Dataset Information

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

ABSTRACT: Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue.

SUBMITTER: Caldwell M

PROVIDER: S-EPMC4596480 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

Caldwell Matthew M Moroz Tracy T Hapuarachchi Tharindi T Bainbridge Alan A Robertson Nicola J NJ Cooper Chris E CE Tachtsidis Ilias I

PloS one 20151007 10

Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MR ...[more]

PMID: 26445281

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Project description:Hypoxic ischaemia encephalopathy is the major cause of brain injury in new-borns. However, to date, useful biomarkers which may be used to early predict neurodevelopmental impairment for proper commencement of hypothermia therapy is still lacking. This study aimed to determine whether the early neuroimaging characteristics and ultrastructural correlates were associated with different injury progressions and brain damage severity outcomes after neonatal hypoxic ischaemia. Longitudinal 7 T MRI was performed within 6 h, 24 h and 7 days after hypoxic ischaemia in rat pups. The brain damage outcome at 7 days post-hypoxic ischaemia assessed using histopathology and MRI were classified as mild, moderate and severe. We found there was a spectrum of different brain damage severity outcomes after the same duration of hypoxic ischaemia. The severity of brain damage determined using MRI correlated well with that assessed by histopathology. Quantitative MRI characteristics denoting water diffusivity in the tissue showed significant differences in the apparent diffusion coefficient deficit volume and deficit ratios within 6 h, at 24 h and 7 days after hypoxic ischaemia among the 3 different outcome groups. The susceptible brain areas to hypoxic ischaemia were revealed by the temporal changes in regional apparent diffusion coefficient values among three outcome groups. Within 6 h post-hypoxic ischaemia, a larger apparent diffusion coefficient deficit volume and deficit ratios and lower apparent diffusion coefficient values were highly associated with adverse brain damage outcome. In the apparent diffusion coefficient deficit areas detected early after hypoxic ischaemia which were highly associated with severe damage outcome, transmission electron microscopy revealed fragmented nuclei; swollen rough endoplasmic reticulum and degenerating mitochondria in the cortex and prominent myelin loss and axon detraction in the white matter. Taken together, different apparent diffusion coefficient patterns obtained early after hypoxic ischaemia are highly associated with different injury progression leading to different brain damage severity outcomes, suggesting the apparent diffusion coefficient characteristics may be applicable to early identify the high-risk neonates for hypothermia therapy.

Project description:There is increasing interest in applying physiological MRI in neonates, based on the premise that physiological parameters may provide an early biomarker of neonatal brain health and injury. Two commonly used techniques are oxygen extraction fraction (OEF) measurement using T2 -relaxation-under-spin-tagging (TRUST) MRI and cerebral blood flow measurement using phase-contrast (PC) quantitative flow MRI, which collectively provide an assessment of the brain's oxygen consumption. However, prior research has only demonstrated proof of principle of these methods in neonates, without characterization or benchmarking of the techniques. This is because available time is limited in neonatal subjects, especially when scans are performed as add-ons to clinical scans (typically less than 5 min). The work presented aims to examine the TRUST and PC MRI sequences systematically in normal neonates, through research-dedicated scan sessions. A series of characterization and optimization studies were conducted in a total of 26 radiographically normal neonates on 3 T systems. Our results show that TRUST MRI at the superior sagittal sinus (SSS) provides an OEF measurement equivalent to that at the internal jugular vein (r = 0.80, n = 10), yet with shorter scan time. Lower resolution provided better precision in the TRUST measurement (p = 0.001, n = 9). Therefore, the preferred OEF measurement is to apply TRUST MRI at the SSS using a spatial resolution of 2.5 mm. For PC MRI, our results showed that non-gated PC MRI yielded blood flow measurements comparable to those from the more time-consuming gated approach in neonates (r = 0.89, n = 7). It was also found that blood flow could be overestimated by 18% when imaging resolution is larger than 0.3 mm (n = 7). Therefore, non-gated PC MRI with a spatial resolution of 0.3 mm is recommended for neonatal applications. In conclusion, this study verifies consistency of neonatal brain oxygenation and flow measurements across acquisition schemes and points to optimal strategies in parameter selection when using these sequences.

Dataset Information

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

Publications

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

Similar Datasets

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