Iwata, O; (2014) Temporal and Spatial Evolution of Cerebral Injury in the Piglet Asphyxia Model: a Comparative Study of Serial Magnetic Resonance Biomarkers and Histopathology. Doctoral thesis , UCL (University College London).

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Abstract

Background: After hypoxia-ischaemia and successful resuscitation, cerebral energy metabolism transiently recovers to the normal level (latent phase); after a variable period of time this phase is followed by secondary energy failure (SEF) in those subjects with an adverse outcome. A better understanding of the regional evolution of SEF may enhance the application of future neuroprotective strategies. Aims: The aim of this thesis was to determine associations between the insult severity, regional SEF evolution, and subsequent histo-pathological brain injury using magnetic resonance biomarkers. Methods: An established piglet model of neonatal encephalopathy was used. 1. Twenty-nine piglets were studied either normothermic or hypothermic (35°C or 33°C during 2-26 hours after hypoxia-ischaemia). 31-phosphorus magnetic resonance spectroscopy (31P MRS) was serially acquired; the brain was assessed histo-pathologically after 48 hours. 2. Global 31P MRS, and maps of apparent diffusion coefficient (ADC) and transverse relaxation time (T2) were serially obtained in 3 control and 18 asphyxiated piglets. Histo-pathological brain injury and MR biomarkers were compared at time periods of 16-48 hours after hypoxia-ischaemia. Results: 1. Severe acute insult, short latent phase, severe SEF and profound histo-pathological brain injury were associated between each other. 2. Transient recovery in phosphocreatine (PCr) higher than its baseline was indicative of absent subsequent evolution of SEF, whereas sub-baseline PCr recovery was suggestive of severe SEF. 3. Global 31P MRS biomarkers and regional ADC obtained just prior to termination and up to 18-24 hours before termination predicted histo-pathological brain injury; the predictive value was optimal for global PCr/ inorganic phosphate (Pi), followed by global PCr/exchangeable high-energy phosphate pool (EPP), Pi/EPP and regional ADC. Conclusions: Although 31P MRS was more accurate, regional ADC predicted subsequent brain injury up to 18 hours in advance of termination. Regional ADC can be used as a sensitive early marker for subsequent tissue injury when 31P MRS is not available.

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