Non-invasive contrast enhanced ultrasound molecular imaging of inflammation in autoimmune myocarditis for prediction of left ventricular fibrosis and remodeling
Autoři:
David C. Steinl aff001; Lifen Xu aff001; Amanda Ochoa-Espinosa aff001; Mukesh Punjabi aff001; Beat A. Kaufmann aff001
Působiště autorů:
Department of Biomedicine, University of Basel, Basel, Switzerland
aff001; Division of Cardiology, University Hospital and University of Basel, Basel, Switzerland
aff002
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224377
Souhrn
Background
Myocarditis can lead to myocyte loss and myocardial fibrosis resulting in dilated cardiomyopathy (DCMP). Currently employed methods for assessing the risk for development of DCMP are inaccurate or rely on invasive myocardial biopsies. We hypothesized that molecular imaging of tissue inflammation with contrast enhanced ultrasound during peak inflammation in myocarditis could predict development of fibrosis and impaired left ventricular function.
Methods and results
Experimental autoimmune myocarditis (EAM) was induced in Balbc mice by injection of the α-myosin heavy chain peptide. Contrast enhanced ultrasound (CEU) using microbubbles targeted to leukocytes (MBLc), to CD4+ lymphocytes (MBCD4), and to the endothelial cell adhesion molecule P-selectin (MBPSel) was performed during the expected EAM peak inflammatory activity 21 days after induction. High resolution ultrasound, invasive hemodynamic measurements and fibrosis quantification were done 63 days after EAM assessment. All tested microbubbles correlated to fibrosis (MBLc spearman r 0.28, p 0.047, MBCD4 r 0.44, p 0.01, MBPSel r 0.73, p 0.02), however, correlations were weak overall and the spread of data was considerable. Also, targeted CEU data on day 21 did not correlate to hemodynamic and functional data on day 63.
Conclusions
Ultrasound molecular imaging using targeted microbubbles during the peak inflammatory activity of myocarditis correlates weakly with later development of fibrosis but not with hemodynamic or left ventricular functional parameters.
Klíčová slova:
Cardiac ventricles – Cardiovascular imaging – Diastole – Fibrosis – Inflammation – Ultrasound imaging – White blood cells – Myocarditis
Zdroje
1. Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. European heart journal. 2013;34(33):2636–48, 48a-48d. doi: 10.1093/eurheartj/eht210 23824828
2. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008;118(6):639–48. doi: 10.1161/CIRCULATIONAHA.108.769489 18645053
3. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, et al. Update on myocarditis. Journal of the American College of Cardiology. 2012;59(9):779–92. doi: 10.1016/j.jacc.2011.09.074 22361396
4. Carlquist JF, Menlove RL, Murray MB, O'Connell JB and Anderson JL. HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies. Circulation. 1991;83(2):515–22. doi: 10.1161/01.cir.83.2.515 1825038
5. Caforio AL, Mahon NJ and McKenna WJ. Cardiac autoantibodies to myosin and other heart-specific autoantigens in myocarditis and dilated cardiomyopathy. Autoimmunity. 2001;34(3):199–204. doi: 10.3109/08916930109007385 11908778
6. Pummerer CL, Luze K, Grassl G, Bachmaier K, Offner F, Burrell SK, et al. Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice. The Journal of clinical investigation. 1996;97(9):2057–62. doi: 10.1172/JCI118642 8621795
7. Steinl DC, Xu L, Khanicheh E, Ellertsdottir E, Ochoa-Espinosa A, Mitterhuber M, et al. Noninvasive Contrast-Enhanced Ultrasound Molecular Imaging Detects Myocardial Inflammatory Response in Autoimmune Myocarditis. Circulation Cardiovascular imaging. 2016;9(8).
8. Lindner JR, Song J, Xu F, Klibanov AL, Singbartl K, Ley K, et al. Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. Circulation. 2000;102(22):2745–50. doi: 10.1161/01.cir.102.22.2745 11094042
9. Lindner JR, Song J, Christiansen J, Klibanov AL, Xu F, Ley K. Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation. 2001;104(17):2107–12. doi: 10.1161/hc4201.097061 11673354
10. Bauer M, Cheng S, Jain M, Ngoy S, Theodoropoulos C et al. Echocardiographic speckle-tracking based strain imaging for rapid cardiovascular phenotyping in mice. Circulation research. 2011;108(8):908–16. doi: 10.1161/CIRCRESAHA.110.239574 21372284
11. Pacher P, Nagayama T, Mukhopadhyay P, Batkai S and Kass DA. Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nat Protoc. 2008;3(9):1422–34. doi: 10.1038/nprot.2008.138 18772869
12. Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, et al. Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis. Circulation. 2018;138(11):1088–99. doi: 10.1161/CIRCULATIONAHA.118.035319 29764898
13. Werner RA, Wakabayashi H, Bauer J, Schutz C, Zechmeister C, Hayakawa N, et al. Longitudinal 18F-FDG PET imaging in a rat model of autoimmune myocarditis. Eur Heart J Cardiovasc Imaging. 2019;20(4):467–74. doi: 10.1093/ehjci/jey119 30102319
14. Baldeviano GC, Barin JG, Talor MV, Srinivasan S, Bedja D, Zheng D, et al. Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. Circulation research. 2010;106(10):1646–55. doi: 10.1161/CIRCRESAHA.109.213157 20378858
Článek vyšel v časopise
PLOS One
2019 Číslo 10
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning
- Risk factors associated with IgA vasculitis with nephritis (Henoch–Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy