title: Near-term fetal hypoxia-ischemia in rabbits: MRI can predict muscle tone abnormalities and deep brain injury.
abstract: OBJECTIVE
  The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia-ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus.
  
  
  METHODS
  Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia-ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia-ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments.
  
  
  RESULTS
  Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits.
  
  
  CONCLUSIONS
  MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia-ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo- to hypertonia may identify patients at risk for developing cerebral palsy.
authors: Department of Pediatrics, NorthShore University Health Systems, Evanston, IL 60202, USA. oldrobys@gmail.com
authors: Alexander
authors: A
authors: Drobyshevsky
authors: Matthew
authors: M
authors: Derrick
authors: Kehuan
authors: K
authors: Luo
authors: Li-Qun
authors: LQ
authors: Zhang
authors: Yi-Ning
authors: YN
authors: Wu
authors: Silvia Honda
authors: SH
authors: Takada
authors: Lei
authors: L
authors: Yu
authors: Sidhartha
authors: S
authors: Tan
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D002547:Cerebral Palsy / Q000453:epidemiology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications*; D005333:Fetus / Q000503:physiopathology; D005865:Gestational Age; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D023421:Models, Animal; D009122:Muscle Hypertonia / Q000503:physiopathology*; D009123:Muscle Hypotonia / Q000503:physiopathology*; D009129:Muscle Tonus / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011817:Rabbits; D012307:Risk Factors; D013997:Time Factors