Early effects of perinatal hypoxia and resuscitation on cerebral perfusion and metabolism assessed by MRI, CEUS and FDG-PET. : Experimental studies in newborn pigs
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AbstractBirth asphyxia is worldwide, still an important cause of child morbidity and mortality. Early detection of cerebral hypoxic ischemic (HI) injury is important in order to start neuroprotective treatment. Neuroimaging methods play an important role in the diagnosis and prognosis, and magnetic resonance imaging (MRI) is considered the most specific and sensitive method. However, MRI is expensive and difficult to perform during the short therapeutic time window after the insult. In asphyctic newborn infants, resuscitation with high-level oxygen ventilation has proven harmful to the organs and consequently resuscitation with air is now recommended. This thesis introduces and evaluates radiological and nuclear medicine methods for use in newborn piglets, to detect early effects and mechanisms of perinatal cerebral HI and resuscitation related to injury. Using a piglet model, cerebral perfusion, diffusion and glucose metabolism were studied. Changes during and after hypoxia/hypoxia-ischemia were correlated to the resuscitation mode and histopathologic findings. In 3 different studies, contrast enhanced ultrasonography (CEUS) and dynamic susceptibility contrast (DSC) enhanced-, diffusion weighted- (DWI) MR imaging, MR spectroscopy (MRS) and Positron emission tomography with fluorodeoxyglucose (FDGPET), were used. Our findings confirmed that HI injury in the piglet could reveal diffusion and MRS changes correlated to injury, and this is in accordance with other clinical studies. After global hypoxia, CEUS revealed changes in cerebral perfusion, with decreased values during resuscitation with 100% O2, not found when using air. The changes in MRI /CEUS perfusion were transient, with poor correlation to diffusion and histopathologic findings. Dynamic FDG-PET detected an immediate decrease of cerebral glucose metabolism after perinatal hypoxia. This may indicate early changes of mild cerebral HI injury. No significant influence of resuscitation with 100% O2 versus air was found. We conclude that the piglet model is suitable for assessing early changes of cerebral diffusion, metabolism and microvascular perfusion after HI injury. MRI, CEUS or FDGPET cannot be used alone in the early detection of cerebral HI injury. These adapted techniques can provide further insights into the mechanisms of perinatal hypoxia-ischemia, where early detection plays an important role for instituting therapy.
List of papers. The papers are removed from the thesis due to copyright restrictions.
Paper I Munkeby BH, de Lange C, Emblem KE, Bjørnerud A, Kro GA, Andresen J, Winther-Larssen EH, Løberg EM, Hald JK. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging Acta Radiol. 2008 Nov;49(9):1049-57 doi:10.1080/02841850802334224
Paper II de Lange C, Brabrand K, Emblem KE, Bjørnerud A, Løberg EM, Saugstad OD, Munkeby BH. Cerebral perfusion in perinatal hypoxia and resuscitation assessed by transcranial contrast-enhanced ultrasound and 3 T MRI in newborn pigs. Invest Radiol. 2011 Nov;46(11):686-96 doi:10.1097/RLI.0b013e3182266431
Paper III de Lange C, Malinen E, Qu H, Johnsrud K, Skretting A, Saugstad OD, Munkeby BH. Dynamic FDG-PET for assessing early effects of cerebral hypoxia and resuscitation in newborn pigs. Eur J Nucl Med. 2012 Feb 2, Epub ahead of print. doi:10.1007/s00259-011-2055-y