{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:15Z","timestamp":1785422715571,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013348","name":"Innosuisse\u2013Schweizerische Agentur f\u00fcr Innovationsf\u00f6rderung","doi-asserted-by":"crossref","award":["56642.1 IP-LS"],"award-info":[{"award-number":["56642.1 IP-LS"]}],"id":[{"id":"10.13039\/501100013348","id-type":"DOI","asserted-by":"crossref"}]},{"award":["56642.1 IP-LS"],"award-info":[{"award-number":["56642.1 IP-LS"]}],"id":[{"id":"https:\/\/ror.org\/05a2bhn71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Background and Purpose: Neurological injury remains a major complication of pediatric cardiac surgery and is closely related to alterations in cerebral blood flow during extracorporeal circulation (ECC). However, the real-time assessment of cerebral perfusion under these conditions has been limited by the lack of magnetic resonance (MR)-compatible perfusion systems. The aim of this pilot feasibility study was to establish a porcine model enabling simultaneous cardiopulmonary bypass (CPB) and real-time MR-based assessment of cerebral blood flow during simulated pediatric cardiac surgery. Methods: We conducted a pilot study on 11 Duroc pigs (14.6 \u00b1 1.4 kg BW), designed in iterative cycles. The experimental setup included an MR-conditional heart-lung machine and a surgical protocol closely mimicking pediatric cardiac surgery. After the initiation of CPB and hemodynamic stabilization, animals were cooled to target temperatures (20 \u00b0C or 28 \u00b0C) depending on the perfusion strategy. Structural and functional MRI, including phase-contrast imaging, arterial spin labeling, diffusion-weighted imaging, and MR spectroscopy, were performed during cooling and rewarming. Procedural feasibility, technical challenges, and optimization strategies were systematically documented. Results: The study successfully established a reproducible porcine model enabling MR imaging during extracorporeal circulation. Key technical challenges, including vascular access, cannulation of the ascending aorta, and blood volume management, were identified and addressed through the iterative refinement of the surgical and perfusion protocols. The use of the Seldinger technique significantly improved cannulation safety and reduced blood loss. Stable CPB conditions and target hypothermic temperatures were achieved in successfully cannulated animals. MRI acquisition during CPB was feasible, providing simultaneous structural and functional assessment of cerebral perfusion. Representative imaging data demonstrate the capability of the model to capture cerebral hemodynamics in real time. Conclusions: This pilot study establishes a novel MR-compatible porcine model for the real-time assessment of cerebral blood flow during extracorporeal circulation. The platform provides a robust foundation for future quantitative investigations of cerebral perfusion, mechanisms of brain injury, and neuroprotective strategies in pediatric cardiac surgery.<\/jats:p>","DOI":"10.3390\/jcdd13050182","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:49:36Z","timestamp":1777362576000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of an MR-Conditional Porcine Model for Real-Time Assessment of Cerebral Blood Flow During Extracorporeal Circulation"],"prefix":"10.3390","volume":"13","author":[{"given":"Michael","family":"Hofmann","sequence":"first","affiliation":[{"name":"Vascular Surgery, Hirslanden, 9016 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0210-7904","authenticated-orcid":false,"given":"Martin O.","family":"Schmiady","sequence":"additional","affiliation":[{"name":"Clinic for Cardiac Surgery, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-6726","authenticated-orcid":false,"given":"Dominik T.","family":"Schulte","sequence":"additional","affiliation":[{"name":"Institute for Dynamic Systems and Control, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6958-7107","authenticated-orcid":false,"given":"Tobias","family":"Aigner","sequence":"additional","affiliation":[{"name":"Clinic for Cardiac Surgery, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Bektas","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"},{"name":"Diagnostic Imaging Research Unit (DIRU), Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Wieser","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Lentini","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-1961","authenticated-orcid":false,"given":"Francesca","family":"Del Chicca","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging Research Unit (DIRU), Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Loeschmann","sequence":"additional","affiliation":[{"name":"Clinic for Cardiac Surgery, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"H\u00fcbler","sequence":"additional","affiliation":[{"name":"Surgery for Congenital Heart Disease, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth O\u2019Gorman","family":"Tuura","sequence":"additional","affiliation":[{"name":"Center for MR Research, Children\u2019s Hospital, University of Zurich, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6411-8871","authenticated-orcid":false,"given":"Marianne","family":"Schmid Daners","sequence":"additional","affiliation":[{"name":"Institute for Dynamic Systems and Control, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-6993","authenticated-orcid":false,"given":"Henning","family":"Richter","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging Research Unit (DIRU), Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","first-page":"54021","article-title":"Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction","volume":"116","author":"Ellenbroek","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hocum Stone, L., Wright, C., Chappuis, E., Messer, M., Ward, H.B., McFalls, E.O., and Kelly, R.F. (2018). Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery. J. Vis. Exp., 57229.","DOI":"10.3791\/57229"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.athoracsur.2010.12.066","article-title":"Minimal safe arterial blood flow during selective antegrade cerebral perfusion at 20 degrees centigrade","volume":"91","author":"Jonsson","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/icvts\/ivx393","article-title":"Deep hypothermic circulatory arrest or tepid regional cerebral perfusion: Impact on haemodynamics and myocardial integrity in a randomized experimental trial","volume":"26","author":"Kellermann","year":"2018","journal-title":"Interdiscip. Cardiovasc. Thorac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/01.mat.0000194058.62228.56","article-title":"MRI of the brain and thorax during extracorporeal membrane oxygenation: Preliminary report from a pig model","volume":"52","author":"Lidegran","year":"2006","journal-title":"ASAIO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.athoracsur.2018.12.012","article-title":"Interrelationship Between Hemodynamics, Brain Volumes, and Outcome in Hypoplastic Left Heart Syndrome","volume":"107","author":"Reich","year":"2019","journal-title":"Ann. Thorac. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.jacc.2012.01.086","article-title":"Percutaneous treatment of patent foramen ovale and atrial septal defects","volume":"60","author":"Tobis","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jtcvs.2004.07.022","article-title":"Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects","volume":"128","author":"Licht","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/ejcts\/ezr286","article-title":"Mortality and neurodevelopmental outcome at 1 year of age comparing hybrid and Norwood procedures","volume":"42","author":"Knirsch","year":"2012","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1111\/dmcn.12242","article-title":"Neurodevelopmental outcome, psychological adjustment, and quality of life in adolescents with congenital heart disease","volume":"55","author":"Schaefer","year":"2013","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/ejcts\/ezt422","article-title":"Cerebral lesions on magnetic resonance imaging correlate with preoperative neurological status in neonates undergoing cardiopulmonary bypass surgery","volume":"45","author":"Bertholdt","year":"2014","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/brain\/awt322","article-title":"Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease","volume":"137","author":"Buchmann","year":"2014","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1177\/0883073815591214","article-title":"Regional Microstructural and Volumetric Magnetic Resonance Imaging (MRI) Abnormalities in the Corpus Callosum of Neonates with Congenital Heart Defect Undergoing Cardiac Surgery","volume":"31","author":"Hagmann","year":"2016","journal-title":"J. Child. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.jpeds.2015.07.006","article-title":"Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes","volume":"167","author":"Buchmann","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14909","DOI":"10.1038\/s41598-020-72009-3","article-title":"Investigating altered brain development in infants with congenital heart disease using tensor-based morphometry","volume":"10","author":"Ng","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.3174\/ajnr.A7328","article-title":"A Uniform Description of Perioperative Brain MRI Findings in Infants with Severe Congenital Heart Disease: Results of a European Collaboration","volume":"42","author":"Stegeman","year":"2021","journal-title":"Am. J. Neuroradiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41390-022-02063-2","article-title":"Neuromonitoring, neuroimaging, and neurodevelopmental follow-up practices in neonatal congenital heart disease: A European survey","volume":"93","author":"Feldmann","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"g7635","DOI":"10.1136\/bmj.g7635","article-title":"Cerebral near infrared spectroscopy oximetry in extremely preterm infants: Phase II randomised clinical trial","volume":"350","author":"Pellicer","year":"2015","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/aas.12736","article-title":"Cerebral microemboli detected by transcranial doppler in patients treated with extracorporeal membrane oxygenation","volume":"60","author":"Marinoni","year":"2016","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1053\/j.semperi.2017.12.007","article-title":"Neuromonitoring in the neonatal ECMO patient","volume":"42","author":"Lin","year":"2018","journal-title":"Semin. Perinatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1161\/CIRCULATIONAHA.112.001089","article-title":"New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest","volume":"127","author":"Beca","year":"2013","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1016\/j.jacc.2018.02.068","article-title":"Neonatal Brain Injury and Timing of Neurodevelopmental Assessment in Patients with Congenital Heart Disease","volume":"71","author":"Peyvandi","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/dmcn.15024","article-title":"Early motor outcomes in infants with critical congenital heart disease are related to neonatal brain development and brain injury","volume":"64","author":"Stegeman","year":"2022","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113838","DOI":"10.1016\/j.jpeds.2023.113838","article-title":"Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: Results from a European Collaboration","volume":"266","author":"Neukomm","year":"2024","journal-title":"J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/dmcn.13747","article-title":"Perioperative neonatal brain injury is associated with worse school-age neurodevelopment in children with critical congenital heart disease","volume":"60","author":"Claessens","year":"2018","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1161\/CIRCULATIONAHA.115.019881","article-title":"Brain in Congenital Heart Disease Across the Lifespan: The Cumulative Burden of Injury","volume":"133","author":"Marelli","year":"2016","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.clp.2013.09.005","article-title":"Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage","volume":"41","author":"Benders","year":"2014","journal-title":"Clin. Perinatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(83)91906-2","article-title":"Non-invasive investigation of cerebral metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy","volume":"321","author":"Cady","year":"1983","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13250","DOI":"10.1038\/s41598-017-13753-x","article-title":"Punctate White Matter Lesions Associated with Altered Brain Development And Adverse Motor Outcome In Preterm Infants","volume":"7","author":"Tusor","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/s41598-023-28634-9","article-title":"Altered white matter connectivity in children with congenital heart disease with single ventricle physiology","volume":"13","author":"Williamson","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1159\/000531179","article-title":"The Introduction of an MR-Conditional Prototype for Cardiopulmonary Bypass Support: Technical Aspects and System Requirements","volume":"64","author":"Hofmann","year":"2023","journal-title":"Eur. Surg. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/aor.70041","article-title":"Hydraulic In Vitro Characterization of MR-Conditional Blood Pumps","volume":"50","author":"Schulte","year":"2025","journal-title":"Artif. Organs"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schulte, D.T., Pietsch, C., Topalovic, N., Hofmann, M., Schmiady, M.O., Weisskopf, M., and Schmid Daners, M. (2025). Preliminary in vitro hemolysis evaluation of MR-conditional blood pumps. Front. Med. Technol., 7.","DOI":"10.3389\/fmedt.2025.1671938"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e70284","DOI":"10.1002\/nbm.70284","article-title":"Cerebral Hemodynamic Changes During Cardiac Surgery: A Feasibility MR Study in Piglets","volume":"39","author":"Schulte","year":"2026","journal-title":"NMR Biomed."},{"key":"ref_35","first-page":"R293","article-title":"Splenic red cell sequestration and blood volume measurements in conscious pigs","volume":"248","author":"Hannon","year":"1985","journal-title":"Am. J. Physiol."},{"key":"ref_36","first-page":"705","article-title":"Alpha-stat vs. pH-stat strategy during hypothermic cardiopulmonary bypass","volume":"17","author":"Baraka","year":"2004","journal-title":"Middle East J. Anaesthesiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1177\/096721090100900614","article-title":"Is deep hypothermia necessary for unilateral antegrade cerebral perfusion during circulatory arrest? A magnetic resonance study in a pig model","volume":"9","author":"Ye","year":"2001","journal-title":"Cardiovasc. Surg."},{"key":"ref_38","first-page":"e65266","article-title":"Pediatric Animal Model of Extracorporeal Cardiopulmonary Resuscitation after Prolonged Circulatory Arrest","volume":"195","author":"Ball","year":"2023","journal-title":"J. Vis. Exp."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.jvs.2013.01.035","article-title":"Impact of hospital volume and type on outcomes of open and endovascular repair of descending thoracic aneurysms in the United States Medicare population","volume":"58","author":"Patel","year":"2013","journal-title":"J. Vasc. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.athoracsur.2013.02.039","article-title":"National outcomes in acute aortic dissection: Influence of surgeon and institutional volume on operative mortality","volume":"95","author":"Chikwe","year":"2013","journal-title":"Ann. Thorac. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.jacc.2012.06.023","article-title":"Contemporary results for proximal aortic replacement in North America","volume":"60","author":"Williams","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/j.athoracsur.2010.06.111","article-title":"Impact of pump flow rate during selective cerebral perfusion on cerebral hemodynamics and metabolism","volume":"90","author":"Haldenwang","year":"2010","journal-title":"Ann. Thorac. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.jtcvs.2009.10.021","article-title":"Effect of pressure management during hypothermic selective cerebral perfusion on cerebral hemodynamics and metabolism in pigs","volume":"139","author":"Haldenwang","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.jtcvs.2007.09.035","article-title":"Optimizing selective cerebral perfusion: Deleterious effects of high perfusion pressures","volume":"135","author":"Halstead","year":"2008","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_45","first-page":"1492","article-title":"The impact of deep and moderate body temperatures on end-organ function during hypothermic circulatory arrest","volume":"40","author":"Khaladj","year":"2011","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S0003-4975(01)02897-1","article-title":"Involvement of apoptosis in neurological injury after hypothermic circulatory arrest: A new target for therapeutic intervention?","volume":"72","author":"Hagl","year":"2001","journal-title":"Ann. Thorac. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.molmet.2017.06.004","article-title":"The Munich MIDY Pig Biobank\u2014A unique resource for studying organ crosstalk in diabetes","volume":"6","author":"Blutke","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1093\/hmg\/ddt287","article-title":"Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle","volume":"22","author":"Klymiuk","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/0300985811402846","article-title":"Swine as models in biomedical research and toxicology testing","volume":"49","author":"Swindle","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/0192623315617562","article-title":"The Use of Minipigs for Preclinical Safety Assessment by the Pharmaceutical Industry: Results of an IQ DruSafe Minipig Survey","volume":"44","author":"Colleton","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1532-429X-12-53","article-title":"An isolated perfused pig heart model for the development, validation and translation of novel cardiovascular magnetic resonance techniques","volume":"12","author":"Schuster","year":"2010","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/uog.1785","article-title":"Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus","volume":"25","author":"Kaltman","year":"2005","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1161\/CIRCULATIONAHA.114.013051","article-title":"Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease","volume":"131","author":"Sun","year":"2015","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jtcvs.2009.08.022","article-title":"Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring","volume":"139","author":"Andropoulos","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_55","first-page":"102","article-title":"Perinatal ontogeny of brain growth in the domestic pig","volume":"223","author":"Pond","year":"2000","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000339311","article-title":"Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: A longitudinal MRI study","volume":"34","author":"Conrad","year":"2012","journal-title":"Dev. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41684-023-01308-9","article-title":"Challenging current scientific practice: How a shift in research methodology could reduce animal use","volume":"53","author":"Richter","year":"2024","journal-title":"Lab Anim."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41593-020-00792-3","article-title":"Increasing the statistical power of animal experiments with historical control data","volume":"24","author":"Bonapersona","year":"2021","journal-title":"Nat. Neurosci."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/5\/182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:38:03Z","timestamp":1777437483000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/5\/182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcdd13050182"],"URL":"https:\/\/doi.org\/10.3390\/jcdd13050182","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]}}}