title: Cerebral perfusion in perinatal hypoxia and resuscitation assessed by transcranial contrast-enhanced ultrasound and 3 T MRI in newborn pigs.
abstract: OBJECTIVE
  Cerebrovascular factors are crucially involved in the early injury after perinatal asphyxia. With magnetic resonance imaging (MRI) and ultrasonography (US), this study aimed to quantify microvascular perfusion changes due to hypoxia and resuscitation, by comparing contrast-enhanced ultrasound (CEUS) to dynamic susceptibility contrast-enhanced (DSC)-MRI and diffusion-weighted MRI.
  
  
  METHODS
  Newborn piglets (n = 12/17) were reoxygenated with 21% (n = 6) or 100% O2 (n = 6) after global hypoxia. Five piglets served as controls. CEUS and MRI were performed before, during, and up to 7 hours after hypoxia. Following are the perfusion parameters for CEUS: peak intensity (PI), area under the curve (AUC), time to peak (TTP), and upslope a and perfusion/diffusion parameters for MRI: relative cerebral blood volume, relative cerebral blood flow, mean transit time, and apparent diffusion coefficient were compared between different regions in the brain across time points and also compared with histology at the end.
  
  
  RESULTS
  In CEUS, compared with the control group, perfusion changed significantly over time, in the hyperoxic group in all regions for PI, AUC in all regions of interests. The changes presented mainly as decreased perfusion during and shortly after resuscitation: for PI in the basal ganglia (BG), cortex, and the whole brain with 50 to 60% (P ≤ 0.001); for AUC in the BG and cortex with 90% (P ≤ 0.02) and in the whole brain with 70% (P = 0.004). In the injured brains (confirmed by histology), significant changes over time were seen in TTP and AUC with mainly increased perfusion during hypoxia: for TTP in the cortex, AUC in the BG and whole brain with 90 to 100% (P ≤ 0.04), and for TTP in the whole brain with 50% (P = 0.02). DSC-MRI showed the same trends in perfusion with regard to relative cerebral blood volume as CEUS. In all pigs exposed to hypoxia, perfusion returned toward baseline values at 7 hours after hypoxia in both methods. Apparent diffusion coefficient decreased significantly after 7 hours in the injured brains in the BG from 114.6 ± 1.2 × 10mm/s to 90.3 ± 24 × 10 mm/s (P = 0.03).
  
  
  CONCLUSIONS
  CEUS and DSC-MRI can detect an early temporal evolution of cerebral perfusion in perinatal hypoxia and resuscitation, reversible after 7 hours. Hyperoxic resuscitation caused early decreased cerebral perfusion, not present in the normoxic group. The combined use of CEUS and DSC-MRI can provide important diagnostic information and give new insights into perinatal vascular hypoxia mechanisms.
authors: Department of Paediatric Research, Oslo University Hospital, Oslo, Norway. charlotte.de.lange@rr-research.no
authors: Charlotte
authors: C
authors: de Lange
authors: Knut
authors: K
authors: Brabrand
authors: Kyrre E
authors: KE
authors: Emblem
authors: Atle
authors: A
authors: Bjornerud
authors: Else Marit
authors: EM
authors: Løberg
authors: Ola Didrik
authors: OD
authors: Saugstad
authors: Berit H
authors: BH
authors: Munkeby
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D003287:Contrast Media / Q000008:administration & dosage; D004453:Echoencephalography / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008833:Microcirculation; D010743:Phospholipids / Q000008:administration & dosage; D012151:Resuscitation / Q000379:methods; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D013552:Swine
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride