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Investigation of brain tissue oxygenation, cytochrome-c-oxidase measured with NIRS and intracellular metabolites measured with MRS during perinatal cerebral hypoxia-ischaemia

Presented at the Neonatal Society 2012 Autumn Meeting.

Tachtsidis I1, Bainbridge A2, Bär E1, Broad K3, Ezzat M3, Faulkner S3, Price D2, Powell E3, Thomas D4, Cady E2, Golay X4, Robertson N3

1 Dept. of Medical Physics and Bioengineering, University College London, UK
2 Medical Physics and Bioengineering, UCLH NHS Foundation Trust, UK
3 Institute for Women’s Health, University College London, UK
4 Institute of Neurology, University College London, UK

Background: Hypoxic-ischaemia (HI) neonatal encephalopathy is associated with high mortality and morbidity rates worldwide. Using magnetic resonance spectroscopy (MRS), our piglet model previously defined the biphasic pattern of energy disruption during and after HI (1). However, the precise relationship between energy failure and cell death are still unclear. To investigate these relationships we have integrated two non-invasive techniques broadband near-infrared spectroscopy (NIRS) and MRS (2). Broadband NIRS can be used to measure the brain tissue oxygenation and the oxidation state of cytochrome-c-oxidase (Δ[oxCCO]). CCO is the terminal electron acceptor of the mitochondrial electron transfer chain (ETC) which catalyses over 95% of oxygen metabolism. In this study we investigate brain oxygenation, CCO and energy-resource changes during transient HI and recovery using simultaneous broadband NIRS and phosphorus (31P) MRS in the piglet.

Methods: 22 healthy piglets (aged <24 hr) were anaesthetised and physiologically monitored. Transient cerebral HI (duration 20 minutes) was induced by reducing the inspired oxygenation and reversibly inflating bilateral carotid artery occluders. Using 31P MRS we measured inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and nucleotide triphosphate (NTP)/epp (epp=exchangeable phosphate pool=Pi+PCr+3NTP). NIRS measured cerebral concentration changes of oxy-haemoglobin (HbO2) and deoxy-haemoglobin (HHb), and cytochrome-c-oxidase oxidation state changes (Δ[oxCCO]).

Results: Simultaneous 31P-MRS and NIRS results are shown in Figure 1. HI rapidly reduced brain oxygenation as shown by changes in haemoglobin difference (Δ[Hbdiff]=Δ[HbO2]-Δ[HHb])) closely followed by a fall in Δ[oxCCO]. PCr/epp fell, and Pi/epp rose, quickly while NTP/epp was buffered initially and only declined when Δ[oxCCO] was significantly lowered. During recovery, metabolic markers for piglet 175 returned to baseline (Figure 1(a)); but they did not for piglet 183 (Figure 1(b)) indicating a severe insult.

Investigation of brain tissue oxygenation, cytochrome-c-oxidase measured with NIRS and intracellular metabolites measured with MRS during perinatal cerebral hypoxia-ischaemia


Figure 1: 31P-MRS and NIRS during HI and recovery; (a) piglet 175; (b) piglet183.

Conclusion: During transient HI, CCO becomes reduced due to oxygen depletion; adenosine triphosphate levels are initially preserved by the creatine kinase reaction leading to PCr decline whereas energy utilisation without oxidative phosphorylation leads to increased Pi. During recovery we have observed high association between the NIRS measurement of Δ[oxCCO] and 31P-MRS. Complementary MRS and NIRS enable better understanding of the cerebral metabolic response to HI and can help evaluate early interventional therapies.

Corresponding author: i.tachtsidis@ucl.ac.uk

References
1. Lorek A. et al. Pediatr.Res.,36,699-706(1994).
2. Tachtsidis I. et al. Biomedical Optics (BIOMED) 2012 JM3A.27 2012.

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