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Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

ABSTRACT: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population.Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard.There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures.ClinicalTrials.gov: NCT01888380.

SUBMITTER: Ruegger CM

PROVIDER: S-EPMC3897955 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

Rüegger Christoph M CM Bartsch Christine C Martinez Rosa Maria RM Ross Steffen S Bolliger Stephan A SA Koller Brigitte B Held Leonhard L Bruder Elisabeth E Bode Peter Karl PK Caduff Rosmarie R Frey Bernhard B Schäffer Leonhard L Bucher Hans Ulrich HU

BMC pediatrics 20140120

<h4>Background</h4>In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autops ...[more]

PMID: 24438163

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Project description:BackgroundNew strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and children in developing countries. However, none of these studies was conducted in areas with an undergoing infectious disease epidemic. We have recently experienced an epidemic of yellow fever (YF) in Brazil. Aiming to provide new information on low-cost post-mortem techniques that could be applied in regions at risk for infectious outbreaks, we tested the efficacy of ultrasound-guided MIA (MIA-US) in the diagnosis of patients who died during the epidemic.Methodology/principal findingsIn this observational study, we performed MIA-US in 20 patients with suspected or confirmed YF and compared the results with those obtained in subsequent CAs. Ultrasound-guided biopsies were used for tissue sampling of liver, kidneys, lungs, spleen, and heart. Liver samples from MIA-US and CA were submitted for RT-PCR and immunohistochemistry for detection of YF virus antigen. Of the 20 patients, 17 had YF diagnosis confirmed after autopsy by histopathological and molecular analysis. There was 100% agreement between MIA-US and CA in determining the cause of death (panlobular hepatitis with hepatic failure) and main disease (yellow fever). Further, MIA-US obtained samples with good quality for molecular studies and for the assessment of the systemic involvement of the disease. Main extrahepatic findings were pulmonary hemorrhage, pneumonia, acute tubular necrosis, and glomerulonephritis. One patient was a 24-year-old, 27-week pregnant woman; MIA-US assessed the placenta and provided adequate placental tissue for analysis.ConclusionsMIA-US is a reliable tool for rapid post-mortem diagnosis of yellow fever and can be used as an alternative to conventional autopsy in regions at risk for hemorrhagic fever outbreaks with limited resources to perform complete diagnostic autopsy.

Project description:BACKGROUND:Minimally invasive autopsy by post mortem magnetic resonance (MR) imaging has been suggested as an alternative for conventional autopsy in view of the declining consented autopsy rates. However, large prospective studies rigorously evaluating the accuracy of such an approach are lacking. We intend to compare the accuracy of a minimally invasive autopsy approach using post mortem MR imaging with that of conventional autopsy in fetuses, newborns and children for detection of the major pathological abnormalities and/or determination of the cause of death. METHODS/DESIGN:We recruited 400 consecutive fetuses, newborns and children referred for conventional autopsy to one of the two participating hospitals over a three-year period. We acquired whole body post mortem MR imaging using a 1.5 T MR scanner (Avanto, Siemens Medical Solutions, Enlargen, Germany) prior to autopsy. The total scan time varied between 90 to 120 minutes. Each MR image was reported by a team of four specialist radiologists (paediatric neuroradiology, paediatric cardiology, paediatric chest & abdominal imaging and musculoskeletal imaging), blinded to the autopsy data. Conventional autopsy was performed according to the guidelines set down by the Royal College of Pathologists (UK) by experienced paediatric or perinatal pathologists, blinded to the MR data. The MR and autopsy data were recorded using predefined categorical variables by an independent person. DISCUSSION:Using conventional post mortem as the gold standard comparator, the MR images will be assessed for accuracy of the anatomical morphology, associated lesions, clinical usefulness of information and determination of the cause of death. The sensitivities, specificities and predictive values of post mortem MR alone and MR imaging along with other minimally invasive post mortem investigations will be presented for the final diagnosis, broad diagnostic categories and for specific diagnosis of each system. CLINICAL TRIAL REGISTRATION:NCT01417962 NIHR PORTFOLIO NUMBER: 6794.

Project description:At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. The top two biological processes were ECM organization and ECM structure organization. Genes involving epidermis development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The top processes involved skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Over half of the enriched biological processes also involved immune function, including antigen processing and presentation. The results provide essential insight regarding newborn infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. To our knowledge, this is the first report on newborn infant skin transcriptomics analysis. When compared to ultraviolet radiation protected adult skin, it highlights the substantial differences between them. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.

Dataset Information

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

Publications

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

Similar Datasets

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