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Title: Temporal and spatial evolution of cerebral injury in the piglet asphyxia model : a comparative study of serial magnetic resonance biomarkers and histopathology
Author: Iwata, O.
ISNI:       0000 0004 5358 0555
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available