X Golay

Brain Cell Death Is Reduced With Cooling by 3.5°C to 5°C but Increased With Cooling by 8.5°C in a Piglet Asphyxia Model

Background and Purpose— In infants with moderate to severe neonatal encephalopathy, whole-body cooling at 33°C to 34°C for 72 hours is standard care with a number needed to treat to prevent a adverse outcome of 6 to 7. The precise brain temperature providing optimal neuroprotection is unknown. Methods— After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24 hours were randomized (each group, n=7) to (1) normothermia (38.5°C throughout) or whole-body cooling 2 to 26 hours after insult to (2) 35°C, (3) 33.5°C, or (4) 30°C. At 48 hours after hypoxia-ischemia, delayed cell death (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and cleaved caspase 3) and microglial ramification (ionized calcium-binding adapter molecule 1) were evaluated. Results— At 48 hours after hypoxia-ischemia, substantial cerebral injury was found in the normothermia and 30°C hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus, and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule, and hippocampus (all P<0.05). Conclusions— Cooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5°C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. Although the relatively wide therapeutic range of a 3.5°C to 5°C drop in temperature reassured, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.

Magnetisation transfer effects of Q2TIPS pulses in ASL

ObjectIn pulsed arterial spin labelling (ASL), Q2TIPS saturation pulses are used to actively control the temporal width of the labelled bolus. However, these Q2TIPS pulses also induce magnetisation transfer (MT) effects in the adjacent tissue. In this work, we investigated how Q2TIPS-related MT alters tissue signal in pulsed ASL and, consequently, CBF quantification.Materials and methodsSeven volunteers were studied at 3xa0tesla using a multi-TI FAIR sequence and 3D-GRASE readout with background suppression. Q2TIPS pulses were used and the spacing between RF pulses was varied to modulate MT effects. Computer simulations were designed to mimic in-vivo signals at multiple TI values.ResultsQ2TIPS-associated MT was found to reduce tissue T1 and M0 values by up to 42 and 50% respectively; leading to a reduction of up to 40% in the effectiveness of background suppression and, therefore, increased sensitivity to motion for the longest TI values. In addition, greater MT effects were associated with reduced grey matter CBF estimates of up to 15%.ConclusionsThe MT effect associated with the Q2TIPS pulse train has a significant effect on tissue signal. It is recommended that MT effects are characterised and both background suppression and Q2TIPS schemes are accordingly optimised to reduce the effects of MT on accuracy and precision of CBF estimation.

Combined Proton Magnetic Resonance Spectroscopy and Near-Infrared Spectroscopy Measurements of Cerebral Blood Volume, Oxygenation, Cytochrome Oxidase, and Intracellular Metabolites During Perinatal Hypoxia-Ischaemia

Background: Hypoxic-ischaemic (HI) neonatal encephalopathy (NE) is associated with high mortality and morbidity rates worldwide. The magnetic resonance spectroscopy (MRS) Lactate/N-acetylaspartate (Lac/NAA) peak-area ratio predicts long term neurodevelopmental outcome.Aims: To investigate brain haemodynamic and metabolic changes during transient HI using simultaneous proton (1H) MRS and broadband near-infra-red spectroscopy (NIRS) in a newborn piglet pre-clinical model.Methods: MRS and NIRS data were acquired simultaneously in 6 healthy newborn anaesthetised male piglets (aged < 24 hr) during, and up to 90 min after transient HI.Results: A swift decline in oxygenation (Hbdiff) upon induction of HI, and associated reduction of cytochrome-c-oxidase (ox-redCCO), was accompanied by increased Lac/Naa (Fig 1A-D). Upon resuscitation there was a hyperaemic phase in 4 out of 6 animals with ox-redCCO and Lac/Naa recovering to baselines. During recovery ox-redCCO and Lac/Naa correlated linearly (p=< 0.0001; Pearson correlation) (Fig. 1D). Two piglets showed no post HI hyperaemic response and incomplete ox-redCCO recovery.Conclusions: The linear relationship between declining Lac/Naa and increasing ox-redCCO after HI suggests mitochondrial utilisation of Lac, instead of pyruvate, as a substrate at least during oxidative energy metabolism recovery. Complementary 1H MRS and NIRS may improve our understanding of cerebral energy metabolism pathways and the response of the newborn brain to HI and govern early interventional therapies.