Publications
148 results found
Lally P, PAULIAH S, MONTALDO P, et al., 2015, Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): A Prospective Multi-Country Study, BMJ Open, Vol: 5, ISSN: 2044-6055
Despite cooling adverse outcomes are seen in upto half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Riggorous evaluation of these therapies in phase II trials using surrogate magnetic resonance biomarkers may speed up thier bench to bedside translation. A recent systematic review of single centres studies have suggested that Magnetic resonance spectroscopy biomarkers offers the best promise, however the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makes is not known.
Ibrahim T, Few K, Greenwood R, et al., 2015, 'Feed and wrap' or sedate and immobilise for neonatal brain MRI?, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 100, Pages: F465-U95, ISSN: 1359-2998
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- Citations: 10
Soo A, Taha S, Lally P, et al., 2015, Assessment of optic nerve development using post-mortem Magnetic Resonance Imaging (MRI) in fetuses and newborns, Prenatal Diagnosis, Vol: 35, Pages: 1262-1264, ISSN: 0197-3851
What's already known about this topic?Biometric studies of fetal orbit and lens development have been shown to correlate with gestational age.No available data on optic nerve measurements in fetuses/neonates.What does this study add?Normal fetal/neonatal optic nerve diameter measurements for gestational age as measured on post‐mortem MRI scans.
Arthurs OJ, Thayyil S, Pauliah SS, et 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
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- Citations: 65
Montaldo P, Chaban B, Lally PJ, et 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.
Montaldo P, Montaldo L, Chaban B, et al., 2015, Perinatal infection as risk factor of neonatal encephalopathy, Asphyxia: Risk Factors, Prevalence and Neurological Impacts, Pages: 55-72, ISBN: 9781634822251
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.
Montaldo P, Pauliah SS, Lally PJ, et al., 2015, Cooling in a low-resource environment: Lost in translation, SEMINARS IN FETAL & NEONATAL MEDICINE, Vol: 20, Pages: 72-79, ISSN: 1744-165X
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- Citations: 45
Arthurs OJ, Thayyil S, Owens CM, et 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
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- Citations: 34
Maaskant JM, Vermeulen H, Apampa B, et al., 2015, Interventions for reducing medication errors in children in hospital, COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSN: 1469-493X
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- Citations: 52
Arthurs OJ, Thayyil S, Addison S, et al., 2014, Diagnostic accuracy of postmortem MRI for musculoskeletal abnormalities in fetuses and children, PRENATAL DIAGNOSIS, Vol: 34, Pages: 1254-1261, ISSN: 0197-3851
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- Citations: 21
Arthurs OJ, Thayyil S, Olsen OE, et 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.
Orasanu E, Melbourne A, Cardoso MJ, et 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.
Lally P, Pauliah S, Price D, et al., 2014, PC.45 Quantification of N-Acetylaspartate Concentration in the Neonatal Brain: Initial Results from the Multi-Centre Marble Study., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Early cerebral proton magnetic resonance spectroscopy (MRS) predicts medium-term outcomes in neonatal encephalopathy (NE). Metabolite peak-area ratios are most commonly used for prognosis, but conflate pathological information from different metabolites. N-acetylaspartate (NAA) is predominantly neuronal and neuronal loss should result in reduced NAA absolute-concentration ([NAA]). Thus, thalamic [NAA] should offer significant prognostic value but is difficult to measure in a clinical setting. We have established a protocol for multi-centre [NAA] measurement with the aim to use it as a surrogate biomarker in phase II clinical trials.
Pauliah S, Narayanan E, Kumutha K, et al., 2014, PC.110 Hypothermia for Encephalopathy in Low and Middle-Income Countries (HELIX): A Feasibility Study., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Therapeutic hypothermia improves outcomes after neonatal encephalopathy in high-income countries, however the safety and efficacy of cooling in low- and middle-income countries (LMIC) is not known.
Pauliah S, Lally P, Bainbridge A, et al., 2014, 8.8 Neonatal Encephalopathy in the Cooling Therapy era - Preliminary Cerebral Magnetic Resonance results from the Marble Consortium., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A13-A14
Although cerebral metabolic changes during neonatal encephalopathy (NE) have been well characterised using magnetic resonance spectroscopy (MRS) in single-centre studies, the widespread effect of therapeutic hypothermia is less clear.
Pauliah S, Lally P, Price D, et 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.
Lally P, Price D, Bainbridge A, et al., 2014, PC.26 Feasibility of Magnetic Resonance Spectroscopy in Examining Thalamic Metabolite Concentrations in a Multi-Centre Study of Neonatal Encephalopathy., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A44-A45
Proton magnetic resonance spectroscopy (MRS) has high prognostic value in hypoxic ischaemic encephalopathy (HIE), however its multi-centre application is limited by inconsistencies between scanners and protocols. N-acetylaspartate (NAA) is predominantly neuronal: cerebral NAA concentration may be a more reliable HIE-severity biomarker than lactate/NAA.
Addison S, Munroe P, Mein C, et al., 2014, 8.2 cardiac ion channelopathies in unexplained stillbirths., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Although cardiac ion channelopathies are reported in up to 15% of sudden infant deaths, the prevalence in unexplained stillbirths is not known.
Addison S, Arthurs O, Lally P, et al., 2014, PFM.25 Assessment of visceral maceration using post-mortem magnetic resonance imaging in fetuses., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Post-mortem magnetic resonance imaging (PM MRI) is increasingly used as an alternative for perinatal autopsy, however the artefacts related to maceration has not been described.
Lally P, Arthurs O, Addison S, et al., 2014, PFM.33 Estimating Maceration Severity Using Whole Body Magnetic Resonance T2 Relaxometry., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1, Pages: A92-A93
Magnetic resonance (MR) imaging is an ideal modality to observe gross global changes in tissue structure, as is present with maceration. As tissue degrades, its MR transverse relaxation time (T2) should increase, with relaxometry methods enabling quantitative measurement of this.
Lally P, Zhang H, Pauliah S, et al., 2014, 8.9 Microstructural Changes in Neonatal Encephalopathy Revealed with the Neurite Orientation Dispersion and Density Imaging (NODDI) Model., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Although diffusion tensor imaging (DTI) fractional anisotropy (FA) is commonly used to quantify neural injury, it is non-specific and affected by a number of microstructural changes.
Taylor AM, Sebire NJ, Ashworth MT, et al., 2014, Postmortem cardiovascular magnetic resonance imaging in fetuses and children a masked comparison study with conventional autopsy, Circulation, Vol: 129, Pages: 1937-1944, ISSN: 0009-7322
Background—Perinatal and pediatric autopsies have declined worldwide in the past decade. We compared the diagnostic accuracy of postmortem, cardiovascular magnetic resonance (CMR) imaging with conventional autopsy and histopathology assessment in fetuses and children.Methods and Results—We performed postmortem magnetic resonance imaging in 400 fetuses and children, using a 1.5-T Siemens Avanto magnetic resonance scanner before conventional autopsy. A pediatric CMR imager reported the CMR images, masked to autopsy information. The pathologists were masked to the information from CMR images. The institutional research ethics committee approved the study, and parental consent was obtained. Assuming a diagnostic accuracy of 50%, 400 cases were required for a 5% precision of estimate. Three cases were excluded from analysis, 2 with no conventional autopsy performed and 1 with insufficient CMR sequences performed. Thirty-eight CMR data sets were nondiagnostic (37 in fetuses ≤24 weeks; 1 in a fetus >24 weeks). In the remaining 359 cases, 44 cardiac abnormalities were noted at autopsy. Overall sensitivity and specificity (95% confidence interval) of CMR was 72.7% (58.2–83.7%) and 96.2% (93.5–97.8%) for detecting any cardiac pathology, with positive and negative predictive values of 72.7% (58.2–83.7%) and 96.2% (93.5–97.8%), respectively. Higher sensitivity of 92.6% (76.6–97.9%), specificity of 99.1% (97.4–99.7%), positive predictive value of 89.3% (72.8–96.3%), and negative predictive value of 99.4% (97.8–99.8%) were seen for major structural heart disease.Conclusions—Postmortem CMR imaging may be a useful alternative to conventional cardiac autopsy in fetuses and children for detecting cardiac abnormalities.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01417962.
Addison S, Arthurs OJ, Thayyil S, 2014, Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice, BRITISH JOURNAL OF RADIOLOGY, Vol: 87, ISSN: 0007-1285
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- Citations: 39
Lally PJ, Price DL, Pauliah SS, et al., 2014, Neonatal encephalopathic cerebral injury in south india assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome, PLOS One, Vol: 9, ISSN: 1932-6203
Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.MethodsWe recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA) using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III.ResultsOf the 54 neonates recruited, Sarnat staging was mild in 30 (56%); moderate in 15 (28%) and severe in 6 (11%), with no encephalopathy in 3 (6%). Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91%) and cortex (n = 31, 70%) while only 12 (27%) had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81%) with 38 (79%) survivors examined aged 3½ years; of these, 16 (42%) had adverse neurodevelopmental outcomes.ConclusionsNo infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue
Robertson NJ, Thayyil S, Cady EB, et al., 2014, Magnetic resonance spectroscopy biomarkers in term perinatal asphyxial encephalopathy: from neuropathological correlates to future clinical applications., Curr Pediatr Rev, Vol: 10, Pages: 37-47
Neonatal brain injury remains a devastating condition, with poor outcomes despite the institution of an effective neuroprotective strategy of therapeutic hypothermia. There is an urgent need to develop additional neuroprotective strategies and to tailor our clinical predictive ability for families and their infants. Such goals could be more readily achieved if reliable early clinical indicators or biomarkers existed. This review will explore the relation between magnetic resonance (MR) imaging biomarkers and the degree of brain pathology observed in our translational piglet model of perinatal asphyxia. We also suggest biomarker relevance at a cellular level. The review will describe the development needed to optimize and simplify the use of biomarkers to speed up future trials of neuroprotection.
Thayyil S, Sebire NJ, Chitty LS, 2013, Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study (vol 382, pg 223, 2013), LANCET, Vol: 382, Pages: 1980-1980, ISSN: 0140-6736
Thayyil S, Sebire NJ, Chitty LS, 2013, Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study (vol 382, pg 223, 2013), LANCET, Vol: 382, Pages: 208-208, ISSN: 0140-6736
Thayyil S, Sebire NJ, Chitty LS, 2013, Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study (vol 382, pg 223, 2013), LANCET, Vol: 382, Pages: 208-208, ISSN: 0140-6736
Thayyil S, Sebire NJ, Chitty LS, et al., 2013, Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study, LANCET, Vol: 382, Pages: 223-233, ISSN: 0140-6736
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- Citations: 205
Thayyil S, Shankaran S, Wade A, et al., 2013, Whole-body cooling in neonatal encephalopathy using phase changing material, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 98, Pages: F280-F281, ISSN: 1359-2998
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- Citations: 35
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