Skip to main content
Top
Published in: Child's Nervous System 9/2018

01-09-2018 | Original Paper

An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis

Authors: Thomas Looi, Karolina Piorkowska, Charles Mougenot, Adam Waspe, Kullervo Hynynen, James Drake

Published in: Child's Nervous System | Issue 9/2018

Login to get access

Abstract

Purpose

Intraventricular hemorrhage (IVH) affects approximately 50% of premature births where 50% further develop post-hemorrhagic ventricular dilation (PHVD). Patients face significant impact to long-term development if PHVD is not managed. Unfortunately, there is no accepted treatment to remove the thrombus caused by IVH. This paper describes an acute and chronic IVH model for use with magnetic resonance-guided focused ultrasound (MRgFUS) thrombolysis.

Methods

A total of 12 pigs (~ 1 month in age) were used in the model (eight acute and four chronic). A pre-operative brain MRI was obtained for ventricular targeting. 1.25 cm3/kg of autologous blood was injected through a burr hole lateral to the midline and anterior of the coronal suture at a rate of 0.6 cm3/min. A craniotomy was performed to simulate a “fontanelle”. Post-operative MRI was used to calculate the clot volume. Chronic piglets were recovered, monitored daily with a neurological scoring system (NSS), and MRI scanned for 21 days.

Results

The clot injection was well tolerated. The average clot size was 3987 mm3 (median = 4330 mm, standard deviation = 739 mm3). Postmortem examination validated the presence of the clot. In the chronic animals, there was an increase in ventricular volume of 30%. Transient neurological impairment immediately followed clot injection and with onset of hydrocephalus in the chronic animals.

Conclusions

This model establishes a measurable and targetable IVH clot in an MRI-based neonatal porcine model. The progressive post-hemorrhagic ventricular dilation in the chronic model is a potential alterable outcome from MRgFUS thrombolysis.
Literature
1.
go back to reference Wellons JC, Shannon CN, Kulkarni AV, Simon TD, Riva-Cambrin J, Whitehead WE, Oakes WJ, Drake JM, Luerssen TG, Walker ML, Kestle JRW (2009) A multicenter retrospective comparison of conversion from temporary to permanent cerebrospinal fluid diversion in very low birth weight infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 4(1):50–55CrossRefPubMedPubMedCentral Wellons JC, Shannon CN, Kulkarni AV, Simon TD, Riva-Cambrin J, Whitehead WE, Oakes WJ, Drake JM, Luerssen TG, Walker ML, Kestle JRW (2009) A multicenter retrospective comparison of conversion from temporary to permanent cerebrospinal fluid diversion in very low birth weight infants with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 4(1):50–55CrossRefPubMedPubMedCentral
2.
go back to reference Ballabh P (2014) Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol 41(1):47–67CrossRefPubMed Ballabh P (2014) Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol 41(1):47–67CrossRefPubMed
3.
go back to reference Volpe JJ (2008) Neurology of the newborn, 5th edn, vol 899. Saunders/Elsevier, Philadelphia Volpe JJ (2008) Neurology of the newborn, 5th edn, vol 899. Saunders/Elsevier, Philadelphia
4.
go back to reference Rademaker KJ, Groeneadaal F, Jansen GH, Eken P, De Vries LS (1994) Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatr 83(6):602–608CrossRefPubMed Rademaker KJ, Groeneadaal F, Jansen GH, Eken P, De Vries LS (1994) Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatr 83(6):602–608CrossRefPubMed
5.
go back to reference Limperopoulos C, Soul JS, Haidar H, Huppi PS, Bassan H, Warfield SK, Robertson RL, Moore M, Akins P, Volpe JJ, du Plessis AJBT-P (2005) Impaired trophic interactions between the cerebellum and the cerebrum among preterm infants. Pediatrics 116(4):844+CrossRefPubMed Limperopoulos C, Soul JS, Haidar H, Huppi PS, Bassan H, Warfield SK, Robertson RL, Moore M, Akins P, Volpe JJ, du Plessis AJBT-P (2005) Impaired trophic interactions between the cerebellum and the cerebrum among preterm infants. Pediatrics 116(4):844+CrossRefPubMed
6.
go back to reference Whitelaw A, Pople I, Cherian S, Evans D (2003) Phase 1 trial of prevention of hydrocephalus after intraventricular hemorrhage in newborn infants by drainage, irrigation, and fibrinolytic therapy. Pediatrics 111(4):759–766CrossRefPubMed Whitelaw A, Pople I, Cherian S, Evans D (2003) Phase 1 trial of prevention of hydrocephalus after intraventricular hemorrhage in newborn infants by drainage, irrigation, and fibrinolytic therapy. Pediatrics 111(4):759–766CrossRefPubMed
7.
go back to reference Futagi Y, Toribe Y, Ogawa K, Suzuki Y (2006) Neurodevelopmental outcome in children with intraventricular hemorrhage. Pediatr Neurol 34(3):219–224CrossRefPubMed Futagi Y, Toribe Y, Ogawa K, Suzuki Y (2006) Neurodevelopmental outcome in children with intraventricular hemorrhage. Pediatr Neurol 34(3):219–224CrossRefPubMed
8.
go back to reference Adams-Chapman I, Hansen NI, Stoll BJ, Higgins R (2008) Neurodevelopmental outcome of extremely low birth weight infants with posthemorrhagic hydrocephalus requiring shunt insertion. Pediatrics 121(5):e1167–e1177CrossRefPubMedPubMedCentral Adams-Chapman I, Hansen NI, Stoll BJ, Higgins R (2008) Neurodevelopmental outcome of extremely low birth weight infants with posthemorrhagic hydrocephalus requiring shunt insertion. Pediatrics 121(5):e1167–e1177CrossRefPubMedPubMedCentral
9.
go back to reference Rohde V, Schaller C, Hassler WE (Apr. 1995) Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry 58(4):447–451CrossRefPubMedPubMedCentral Rohde V, Schaller C, Hassler WE (Apr. 1995) Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry 58(4):447–451CrossRefPubMedPubMedCentral
10.
go back to reference Webb AJS, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF (Jun. 2012) Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke 43(6):1666–1668CrossRefPubMedPubMedCentral Webb AJS, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF (Jun. 2012) Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke 43(6):1666–1668CrossRefPubMedPubMedCentral
11.
go back to reference Manco-Johnson MJ, Grabowski EF, Hellgreen M, Kemanhli AS, Massicote MP, Muntean W, Peters M, Schlegel N, Wang M, Nowak-Gottl U (2002) Recommendations for tPA thrombolysis in children. Thromb Haemost 88(1):157–158CrossRefPubMed Manco-Johnson MJ, Grabowski EF, Hellgreen M, Kemanhli AS, Massicote MP, Muntean W, Peters M, Schlegel N, Wang M, Nowak-Gottl U (2002) Recommendations for tPA thrombolysis in children. Thromb Haemost 88(1):157–158CrossRefPubMed
12.
go back to reference Whitelaw A, Evans D, Carter M, Thoresen M, Wroblewska J, Mandera M, Swietlinski J, Simpson J, Hajivassiliou C, Hunt LP, Pople I (2007) Randomized clinical trial of prevention of hydrocephalus after intraventricular hemorrhage in preterm infants: brain-washing versus tapping fluid. Pediatrics 119(5):e1071–e1078CrossRefPubMed Whitelaw A, Evans D, Carter M, Thoresen M, Wroblewska J, Mandera M, Swietlinski J, Simpson J, Hajivassiliou C, Hunt LP, Pople I (2007) Randomized clinical trial of prevention of hydrocephalus after intraventricular hemorrhage in preterm infants: brain-washing versus tapping fluid. Pediatrics 119(5):e1071–e1078CrossRefPubMed
13.
go back to reference Whitelaw A, Jary S, Kmita G, Wroblewska J, Musialik-Swietlinska E, Mandera M, Hunt L, Carter M, Pople I (2010) Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics 125(4):e852–e858CrossRefPubMed Whitelaw A, Jary S, Kmita G, Wroblewska J, Musialik-Swietlinska E, Mandera M, Hunt L, Carter M, Pople I (2010) Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics 125(4):e852–e858CrossRefPubMed
14.
go back to reference Monteith SJ, Harnof S, Medel R, Popp B, Max Wintermark M, Lopes BS, Kassell NF, Jeff Elias W, Snell J, Eames M, Zadicario E, Moldovan K, Sheehan J (2013) Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound. J Neurosurg 118(5):1035–1045CrossRefPubMed Monteith SJ, Harnof S, Medel R, Popp B, Max Wintermark M, Lopes BS, Kassell NF, Jeff Elias W, Snell J, Eames M, Zadicario E, Moldovan K, Sheehan J (2013) Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound. J Neurosurg 118(5):1035–1045CrossRefPubMed
15.
go back to reference Wright C, Hynynen K, Goertz D (2012) In vitro and in vivo high intensity focused ultrasound thrombolysis. Investig Radiol 47(4):217–225CrossRef Wright C, Hynynen K, Goertz D (2012) In vitro and in vivo high intensity focused ultrasound thrombolysis. Investig Radiol 47(4):217–225CrossRef
16.
go back to reference Burgess A, Huang Y, Waspe AC, Ganguly M, Goertz DE, Hynynen K (2012) High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke. PLoS One 7(8):e42311CrossRefPubMedPubMedCentral Burgess A, Huang Y, Waspe AC, Ganguly M, Goertz DE, Hynynen K (2012) High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke. PLoS One 7(8):e42311CrossRefPubMedPubMedCentral
17.
go back to reference Aquilina K, Hobbs C, Cherian S, Tucker A, Porter H, Whitelaw A, Thoresen M (2007) A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation. J Neurosurg 107(2 Suppl):126–136PubMed Aquilina K, Hobbs C, Cherian S, Tucker A, Porter H, Whitelaw A, Thoresen M (2007) A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation. J Neurosurg 107(2 Suppl):126–136PubMed
18.
go back to reference Gold HK, Yasuda T, Jang IK, Guerrero JL, Fallon JT, Leinbach RC, Collen D (1991) Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus. Circulation 83(6 Suppl):IV26–IV40PubMed Gold HK, Yasuda T, Jang IK, Guerrero JL, Fallon JT, Leinbach RC, Collen D (1991) Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus. Circulation 83(6 Suppl):IV26–IV40PubMed
19.
go back to reference Lekic T, Manaenko A, Rolland W, Krafft PR, Peters R, Hartman RE, Altay O, Tang J, Zhang JH (2012) Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus. Exp Neurol 236(1):69–78CrossRefPubMedPubMedCentral Lekic T, Manaenko A, Rolland W, Krafft PR, Peters R, Hartman RE, Altay O, Tang J, Zhang JH (2012) Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus. Exp Neurol 236(1):69–78CrossRefPubMedPubMedCentral
20.
go back to reference Turbeville DF, Bowen FW, Killam AP (1976) Intracranial hemorrhages in kittens: hypernatremia versus hypoxia. J Pediatr 89(2):294–297CrossRefPubMed Turbeville DF, Bowen FW, Killam AP (1976) Intracranial hemorrhages in kittens: hypernatremia versus hypoxia. J Pediatr 89(2):294–297CrossRefPubMed
21.
go back to reference Pasternak JF, Groothuis DR, Fischer JM, Fischer DP (1983) Regional cerebral blood flow in the beagle puppy model of neonatal intraventricular hemorrhage: studies during systemic hypertension. Neurology 33(5):559–566CrossRefPubMed Pasternak JF, Groothuis DR, Fischer JM, Fischer DP (1983) Regional cerebral blood flow in the beagle puppy model of neonatal intraventricular hemorrhage: studies during systemic hypertension. Neurology 33(5):559–566CrossRefPubMed
22.
go back to reference Castellá M, Buckberg GD, Tan Z (2005) Neurologic preservation by Na+-H+ exchange inhibition prior to 90 minutes of hypothermic circulatory arrest. Ann Thorac Surg 79(2):646–654CrossRefPubMed Castellá M, Buckberg GD, Tan Z (2005) Neurologic preservation by Na+-H+ exchange inhibition prior to 90 minutes of hypothermic circulatory arrest. Ann Thorac Surg 79(2):646–654CrossRefPubMed
23.
go back to reference Hess M, Looi T, Lasso A, Fichtinger G, Drake J (2015) Quantification of intraventricular blood clot in MR-guided focused ultrasound surgery. Proc SPIE 9415:94152J–94152J–9CrossRef Hess M, Looi T, Lasso A, Fichtinger G, Drake J (2015) Quantification of intraventricular blood clot in MR-guided focused ultrasound surgery. Proc SPIE 9415:94152J–94152J–9CrossRef
24.
go back to reference Looi T, Khokhlova VA, Mougenot C, Hynynen K, Drake JM (2016) In vivo feasibiliy study of boiling histotripsy with clinical Sonalleve system with a neurological porcine model, in 16th International Symposium on Therapeutic Ultrasound. Looi T, Khokhlova VA, Mougenot C, Hynynen K, Drake JM (2016) In vivo feasibiliy study of boiling histotripsy with clinical Sonalleve system with a neurological porcine model, in 16th International Symposium on Therapeutic Ultrasound.
25.
go back to reference Barbier A, Boivin A, Yoon W, Vallerand D, Platt RW, Audibert F, Barrington KJ, Shah PS, Nuyt AM (2013) New reference curves for head circumference at birth, by gestational age. Pediatrics 131:e1158–e1167CrossRefPubMed Barbier A, Boivin A, Yoon W, Vallerand D, Platt RW, Audibert F, Barrington KJ, Shah PS, Nuyt AM (2013) New reference curves for head circumference at birth, by gestational age. Pediatrics 131:e1158–e1167CrossRefPubMed
Metadata
Title
An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis
Authors
Thomas Looi
Karolina Piorkowska
Charles Mougenot
Adam Waspe
Kullervo Hynynen
James Drake
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 9/2018
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-018-3816-8

Other articles of this Issue 9/2018

Child's Nervous System 9/2018 Go to the issue