Contrast Enhanced Ultrasound in COVID-19

Summary

Initial data from COVID-19 patients suggests that one of the primary causes of death is significant endothelial injury leading to blood clotting and impaired multiorgan microvascular perfusion. The current study uses a safe, convenient bedside imaging tool called contrast-enhanced ultrasound (CEUS) to estimate the extent of microvascular perfusion impairment in the heart, kidneys and/or brain of COVID-19 pediatric patients in vivo and assess the significance of imaging findings by correlating to clinical outcomes. This pilot study will be conducted at one site, The Children's Hospital of Philadelphia. The investigators plan to enroll and evaluate 30 patients.

Timeline

Start

2020-12-18

Primary completion

2021-09-17

Completion

2021-09-17

Publications

• Background Belhadjer Z, Meot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J, Ovaert C, Hascoet S, Selegny M, Malekzadeh-Milani S, Maltret A, Bosser G, Giroux N, Bonnemains L, Bordet J, Di Filippo S, Mauran P, Falcon-Eicher S, Thambo JB, Lefort B, Moceri P, Houyel L, Renolleau S, Bonnet D. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation. 2020 Aug 4;142(5):429-436. doi: 10.1161/CIRCULATIONAHA.120.048360. Epub 2020 May 17.
• Background Abdel-Mannan O, Eyre M, Lobel U, Bamford A, Eltze C, Hameed B, Hemingway C, Hacohen Y. Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children. JAMA Neurol. 2020 Nov 1;77(11):1440-1445. doi: 10.1001/jamaneurol.2020.2687.
• Background Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, Kneen R, Defres S, Sejvar J, Solomon T. Neurological associations of COVID-19. Lancet Neurol. 2020 Sep;19(9):767-783. doi: 10.1016/S1474-4422(20)30221-0. Epub 2020 Jul 2.
• Background Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 31;368:m1295. doi: 10.1136/bmj.m1295. No abstract available.
• Background Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020 May 1;116(6):1097-1100. doi: 10.1093/cvr/cvaa078.
• Background Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, Mou HM, Wang LH, Zhang HR, Fu WJ, Luo T, Liu F, Guo QN, Chen C, Xiao HL, Guo HT, Lin S, Xiang DF, Shi Y, Pan GQ, Li QR, Huang X, Cui Y, Liu XZ, Tang W, Pan PF, Huang XQ, Ding YQ, Bian XW. [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020 May 8;49(5):411-417. doi: 10.3760/cma.j.cn112151-20200312-00193. Chinese.
• Background Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
• Background Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.
• Background Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. 2020 Mar 17;94(7):e00127-20. doi: 10.1128/JVI.00127-20. Print 2020 Mar 17.
• Background Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829-838. doi: 10.1016/j.kint.2020.03.005. Epub 2020 Mar 20.
• Background Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
• Background Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, da Silva LFF, de Oliveira EP, Saldiva PHN, Mauad T, Negri EM. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost. 2020 Jun;18(6):1517-1519. doi: 10.1111/jth.14844. No abstract available.
• Background Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020 Jun;220:1-13. doi: 10.1016/j.trsl.2020.04.007. Epub 2020 Apr 15.
• Background Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 Jul;8(7):681-686. doi: 10.1016/S2213-2600(20)30243-5. Epub 2020 May 27.
• Background GOLD E, CARVER DH, HEINEBERG H, ADELSON L, ROBBINS FC. Viral infection. A possible cause of sudden, unexpected death in infants. N Engl J Med. 1961 Jan 12;264:53-60. doi: 10.1056/NEJM196101122640201. No abstract available.
• Background Ma F, Cang Y, Zhao B, Liu Y, Wang C, Liu B, Wu T, Song Y, Peng A. Contrast-enhanced ultrasound with SonoVue could accurately assess the renal microvascular perfusion in diabetic kidney damage. Nephrol Dial Transplant. 2012 Jul;27(7):2891-8. doi: 10.1093/ndt/gfr789. Epub 2012 Apr 24.
• Background Cao W, Cui S, Yang L, Wu C, Liu J, Yang F, Liu Y, Bin J, Hou FF. Contrast-Enhanced Ultrasound for Assessing Renal Perfusion Impairment and Predicting Acute Kidney Injury to Chronic Kidney Disease Progression. Antioxid Redox Signal. 2017 Dec 10;27(17):1397-1411. doi: 10.1089/ars.2017.7006. Epub 2017 Aug 22.
• Background Putz FJ, Erlmeier A, Wiesinger I, Verloh N, Stroszczynski C, Banas B, Jung EM. Contrast-enhanced ultrasound (CEUS) in renal imaging at an interdisciplinary ultrasound centre: Possibilities of dynamic microvascularisation and perfusion. Clin Hemorheol Microcirc. 2017;66(4):293-302. doi: 10.3233/CH-179103.
• Background Schneider AG, Goodwin MD, Schelleman A, Bailey M, Johnson L, Bellomo R. Contrast-enhanced ultrasound to evaluate changes in renal cortical perfusion around cardiac surgery: a pilot study. Crit Care. 2013 Jul 12;17(4):R138. doi: 10.1186/cc12817.
• Background Goyal A, Yu FTH, Tenwalde MG, Chen X, Althouse A, Villanueva FS, Pacella JJ. Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction. Ultrasound Med Biol. 2017 Jul;43(7):1391-1400. doi: 10.1016/j.ultrasmedbio.2017.02.013. Epub 2017 Apr 7.
• Background Istvanic F, Yu GZ, Yu FTH, Powers J, Chen X, Pacella JJ. Sonoreperfusion therapy for microvascular obstruction: A step toward clinical translation. Ultrasound Med Biol. 2020 Mar;46(3):712-720. doi: 10.1016/j.ultrasmedbio.2019.11.011. Epub 2020 Jan 7.
• Background Hwang M. Introduction to contrast-enhanced ultrasound of the brain in neonates and infants: current understanding and future potential. Pediatr Radiol. 2019 Feb;49(2):254-262. doi: 10.1007/s00247-018-4270-1. Epub 2018 Oct 23.
• Background Hwang M, Riggs BJ, Katz J, Seyfert D, Northington F, Shenandoah R, Burd I, McArthur J, Darge K, Thimm MA, Huisman TAGM. Advanced Pediatric Neurosonography Techniques: Contrast-Enhanced Ultrasonography, Elastography, and Beyond. J Neuroimaging. 2018 Mar;28(2):150-157. doi: 10.1111/jon.12492. Epub 2017 Dec 27.
• Background Hwang M, De Jong RM Jr, Herman S, Boss R, Riggs B, Tekes-Brady A, Spevak M, Poretti A, Soares BP, Bailey CR, Dunn E, Shin SS, Shrot S, Huisman TAGM. Novel Contrast-Enhanced Ultrasound Evaluation in Neonatal Hypoxic Ischemic Injury: Clinical Application and Future Directions. J Ultrasound Med. 2017 Nov;36(11):2379-2386. doi: 10.1002/jum.14289. Epub 2017 Jun 26.
• Background Hwang M, Riggs BJ, Saade-Lemus S, Huisman TA. Bedside contrast-enhanced ultrasound diagnosing cessation of cerebral circulation in a neonate: A novel bedside diagnostic tool. Neuroradiol J. 2018 Dec;31(6):578-580. doi: 10.1177/1971400918795866. Epub 2018 Sep 7.
• Background Hwang M, Sridharan A, Darge K, Riggs B, Sehgal C, Flibotte J, Huisman TAGM. Novel Quantitative Contrast-Enhanced Ultrasound Detection of Hypoxic Ischemic Injury in Neonates and Infants: Pilot Study 1. J Ultrasound Med. 2019 Aug;38(8):2025-2038. doi: 10.1002/jum.14892. Epub 2018 Dec 17.
• Background Benjamin JL, Dennis R, White S Jr, Munson D, Anupindi SA, Piskunowicz M, Darge K, Gokli A, Hwang M. Improved Diagnostic Sensitivity of Bowel Disease of Prematurity on Contrast-Enhanced Ultrasound. J Ultrasound Med. 2020 May;39(5):1031-1036. doi: 10.1002/jum.15168. Epub 2019 Nov 9.
• Background Hwang M, Hariri G, Lyshchik A, Hallahan DE, Fleischer AC. Correlation of quantified contrast-enhanced sonography with in vivo tumor response. J Ultrasound Med. 2010 Apr;29(4):597-607. doi: 10.7863/jum.2010.29.4.597.
• Results Tierradentro-Garcia LO, Sridharan A, Hwang M. Transtemporal brain contrast-enhanced ultrasound in children: preliminary experience in patients without neurological disorders. J Ultrasound. 2023 Mar;26(1):201-210. doi: 10.1007/s40477-022-00713-z. Epub 2022 Aug 27.
• Results Hwang M, Tierradentro-Garcia LO, Haddad S, Poznick L, Kilbaugh T, Chiotos K. Feasibility of Contrast-Enhanced Ultrasound for Assessing Cardiac and Renal Microvascular Flow in Patients With Multisystem Inflammatory Syndrome in Children. Clin Pediatr (Phila). 2022 Mar;61(3):241-247. doi: 10.1177/00099228211073288. Epub 2022 Jan 26. No abstract available.

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