Abstract
Introduction:
Appeal for the domestic pig as a preclinical model for neurodevelopmental research is increasing. One limitation, however, is lack of magnetic resonance imaging (MRI) methods for brain volume quantification in the neonatal piglet. The purpose of this study was to develop and validate MRI methods for estimating brain volume in piglets.
Results:
The results showed that MRI and manual segmentation reliably estimated the changes in volume of different brain regions in 2- and 5-wk-old piglets. Substantial increases in the volumes of all brain regions examined were evident during the 3-wk period.
Discussion:
MRI can provide accurate estimates of brain region volume during the neonatal period in piglets. A piglet model that can be used in longitudinal studies may be useful for investigating how experimental (e.g., nutrition, infection) factors affect brain growth and development.
Methods:
Anatomic MRI data (non-longitudinal) were acquired 2- and 5-wk-old piglets using a three-dimensional T1-weighted magnetization-prepared gradient echo (MPRAGE) sequence on a MAGNETOM Trio 3T imager. Manual segmentation was performed for volume estimates of total brain, cortical, diencephalon, brainstem, cerebellar, and hippocampal regions. The MRI-based hippocampal volume estimates in 2- and 5-wk-old piglets were validated using histological techniques and the Cavalieri method.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Dixon JA, Spinale FG. Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail 2009;2:262–71.
Bellinger DA, Merricks EP, Nichols TC . Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance, and cardiovascular complications. ILAR J 2006;47:243–58.
Miller ER, Ullrey DE . The pig as a model for human nutrition. Annu Rev Nutr 1987;7:361–82.
Lind NM, Moustgaard A, Jelsing J, Vajta G, Cumming P, Hansen AK . The use of pigs in neuroscience: modeling brain disorders. Neurosci Biobehav Rev 2007;31:728–51.
Pond WG, Boleman SL, Fiorotto ML, et al. Perinatal ontogeny of brain growth in the domestic pig. Proc Soc Exp Biol Med 2000;223:102–8.
Dobbing J, Sands J . Comparative aspects of the brain growth spurt. Early Hum Dev 1979;3:79–83.
Dickerson JWT, Dobbing J . Prenatal and postnatal growth and development of the central nervous system of the pig. Proc R Soc Lond 1967;166:384–95.
Thibault KL, Margulies SS . Age-dependent material properties of the porcine cerebrum: effect on pediatric inertial head injury criteria. J Biomech 1998;31:1119–26.
Dilger RN, Johnson RW . Behavioral assessment of cognitive function using a translational neonatal piglet model. Brain Behav Immun 2010;24:1156–65.
Ganessunker D, Gaskins HR, Zuckermann FA, Donovan SM . Total parenteral nutrition alters molecular and cellular indices of intestinal inflammation in neonatal piglets. JPEN J Parenter Enteral Nutr 1999;23:337–44.
Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR . Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med 2000;343:378–84.
Giedd JN, Vaituzis AC, Hamburger SD,et al. Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years. J Comp Neurol 1996;366:223–30.
Knickmeyer RC, Gouttard S, Kang C,et al. A structural MRI study of human brain development from birth to 2 years. J Neurosci 2008;28:12176–82.
Giedd JN, Blumenthal J, Jeffries NO,et al. Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 1999;2:861–3.
Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO . A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 1994;51:874–87.
Gilmore JH, Lin W, Prastawa MW,et al. Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. J Neurosci 2007;27:1255–60.
Dubois J, Benders M, Cachia A,et al. Mapping the early cortical folding process in the preterm newborn brain. Cereb Cortex 2008;18:1444–54.
Thompson DK, Wood SJ, Doyle LW, et al. Neonate hippocampal volumes: prematurity, perinatal predictors, and 2-year outcome. Ann Neurol 2008;63:642–51.
Beauchamp MH, Thompson DK, Howard K, et al. Preterm infant hippocampal volumes correlate with later working memory deficits. Brain 2008;131(Pt 11):2986–94.
Jelsing J, Rostrup E, Markenroth K, et al. Assessment of in vivo MR imaging compared to physical sections in vitro–a quantitative study of brain volumes using stereology. Neuroimage 2005;26:57–65.
Kuluz J, Samdani A, Benglis D, et al. Pediatric spinal cord injury in infant piglets: description of a new large animal model and review of the literature. J Spinal Cord Med 2010;33:43–57.
Rosendal F, Pedersen M, Sangill R, et al. MRI protocol for in vivo visualization of the Göttingen minipig brain improves targeting in experimental functional neurosurgery. Brain Res Bull 2009;79:41–5.
Sandberg DI, Crandall KM, Koru-Sengul T, et al. Pharmacokinetic analysis of etoposide distribution after administration directly into the fourth ventricle in a piglet model. J Neurooncol 2010;97:25–32.
Björkman ST, Miller SM, Rose SE, Burke C, Colditz PB . Seizures are associated with brain injury severity in a neonatal model of hypoxia-ischemia. Neuroscience 2010;166:157–67.
Munkeby BH, De Lange C, Emblem KE, et al. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging. Acta Radiol 2008;49:1049–57.
Shi F, Fan Y, Tang S, Gilmore JH, Lin W, Shen D . Neonatal brain image segmentation in longitudinal MRI studies. Neuroimage 2010;49:391–400.
Saikali S, Meurice P, Sauleau P, et al. A three-dimensional digital segmented and deformable brain atlas of the domestic pig. J Neurosci Methods 2010;192:102–9.
Cotter D, Miszkiel K, Al-Sarraj S, et al. The assessment of postmortem brain volume; a comparison of stereological and planimetric methodologies. Neuroradiology 1999;41:493–6.
Boardman JP, Counsell SJ, Rueckert D, et al. Abnormal deep grey matter development following preterm birth detected using deformation-based morphometry. Neuroimage 2006;32:70–8.
Bokde AL, Teipel SJ, Schwarz R, et al. Reliable manual segmentation of the frontal, parietal, temporal, and occipital lobes on magnetic resonance images of healthy subjects. Brain Res Brain Res Protoc 2005;14:135–45.
Yu X, Zhang Y, Lasky RE, Datta S, Parikh NA, Narayana PA . Comprehensive brain MRI segmentation in high risk preterm newborns. PLoS ONE 2010;5:e13874.
Brinkmann BH, Manduca A, Robb RA . Optimized homomorphic unsharp masking for MR grayscale inhomogeneity correction. IEEE Trans Med Imaging 1998;17:161–71.
Félix B, Léger ME, Albe-Fessard D, Marcilloux JC, Rampin O, Laplace JP . Stereotaxic atlas of the pig brain. Brain Res Bull 1999;49:1–137.
Bobinski M, de Leon MJ, Wegiel J, et al. The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer’s disease. Neuroscience 2000;95:721–5.
Bland JM, Altman DG . Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.
British Standards Institution 1998 Accuracy (trueness and precision) of measurement methods and results. Alternative methods for the determination of the precision of a standard measurement method. BS ISO 5725-5:1998.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Conrad, M., Dilger, R., Nickolls, A. et al. Magnetic resonance imaging of the neonatal piglet brain. Pediatr Res 71, 179–184 (2012). https://doi.org/10.1038/pr.2011.21
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2011.21
This article is cited by
-
A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
Fluids and Barriers of the CNS (2021)
-
Cerebral organoids and their potential for studies of brain diseases in domestic animals
Veterinary Research (2021)
-
Comparing interspecific socio-communicative skills of socialized juvenile dogs and miniature pigs
Animal Cognition (2019)
