Novel Applications and Refinements of Current Imaging Techniques in Perinatal and Childhood Death Investigation
Lead Research Organisation:
University College London
Department Name: Institute of Child Health
Abstract
Background:
It is estimated that 1 in 80 pregnancies in the UK will result in a termination or stillbirth due to an abnormality of the baby. An autopsy can provide information on the cause of death and help change management in future pregnancies (1), however many parents refuse this examination as they feel their child has suffered through enough. This means they miss out on valuable information about why their child died and whether future children will suffer a similar fate.
'Less invasive' ways for investigating the cause of death using imaging have been pioneered at our institution and shown that by using magnetic resonance imaging (MRI) together with 'key-hole' surgery methods to obtain tissue samples, we get the same answer as autopsy in >90% (2) cases. This method is however expensive and unfortunately not widely available. We believe we can improve on this technique by using ultrasound imaging with needle biopsies which makes fewer and smaller marks to the skin and would be easier to roll-out nationally if it can achieve a similar level of accuracy as a full autopsy.
Aims:
This study will test how good ultrasound guided needle tissue biopsies are compared to autopsy. We will also investigate how good different imaging tests are when used alone and in combination with tissue sampling
Methods:
Parents who consent for childhood autopsy will be offered a series of imaging tests and less invasive needle biopsies. We will then compare these results with our current autopsy results and test for any differences in findings.
Applications and benefits:
Parents tell us that they want the 'minimum necessary' approach to autopsy during this very difficult and emotional time for them. By showing that a less invasive, imaging-led technique is achievable and can give accurate results, we intend to offer parents an alternative method for discovering the cause for their child's death. This means not only offering needle biopsies, but also understanding when imaging alone would be sufficient in coming to a diagnosis.
The information gathered by using an alternative, more acceptable method of investigation may help parents in their grieving process by providing closure and understanding for reasons behind their child's death, and help to understand whether future children are at increased risk of similar diseases.
Increasing the rate of uptake of this investigation may also mean we can better understand and explore reasons behind why children die. This can help inform public health policies and initiatives in improving maternal and child health. At present not all centres in the UK can offer a less invasive method of investigation. If this research can provide evidence for better practice, we hope this will set the foundations of a new NHS autopsy service.
(1) Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When? Where? Why? Lancet 2005; 365:891-900
(2) Thayyil S, Sebire NJ, Chitty LS et al Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study. Lancet 2013; 382: 223-233
It is estimated that 1 in 80 pregnancies in the UK will result in a termination or stillbirth due to an abnormality of the baby. An autopsy can provide information on the cause of death and help change management in future pregnancies (1), however many parents refuse this examination as they feel their child has suffered through enough. This means they miss out on valuable information about why their child died and whether future children will suffer a similar fate.
'Less invasive' ways for investigating the cause of death using imaging have been pioneered at our institution and shown that by using magnetic resonance imaging (MRI) together with 'key-hole' surgery methods to obtain tissue samples, we get the same answer as autopsy in >90% (2) cases. This method is however expensive and unfortunately not widely available. We believe we can improve on this technique by using ultrasound imaging with needle biopsies which makes fewer and smaller marks to the skin and would be easier to roll-out nationally if it can achieve a similar level of accuracy as a full autopsy.
Aims:
This study will test how good ultrasound guided needle tissue biopsies are compared to autopsy. We will also investigate how good different imaging tests are when used alone and in combination with tissue sampling
Methods:
Parents who consent for childhood autopsy will be offered a series of imaging tests and less invasive needle biopsies. We will then compare these results with our current autopsy results and test for any differences in findings.
Applications and benefits:
Parents tell us that they want the 'minimum necessary' approach to autopsy during this very difficult and emotional time for them. By showing that a less invasive, imaging-led technique is achievable and can give accurate results, we intend to offer parents an alternative method for discovering the cause for their child's death. This means not only offering needle biopsies, but also understanding when imaging alone would be sufficient in coming to a diagnosis.
The information gathered by using an alternative, more acceptable method of investigation may help parents in their grieving process by providing closure and understanding for reasons behind their child's death, and help to understand whether future children are at increased risk of similar diseases.
Increasing the rate of uptake of this investigation may also mean we can better understand and explore reasons behind why children die. This can help inform public health policies and initiatives in improving maternal and child health. At present not all centres in the UK can offer a less invasive method of investigation. If this research can provide evidence for better practice, we hope this will set the foundations of a new NHS autopsy service.
(1) Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When? Where? Why? Lancet 2005; 365:891-900
(2) Thayyil S, Sebire NJ, Chitty LS et al Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study. Lancet 2013; 382: 223-233
Technical Summary
Objective: To develop a less invasive alternative to standard autopsy, thereby increasing parental acceptance rates of the post-mortem examination and information for causes of perinatal death.
Outcomes: Technique optimisation and establishment of diagnostic accuracy rates in post-mortem imaging and ultrasound guided organ biopsies for perinatal death investigation.
Methods: All fetuses referred for perinatal autopsy with tissue sampling will undergo a post-mortem MRI (if >500g) or micro-computed tomography (if <500g), and a comprehensive ultrasound study. The studies will be reported by radiologists specialising in post-mortem imaging, blinded to the results from the other modalities. After the initial radiology review, consensus imaging will take place and an ultrasound biopsy of target organs (liver, spleen, lungs, heart, and kidneys) will be performed. This will then be followed by the standard conventional autopsy (gold standard).
Diagnostic accuracy rates for MRI, micro-computed tomography and ultrasound imaging, both alone and in conjunction, will be established. Results from the ultrasound guided biopsy relating to both tissue yield and pathological diagnosis will be compared to autopsy findings. Where tissue yield is insufficient, technique will be adapted with either differing organ approach or biopsy needle calibre to ensure best possible tissue samples.
Scientific opportunities: If diagnostic accuracy and parental acceptance rates are high, medical opportunities will be created that allow increased monitoring of trends and explanation for causes of perinatal death. This raw data is currently lacking given the poor autopsy uptake rates.
The long term aim is for image led perinatal autopsy to become the 'best practice' and promote widespread NHS adoption for service delivery. Our results could then contribute to epidemiological studies and inform future public health initiatives.
Outcomes: Technique optimisation and establishment of diagnostic accuracy rates in post-mortem imaging and ultrasound guided organ biopsies for perinatal death investigation.
Methods: All fetuses referred for perinatal autopsy with tissue sampling will undergo a post-mortem MRI (if >500g) or micro-computed tomography (if <500g), and a comprehensive ultrasound study. The studies will be reported by radiologists specialising in post-mortem imaging, blinded to the results from the other modalities. After the initial radiology review, consensus imaging will take place and an ultrasound biopsy of target organs (liver, spleen, lungs, heart, and kidneys) will be performed. This will then be followed by the standard conventional autopsy (gold standard).
Diagnostic accuracy rates for MRI, micro-computed tomography and ultrasound imaging, both alone and in conjunction, will be established. Results from the ultrasound guided biopsy relating to both tissue yield and pathological diagnosis will be compared to autopsy findings. Where tissue yield is insufficient, technique will be adapted with either differing organ approach or biopsy needle calibre to ensure best possible tissue samples.
Scientific opportunities: If diagnostic accuracy and parental acceptance rates are high, medical opportunities will be created that allow increased monitoring of trends and explanation for causes of perinatal death. This raw data is currently lacking given the poor autopsy uptake rates.
The long term aim is for image led perinatal autopsy to become the 'best practice' and promote widespread NHS adoption for service delivery. Our results could then contribute to epidemiological studies and inform future public health initiatives.
Planned Impact
The main objective of this research is to address whether and how less invasive, imaging-led methods for perinatal death investigation should be integrated into existing care pathways. Conventional autopsy uptake rates are currently low, meaning raw data regarding perinatal death diagnoses are lacking.
The main beneficiaries of this research would be parents and clinicians wishing to make a fully informed, evidence-based choice regarding alternative methods to the conventional perinatal autopsy. Parents would benefit as they will be offered a method that is non-disfiguring to their child, whilst still obtaining useful clinical information to inform future family planning. Clinicians would benefit by having clear guidelines (informed by the evidence produced in this research) regarding appropriate clinical indications for referral and diagnostic accuracy rates of different imaging modalities (including image-led tissue sampling options). Both these benefits hand-in-hand would represent an improvement in patient centred, individualised care with tailored counselling at a very emotional and difficult time.
Further advantages for clinicians would include opportunities for subspecialty training in 'image-led' post-mortem techniques. This would mainly benefit radiologists and pathologists with an interest in post-mortem medicine. With potential increases in demand and wider usage of the imaging techniques, there would be more focus on refining and developing these skills, in turn again benefitting future patients.
On a wider societal level, other beneficiaries would include the National Health Service, global policy makers and public health doctors. Our plan is for the results to eventually feed into an economic evaluation. If image-led post-mortem examinations are found to be clinically and economically advantageous, the introduction of such procedures as a 'new standard' may offer cost-saving benefits to our healthcare system. A more widely available and acceptable method of capturing causes of deaths could also allow better allocation of resources to inform public health initiatives both locally and world-wide, especially in socioeconomically deprived countries where the perinatal death rates are far higher.
Detailed measures of success and proposed milestones are fully outlined in our 'Pathways to Impact' statement. In the short term (within the first year), we shall present our preliminary work regarding imaging and image led biopsy techniques at international conferences and peer reviewed journals. By the end of the study (year 3), the final results regarding diagnostic accuracy rates and appropriate clinical indications for imaging-led procedures will be converted into peer-reviewed publications, technical reports to the Royal Colleges regarding best practice for 'image-led' post-mortem examinations and lay summaries for stakeholders and interested charity groups (GOSH charity, ARC - antenatal results and choices, SANDS - stillbirth and neonatal death charity). The lay documentation will be created in corroboration with our LIA -EAP (Less Invasive Autopsy External Advisory Panel).
In the longer term, we will identify a health economics team to devise a cost saving calculation on benefits to the NHS, should our techniques be integrated into patient care. We also hope to explore the feasibility of using our techniques in less developed countries to inform and enable ways of identifying and reducing perinatal death rates worldwide. This will be achieved via contact and discussion with current global health medicine project leaders (such as CaDMIA, World Federation of Paediatric Imaging (WFPI) and the global health taskforce of the British Society of Paediatric Radiology (BSPR)).
The main beneficiaries of this research would be parents and clinicians wishing to make a fully informed, evidence-based choice regarding alternative methods to the conventional perinatal autopsy. Parents would benefit as they will be offered a method that is non-disfiguring to their child, whilst still obtaining useful clinical information to inform future family planning. Clinicians would benefit by having clear guidelines (informed by the evidence produced in this research) regarding appropriate clinical indications for referral and diagnostic accuracy rates of different imaging modalities (including image-led tissue sampling options). Both these benefits hand-in-hand would represent an improvement in patient centred, individualised care with tailored counselling at a very emotional and difficult time.
Further advantages for clinicians would include opportunities for subspecialty training in 'image-led' post-mortem techniques. This would mainly benefit radiologists and pathologists with an interest in post-mortem medicine. With potential increases in demand and wider usage of the imaging techniques, there would be more focus on refining and developing these skills, in turn again benefitting future patients.
On a wider societal level, other beneficiaries would include the National Health Service, global policy makers and public health doctors. Our plan is for the results to eventually feed into an economic evaluation. If image-led post-mortem examinations are found to be clinically and economically advantageous, the introduction of such procedures as a 'new standard' may offer cost-saving benefits to our healthcare system. A more widely available and acceptable method of capturing causes of deaths could also allow better allocation of resources to inform public health initiatives both locally and world-wide, especially in socioeconomically deprived countries where the perinatal death rates are far higher.
Detailed measures of success and proposed milestones are fully outlined in our 'Pathways to Impact' statement. In the short term (within the first year), we shall present our preliminary work regarding imaging and image led biopsy techniques at international conferences and peer reviewed journals. By the end of the study (year 3), the final results regarding diagnostic accuracy rates and appropriate clinical indications for imaging-led procedures will be converted into peer-reviewed publications, technical reports to the Royal Colleges regarding best practice for 'image-led' post-mortem examinations and lay summaries for stakeholders and interested charity groups (GOSH charity, ARC - antenatal results and choices, SANDS - stillbirth and neonatal death charity). The lay documentation will be created in corroboration with our LIA -EAP (Less Invasive Autopsy External Advisory Panel).
In the longer term, we will identify a health economics team to devise a cost saving calculation on benefits to the NHS, should our techniques be integrated into patient care. We also hope to explore the feasibility of using our techniques in less developed countries to inform and enable ways of identifying and reducing perinatal death rates worldwide. This will be achieved via contact and discussion with current global health medicine project leaders (such as CaDMIA, World Federation of Paediatric Imaging (WFPI) and the global health taskforce of the British Society of Paediatric Radiology (BSPR)).
Publications
Apps J
(2018)
CRAN-32. CASE BASED LEARNING: THREE CENTURIES OF LESSONS FROM TWO CRANIOPHARYNGEOMA PATIENTS
in Neuro-Oncology
Apps JR
(2019)
Learning from cases: Analysis of two cases of craniopharyngioma from the 19 th to the 21 st centuries.
in F1000Research
Bruno C
(2022)
Central Venous Catheter Malfunction in Children: A Bioengineering Approach.
in Clinical journal of the American Society of Nephrology : CJASN
Caro-Dominguez P
(2020)
Thoracic imaging of coronavirus disease 2019 (COVID-19) in children: a series of 91 cases.
in Pediatric radiology
Castro APG
(2019)
Finite element modelling of the developing infant femur using paired CT and MRI scans.
in PloS one
Chambers G
(2023)
Current and future funding streams for paediatric postmortem imaging: European Society of Paediatric Radiology survey results.
in Pediatric radiology
Ciet P
(2023)
The unintended consequences of artificial intelligence in paediatric radiology.
in Pediatric radiology
D'Arco F
(2022)
Guidelines for magnetic resonance imaging in pediatric head and neck pathologies: a multicentre international consensus paper.
in Neuroradiology
Davendralingam N
(2021)
Artificial intelligence in paediatric radiology: Future opportunities.
in The British journal of radiology
Davendralingam N
(2021)
Ligamentum arteriosum calcification on paediatric postmortem computed tomography.
in Pediatric radiology
Decrausaz SL
(2022)
Evaluation of dual-energy X-ray absorptiometry compared to magnetic resonance imaging for collecting measurements of the human bony pelvis.
in American journal of human biology : the official journal of the Human Biology Council
Del Valle I
(2023)
An integrated single-cell analysis of human adrenal cortex development.
in JCI insight
Docter D
(2023)
Microfocus computed tomography for fetal postmortem imaging: an overview.
in Pediatric radiology
Dupré M
(2024)
Paediatric radiology training in the UK: a national trainee survey by the British Society of Paediatric Radiologists (BSPR).
in Clinical radiology
Edwards H
(2023)
Forensic post-mortem CT in children.
in Clinical radiology
Edwards H
(2023)
Forensic post-mortem CT in children.
in Clinical radiology
Fagan A
(2022)
Cinematic rendering of paediatric musculoskeletal pathologies: initial experiences with CT.
in Clinical radiology
Frauenfelder C
(2021)
Micro-CT Imaging of Pediatric Thyroglossal Duct Cysts: A Prospective Case Series.
in Frontiers in pediatrics
Gaunt T
(2019)
Emergency imaging in paediatric oncology: a pictorial review.
in Insights into imaging
Goergen SK
(2019)
Diagnostic assessment of foetal brain malformations with intra-uterine MRI versus perinatal post-mortem MRI.
in Neuroradiology
Hannon E
(2022)
Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model.
in iScience
Harty MP
(2023)
Current utilization of pediatric postmortem imaging in North America: a questionnaire-based survey.
in Pediatric radiology
Hemke R
(2020)
Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis: ESSR-ESPR points to consider.
in European radiology
Hutchinson JC
(2017)
Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT).
in The British journal of radiology
Hutchinson JC
(2018)
Postmortem microfocus computed tomography for early gestation fetuses: a validation study against conventional autopsy.
in American journal of obstetrics and gynecology
Description | BNS / ISFRI expert consensus statement for post mortem neurological imaging |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | expert consensus statement regarding appropriate clinical and forensic post mortem neurological imaging. |
URL | https://pubmed.ncbi.nlm.nih.gov/29533475/ |
Description | BSPR National Working Group on Imaging in Suspect Physical Abuse |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Former BSPR National Working Group on Imaging in Suspect Physical Abuse Advisory body to: President of the Family Division Working Group on Medical Experts in the Family Courts |
URL | https://www.judiciary.uk/publications/the-president-of-the-family-divisions-working-group-on-medical... |
Description | Current state of perinatal postmortem magnetic resonance imaging: ESPR recommendations |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | Established post mortem MRI protocols Current state of perinatal postmortem magnetic resonance imaging: European Society of Paediatric Radiology questionnaire-based survey and recommendations |
URL | https://pubmed.ncbi.nlm.nih.gov/33367939/ |
Description | EIBIR - Strategic research agenda for biomedical imaging |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | This Strategic Research Agenda identifies current challenges and needs in healthcare, illustrates how biomedical imaging and derived data can help to address these, and aims to stimulate dedicated research funding efforts.Medicine is currently moving towards a more tailored, patient-centric approach by providing personalised solutions for the individual patient. Innovation in biomedical imaging plays a key role in this process as it addresses the current needs for individualised prevention, treatment, therapy response monitoring, and image-guided surgery.The use of non-invasive biomarkers facilitates better therapy prediction and monitoring, leading to improved patient outcomes. Innovative diagnostic imaging technologies provide information about disease characteristics which, coupled with biological, genetic and -omics data, will contribute to an individualised diagnosis and therapy approach.In the emerging field of theranostics, imaging tools together with therapeutic agents enable the selection of best treatments and allow tailored therapeutic interventions.For prenatal monitoring, the use of innovative imaging technologies can ensure an early detection of malfunctions or disease.The application of biomedical imaging for diagnosis and management of lifestyle-induced diseases will help to avoid disease development through lifestyle changes.Artificial intelligence and machine learning in imaging will facilitate the improvement of image interpretation and lead to better disease prediction and therapy planning.As biomedical imaging technologies and analysis of existing imaging data provide solutions to current challenges and needs in healthcare, appropriate funding for dedicated research is needed to implement the innovative approaches for the wellbeing of citizens and patients. |
URL | https://pubmed.ncbi.nlm.nih.gov/30693378/ |
Description | ESPR 2019 strategic research agenda: improving imaging for tomorrow's children |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | European Society of Paediatric Radiology 2019 strategic research agenda: improving imaging for tomorrow's children Pediatr Radiol 2019 Jul;49(8):983-989. Owen J Arthurs 1 2 , Rick R van Rijn 3 , Claudio Granata 4 , Luciana Porto 5 , F Wolfgang Hirsch 6 , Karen Rosendahl 7 8 Affiliations |
URL | https://pubmed.ncbi.nlm.nih.gov/31115616/ |
Description | Management strategies for children with COVID-19: ESPR practical recommendations |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | Management strategies for children with COVID-19: ESPR practical recommendations |
URL | https://pubmed.ncbi.nlm.nih.gov/32621013/ |
Description | NR-POCUS in paediatrics - ESPR position paper |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | Non-radiologist-performed point-of-care ultrasonography in paediatrics - European Society of Paediatric Radiology position paper |
URL | https://pubmed.ncbi.nlm.nih.gov/33211186/ |
Description | Professional development and research are being neglected: a commentary on the 2019 RCR radiologists' supporting professional activities (SPA) survey |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | Professional development and research are being neglected: a commentary on the 2019 RCR radiologists' supporting professional activities (SPA) survey RCR academic committee |
URL | https://pubmed.ncbi.nlm.nih.gov/32204894/ |
Guideline Title | The radiological investigation of suspected physical abuse in children |
Description | RCR The radiological investigation of suspected physical abuse in children |
Geographic Reach | National |
Policy Influence Type | Citation in clinical guidelines |
Impact | improved diagnosis of rib fractures in children suspected of physical abuse |
URL | https://www.rcr.ac.uk/publication/radiological-investigation-suspected-physical-abuse-children |
Description | Albert Baert Fellowship - European Society of Radiology |
Amount | € 4,500 (EUR) |
Organisation | European Society of Radiology |
Sector | Charity/Non Profit |
Country | Austria |
Start | 07/2019 |
End | 07/2019 |
Description | BIR Siemens Research Award |
Amount | £1,000 (GBP) |
Organisation | British Institute of Radiology (BIR) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2017 |
End | 03/2018 |
Description | European Society of Radiology - Best oral presentation award |
Amount | £350 (GBP) |
Organisation | European Society of Radiology |
Sector | Charity/Non Profit |
Country | Austria |
Start | 03/2020 |
End | 03/2020 |
Description | Guy Sebag Research Award |
Amount | € 10,000 (EUR) |
Organisation | European Society of Paediatric Radiology (ESPR) |
Sector | Charity/Non Profit |
Country | France |
Start | 10/2017 |
End | 10/2018 |
Description | IRIYA - Introduction to Research for International Young Academics |
Amount | |
Organisation | Radiological Society of North America, RSNA |
Sector | Learned Society |
Country | United States |
Start | 11/2017 |
End | 12/2017 |
Description | Invest in Youth |
Amount | |
Organisation | European Society of Paediatric Radiology (ESPR) |
Sector | Charity/Non Profit |
Country | France |
Start | 03/2017 |
End | 03/2017 |
Description | RCR Pump Priming Grant |
Amount | £10,000 (GBP) |
Organisation | Academy of Medical Royal Colleges |
Department | Royal College of Radiologists |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2017 |
End | 10/2018 |
Description | Radiological Society of North America, RSNA - Magna Cum Laude Award for best poster |
Amount | £0 (GBP) |
Organisation | Radiological Society of North America, RSNA |
Sector | Learned Society |
Country | United States |
Start | 12/2018 |
End | 12/2018 |
Description | UCL Cheltenham Festival Travel Award |
Amount | £500 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2018 |
End | 06/2018 |
Description | UCL collaboration on Placental Micro CT |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided Micro CT imaging in kind to UCL project on placental imaging; |
Collaborator Contribution | bioengineering 3D evaluation has established placental vascular network |
Impact | doi: 10.1002/jbio.201900167 doi: 10.1016/j.placenta.2019.09.014 doi: 10.1016/j.placenta.2017.09.013 |
Start Year | 2016 |
Description | BIR Podcast |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | BIR Podcast - interview with Dr Owen Arthurs |
Year(s) Of Engagement Activity | 2019 |
URL | http://www.birpublications.org/page/podcasts/2019/post-mortem-paediatric-imaging/ |
Description | Press release, Aunt Minnie |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Post Mortem Pediatric Imaging proves value Press release by Aunt Minnie.com, 20 May 2019 |
Year(s) Of Engagement Activity | 2019 |
URL | http://www.auntminnieeurope.com/617393 |