Monitoring cerebral metabolism following newborn brain injury Event as iCalendar


18 July 2016

3 - 4pm

Venue: Room 201

Location: 70 Symonds St, Auckland Central

A seminar by Dr Subhabrata Mitra, Clinical Research Associate, Neonatology, Institute for Woman’s Health, University College London and Honorary Consultant, Neonatal Unit, University College London Hospital.


Perinatal brain injury remains a significant cause of morbidity and mortality in newborn infants. Thalamic Lac/NAA peak area ratio on 1H MRS is the best available outcome biomarker following hypoxic ischaemic encephalopathy (HIE); Lac/NAA > 0.3 is associated with poor neurodevelopment outcome.

Cytochrome-c-oxidase (CCO) plays a central role in cerebral mitochondrial oxidative metabolism and ATP synthesis. Using a novel broadband near infrared spectroscopy (NIRS) system, we monitored the changes in the oxidation state of CCO and investigated the impact of pressure passivity of cerebral metabolism (CCO), oxygenation (HbD=HbO2-HHb) and cerebral blood volume (HbT=HbO2+HHb) following HIE.

Ethical approval and informed consent were obtained. Δ[oxCCO], Δ[HbD] and Δ[HbT] were measured in 23 term infants following HIE during therapeutic hypothermia. Physiological and NIRS data were synchronised. 60 minute episodes of stable dataset from each infant at a mean age of 48hrs were examined with MATLAB based wavelet analysis. Wavelet semblance (measure of phase differences) was used to compare arterial blood pressure (ABP) with CCO, HbD and HbT. We also investigated recurrent seizures in one infant during the rewarming period.

CCO/ABP semblance was better correlated with Lac/NAA (r=0.49, p=0.02) compared to HbD/ABP semblance (r=0.27, p=0.21) and HbT/ABP semblance (r=0.23, p=0.28). CCO/ABP semblance was significantly different between two groups of infants with good outcome (Lac/NAA<0.3 (n=12)) and poor neurodevelopmental outcome (Lac/NAA>0.3 (n=11)) (p=0.04). HbD/ABP and HbT/ABP semblance were not significantly different between the groups.

At the start of each seizure (indicated by a rise in the baseline of the aEEG), the Δ[oxCCO] increased by 3.30 ± 1 μMol/L. After aEEG peak, the Δ[oxCCO] starts to drop and it drops progressively to a lower baseline, which at the end of 90 minutes was at -4.19 μMol/L. Principal component analysis demonstrated a positive correlation between Δ[oxCCO] and mean aEEG of 0.51 ± 0.22 during all seizures.

Pressure passive changes in cerebral mitochondrial CCO following HIE were associated with poor outcome. CCO/ABP semblance was better associated with Lac/NAA, an established outcome biomarker following HIE, in comparison to both HbD/ABP and HbT/ABP semblance. A rapid increase in Δ[oxCCO] at the onset of seizures indicate an increase in mitochondrial energy consumption as the neuronal energy demand increases. The progressive fall in the Δ[oxCCO] baseline during repeated seizures indicates a continuing depletion of mitochondrial redox state and might explain the harmful effects of recurrent seizures.