Skip to main content
Top
Published in: Pediatric Surgery International 1/2010

01-01-2010 | Original Article

Microscopic magnetic resonance in congenital diaphragmatic hernia and associated malformations in rats

Authors: Montserrat Bret, Ana Lourdes Luis, Emilio Cuesta, Federica Pederiva, Rosa Aras, Leopoldo Martinez, Juan A. Tovar

Published in: Pediatric Surgery International | Issue 1/2010

Login to get access

Abstract

Background/aim

The research on congenital diaphragmatic hernia (CDH) is often carried out on the nitrofen fetal rat model in which most investigations involve microdissections and fastidious assessment of serial sections of different anatomic areas. Current microscopic magnetic resonance (MMR) equipment allows detailed anatomic studies of alive, fresh or fixed fetuses. The purpose of the present study was to demonstrate that CDH itself and most of the associated malformations are adequately imaged and measured by MMR.

Materials and methods

Fetuses from pregnant rats treated with either i.g. vehicle (control, n = 10) or 100 mg nitrofen (only those with CDH, n = 18) on E9.5 were recovered on E21 (term = E22) and total body was scanned by MMR under sedation in a 7 T MRI system (Bruker Medical, Ettlingen, Germany). CDH was detected with a coronal multislice fast spin echo sequence with a long repetition time and short effective echo time. Oblique MPR and 3D reconstructions were used. All studies were processed with attention to the hernia and its contents and the structure of the tracheobronchial tree and the lung, the heart and great vessels, the thymus and cervico-thoracic vertebrae. The findings in both groups were compared.

Results

Congenital diaphragmatic hernia, lung hypoplasia and parenchymal features were clearly depicted. Tracheal ring anomalies were also demonstrated. The thymus was significantly smaller in CDH pups (2.9 × 1 × 2.4 mm) than in controls (4 × 1.3 × 2.8 mm) (p < 0.01). MRI was particularly performant for imaging cardiovascular anomalies: 4 double aortic arches, 3 Fallots, 3 right aortic arches, 3 ventricular septal defects and 1 aberrant subclavian artery.

Conclusions

Microscopic magnetic resonance involves refined and expensive equipment but it provides a powerful research tool for the study of CDH and other malformations in rat fetuses. Further work on this area is warranted.
Literature
1.
go back to reference Tovar JA (2007) Stephen L. Gans distinguished overseas lecture. The neural crest in pediatric surgery. J Pediatr Surg 42(6):915–926CrossRefPubMed Tovar JA (2007) Stephen L. Gans distinguished overseas lecture. The neural crest in pediatric surgery. J Pediatr Surg 42(6):915–926CrossRefPubMed
2.
go back to reference Kluth D, Kangah R, Reich P, Tenbrinck R, Tibboel D, Lambrecht W (1990) Nitrofen-induced diaphragmatic hernias in rats: an animal model. J Pediatr Surg 25(8):850–854CrossRefPubMed Kluth D, Kangah R, Reich P, Tenbrinck R, Tibboel D, Lambrecht W (1990) Nitrofen-induced diaphragmatic hernias in rats: an animal model. J Pediatr Surg 25(8):850–854CrossRefPubMed
3.
go back to reference Tenbrinck R, Tibboel D, Gaillard JL, Kluth D, Bos AP, Lachmann B, Molenaar JC (1990) Experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg 25(4):426–429CrossRefPubMed Tenbrinck R, Tibboel D, Gaillard JL, Kluth D, Bos AP, Lachmann B, Molenaar JC (1990) Experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg 25(4):426–429CrossRefPubMed
4.
go back to reference Tenbrinck R, Gaillard JL, Tibboel D, Kluth D, Lachmann B, Molenaar JC (1992) Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg 27(7):862–865CrossRefPubMed Tenbrinck R, Gaillard JL, Tibboel D, Kluth D, Lachmann B, Molenaar JC (1992) Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg 27(7):862–865CrossRefPubMed
5.
go back to reference Alfonso LF, Vilanova J, Aldazabal P, Lopez de Torre B, Tovar JA (1993) Lung growth and maturation in the rat model of experimentally induced congenital diaphragmatic hernia. Eur J Pediatr Surg 3(1):6–11CrossRefPubMed Alfonso LF, Vilanova J, Aldazabal P, Lopez de Torre B, Tovar JA (1993) Lung growth and maturation in the rat model of experimentally induced congenital diaphragmatic hernia. Eur J Pediatr Surg 3(1):6–11CrossRefPubMed
6.
go back to reference Kluth D, Keijzer R, Hertl M, Tibboel D (1996) Embryology of congenital diaphragmatic hernia. Semin Pediatr Surg 5(4):224–233PubMed Kluth D, Keijzer R, Hertl M, Tibboel D (1996) Embryology of congenital diaphragmatic hernia. Semin Pediatr Surg 5(4):224–233PubMed
7.
go back to reference Kim WG, Suh JW, Chi JG (1999) Nitrofen-induced congenital malformations of the heart and great vessels in rats: an animal model. J Pediatr Surg 34(12):1782–1786CrossRefPubMed Kim WG, Suh JW, Chi JG (1999) Nitrofen-induced congenital malformations of the heart and great vessels in rats: an animal model. J Pediatr Surg 34(12):1782–1786CrossRefPubMed
8.
go back to reference Losty PD, Connell MG, Freese R, Laval S, Okoye BO, Smith A, Kluth D, Lloyd DA (1999) Cardiovascular malformations in experimental congenital diaphragmatic hernia. J Pediatr Surg 34(8):1203–1207CrossRefPubMed Losty PD, Connell MG, Freese R, Laval S, Okoye BO, Smith A, Kluth D, Lloyd DA (1999) Cardiovascular malformations in experimental congenital diaphragmatic hernia. J Pediatr Surg 34(8):1203–1207CrossRefPubMed
9.
go back to reference Migliazza L, Otten C, Xia H, Rodriguez JI, Diez-Pardo JA, Tovar JA (1999) Cardiovascular malformations in congenital diaphragmatic hernia: human and experimental studies. J Pediatr Surg 34(9):1352–1358CrossRefPubMed Migliazza L, Otten C, Xia H, Rodriguez JI, Diez-Pardo JA, Tovar JA (1999) Cardiovascular malformations in congenital diaphragmatic hernia: human and experimental studies. J Pediatr Surg 34(9):1352–1358CrossRefPubMed
10.
go back to reference Migliazza L, Xia H, Alvarez JI, Arnaiz A, Diez-Pardo JA, Alfonso LF, Tovar JA (1999) Heart hypoplasia in experimental congenital diaphragmatic hernia. J Pediatr Surg 34(5):706–710 (discussion 710–701)CrossRefPubMed Migliazza L, Xia H, Alvarez JI, Arnaiz A, Diez-Pardo JA, Alfonso LF, Tovar JA (1999) Heart hypoplasia in experimental congenital diaphragmatic hernia. J Pediatr Surg 34(5):706–710 (discussion 710–701)CrossRefPubMed
11.
go back to reference Xia H, Migliazza L, Diez-Pardo JA, Tovar JA (1999) The tracheobronchial tree is abnormal in experimental congenital diaphragmatic hernia. Pediatr Surg Int 15(3–4):184–187CrossRefPubMed Xia H, Migliazza L, Diez-Pardo JA, Tovar JA (1999) The tracheobronchial tree is abnormal in experimental congenital diaphragmatic hernia. Pediatr Surg Int 15(3–4):184–187CrossRefPubMed
12.
go back to reference Yu J, Gonzalez S, Rodriguez JI, Diez-Pardo JA, Tovar JA (2001) Neural crest-derived defects in experimental congenital diaphragmatic hernia. Pediatr Surg Int 17(4):294–298CrossRefPubMed Yu J, Gonzalez S, Rodriguez JI, Diez-Pardo JA, Tovar JA (2001) Neural crest-derived defects in experimental congenital diaphragmatic hernia. Pediatr Surg Int 17(4):294–298CrossRefPubMed
13.
go back to reference Pederiva F, Rodriguez JI, Ruiz-Bravo E, Martinez L, Tovar JA (2009) Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction. J Pediatr Surg 44(3):496–499CrossRefPubMed Pederiva F, Rodriguez JI, Ruiz-Bravo E, Martinez L, Tovar JA (2009) Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction. J Pediatr Surg 44(3):496–499CrossRefPubMed
14.
go back to reference Pederiva F, Lopez RA, Martinez L, Tovar JA (2009) Tracheal innervation is abnormal in rats with experimental congenital diaphragmatic hernia. J Pediatr Surg 44(6):1159–1164CrossRefPubMed Pederiva F, Lopez RA, Martinez L, Tovar JA (2009) Tracheal innervation is abnormal in rats with experimental congenital diaphragmatic hernia. J Pediatr Surg 44(6):1159–1164CrossRefPubMed
15.
go back to reference Martinez L, Pederiva F, Martinez-Calonge W, Aras-Lopez R, Tovar JA (2009) The myenteric plexus of the esophagus is abnormal in an experimental congenital diaphragmatic hernia model. Eur J Pediatr Surg 19(3):163–167CrossRefPubMed Martinez L, Pederiva F, Martinez-Calonge W, Aras-Lopez R, Tovar JA (2009) The myenteric plexus of the esophagus is abnormal in an experimental congenital diaphragmatic hernia model. Eur J Pediatr Surg 19(3):163–167CrossRefPubMed
16.
go back to reference Pederiva F, Rodriguez JI, Ruiz-Bravo El, Martinez L, Tovar JA (2008) Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia. A likely cause of motor dysfunction. J Pediatr Surg 44(3):496–499CrossRef Pederiva F, Rodriguez JI, Ruiz-Bravo El, Martinez L, Tovar JA (2008) Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia. A likely cause of motor dysfunction. J Pediatr Surg 44(3):496–499CrossRef
17.
go back to reference Pederiva F, Aras Lopez R, Martinez L, Tovar JA (2008) Abnormal development of tracheal innervation in rats with experimental diaphragmatic hernia. Pediatr Surg Int 24(12):1341–1346CrossRefPubMed Pederiva F, Aras Lopez R, Martinez L, Tovar JA (2008) Abnormal development of tracheal innervation in rats with experimental diaphragmatic hernia. Pediatr Surg Int 24(12):1341–1346CrossRefPubMed
18.
go back to reference Vallee JP, Ivancevic MK, Nguyen D, Morel DR, Jaconi M (2004) Current status of cardiac MRI in small animals. MAGMA 17(3–6):149–156CrossRefPubMed Vallee JP, Ivancevic MK, Nguyen D, Morel DR, Jaconi M (2004) Current status of cardiac MRI in small animals. MAGMA 17(3–6):149–156CrossRefPubMed
19.
go back to reference Orita J, Sato E, Saburi S, Nishida T, Toyoda Y (1996) Magnetic resonance imaging of the internal structure of the mouse fetus. Exp Anim 45(2):171–174CrossRefPubMed Orita J, Sato E, Saburi S, Nishida T, Toyoda Y (1996) Magnetic resonance imaging of the internal structure of the mouse fetus. Exp Anim 45(2):171–174CrossRefPubMed
20.
go back to reference Hogers B, Gross D, Lehmann V, Zick K, De Groot HJ, Gittenberger-De Groot AC, Poelmann RE (2000) Magnetic resonance microscopy of mouse embryos in utero. Anat Rec 260(4):373–377CrossRefPubMed Hogers B, Gross D, Lehmann V, Zick K, De Groot HJ, Gittenberger-De Groot AC, Poelmann RE (2000) Magnetic resonance microscopy of mouse embryos in utero. Anat Rec 260(4):373–377CrossRefPubMed
21.
go back to reference Schneider JE, Bamforth SD, Farthing CR, Clarke K, Neubauer S, Bhattacharya S (2003) High-resolution imaging of normal anatomy, and neural and adrenal malformations in mouse embryos using magnetic resonance microscopy. J Anat 202(2):239–247CrossRefPubMed Schneider JE, Bamforth SD, Farthing CR, Clarke K, Neubauer S, Bhattacharya S (2003) High-resolution imaging of normal anatomy, and neural and adrenal malformations in mouse embryos using magnetic resonance microscopy. J Anat 202(2):239–247CrossRefPubMed
22.
go back to reference Schneider JE, Bamforth SD, Grieve SM, Clarke K, Bhattacharya S, Neubauer S (2003) High-resolution, high-throughput magnetic paragraph sign resonance imaging of mouse embryonic paragraph sign anatomy using a fast gradient-echo sequence. MAGMA 16(1):43–51CrossRefPubMed Schneider JE, Bamforth SD, Grieve SM, Clarke K, Bhattacharya S, Neubauer S (2003) High-resolution, high-throughput magnetic paragraph sign resonance imaging of mouse embryonic paragraph sign anatomy using a fast gradient-echo sequence. MAGMA 16(1):43–51CrossRefPubMed
23.
go back to reference Dhenain M, Ruffins SW, Jacobs RE (2001) Three-dimensional digital mouse atlas using high-resolution MRI. Dev Biol 232(2):458–470CrossRefPubMed Dhenain M, Ruffins SW, Jacobs RE (2001) Three-dimensional digital mouse atlas using high-resolution MRI. Dev Biol 232(2):458–470CrossRefPubMed
24.
go back to reference Petiet A, Hedlund L, Johnson GA (2007) Staining methods for magnetic resonance microscopy of the rat fetus. J Magn Reson Imag 25(6):1192–1198CrossRef Petiet A, Hedlund L, Johnson GA (2007) Staining methods for magnetic resonance microscopy of the rat fetus. J Magn Reson Imag 25(6):1192–1198CrossRef
25.
go back to reference Schneider JE, Bamforth SD, Farthing CR, Clarke K, Neubauer S, Bhattacharya S (2003) Rapid identification and 3D reconstruction of complex cardiac malformations in transgenic mouse embryos using fast gradient echo sequence magnetic resonance imaging. J Mol Cell Cardiol 35(2):217–222CrossRefPubMed Schneider JE, Bamforth SD, Farthing CR, Clarke K, Neubauer S, Bhattacharya S (2003) Rapid identification and 3D reconstruction of complex cardiac malformations in transgenic mouse embryos using fast gradient echo sequence magnetic resonance imaging. J Mol Cell Cardiol 35(2):217–222CrossRefPubMed
26.
go back to reference Schneider JE, Bose J, Bamforth SD, Gruber AD, Broadbent C, Clarke K, Neubauer S, Lengeling A, Bhattacharya S (2004) Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique. BMC Dev Biol 4:16CrossRefPubMed Schneider JE, Bose J, Bamforth SD, Gruber AD, Broadbent C, Clarke K, Neubauer S, Lengeling A, Bhattacharya S (2004) Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique. BMC Dev Biol 4:16CrossRefPubMed
27.
go back to reference Schneider JE, Bhattacharya S (2004) Making the mouse embryo transparent: identifying developmental malformations using magnetic resonance imaging. Birth Defects Res C Embryo Today 72(3):241–249CrossRefPubMed Schneider JE, Bhattacharya S (2004) Making the mouse embryo transparent: identifying developmental malformations using magnetic resonance imaging. Birth Defects Res C Embryo Today 72(3):241–249CrossRefPubMed
28.
go back to reference Hoydu AK, Kitano Y, Kriss A, Hensley H, Bergey P, Flake A, Hubbard A, Leigh JS Jr (2000) In vivo, in utero microscopic magnetic resonance imaging: application in a rat model of diaphragmatic hernia. Magn Reson Med 44(2):331–335CrossRefPubMed Hoydu AK, Kitano Y, Kriss A, Hensley H, Bergey P, Flake A, Hubbard A, Leigh JS Jr (2000) In vivo, in utero microscopic magnetic resonance imaging: application in a rat model of diaphragmatic hernia. Magn Reson Med 44(2):331–335CrossRefPubMed
29.
go back to reference Danzer E, Schwarz U, Wehrli S, Radu A, Adzick NS, Flake AW (2005) Retinoic acid induced myelomeningocele in fetal rats: characterization by histopathological analysis and magnetic resonance imaging. Exp Neurol 194(2):467–475CrossRefPubMed Danzer E, Schwarz U, Wehrli S, Radu A, Adzick NS, Flake AW (2005) Retinoic acid induced myelomeningocele in fetal rats: characterization by histopathological analysis and magnetic resonance imaging. Exp Neurol 194(2):467–475CrossRefPubMed
30.
go back to reference Aoki I, Wu YJ, Silva AC, Lynch RM, Koretsky AP (2004) In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI. Neuroimage 22(3):1046–1059CrossRefPubMed Aoki I, Wu YJ, Silva AC, Lynch RM, Koretsky AP (2004) In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI. Neuroimage 22(3):1046–1059CrossRefPubMed
31.
go back to reference Schwindt W, Burke M, Pillekamp F, Luhmann HJ, Hoehn M (2004) Functional magnetic resonance imaging and somatosensory evoked potentials in rats with a neonatally induced freeze lesion of the somatosensory cortex. J Cereb Blood Flow Metab 24(12):1409–1418CrossRefPubMed Schwindt W, Burke M, Pillekamp F, Luhmann HJ, Hoehn M (2004) Functional magnetic resonance imaging and somatosensory evoked potentials in rats with a neonatally induced freeze lesion of the somatosensory cortex. J Cereb Blood Flow Metab 24(12):1409–1418CrossRefPubMed
32.
go back to reference Meng S, Qiao M, Scobie K, Tomanek B, Tuor UI (2006) Evolution of magnetic resonance imaging changes associated with cerebral hypoxia–ischemia and a relatively selective white matter injury in neonatal rats. Pediatr Res 59(4 Pt 1):554–559CrossRefPubMed Meng S, Qiao M, Scobie K, Tomanek B, Tuor UI (2006) Evolution of magnetic resonance imaging changes associated with cerebral hypoxia–ischemia and a relatively selective white matter injury in neonatal rats. Pediatr Res 59(4 Pt 1):554–559CrossRefPubMed
33.
go back to reference Fau S, Po C, Gillet B, Sizonenko S, Mariani J, Meric P, Charriaut-Marlangue C (2007) Effect of the reperfusion after cerebral ischemia in neonatal rats using MRI monitoring. Exp Neurol 208(2):297–304PubMed Fau S, Po C, Gillet B, Sizonenko S, Mariani J, Meric P, Charriaut-Marlangue C (2007) Effect of the reperfusion after cerebral ischemia in neonatal rats using MRI monitoring. Exp Neurol 208(2):297–304PubMed
34.
go back to reference Wideroe M, Olsen O, Pedersen TB, Goa PE, Kavelaars A, Heijnen C, Skranes J, Brubakk AM, Brekken C (2009) Manganese-enhanced magnetic resonance imaging of hypoxic–ischemic brain injury in the neonatal rat. Neuroimage 45(3):880–890CrossRefPubMed Wideroe M, Olsen O, Pedersen TB, Goa PE, Kavelaars A, Heijnen C, Skranes J, Brubakk AM, Brekken C (2009) Manganese-enhanced magnetic resonance imaging of hypoxic–ischemic brain injury in the neonatal rat. Neuroimage 45(3):880–890CrossRefPubMed
35.
go back to reference Huang GY, Wessels A, Smith BR, Linask KK, Ewart JL, Lo CW (1998) Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development. Dev Biol 198(1):32–44CrossRefPubMed Huang GY, Wessels A, Smith BR, Linask KK, Ewart JL, Lo CW (1998) Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development. Dev Biol 198(1):32–44CrossRefPubMed
36.
go back to reference Smith BR (2001) Magnetic resonance microscopy in cardiac development. Microsc Res Tech 52(3):323–330CrossRefPubMed Smith BR (2001) Magnetic resonance microscopy in cardiac development. Microsc Res Tech 52(3):323–330CrossRefPubMed
37.
go back to reference Wu Y, Wu EX (2009) MR study of postnatal development of myocardial structure and left ventricular function. J Magn Reson Imag 30(1):47–53CrossRef Wu Y, Wu EX (2009) MR study of postnatal development of myocardial structure and left ventricular function. J Magn Reson Imag 30(1):47–53CrossRef
38.
go back to reference Lima JA, Desai MY (2004) Cardiovascular magnetic resonance imaging: current and emerging applications. J Am Coll Cardiol 44(6):1164–1171CrossRefPubMed Lima JA, Desai MY (2004) Cardiovascular magnetic resonance imaging: current and emerging applications. J Am Coll Cardiol 44(6):1164–1171CrossRefPubMed
39.
go back to reference Petiet AE, Kaufman MH, Goddeeris MM, Brandenburg J, Elmore SA, Johnson GA (2008) High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database. Proc Natl Acad Sci USA 105(34):12331–12336CrossRefPubMed Petiet AE, Kaufman MH, Goddeeris MM, Brandenburg J, Elmore SA, Johnson GA (2008) High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database. Proc Natl Acad Sci USA 105(34):12331–12336CrossRefPubMed
Metadata
Title
Microscopic magnetic resonance in congenital diaphragmatic hernia and associated malformations in rats
Authors
Montserrat Bret
Ana Lourdes Luis
Emilio Cuesta
Federica Pederiva
Rosa Aras
Leopoldo Martinez
Juan A. Tovar
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Pediatric Surgery International / Issue 1/2010
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-009-2518-4

Other articles of this Issue 1/2010

Pediatric Surgery International 1/2010 Go to the issue