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Objective: To determine the additional yield from autopsy following prenatal ultrasound and post-mortem magnetic resonance imaging (PMMR) for structural abnormalities., Method: PMMR was performed on consecutive fetuses over a 6-year period. Prenatal ultrasound and PMMR findings were categorised as concordant, partially concordant or discordant findings. The yield of new and clinically significant information from autopsy was assessed. Diagnostic accuracies for both modalities were calculated, using autopsy as reference standard., Results: Our study consisted of 81 fetuses. PMMR and prenatal ultrasound findings were concordant in 44/81 (54.3%), partially concordant in 26/81 (32.1%) and discordant in 11/81 (13.6%) cases. In 19/81 cases (23%), autopsy provided additional information, which appeared clinically significant in 12 cases. In 10 of those 12 cases, there was discordance between PMMR and ultrasound. In only 2 of 44 cases where ultrasound and PMMR were concordant, did autopsy provide clinically significant information. Diagnostic accuracy rates for ultrasound were sensitivity of 76.8% (66.6%, 84.6%), specificity of 92.5% (88.9%, 95.0%). For PMMR the sensitivity was 79.0% (68.9%, 86.5%), specificity 97.9% (95.5%, 99.0%). PMMR had a significantly higher concordance rate with autopsy than ultrasound (89.0 vs 93.8%; P < .001)., Conclusion: Where PMMR and ultrasound are concordant, there is little additional yield from autopsy., (© 2019 John Wiley & Sons, Ltd.)

Objective: 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., Methods: We compared pre-autopsy PMMR with conventional autopsy for the detection of (1) major pathological abnormalities related to the cause of death and (2) all diagnostic findings in five different body organ systems. PMMR was reported blinded to autopsy findings., Results: In 201 cases, 123/146 (84.2%) of major abnormalities were identified by PMMR. Overall diagnostic accuracy of PMMR was 89.6% [95% confidence interval (CI): 84.3, 93.2%] across all cases, with high concordance 91.8% (95% CI: 89.9, 93.4%) across most organ systems. Our study showed higher concordance than single reporter statistics previously reported in neurological [92.2% vs 73.8%; diff 18.4% (95% CI: 11.0, 25.4%) p < 0.01] and thoracic systems [93.7% vs 81.2%; diff 12.5% (95% CI: 6.3, 18.4%) p < 0.01] and slightly better overall [91.8% vs 87.1%; diff 4.7% (95% CI: 2.1, 7.3%) p < 0.01]., Conclusion: The PMMR examinations can be reliably reported by a single radiologist, following a period of experience and training with this specific modality, with high-diagnostic accuracy for all organ systems. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)

Objectives: To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children., Methods: We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related to the cause of death and (b) all diagnostic findings in five different body organ systems., Results: Eighty two cases (53 fetuses and 29 children) underwent PMCT and PMMR prior to autopsy, at which 55 major abnormalities were identified. Significantly more PMCT than PMMR examinations were non-diagnostic (18/82 vs. 4/82; 21.9 % vs. 4.9 %, diff 17.1 % (95 % CI 6.7, 27.6; p < 0.05)). PMMR gave an accurate diagnosis in 24/55 (43.64 %; 95 % CI 31.37, 56.73 %) compared to 18/55 PMCT (32.73 %; 95 % CI 21.81, 45.90). PMCT was particularly poor in fetuses <24 weeks, with 28.6 % (8.1, 46.4 %) more non-diagnostic scans. Where both PMCT and PMMR were diagnostic, PMMR gave slightly higher diagnostic accuracy than PMCT (62.8 % vs. 59.4 %)., Conclusion: Unenhanced PMCT has limited value in detection of major pathology primarily because of poor-quality, non-diagnostic fetal images. On this basis, PMMR should be the modality of choice for non-invasive PM imaging in fetuses and children., Key Points: • Overall 17.1 % more PMCT examinations than PMMR were non-diagnostic • 28.6 % more PMCT were non-diagnostic than PMMR in fetuses <24 weeks • PMMR detected almost a third more pathological abnormalities than PMCT • PMMR gave slightly higher diagnostic accuracy when both were diagnostic.

As post-mortem MRI (PMMR) becomes more widely used for investigation following perinatal and paediatric deaths, the best possible images should be acquired. In this article, we review the most widely used published PMMR sequences, together with outlining our acquisition protocol and sequence parameters for foetal, perinatal and paediatric PMMR. We give examples of both normal and abnormal appearances, so that the reader can understand the logic behind each acquisition step before interpretation, as a useful day-to-day reference guide to performing PMMR.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to compare the diagnostic accuracy of postmortem magnetic resonance (PMMR) imaging specifically for musculoskeletal pathology in fetuses and children, compared with conventional autopsy, with radiographic and histopathology assessment., Methods: Institutional ethics approval and parental consent was obtained. A total of 400 cases underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data, respectively., Results: A total of 400 cases were reported, with 277 (69%) fetuses (185 ≤24 weeks' gestation and 92 >24 weeks' gestation) and 123 children (42 newborns aged <1 month, 53 infants ≤12 months and 28 children ≤16 years). Musculoskeletal (MSK) abnormalities were found at autopsy in 47/400 (11.7%). Overall sensitivity and specificity (with 95% confidence interval) of PMMR for MSK pathology were 51.1% (37.0, 65.0) and 98.2% (96.2, 99.2), with positive and negative predictive values of 79.3% (61.6, 90.2) and 93.8% (90.8, 95.9), respectively. Overall accuracy between PMMR and autopsy for MSK abnormalities was 92.7% (89.7, 94.9). In some cases, PMMR detected MSK abnormalities not routinely examined for or detected at traditional autopsy., Conclusion: Minimally invasive autopsy has good diagnostic accuracy for the exclusion of MSK abnormalities, but sensitivity is relatively poor. When PMMR is used with clinical examination and skeletal radiographs, all skeletal and soft tissue abnormalities of clinical significance are likely to be detected, even if not directly relevant to the cause of death., (© 2014 John Wiley & Sons, Ltd.)

Objectives: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy., Methods: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded 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 thoracic pathology 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 anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection., Conclusions: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities., Key Points: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology.

Background: Post-mortem MRI is a potential diagnostic alternative to conventional autopsy, but few large prospective studies have compared its accuracy with that of conventional autopsy. We assessed the accuracy of whole-body, post-mortem MRI for detection of major pathological lesions associated with death in a prospective cohort of fetuses and children., Methods: In this prospective validation study, we did pre-autopsy, post-mortem, whole-body MRI at 1·5 T in an unselected population of fetuses (≤24 weeks' or >24 weeks' gestation) and children (aged <16 years) at two UK centres in London between March 1, 2007 and Sept 30, 2011. With conventional autopsy as the diagnostic gold standard, we assessed MRI findings alone, or in conjunction with other minimally invasive post-mortem investigations (minimally invasive autopsy), for accuracy in detection of cause of death or major pathological abnormalities. A radiologist and pathologist who were masked to the autopsy findings indicated whether the minimally invasive autopsy would have been adequate. The primary outcome was concordance rate between minimally invasive and conventional autopsy., Findings: We analysed 400 cases, of which 277 (69%) were fetuses and 123 (31%) were children. Cause of death or major pathological lesion detected by minimally invasive autopsy was concordant with conventional autopsy in 357 (89·3%, 95% CI 85·8-91·9) cases: 175 (94·6%, 90·3-97·0) of 185 fetuses at 24 weeks' gestation or less, 88 (95·7%, 89·3-98·3) of 92 fetuses at more than 24 weeks' gestation, 34 (81·0%, 66·7-90·0) [corrected] of 42 newborns aged 1 month or younger, 45 (84·9%, 72·9-92·1) of 53 infants aged older than 1 month to 1 year or younger, and 15 (53·6%, 35·8-70·5) of 28 children aged older than 1 year to 16 years or younger. The dedicated radiologist or pathologist review of the minimally invasive autopsy showed that in 165 (41%) cases a full autopsy might not have been needed; in these cases, concordance between autopsy and minimally invasive autopsy was 99·4% (96·6-99·9)., Interpretation: Minimally invasive autopsy has accuracy similar to that of conventional autopsy for detection of cause of death or major pathological abnormality after death in fetuses, newborns, and infants, but was less accurate in older children. If undertaken jointly by pathologists and radiologists, minimally invasive autopsy could be an acceptable alternative to conventional autopsy in selected cases., Funding: Policy research Programme, Department of Health, UK., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Our aim was to identify sub-groups of right ventricular outflow tract morphology that would be suitable for percutaneous pulmonary valve implantation and to document their prevalence in our patient population., Materials and Methods: Eighty-three consecutive patients with right ventricular outflow tract dysfunction (5-41 years, 76% tetralogy of Fallot) referred to our center for cardiovascular magnetic resonance were studied. A morphological classification was created according to visual assessment of three-dimensional reconstructions and detailed measurement. Diagnosis, right ventricular outflow tract type, surgical history and treatment outcomes were documented., Results: Right ventricular outflow tract morphology was heterogeneous; nevertheless, 5 patterns were visually identified. Type I, a pyramidal morphology, was most prevalent (49%) and related to the presence of a transannular patch. Other types (II-V) were seen more commonly in patients with conduits. Two patients had unclassifiable morphology. Ninety-five percent of patients were assigned to the correct morphological classification by visual assessment alone. Percutaneous pulmonary valve implantation was performed successfully in 10 patients with Type II-V morphology and in 1 patient with unclassifiable morphology. Percutaneous implantation was not performed in patients with Type I morphology. Only right ventricular outflow tract diameters < 22 mm in diameter were suitable for the current device., Conclusions: We have created a morphological classification of the RVOT in patients referred for assessment of RVOT dysfunction. Though only 13% of our patients underwent percutaneous implantation, > 50% of outflow tract morphologies may be suitable for this approach, in particular with the development of new devices appropriate for larger outflow.

Epilepsy research for the design of seizure detection/prediction neuroprosthetics has been faced with the search for electrophysiologic control parameters that can be used to infer the epileptic state of the animal and be leveraged at a later time to deliver neurotherapeutic feedback. The analysis presented here uses multi-microelectrode array technology to provide an electrophysiologic quantification of a hippocampal neural ensemble during the latent period of epileptogenesis. Through the use of signal processing system identification methodologies, we were able to assess the spatial and temporal interrelations of ensembles of hippocampal neurons and relate them to the evolution of the epileptic condition. High-field magnetic resonance (MR) imaging was used to determine the location of electrode placement and to evaluate hippocampal pyramidal cell structural damage. Long-term single unit activity analysis suggests that hippocampal neurons in both CA1-2 and dentate regions increase the number of occurrences and duration of their bursting activity after injury to the contra-lateral hippocampus. The trends inferred from both single neuron and ensemble analysis suggests that the evolution into epilepsy is not abrupt but modulates gradually from the time of injury.

Objective: To evaluate perinatal body organ apparent diffusion coefficient (ADC) values at postmortem magnetic resonance imaging (PMMR) in order to evaluate postmortem changes. Methods: Postmortem diffusion-weighted imaging (DWI) of the thorax and abdomen were performed with diffusion gradient values b = 0, 500, and 1000 s/mm on 15 foetal and childhood cases (mean 33.3 ± 7.8 weeks gestation) compared to 44 live infants (mean age 75.5 ± 53.4 days). Mean ADC values were calculated from regions of interest (ROIs) for the lungs, liver, spleen and renal cortex, compared to normative live infantile body ADC values of similar gestational age. Results: Mean ADC values were significantly lower in postmortem cases than in normal controls for liver (0.88 10 mm/s ± SD 0.39 vs. 1.13 ± 0.13; p < 0.05) and renal cortex (0.85 ± 0.26 vs. 1.19 ± 0.13; p < 0.05) but not spleen or muscle. Mean lung ADC values were significantly higher than normal controls (1.06 ± 0.18 vs. 0 ± 0; p < 0.001), and there was a significant correlation between postmortem interval and lung ADC (R = 0.55). Conclusion: Lung PMMR ADC values are related to postmortem interval, making them a potential marker of time since death. Further research is needed to understand the organ-specific changes which occur in the postmortem period. Key Points: • Liver and spleen PM ADC values were lower than controls. • Lung ADC changes correlate with PM interval. • These findings may be useful in medicolegal cases. [ABSTRACT FROM AUTHOR]

Objective: Chronic pulmonary regurgitation (PR) has deleterious effects on right ventricular (RV) function in repaired tetralogy of Fallot (ToF). However, there are little data regarding right ventricular outflow tract (RVOT) contractile dysfunction in response to chronic PR and on both RV and LV volumes and function. Methods: We retrospectively identified consecutive patients with PR who were referred for magnetic resonance imaging quantification of “free PR” detected on echocardiography between 2003 and 2008. Patients had ToF and a transannular patch procedure (n = 30, 25.1 ± 1.2 years) or PR resulting from valvar pulmonary stenosis treated with surgical or percutaneous valvotomy (n = 30, 26.6 ± 1.8 years). Results: The ToF and the PS groups were well matched for age at scan, age at repair surgery in ToF or initial valvotomy in PS, duration of exposure to PR, body surface area, heart rate, PR fraction, net forward pulmonary artery flow, and main and branch pulmonary artery dimensions. Severe PR fractions were identified in both groups (ToF: 40% ± 1% vs PS: 37% ± 2%, P = .2). Indexed RV and LV end-diastolic volumes were similar for both ToF and PS groups (RV end-diastolic volume index: 137 ± 6 mL/m2 vs 128 ± 5 mL/m2, P = .2, and LV end-diastolic volume index: 72 ± 2 mL/m2 vs 67 ± 2 mL/m2, P = .1, respectively). RV mass was also similar between groups (95 ± 5 g vs 81 ± 6 g, respectively, P = .08). However, indexed RV and LV end-systolic volumes were consistently higher in ToF when compared with PS (RV end-systolic volume index: 70 ± 5 mL/m2 vs 54 ± 3 mL/m2, P < .01, and LV end-systolic volume index: 29 ± 1 mL/m2 vs 22 ± 1 mL/m2, P < .01, respectively). These changes were reflected in lower biventricular systolic function in patients with ToF when compared with PS (RV ejection fraction: 52% ± 1.5% vs 59% ± 1%, P < .001, and LV ejection fraction: 61% ± 1% vs 67 ± 1%, P < .001, respectively). Although RV transannular plane systolic excursion was not significantly different between the groups (P = .86), the RV outflow tract was considered contractile in only 50% of patients with ToF compared with 93% of patients with PS (P = .0004). RV volumes and function were similar when only patients with contractile RV outflow tracts were compared. Conclusions: RV outflow tract patch dysfunction in repaired ToF is responsible for higher end-systolic volumes and thus lower global measures of ventricular systolic function. These findings were not evident in cases of PS treated with valvotomy with comparable amount of PR. These observations highlight the importance of the initial repair surgery in ToF for late outcomes. [Copyright &y& Elsevier]

Abstract: Structural changes in limbic regions are often observed in individuals with temporal lobe epilepsy (TLE) and in animal models. However, the brain structural changes during the evolution into epilepsy remain largely unknown. Therefore, the purpose of this study was to define the temporal changes in limbic structures after experimental status epilepticus (SE) during the latency period of epileptogenesis in vivo, with quantitative diffusion tensor imaging (DTI) and T2 relaxometry in an animal model of chronic TLE. A pair of fifty micron electrodes was implanted into the ventral hippocampus in twelve male adult rats. Self-sustaining SE was induced with electrical stimulation in eleven rats. Three rats served as age-matched controls. In vivo diffusion tensor and T2 magnetic resonance imaging (MRI) was performed at 11.1 Tesla, pre- and post-implantation of electrodes and 3, 5, 7, 10, 20, 40 and 60days post-SE to assess structural changes. Spontaneous seizures were identified with continuous time-locked video-monitoring. Following imaging in vivo, fixed, excised brains were MR imaged at 17.6 Tesla. Subsequently, histological analysis was correlated with MRI results. Following SE, 8/11 injured rats developed spontaneous seizures. Unique to these 8 rats, early T2, diffusivity and anisotropy changes were observed in vivo within the parahippocampal gyrus (contralateral) and fimbria (bilateral). In excised brains, bilateral increase in anisotropy was observed in the dentate gyrus, corresponding to mossy fiber sprouting as determined by Timm staining. Using T2 relaxometry and DTI, specific transient and long-term structural changes were observed only in rats that developed spontaneous limbic seizures. [Copyright &y& Elsevier]