Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia

Abstract

Objective

Contrast-enhanced ultrasound (CEUS) is advantageous for evaluating microcirculation, and has been applied to assess arthritis in previous studies. However, CEUS examinations have not been studied for hemophilia arthritis. Hemophilia arthritis is different from other arthritis, because it is induced by spontaneous joint bleeding. Hence, CEUS may have special value in evaluating hemophilia arthritis. The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients.

Methods

From August 2016 to January 2017, 81 severe hemophilia A patients, who were referred to our hospital for ultrasound joint assessment with conventional ultrasound, were enrolled. Among these 81 patients, 46 patients consented for CEUS examinations on the same day.

Results

Compared to color Doppler flow imaging (CDFI), four more joints presented with a blood flow signal under CEUS mode. In addition, the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound. The ultrasound scores (including the total grey-scale ultrasound score, joint effusion/hemarthrosis, synovial hypertrophy, CDFI semi-quantitative score, and CEUS semi-quantitative score) were significantly higher in the joint bleeding group than in the no joint bleeding group (P<0.05). Furthermore, these ultrasound scores were positively correlated with the joint bleeding frequency, and had the highest correlation with the CEUS score (r=0.620, P<0.05).

Conclusion

CEUS can more accurately assess the degree of synovial hypertrophy and vascularization, and diagnose synovitis, when compared to conventional ultrasound. In addition, CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding, and providing more reliable evidence for individualized treatment.

Keywords

contrast-enhanced ultrasound / hemophilia arthropathy / synovial hypertrophy / synovial vascularity

References

[1] SrivastavaA, BrewerAK, Mauser-BunschotenEP, et al.. Guidelines for the management of hemophilia. Haemophilia, 2013, 19(1): e1-e47

[2] FischerK, PoonnooseP, DunnAL, et al.. Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective. Haemophilia, 2017, 23(1): 11-24

[3] ZhaoY, XiaoJ, YangR, et al.. Efficacy of standard prophylaxis versus on-demand treatment with bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS) in Chinese children with severe hemophilia A. Pediatr Hematol Oncol, 2017, 34(3): 146-156

[4] SunJ, HilliardPE, FeldmanBM, et al.. Chinese Hemophilia Joint Health Score 2.1 reliability study. Haemophilia, 2014, 20(3): 435-440

[5] CookeE, ZhouJ, WyseureT, et al.. Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice. Thromb Haemost, 2018, 118(6): 1036-1047

[6] BarnesRFW, CramerTJ, HughesTH, et al.. The hypertension of hemophilia is associated with vascular remodeling in the joint. Microcirculation, 2017, 24(7): e12387

[7] PullesAE, MastbergenSC, SchutgensREG, et al.. Pathophysiology of hemophilic arthropathy and potential targets for therapy. Pharmacol Res, 2017, 115: 192-199

[8] KidderW, ChangEY, MoranC, et al.. Persistent Vascular Remodeling and Leakiness are Important Components of the Pathobiology of Re-bleeding in Hemophilic Joints: Two Informative Cases. Microcirculation, 2016, 23(5): 373-378

[9] OstergaardM, HansenM, StoltenbergM, et al.. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis. Arthritis Rheum, 1999, 42(5): 918-929

[10] MacchioniP, MagnaniM, MulèR, et al.. Ultrasonographic predictors for the development of joint damage in rheumatoid arthritis patients: a single joint prospective study. Clin Exp Rheumatol, 2013, 31(1): 8-17

[11] BhatV, OlmerM, JoshiS, et al.. Vascular remodeling underlies rebleeding in hemophilic arthropathy. Am J Hematol, 2015, 90(11): 1027-1035

[12] ZetterbergE, PalmbladJ, WallenstenR, et al.. Angiogenesis is increased in advanced haemophilic joint disease and characterised by normal pericyte coverage. Eur J Haematol, 2014, 92(3): 256-262

[13] KeshavaSN, GibikoteSV, MohantaA, et al.. Ultrasound and magnetic resonance imaging of healthy paediatric ankles and knees: a baseline for comparison with haemophilic joints. Haemophilia, 2015, 21(3): e210-e222

[14] SolimanM, DarugeP, DertkigilSSJ, et al.. Imaging of haemophilic arthropathy in growing joints: pitfalls in ultrasound and MRI. Haemophilia, 2017, 23(5): 660-672

[15] MaF, LiY, XiaoL, et al.. Diagnostic and score value of ultrasound and magnetic resonance imaging in hemophilia arthropathy. Zhonghua Chaosheng Yingxiangxue Zazhi (Chinese), 2016, 25(6): 525-529

[16] DoriaAS, KeshavaSN, MohantaA, et al.. Diagnostic accuracy of ultrasound for assessment of hemophilic arthropathy: MRI correlation. Am J Roentgenol, 2015, 204(3): W336-W347

[17] AgostinoM, TerslevL, AegerterP, et al.. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardised, consensus-based scoring system. RMD Open, 2017, 3(1): e428

[18] MartinoliC, DellaCAO, Di MinnoG, et al.. Development and definition of a simplified scanning procedure and scoring method for Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US). Thromb Haemost, 2013, 109(6): 1170-1179

[19] PoonnoosePM, HilliardP, DoriaAS, et al.. Correlating clinical and radiological assessment of joints in haemophilia: results of a cross sectional study. Haemophilia, 2016, 22(6): 925-933

[20] SchmidtWA, LkerLV, ZacherJ, et al.. Colour Doppler ultrasonography to detect pannus in knee joint synovitis. Clin Exp Rheumatol, 2000, 18(4): 439-444

[21] IagnoccoA, EpisO, DelleSA, et al.. Ultrasound imaging for the rheumatologist. XVII. Role of colour Doppler and power Doppler. Clin Exp Rheumatol, 2008, 26(5): 759-762

[22] OhrndorfS, HenschA, NaumannL, et al.. Contrast-enhanced ultrasonography is more sensitive than grayscale and power Doppler ultrasonography compared to MRI in therapy monitoring of rheumatoid arthritis patients. Ultraschall Med, 2011, 32(Suppl 2): E38-E44

[23] KlauserAS, FranzM, AroraR, et al.. Detection of vascularity in wrist tenosynovitis: power doppler ultrasound compared with contrast-enhanced grey-scale ultrasound. Arthritis Res Ther, 2010, 12(6): R209

[24] CaoW, CuiS, YangL, et al.. Contrast-Enhanced Ultrasound for Assessing Renal Perfusion Impairment and Predicting Acute Kidney Injury to Chronic Kidney Disease Progression. Antioxid Redox Signal, 2017, 27(17): 1397-1411

[25] FioccoU, StramareR, CoranA, et al.. Vascular perfusion kinetics by contrast-enhanced ultrasound are related to synovial microvascularity in the joints of psoriatic arthritis. Clin Rheumatol, 2015, 34(11): 1903-1912

[26] KlauserAS, FranzM, BellmannWR, et al.. Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis-subjective grading versus computer-aided objective quantification. Ultraschall Med, 2011, 32(Suppl 2): E31-E37

[27] SongIH, AlthoffCE, HermannKG, et al.. Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI. Ann Rheum Dis, 2009, 68(1): 75-83

[28] KlauserA, DemharterJ, De MarchiA, et al.. Contrast enhanced gray-scale sonography in assessment of joint vascularity in rheumatoid arthritis: results from the IACUS study group. Eur Radiol, 2005, 15(12): 2404-2410

[29] StramareR, CoranA, FaccinettoA, et al.. MR and CEUS monitoring of patients with severe rheumatoid arthritis treated with biological agents: a preliminary study. Radiol Med, 2014, 119(6): 422-431

[30] SongIH, BurmesterGR, BackhausM, et al.. 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. Ann Rheum Dis, 2008, 67(1): 19-25

[31] AndersenM, EllegaardK, HebsgaardJB, et al.. Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study. Ann Rheum Dis, 2014, 73(4): 678-683

[32] LiuH, HuangC, ChenS, et al.. Value of contrast-enhanced ultrasound for detection of synovial vascularity in experimental rheumatoid arthritis: an exploratory study. J Int Med Res, 2019, 47(11): 5740-5751

[33] NtouliaA, AnupindiSA, DargeK, et al.. Applications of contrast-enhanced ultrasound in the pediatric abdomen. Abdom Radiol, 2018, 43(4): 948-959