The role of artificial intelligence in paediatric cardiovascular magnetic resonance imaging.

Artificial intelligence (AI) offers the potential to change many aspects of paediatric cardiac imaging. At present, there are only a few clinically validated examples of AI applications in this field. This review focuses on the use of AI in paediatric cardiovascular MRI, using examples from paediatric cardiovascular MRI, adult cardiovascular MRI and other radiologic experience.

Avocado Consumption Alters Gastrointestinal Bacteria Abundance and Microbial Metabolite Concentrations among Adults with Overweight or Obesity: A Randomized Controlled Trial.

BACKGROUND: Avocados are rich in dietary fiber and monounsaturated fatty acids (MUFAs), nutrients that have been independently connected to metabolic health benefits and the gastrointestinal microbiota. OBJECTIVES: We aimed to evaluate the impact of avocado consumption on the gastrointestinal microbiota and microbial metabolites, secondary outcomes of the Persea americana for Total Health (PATH) study, and conduct exploratory analyses to assess relations between the fecal microbiota, fecal metabolites, and health markers. METHODS: Adults [n = 163, 25-45 y, BMI (kg/m2) ≥ 25.0] were enrolled in the PATH study, a 12-wk investigator-blinded trial where participants were batch randomized to match the 2 groups by age, sex, visceral adiposity, and fasting glucose concentrations. Participants consumed isocaloric meals with or without avocado (175 g, men; 140 g, women) once daily for 12 wk. The fecal microbiota was assessed with 16S ribosomal RNA gene (V4 region) sequencing and analysis using DADA2 and QIIME2. Fecal fatty acid and bile acid concentrations were quantified using GC and LC-MS. Per-protocol (≥80% meal consumption) and intent-to-treat analyses were conducted using univariate ANOVA and Mann-Whitney U tests. Bivariate correlations were conducted between fecal microbiota, fecal metabolites, and health measures. RESULTS: The avocado treatment increased ɑ diversity and enriched Faecalibacterium, Lachnospira, and Alistipes between 26% and 65% compared with the control group. The avocado group had 18% greater fecal acetate, 70% greater stearic acid, and 98% greater palmitic acid concentrations than the control group, while the concentrations of the bile acids cholic and chenodeoxycholic acid were 91% and 57% lower, respectively. CONCLUSIONS: Daily avocado consumption resulted in lower fecal bile acid concentrations, greater fecal fatty acid and SCFAs, and greater relative abundances of bacteria capable of fiber fermentation, providing evidence that this nutrient-dense food affects digestive physiology, as well as the composition and metabolic functions of the intestinal microbiota. This trial was registered at www.clinicaltrials.gov as NCT02740439.

Comprehensive MRI assessment of the cardiovascular responses to food ingestion in Fontan physiology.

In univentricular (Fontan) physiology, peripheral and splanchnic vascular tone may be raised to counteract reduced cardiac output (CO) and elevated central venous pressure and thus maintain vital organ perfusion. This could negatively affect the normal cardiovascular response to food ingestion, where mesenteric vasodilation and a concurrent rise in CO are central. We sought to elucidate this using rapid cardiovascular MRI. Thirty fasting subjects (50% controls, 40% women and 60% men) ingested a standardized meal. Responses over ~50 min in mean arterial pressure (MAP), CO, and blood flow in all major aortic branches were measured, and regional vascular impedance (Z0) was calculated. Differences from baseline and between groups were assessed by repeated-measures mixed models. Compared with the control group, the Fontan patient group had greater fasting Z0 of the legs and kidneys, resulting in greater systemic Z0 and similar MAP. They further had similar blood flow to the digestive organs at baseline, despite larger variation in mesenteric resistance. Postprandially, blood flow to the legs decreased in the control group but not in the Fontan patient group. Increases in CO and superior mesenteric blood flow were similar in both groups, but the celiac response was blunted in the Fontan patient group. No significant differences in MAP responses were observed. In conclusion, alterations in vascular tone to counteract adverse hemodynamics and raised hepatic afterload may blunt vasoreactivity in the legs and the celiac axis in Fontan physiology. Further study is needed to determine whether blunted celiac or mesenteric vasoreactivity is linked to deteriorating hemodynamics and poor prognosis in Fontan patients.NEW & NOTEWORTHY Novel data on cardiovascular physiology in response to a meal in Fontan patients are presented. Using a previously validated dynamic MRI protocol, we demonstrated that the usual increase in cardiac output and the dilation of the superior mesenteric artery are preserved in clinically well Fontan patients. In contrast, vasoconstriction of the legs may have prevented redistribution of blood flow from this region in response to the meal. This may also affect responses to other types of stress. Celiac vasodilation was also absent in Fontan patients. This may be due to abnormal hepatic circulation. The proposed protocol may be used to study Fontan complications secondary to abnormal regional hemodynamics.

A review of dietary and microbial connections to depression, anxiety, and stress.

Objective: Pre-clinical evidence suggests that the gastrointestinal microbiota contributes to mood and behavior disorders. Among humans, diet quality and patterns, which also impact the gastrointestinal microbiota, have been linked to depression, anxiety, and stress. This review summarizes findings from clinical studies using dietary intervention to improve depression, anxiety, or stress and the role the gastrointestinal microbiota may have in these disorders.Methods: A literature search was conducted using the keywords microbiome, microbiota, depression, anxiety, stress, diet, dietary pattern, diet quality, fiber, prebiotics, probiotics, and mood.Results: Mood was improved by enhancing diet quality. Fructooligosaccharide and galactooligosaccharide improved anxiety and depression in participants consuming ≥ 5 g/day. Additionally, bifidobacteria were enriched in subjects consuming ≥ 5 g/day. Probiotic consumption improved psychological or biological measures of depression, anxiety, or stress in individuals predisposed to a mood disorder. Probiotics suppressed biological markers of stress in healthy individuals in a strain-dependent manner.Discussion: High-quality diets, prebiotics, and probiotics may beneficially affect mood. Habitual diets rich in dietary fiber and omega-3-polyunsaturated fatty acids may be linked to reduced risk of developing symptoms of depression, anxiety, and stress; however, additional studies are necessary. Certain probiotics may enhance mood, but their influence on the gastrointestinal microbiota requires further investigation.

Associations among diet, the gastrointestinal microbiota, and negative emotional states in adults.

Objective: Habitual diet impacts mood and the human gastrointestinal (GI) microbiota. Yet, studies infrequently control for diet when evaluating associations between mood and GI microbiota. Accordingly, we aimed to investigate relationships among diet, GI microbiota, and mood in adults without mood disorders by conducting a cross-sectional examination of dietary intake, subjective emotional state, and fecal microbial taxa abundances. Methods: Adults (N = 133; 25-45 years of age) without physician-diagnosed mood disorders were studied. Fecal DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced. Sequences were analyzed using QIIME2. Subjective mood state was assessed using the 42-item Depression, Anxiety, and Stress Scale (DASS-42). Habitual dietary intake was measured with the National Cancer Institute's Diet History Questionnaire II, and diet quality was evaluated with the 2010 Healthy Eating Index (HEI). Results: Relationships were observed between 28 bacterial taxa and DASS-42 scores. Sex-dependent associations were observed among 21 bacterial taxa and DASS-42 scores, including an inverse relationship between Anxiety scale scores and Bifidobacterium in females and an inverse relationship between Depression scale scores and Lactobacillus in males. HEI total fruit and dairy components were inversely associated with Depression and Stress scales, respectively. Conclusions: These results suggest GI microbes are related to mood in adults without diagnosed mood disorders and that these relationships differ by sex and are influenced by dietary fiber intake. Incorporating dietary intake data in gut-microbiota-brain studies may help clarify the roles of specific microbes and dietary components in mental health symptoms.

Faecal calprotectin concentrations in neonates with CHD: pilot study.

Neonates with CHD are at increased risk of developing necrotising enterocolitis due to mesenteric hypoperfusion. Necrotising enterocolitis results in repeated feed interruptions contributing to poor growth during the early post-operative phase. Poor weight gain and longer hospital stay are risk factors for death in neonates with CHD. Abdominal radiography is used as a diagnostic tool for necrotising enterocolitis; however, its utility is limited in the early stages of necrotising enterocolitis when pneumatosis intestinalis is absent. Calprotectin is a neutrophil activation biomarker, and elevated levels are evident in inflammatory diseases such as necrotising enterocolitis. The aim of this study was to determine whether there is a correlation between faecal calprotectin concentration and gut inflammation in neonates with CHD. This prospective single-centre study recruited newly diagnosed term patients with duct-dependent CHD between March 2018 and March 2019. Faecal calprotectin concentrations were measured in post-surgical patients using enzyme-linked immunosorbent assay methods. A total of 30 patients were included in the analysis. Calprotectin concentration for patients who developed necrotising enterocolitis was 3528 µg/g compared with 390 µg/g without, compared with 1339 µg/g in patients with suspected necrotising enterocolitis (p = 0.0001). Patients with suspected necrotising enterocolitis had a significantly longer length of hospital stay, on average 18 days longer compared to patients without necrotising enterocolitis (p = 0.03). Faecal calprotectin concentrations may reflect severity of gut inflammation in neonates with CHD. Suspected necrotising enterocolitis contributes to longer days nil by mouth and an increase in length of hospital stay.

Is traditional perinatal autopsy needed after detailed fetal ultrasound and post-mortem MRI?

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.

Aberrant developmental titin splicing and dysregulated sarcomere length in Thymosin ß4 knockout mice.

Sarcomere assembly is a highly orchestrated and dynamic process which adapts, during perinatal development, to accommodate growth of the heart. Sarcomeric components, including titin, undergo an isoform transition to adjust ventricular filling. Many sarcomeric genes have been implicated in congenital cardiomyopathies, such that understanding developmental sarcomere transitions will inform the aetiology and treatment. We sought to determine whether Thymosin ß4 (Tß4), a peptide that regulates the availability of actin monomers for polymerization in non-muscle cells, plays a role in sarcomere assembly during cardiac morphogenesis and influences adult cardiac function. In Tß4 null mice, immunofluorescence-based sarcomere analyses revealed shortened thin filament, sarcomere and titin spring length in cardiomyocytes, associated with precocious up-regulation of the short titin isoforms during the postnatal splicing transition. By magnetic resonance imaging, this manifested as diminished stroke volume and limited contractile reserve in adult mice. Extrapolating to an in vitro cardiomyocyte model, the altered postnatal splicing was corrected with addition of synthetic Tß4, whereby normal sarcomere length was restored. Our data suggest that Tß4 is required for setting correct sarcomere length and for appropriate splicing of titin, not only in the heart but also in skeletal muscle. Distinguishing between thin filament extension and titin splicing as the primary defect is challenging, as these events are intimately linked. The regulation of titin splicing is a previously unrecognised role of Tß4 and gives preliminary insight into a mechanism by which titin isoforms may be manipulated to correct cardiac dysfunction.

Piloting the Use of Patient-Specific Cardiac Models as a Novel Tool to Facilitate Communication During Cinical Consultations.

This pilot study aimed to assess the impact of using patient-specific three-dimensional (3D) models of congenital heart disease (CHD) during consultations with adolescent patients. Adolescent CHD patients (n = 20, age 15-18 years, 15 male) were asked to complete two questionnaires during a cardiology transition clinic at a specialist centre. The first questionnaire was completed just before routine consultation with the cardiologist, the second just after the consultation. During the consultation, each patient was presented with a 3D full heart model realised from their medical imaging data. The model was used by the cardiologist to point to main features of the CHD. Outcome measures included rating of health status, confidence in explaining their condition to others, name and features of their CHD (as a surrogate for CHD knowledge), impact of CHD on their lifestyle, satisfaction with previous/current visits, positive/negative features of the 3D model, and open-ended feedback. Significant improvements were registered in confidence in explaining their condition to others (p = 0.008), knowledge of CHD (p < 0.001) and patients' satisfaction (p = 0.005). Descriptions of CHD and impact on lifestyle were more eloquent after seeing a 3D model. The majority of participants reported that models helped their understanding and improved their visit, with a non-negligible 30% of participants indicating that the model made them feel more anxious about their condition. Content analysis of open-ended feedback revealed an overall positive attitude of the participants toward 3D models. Clinical translation of 3D models of CHD for communication purposes warrants further exploration in larger studies.

Physiological adaptations to chronic stress in healthy humans - why might the sexes have evolved different energy utilisation strategies?

KEY POINTS: The human stress response activates the autonomic nervous system and endocrine systems to increase performance during environmental challenges. This response is usually beneficial, improving the chance of overcoming environmental challenges, but costs resources such as energy. Humans and other animals are known to adapt their responses to acute stress when they are stimulated chronically, presumably to optimise resource utilisation. Characterisation of these adaptations has been limited. Using advanced imaging techniques, we show that cardiovascular and endocrine physiology, reflective of energy utilisation during acute stress, and energy storage (fat) differ between the sexes when they are exposed to chronic stress. We examine possible evolutionary explanations for these differences, related to energy use, and point out how these physiological differences could underpin known disparities between the sexes in their risk of important cardiometabolic disorders such as obesity and cardiovascular disease. ABSTRACT: Obesity and associated diseases, such as cardiovascular disease, are the dominant human health problems in the modern era. Humans develop these conditions partly because they consume excess energy and exercise too little. Stress might be one of the factors contributing to these disease-promoting behaviours. We postulate that sex-specific primordial energy optimisation strategies exist, which developed to help cope with chronic stress but have become maladaptive in modern societies, worsening health. To demonstrate the existence of these energy optimisation strategies, we recruited 88 healthy adults with varying adiposity and chronic stress exposure. Cardiovascular physiology at rest and during acute stress (Montreal Imaging Stress Task), and body fat distribution were measured using advanced magnetic resonance imaging methods, together with endocrine function, cardiovascular energy use and cognitive performance. Potential confounders such as lifestyle, social class and employment were accounted for. We found that women exposed to chronic stress had lower adiposity, greater acute stress cardiovascular responses and better cognitive performance. Conversely, chronic stress-exposed men had greater adiposity and lower cardiovascular responses to acute stress. These results provide initial support for our hypothesis that differing sex-specific energy conservation strategies exist. We propose that these strategies have initially evolved to benefit humans but are now maladaptive and increase the risk of disorders such as obesity, especially in men exposed to chronic stress.

Comprehensive assessment of the global and regional vascular responses to food ingestion in humans using novel rapid MRI.

Ingestion of food is known to increase mesenteric blood flow. It is not clear whether this increased flow demand is compensated by a rise in cardiac output (CO) alone or by redistribution of blood flow from other organs. We used a new comprehensive imaging method to assess the human cardiovascular response to food ingestion. Following a 12-h fast, blood flow in segments of the aorta and in organ-specific arteries, and ventricular volumes were assessed in 20 healthy adults using MRI at rest and following ingestion of a high-energy liquid meal. Systemic vascular resistance (SVR) fell substantially and CO rose significantly. Blood pressure remained stable. These changes were predominantly driven by a rapid fall in mesenteric vascular resistance, resulting in over four times more intestinal blood flow. Renal vascular resistance also declined but less dramatically. No changes in blood flow to the celiac territory, the brain, or the limbs were observed. In conclusion, this is the first study to fully characterize systemic and regional changes in vascular resistance after food ingestion in humans. Our findings show that the postprandial drop in SVR is fully compensated for by increased CO and not by redistribution of blood from other organs. With the exception of a modest increase in renal blood flow, there was no evidence of altered blood flow to nondigestive organs. The proposed oral food challenge protocol can be applied safely in an MRI environment and may be useful for studying the involvement of the gut in systemic or cardiovascular disease.

Isometric stress in cardiovascular magnetic resonance-a simple and easily replicable method of assessing cardiovascular differences not apparent at rest.

INTRODUCTION: Isometric exercise may unmask cardiovascular disease not evident at rest, and cardiovascular magnetic resonance (CMR) imaging is proven for comprehensive resting assessment. This study devised a simple isometric exercise CMR methodology and assessed the hemodynamic response evoked by isometric exercise. METHODS: A biceps isometric exercise technique was devised for CMR, and 75 healthy volunteers were assessed at rest, after 3-minute biceps exercise, and 5-minute of recovery using: 1) blood pressure (BP) and 2) CMR measured aortic flow and left ventricular function. Total peripheral resistance (SVR) and arterial compliance (TAC), cardiac output (CO), left ventricular volumes and function (ejection fraction, stroke volume, power output), blood pressure (BP), heart rate (HR), and rate pressure product were assessed at all time points. RESULTS: Image quality was preserved during stress. During exercise there were increases in CO (+14.9 %), HR (+17.0 %), SVR (+9.8 %), systolic BP (+22.4 %), diastolic BP (+25.4 %) and mean BP (+23.2 %). In addition, there were decreases in TAC (-22.0 %) and left ventricular ejection fraction (-6.3 %). Age and body mass index modified the evoked response, even when resting measures were similar. CONCLUSIONS: Isometric exercise technique evokes a significant cardiovascular response in CMR, unmasking physiological differences that are not apparent at rest. KEY POINTS: • Isometric exercise unmasks cardiovascular differences not evident at rest. • CMR is the reference standard for non-invasive cardiovascular assessment at rest. • A new easily replicable method combines isometric exercise with CMR. • Significant haemodynamic changes occur and differences are unmasked. • The physiological, isometric CMR stressor can be easily replicated.

Comparison of diagnostic performance for perinatal and paediatric post-mortem imaging: CT versus MRI.

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.

Numerical model of a valvuloplasty balloon: in vitro validation in a rapid-prototyped phantom.

BACKGROUND: Patient-specific simulations can provide insight into the mechanics of cardiovascular procedures. Amongst cardiovascular devices, non-compliant balloons are used in several minimally invasive procedures, such as balloon aortic valvuloplasty. Although these balloons are often included in the computer simulations of these procedures, validation of the balloon behaviour is often lacking. We therefore aim to create and validate a computational model of a valvuloplasty balloon. METHODS: A finite element (FE) model of a valvuloplasty balloon (Edwards 9350BC23) was designed, including balloon geometry and material properties from tensile testing. Young's Modulus and distensibility of different rapid prototyping (RP) rubber-like materials were evaluated to identify the most suitable compound to reproduce the mechanical properties of calcified arteries in which such balloons are likely to be employed clinically. A cylindrical, simplified implantation site was 3D printed using the selected material and the balloon was inflated inside it. The FE model of balloon inflation alone and its interaction with the cylinder were validated by comparison with experimental Pressure-Volume (P-V) and diameter-Volume (d-V) curves. RESULTS: Root mean square errors (RMSE) of pressure and diameter were RMSE P = 161.98 mmHg (3.8 % of the maximum pressure) and RMSE d = 0.12 mm (<0.5 mm, within the acquisition system resolution) for the balloon alone, and RMSE P = 94.87 mmHg (1.9 % of the maximum pressure) and RMSE d = 0.49 mm for the balloon inflated inside the simplified implantation site, respectively. CONCLUSIONS: This validated computational model could be used to virtually simulate more realistic valvuloplasty interventions.

A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta.

BACKGROUND: Medical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements. METHODS: Steps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient's anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters. RESULTS: The computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors. CONCLUSIONS: The suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease.

Postmortem cardiovascular magnetic resonance imaging in fetuses and children: a masked comparison study with conventional autopsy.

BACKGROUND: Perinatal and pediatric autopsies have declined worldwide in the past decade. We compared the diagnostic accuracy of postmortem, cardiovascular magnetic resonance (CMR) imaging with conventional autopsy and histopathology assessment in fetuses and children. METHODS AND RESULTS: We performed postmortem magnetic resonance imaging in 400 fetuses and children, using a 1.5-T Siemens Avanto magnetic resonance scanner before conventional autopsy. A pediatric CMR imager reported the CMR images, masked to autopsy information. The pathologists were masked to the information from CMR images. The institutional research ethics committee approved the study, and parental consent was obtained. Assuming a diagnostic accuracy of 50%, 400 cases were required for a 5% precision of estimate. Three cases were excluded from analysis, 2 with no conventional autopsy performed and 1 with insufficient CMR sequences performed. Thirty-eight CMR data sets were nondiagnostic (37 in fetuses ≤24 weeks; 1 in a fetus >24 weeks). In the remaining 359 cases, 44 cardiac abnormalities were noted at autopsy. Overall sensitivity and specificity (95% confidence interval) of CMR was 72.7% (58.2-83.7%) and 96.2% (93.5-97.8%) for detecting any cardiac pathology, with positive and negative predictive values of 72.7% (58.2-83.7%) and 96.2% (93.5-97.8%), respectively. Higher sensitivity of 92.6% (76.6-97.9%), specificity of 99.1% (97.4-99.7%), positive predictive value of 89.3% (72.8-96.3%), and negative predictive value of 99.4% (97.8-99.8%) were seen for major structural heart disease. CONCLUSIONS: Postmortem CMR imaging may be a useful alternative to conventional cardiac autopsy in fetuses and children for detecting cardiac abnormalities. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01417962.

Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH.

Patient-specific finite element models to support clinical decisions: A lesson learnt from a case study of percutaneous pulmonary valve implantation.

OBJECTIVES AND BACKGROUND: Patient-specific finite element (FE) simulations were used to assess different transcatheter valve devices and help select the most appropriate treatment strategy for a patient (17-year-old male) with borderline dimensions for Melody® percutaneous pulmonary valve implantation (PPVI). METHODS AND RESULTS: Patient-specific implantation site morphology was derived from cardiovascular magnetic resonance (CMR) images along with the implantation site mechanical behavior by coupling systolic/diastolic dimensions and the pressure gradient in a linear elastic model, and iterative tuning. In this way, the model accounted for the mechanical response not only of the arterial wall, but also of the surrounding tissue. Four stents (2 balloon-expandable including prestenting and 2 self-expandable) were virtually implanted and the stent final configuration, anchoring, migration forces, arterial wall stresses, paravalvular regurgitation, and device mechanical performance were evaluated. A Sapien29 device with prestenting was indicated as the optimal approach for this specific patient as it had a fully open valve, safe anchoring along the entire circumference, low risk of paravalvular leak, and arterial rupture. However, at the time of the PPVI procedure, after balloon sizing, device implantation was suspended due to perceived high risk of device embolization. CONCLUSIONS: FE analysis allows a comparison between different treatment scenarios to add information to the clinical decision making process. However, further studies are required to fully predict patient-specific response to stenting and therefore true clinical outcomes.

Diffusion-weighted perinatal postmortem magnetic resonance imaging as a marker of postmortem interval.

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(2) 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(-3) mm(2)/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(2) = 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.