Research impact

MaRIAS (Magnetic Resonance Imaging Autopsy Study)
(Funding: Department of Health): A largest ever multicentre study of whole-body MRI in the world led by Dr Sudhin Thayyil (Lancet 2009 and 2013). This work has been adopted by the Royal Colleges and is now used as a clinical tool in many tertiary centres in the UK.

TOBY (Total Body Cooling) Trial 
(Funding: MRC) A major multicentre whole body cooling trial led by Professor D Azzopardi (NEJM 2009), confirming the results of the previous whole body cooling trial by Prof Seetha Shankaran for the NICHD NRN, USA (NEJM 2005). This trial has had a key role in speeding up the clinical adoption of cooling therapy as a standard of care in the NHS.


Summaries of our immediate past work and the research outputs are given below:

Past research and impact

Cardiac Ion Channelopathies in Unexplained Stillbirths (CICUS)

The CICUS is a large study into post-mortem genetic testing for cardiac ion channelopathies in unexplained stillbirths, led by Dr Thayyil in collaboration with Prof Patricia Munroe at the Genome Centre (Barts and The London).


Publications

Postmortem Genetic Testing for Cardiac Ion Channelopathies in Stillbirths. Patricia B. Munroe, Shea Addison, Dominic J. Abrams, Neil J. Sebire, James Cartwright, Ian Donaldson, Marta M. Cohen, Charles Mein, Andrew Tinker, Stephen C. Harmer, Qadeer Aziz, Anna Terry, Monika Struebig, Helen R. Warren, Bhumita Vadgama, Darren J. Fowler, Donald Peebles, Andrew M. Taylor, Peter J. Lally, Sudhin Thayyil. Circulation Genomics and Precision Medicine 2018 (http://circgenetics.ahajournals.org/content/11/1/e001817)

Cardiac ion channelopathies in unexplained stillbirths. Addison S, Munroe P, Mein C, Cohen M, Fowler D, Sebire Nj, Peebles D, Taylor A, Abrams D, Thayyil S. Arch Dis Child Fetal Neonatal Ed. 2014 Jun;99

High-quality genomic DNA extraction from postmortem fetal tissue. Addison S, Sebire NJ, Taylor AM, Abrams D, Peebles D, Mein C, Munroe PB, Thayyil S. J Matern Fetal Neonatal Med. 2012

 

MaRIAS (Magnetic Resonance Imaging Autopsy Study)

The MaRIAS was a large prospective comparative study of whole body MR imaging with conventional autopsy in 400 fetuses, newborns and children, led by Dr Thayyil. This work has shown that MR imaging can be used as an alternative for autopsy in fetuses, newborns, and infants, however, the accuracy was poor in older children, where histological sampling of visceral organs by an endoscopic approach was important. This work has been adopted by the Royal Colleges. Based on these results, the Department of Health (UK) has now commissioned further work to explore endoscopic sampling alongside MR imaging, prior to rolling this out as a clinical tool in the NHS.


Publications

Diagnostic accuracy of post-mortem MRI for musculoskeletal abnormalities in fetuses and children. Arthurs OJ, Thayyil S, Addison S, Wade A, Jones R, Norman W, Scott R, Robertson NJ, Chitty LS, Taylor AM, Sebire NJ, Offiah AC; for the Magnetic Resonance Imaging Autopsy Study (MaRIAS) Collaborative Group. Prenat Diagn. 2014 Jul 14.

Postmortem cardiovascular magnetic resonance imaging in fetuses and children: a masked comparison study with conventional autopsy. Taylor AM, Sebire NJ, Ashworth MT, Schievano S, Scott RJ, Wade A, Chitty LS, Robertson N, Thayyil S; Magnetic Resonance Imaging Autopsy Study Collaborative Group. Circulation. 2014 May 13;129(19):1937-44.

Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice. Addison S, Arthurs OJ, Thayyil S. Br J Radiol. 2014 Apr;87(1036):20130621.

Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study. Thayyil S, Sebire NJ, Chitty LS, Wade A, Chong W, Olsen O, Gunny RS, Offiah AC, Owens CM, Saunders DE, Scott RJ, Jones R, Norman W, Addison S, Bainbridge A, Cady EB, Vita ED, Robertson NJ, Taylor AM; MARIAS collaborative group. Lancet. 2013 Jul 20;382(9888):223-33.

Acceptability of a minimally invasive perinatal/paediatric autopsy: healthcare professionals' views and implications for practice. Ben-Sasi K, Chitty LS, Franck LS, Thayyil S, Judge-Kronis L, Taylor AM, Sebire NJ. Prenat Diagn. 2013 Apr;33(4):307-12.

Normal ascent of the conus medullaris: a post-mortem foetal MRI study. Arthurs OJ, Thayyil S, Wade A, Chong WK, Sebire NJ, Taylor AM; Magnetic Resonance Imaging Autopsy Study Collaborative Group.J Matern Fetal Neonatal Med. 2013 May;26(7):697-702.

MR determination of neonatal spinal canal depth. Arthurs O, Thayyil S, Wade A, Chong WK, Sebire NJ, Taylor AM. Eur J Radiol. 2012 Aug;81(8):e813-6.

Post-mortem magnetic resonance imaging in the fetus, infant and child: a comparative study with conventional autopsy (MaRIAS Protocol). Thayyil S, Sebire NJ, Chitty LS, Wade A, Olsen O, Gunny RS, Offiah A, Saunders DE, Owens CM, Chong WK, Robertson NJ, Taylor AM. BMC Pediatr. 2011 Dec 22;11:120.

Minimally invasive perinatal autopsies using magnetic resonance imaging and endoscopic postmortem examination ("keyhole autopsy"): feasibility and initial experience. Sebire NJ, Weber MA, Thayyil S, Mushtaq I, Taylor A, Chitty LS. J Matern Fetal Neonatal Med. 2012 May;25(5):513-8.

Post-mortem cerebral magnetic resonance imaging T1 and T2 in fetuses, newborns and infants. Thayyil S, De Vita E, Sebire NJ, Bainbridge A, Thomas D, Gunny R, Chong K, Lythgoe MF, Golay X, Robertson NJ, Cady EB, Taylor AM. Eur J Radiol. 2012 Mar;81(3):e232-8.

Reconstruction of fetal and infant anatomy using rapid prototyping of post-mortem MR images. Schievano S, Sebire NJ, Robertson NJ, Taylor AM, Thayyil S. Insights Imaging. 2010 Sep;1(4):281-286.

Minimally invasive fetal postmortem examination using magnetic resonance imaging and computerised tomography: current evidence and practical issues. Thayyil S, Chitty LS, Robertson NJ, Taylor AM, Sebire NJ. Prenat Diagn. 2010 Aug;30(8):713-8.

Less invasive autopsy: an evidenced based approach. Thayyil S. Arch Dis Child. 2011 Jul;96(7):681-7.

Diagnostic accuracy of post-mortem magnetic resonance imaging in fetuses, children and adults: a systematic review. Thayyil S, Chandrasekaran M, Chitty LS, Wade A, Skordis-Worrall J, Bennett-Britton I, Cohen M, Withby E, Sebire NJ, Robertson NJ, Taylor AM. Eur J Radiol. 2010 Jul;75(1):e142-8.

Post-mortem examination of human fetuses: a comparison of whole-body high-field MRI at 9.4 T with conventional MRI and invasive autopsy. Thayyil S, Cleary JO, Sebire NJ, Scott RJ, Chong K, Gunny R, Owens CM, Olsen OE, Offiah AC, Parks HG, Chitty LS, Price AN, Yousry TA, Robertson NJ, Lythgoe MF, Taylor AM. Lancet. 2009 Aug 8;374(9688):467-75.

Prospective parental consent for autopsy research following sudden unexpected childhood deaths: a successful model. Thayyil S, Robertson NJ, Scales A, Weber MA, Jacques TS, Sebire NJ, Taylor AM; MaRIAS (Magnetic Resonance Imaging Autopsy Study) Collaborative Group. Arch Dis Child. 2009 May;94(5):354-8.

A semi-automated method for non-invasive internal organ weight estimation by post-mortem magnetic resonance imaging in fetuses, newborns and children. Thayyil S, Schievano S, Robertson NJ, Jones R, Chitty LS, Sebire NJ, Taylor AM; MaRIAS (Magnetic Resonance Imaging Autopsy Study) Collaborative group. Eur J Radiol. 2009 Nov;72(2):321-6.

Parental consent for research and sudden infant death. Thayyil S, Robertson NJ, Scales A, Sebire NJ, Taylor AM. Lancet. 2008 Aug 30;372(9640):715.

PEACOCK TRIAL: (Phase Changing Material for Whole Body Cooling)

The Peacock trial was a prospective cohort study evaluating the brain injury and long-term neurological outcomes after neonatal encephalopathy in south India, led by Dr Thayyil. We also evaluated the feasibility of providing therapeutic hypothermia using phase changing material in this study; however, this device was effective only when the ambient temperatures were low.


Publications

Neonatal encephalopathic cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome. Lally PJ, Price DL, Pauliah SS, Bainbridge A, Kurien J, Sivasamy N, Cowan FM, Balraj G, Ayer M, Satheesan K, Ceebi S, Wade A, Swamy R, Padinjattel S, Hutchon B, Vijayakumar M, Nair M, Padinharath K, Zhang H, Cady EB, Shankaran S, Thayyil S. PLoS One. 2014 Feb 5;9(2):e87874.

Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. PLoS One. 2013;8(3):e58834.

Whole-body cooling in neonatal encephalopathy using phase changing material. Thayyil S, Shankaran S, Wade A, Cowan FM, Ayer M, Satheesan K, Sreejith C, Eyles H, Taylor AM, Bainbridge A, Cady EB, Robertson NJ, Price D, Balraj G. Arch Dis Child Fetal Neonatal Ed. 2013 May;98(3):F280-1.

Brain cooling in babies: are we ready for clinical trials in developing countries? Thayyil S. Indian Pediatr. 2011 Jun;48(6):441-2.
Ethical and practical issues relating to the global use of therapeutic hypothermia for perinatal asphyxial encephalopathy. Wilkinson DJ, Thayyil S, Robertson NJ. Arch Dis Child Fetal Neonatal Ed. 2011 Jan;96(1):F75-8.

University College London (UCL) Symposia on neonatal neurology and neuroprotection. Thayyil S, Robertson NJ. Indian Pediatr. 2010 May;47(5):395.

Global application of therapeutic hypothermia to treat perinatal asphyxial encephalopathy. Thayyil S, Bhutta ZA, Ramji S, Costello AM, Robertson NJ. Int Health. 2010 Jun;2(2):79-81.
Techniques for therapeutic hypothermia during transport and in hospital for perinatal asphyxial encephalopathy. Robertson NJ, Kendall GS, Thayyil S. Semin Fetal Neonatal Med. 2010 Oct;15(5):276-86.

Therapeutic hypothermia for neonatal encephalopathy implications for neonatal units in India. Thayyil S, Costello A, Shankaran S, Robertson NJ. Indian Pediatr. 2009 Apr;46(4):283-9.

TOBY (Total Body Cooling) Trial and follow up study (TOBY Children)

The TOBY Trial was a randomised controlled trial of whole body cooling in neonatal encephalopathy, led by Prof Denis Azzopardi, which confirmed the findings of the earlier Cool Cap trial and NICHD whole body cooling trial. The pooled data from these three clinical trials provided conclusive evidence for the safety and efficacy of whole body cooling in reducing death and improving survival with normal neurological outcome after neonatal encephalopathy in high-income countries. Cooling therapy is now the standard of care in neonatal encephalopathy in all high-income countries.


Publications

Effects of hypothermia for perinatal asphyxia on childhood outcomes. Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, Goodwin J, Halliday HL, Juszczak E, Kapellou O, Levene M, Linsell L, Omar O, Thoresen M, Tusor N, Whitelaw A, Edwards AD; TOBY Study Group. N Engl J Med. 2014 Jul 10;371(2):140-9.

Predictive value of the amplitude-integrated EEG in infants with hypoxic ischaemic encephalopathy: data from a randomised trial of therapeutic hypothermia. Azzopardi D; TOBY study group. Arch Dis Child Fetal Neonatal Ed. 2014 Jan;99(1):F80-2.

Implementation and conduct of therapeutic hypothermia for perinatal asphyxial encephalopathy in the UK - analysis of national data. Azzopardi D, Strohm B, Linsell L, Hobson A, Juszczak E, Kurinczuk JJ, Brocklehurst P, Edwards AD; UK TOBY Cooling Register. PLoS One. 2012;7(6):e38504.

Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates. Strohm B, Hobson A, Brocklehurst P, Edwards AD, Azzopardi D; UK TOBY Cooling Register. Pediatrics. 2011 Aug;128(2):e450-2.

Cost-effectiveness of therapeutic hypothermia to treat neonatal encephalopathy. Regier DA, Petrou S, Henderson J, Eddama O, Patel N, Strohm B, Brocklehurst P, Edwards AD, Azzopardi D. Value Health. 2010 Sep-Oct;13(6):695-702.

Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Lancet Neurol. 2010 Jan;9(1):39-45.

Moderate hypothermia to treat perinatal asphyxial encephalopathy. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. N Engl J Med. 2009 Oct 1;361(14):1349-58.

Temperature control during therapeutic moderate whole-body hypothermia for neonatal encephalopathy. Strohm B, Azzopardi D; UK TOBY Cooling Register Study Group. Arch Dis Child Fetal Neonatal Ed. 2010 Sep;95(5):F373-5.

Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial. Azzopardi D, Strohm B, Edwards AD, Halliday H, Juszczak E, Levene M, Thoresen M, Whitelaw A, Brocklehurst P; Steering Group and TOBY Cooling Register participants. Arch Dis Child Fetal Neonatal Ed. 2009 Jul;94(4):F260-4.

The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. Azzopardi D, Brocklehurst P, Edwards D, Halliday H, Levene M, Thoresen M, Whitelaw A; TOBY Study Group. BMC Pediatr. 2008 Apr 30;8:17.

TOBY Xenon

The TOBY Xe is a phase II randomised controlled trial of low dose (30%) delayed Xenon therapy (up to 12 hours) in babies with neonatal encephalopathy undergoing rescue hypothermic neuroprotection, led by Prof Denis Azzopardi. This study has now completed recruitment at Imperial College London, and the results will be published in the near future.


Publications

Anticonvulsant effect of xenon on neonatal asphyxial seizures. Azzopardi D, Robertson NJ, Kapetanakis A, Griffiths J, Rennie JM, Mathieson SR, Edwards AD. Arch Dis Child Fetal Neonatal Ed. 2013 Sep;98(5):F437-9.