Owen J. Arthurs

Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice

Although post-mortem MRI (PMMR) was proposed as an alternative to conventional autopsy more than a decade ago, the lack of systematic validation has limited its clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with ancillary investigations has now been shown to be as accurate as conventional autopsy in foetuses, newborns and infants and is particularly useful for cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR provides a permanent three-dimensional auditable record, with accurate estimation of internal organ volumes. MIA is becoming highly acceptable to parents and professionals, and there is widespread political support and public interest in its clinical implementation in the UK. In the short to medium term, it is desirable that a supraregional network of specialist centres should be established to provide this service within the current National Health Service framework.

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

BACKGROUND To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. METHODS Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. RESULTS Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). CONCLUSIONS PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities.

Duodenal haematoma following endoscopy as a marker of coagulopathy

BackgroundIntramural duodenal haematomas (IDHs) are a rare complication of endoscopic biopsy but can cause significant morbidity and mortality, including duodenal obstruction, hospitalization and needing intravenous feeding. They are extremely uncommon in those with normal haematology.ObjectiveTo describe the occurrence of IDHs following endoscopic biopsy in our institution.Materials and methodsWe identified three patients who developed a post biopsy IDH during an 18-month period (2010–2012) in a retrospective search of our hospital pathology and imaging databases.ResultsAll three children had complex medical problems and presented with gastrointestinal symptoms including severe abdominal pain, reflux, poor feeding and abnormal gut transit time. All underwent normal upper GI endoscopy with duodenal biopsy. Following endoscopy, they presented with intermittent GI obstruction with severe abdominal pain, distension and bilious vomiting or symptoms of pancreatitis, had imaging features of IDH and were managed conservatively making a full recovery. Initial haematology including platelet counts were normal, but two children were subsequently found to have platelet dysfunction and the third to have an unclassified coagulopathy.ConclusionIDHs may be the presenting factor in children with unsuspected bleeding problems. We present these findings to raise awareness of the imaging features and clinical impact of these cases because better understanding of these risk factors may help to avoid these complications in children in the future.

Current issues in postmortem imaging of perinatal and forensic childhood deaths

Perinatal autopsy practice is undergoing a state of change with the introduction of evidence-based cross-sectional imaging, driven primarily by parental choice. In particular, the introduction of post mortem magnetic resonance imaging (PMMR) has helped to advance less-invasive perinatal autopsy in the United Kingdom (UK) and Europe. However, there are limitations to PMMR and other imaging techniques which need to be overcome, particularly with regard to imaging very small fetuses. Imaging is also now increasingly used to investigate particular deaths in childhood, such as suspected non-accidental injury (NAI) and sudden unexpected death in infancy (SUDI). Here we focus on current topical developments the field, with particular emphasis on the application of imaging to perinatal autopsy, and pediatric forensic deaths. Different imaging modalities and their relative advantages and disadvantages are discussed, together with other benefits of more advanced cross-sectional imaging which currently lie in the research domain. Whilst variations in local imaging service provision and need may determine different practice patterns, and access to machines and professionals with appropriate expertise and experience to correctly interpret the findings may limit current practices, we propose that gold standard perinatal and pediatric autopsy services would include complete PMMR imaging prior to autopsy, with PMCT in suspicious childhood deaths. This approach would provide maximal diagnostic yield to the pathologist, forensic investigator and most importantly, the parents.

Postmortem cardiac imaging in fetuses and children

Fetal and pediatric cardiac autopsies have a crucial role in the counseling of parents with regard to both the cause of death of their child and the implications of such findings for future pregnancies, as well as for quality assurance of antenatal screening programs and antemortem diagnostic procedures. Postmortem imaging allows an opportunity to investigate the heart in situ prior to dissection, and both postmortem CT and postmortem MRI have shown excellent accuracy in detecting the majority of clinically significant cardiac lesions in the perinatal and pediatric population. As less-invasive autopsy becomes increasingly popular, clinical guidelines for maximal diagnostic yield in specific circumstances can be developed.

Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

To assess the clinical relevance of transgenic and patient‐derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post‐mortem microcomputed tomography (μ‐CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mice, and of patient‐derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ‐CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1‐weighted signal enhancement in the solid tumor component following Gd‐DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1‐weighted images. Ex vivo μ‐CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ‐CT and verified by histological sections of patient‐derived ACP xenografts. The Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient‐derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.

Learning effect on perinatal post‐mortem magnetic resonance imaging reporting: single reporter diagnostic accuracy of 200 cases

The objective of the study is to compare diagnostic accuracy of perinatal post‐mortem magnetic resonance (PMMR) imaging against conventional autopsy, when reported by a single‐blinded observer for all organ systems following a period of initial experience.

ESPR postmortem imaging task force: where we begin.

A new task force on postmortem imaging was established at the annual meeting of the European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The postmortem task force is separate from the child abuse task force as it covers all aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of the task force is the guidance and standardization of non-radiographic postmortem imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines the starting point of the task force, with a mission statement, outline of current experience, and short- and long-term goals.

Diffusion-weighted post-mortem magnetic resonance imaging of the human fetal brain in situ

PURPOSE To evaluate perinatal brain apparent diffusion coefficient (ADC) values at postmortem MRI (PMMR) in order to evaluate post mortem changes. MATERIALS AND METHODS Postmortem brain MRI was performed with diffusion gradient values b=0, 500, and 1000s/mm(2) on 43 fetal cases. Mean ADC values were calculated from 7 regions of interest (ROIs) throughout the brain. RESULTS 43 fetuses were evaluated with median gestational age 36 weeks (range 21-41). Overall, fetal brain ADC varied with maceration score, but not with gestational age or post mortem interval. The best single predictor of brain ADC was maceration score, which accounted for 52% of data variation for frontal cortex (p<0.001) and 44% in basal ganglia (p<0.001), and between 24% and 32% in all five of the other included brain areas. Gestation was only significantly associated with occipital ADC changes and post mortem interval only significantly associated with basal ganglia ADC changes. Median intra-observer and inter-observer variability was 6.0% (95% range 1.0%-18.1%) and 8.0% (95% range 0.2%-33.9%) respectively. CONCLUSION DWI characteristics in different fetal brain areas following death are multifactorial, with maceration the strongest predictor in most anatomical areas. Deep grey matter areas are also affected by gestation and post mortem interval. With better models, brain ADC may be useful to estimate the degree of maceration where gestation and post mortem interval is unknown.

Postmortem image‐guided biopsy for less‐invasive diagnosis of congenital intracranial teratoma

In certain cases, postmortem magnetic resonance imaging (PM-MRI) can obviate the need for formal autopsy and dissection by providing high-quality imaging which can guide tissue sampling. Percutaneous needle organ biopsy to obtain tissue samples for microscopic examination, as part of the less-invasive perinatal autopsy, has been described previously1 and endoscopicor laparoscopic-guided sampling has also been piloted2. We present a case of congenital malformation in