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  • Journal article
    Arthurs OJ, Thayyil S, Pauliah SS, Jacques TS, Chong WK, Gunny R, Saunders D, Addison S, Lally P, Cady E, Jones R, Norman W, Scott R, Robertson NJ, Wade A, Chitty L, Taylor AM, Sebire NJet al., 2015,

    Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children

    , CLINICAL RADIOLOGY, Vol: 70, Pages: 872-880, ISSN: 0009-9260
  • Journal article
    Montaldo P, Chaban B, Lally PJ, Sebire NJ, Taylor AM, Thayyil Set al., 2015,

    Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy

    , European Journal of Paediatric Neurology, Vol: 19, Pages: 665-671, ISSN: 1090-3798

    Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI.Methods:We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy.Results:There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images.Conclusion:Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice.

  • Book chapter
    Montaldo P, Montaldo L, Chaban B, Thayyil Set al., 2015,

    Perinatal infection as risk factor of neonatal encephalopathy

    , Asphyxia: Risk Factors, Prevalence and Neurological Impacts, Pages: 55-72, ISBN: 9781634822251

    © 2015 by Nova Science Publishers, Inc. All rights reserved. Fetal exposure to inflammation and infection has been shown to increase brain vulnerability to hypoxia-ischemia via stimulation of immune and inflammatory responses, chemotaxis, toll-like receptors and cell death. Perinatal infection is a potentially modifiable, risk factor for encephalopathy that has been linked to adverse outcomes. Nevertheless, the exact role of perinatal infection among neonates with a history of encephalopathy, is not yet completely understood. Emerging experimental data suggest that hypothermia may not be neuroprotective after a bacterial lipopolysaccharide-sensitized encephalopathy brain injury whereas it can be neuroprotective if a bacterial lipopolysaccharide-sensitized encephalopathy is not present. Hence, therapeutic hypothermia in the presence of infection might even be deleterious as hypothermia may impair innate immune function, including neutrophil migration and function. This chapter aims to discuss how an infective insult can affect the vulnerability of the neonatal brain to the hypoxic damage. We review whether newborns with encephalopathy and signs of neonatal sepsis are associated with a higher risk of neonatal brain injury and worse long-term neurodevelopmental outcome. Finally, we highlight new therapeutic strategies in this scenario.

  • Journal article
    Montaldo P, Pauliah SS, Lally PJ, Olson L, Thayyil Set al., 2015,

    Cooling in a low-resource environment: Lost in translation

    , SEMINARS IN FETAL & NEONATAL MEDICINE, Vol: 20, Pages: 72-79, ISSN: 1744-165X
  • Journal article
    Arthurs OJ, Thayyil S, Owens CM, Olsen OE, Wade A, Addison S, Jones R, Norman W, Scott RJ, Robertson NJ, Taylor AM, Chittyi LS, Sebire NJet al., 2015,

    Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

    , EUROPEAN JOURNAL OF RADIOLOGY, Vol: 84, Pages: 474-481, ISSN: 0720-048X
  • Journal article
    Maaskant JM, Vermeulen H, Apampa B, Fernando B, Ghaleb MA, Neubert A, Thayyil S, Soe Aet al., 2015,

    Interventions for reducing medication errors in children in hospital

  • Journal article
    Arthurs OJ, Thayyil S, Addison S, Wade A, Jones R, Norman W, Scott R, Robertson NJ, Chitty LS, Taylor AM, Sebire NJ, Offiah ACet al., 2014,

    Diagnostic accuracy of postmortem MRI for musculoskeletal abnormalities in fetuses and children

    , PRENATAL DIAGNOSIS, Vol: 34, Pages: 1254-1261, ISSN: 0197-3851
  • Journal article
    Arthurs OJ, Thayyil S, Olsen OE, Addison S, Wade A, Jones R, Norman W, Scott RJ, Robertson NJ, Taylor AM, Chitty LS, Sebire NJ, Owens CMet al., 2014,

    Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

    , European Radiology, Vol: 24, Pages: 2876-2884, ISSN: 1432-1084

    Objectives To compare the diagnostic accuracy of postmortemmagnetic resonance imaging (PMMR) specificallyfor non-cardiac thoracic pathology in fetuses and children,compared with conventional autopsy.Methods Institutional ethics approval and parental consentwas obtained. A total of 400 unselected fetuses and childrenunderwent PMMR before conventional autopsy, reportedblinded to the other dataset.Results Of 400 non-cardiac thoracic abnormalities, 113(28 %) were found at autopsy. Overall sensitivity and specificity(95 % confidence interval) of PMMR for any thoracicpathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7,89.2) respectively, with positive predictive value (PPV)53.7 % (42.9, 64.0) and negative predictive value (NPV)77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1,76.2). PMMR was most sensitive at detecting anatomicalabnormalities, including pleural effusions and lung or thoracichypoplasia, but particularly poor at detecting infection.Conclusions PMMR currently has relatively poor diagnosticdetection rates for the commonest intra-thoracic pathologiesidentified at autopsy in fetuses and children, including respiratorytract infection and diffuse alveolar haemorrhage. Thereasonable NPV suggests that normal thoracic appearancesat PMMR exclude the majority of important thoraciclesions at autopsy, and so could be useful in the contextof minimally invasive autopsy for detecting non-cardiacthoracic abnormalities.

  • Journal article
    Orasanu E, Melbourne A, Cardoso MJ, Modat M, Taylor AM, Thayyil S, Ourselin Set al., 2014,

    Brain volume estimation from post-mortem newborn and fetal MRI

    , NeuroImage: Clinical, Vol: 6, Pages: 438-444, ISSN: 2213-1582

    Objective:Minimally invasive autopsy using post-mortem magnetic resonance imaging (MRI) is a valid alternative to conventional autopsy in fetuses and infants. Estimation of brain weight is an integral part of autopsy, but manual segmentation of organ volumes on MRI is labor intensive and prone to errors, therefore unsuitable for routine clinical practice. In this paper we aim to show that volumetric measurements of the post-mortem fetal and neonatal brain can be accurately estimated using semi-automatic techniques and a high correlation can be found with the weights measured from conventional autopsy results.Methods:The brains of 17 newborn subjects, part of Magnetic Resonance Imaging Autopsy Study (MaRIAS), were segmented from post-mortem MR images into cerebrum, cerebellum and brainstem using a publicly available neonate brain atlas and semi-automatic segmentation algorithm. The results of the segmentation were averaged to create a new atlas, which was then used for the automated atlas-based segmentation of 17 MaRIAS fetus subjects. As validation, we manually segmented the MR images from 8 subjects of each cohort and compared them with the automatic ones. The semi-automatic estimation of cerebrum weight was compared with the results of the conventional autopsy.Results:The Dice overlaps between the manual and automatic segmentations are 0.991 and 0.992 for cerebrum, 0.873 and 0.888 for cerebellum and 0.819 and 0.815 for brainstem, for newborns and fetuses, respectively. Excellent agreement was obtained between the estimated MR weights and autopsy gold standard ones: mean absolute difference of 5 g and 2% maximum error for the fetus cohort and mean absolute difference of 20 g and 11% maximum error for the newborn one.Conclusions:The high correlation between the obtained segmentation and autopsy weights strengthens the idea of using post-mortem MRI as an alternative for conventional autopsy of the brain.

  • Journal article
    Pauliah S, Lally P, Price D, Bainbridge A, Kurien J, Sivaswami N, Cowan F, Balraj G, Swamy R, Madhavan V, Nair M, Krishnakumar P, Cady E, Shankaran S, Thayyil Set al., 2014,

    PC.106 Cerebral Injury and Early Childhood Neurodevelopmental Outcome following Neonatal Encephalopathy in a Middle-income Country.

    , Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A72-A73

    Although neonatal encephalopathy (NE), accounts for 1 million neonatal deaths annually in low-and middle-income countries (LMIC), underlying brain injury and long term outcomes are not well characterised in LMIC.

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