ´ Paris-Descartes, Paris, France. Address correspondence to Maria-Antonietta D’Agostino, MD, PhD, Rheumatology Department, Ambroise Pare ´ Hos- pital 9, avenue Charles de Gaulle, 92100 Boulogne- Billancourt, France. E-mail: maria-antonietta.dagostino@ apr.aphp.fr. Submitted for publication January 8, 2013; accepted in revised form September 24, 2013. Arthritis Care & Research Vol. 66, No. 1, January 2014, pp 131–138 DOI 10.1002/acr.22195 © 2014, American College of Rheumatology SPECIAL THEME ARTICLE: CLINICAL IMAGING AND THE RHEUMATIC DISEASES 131