Search

The objective of the study was to compare the use of neonatal conventional brain magnetic resonance imaging (MRI) with that of clinical factors and socioeconomic status (SES) to predict long-term neurodevelopment in children with severe congenital heart disease (CHD).In this prospective cohort study, perioperative MRIs were acquired in 57 term-born infants with CHD undergoing cardiopulmonary bypass surgery during their first year of life. Total brain volume (TBV) was measured using an automated method. Brain injury severity (BIS) was assessed by an established scoring system. The neurodevelopmental outcome was assessed at 6 years using standardized test batteries. A multiple linear regression model was used for cognitive and motor outcomes with postoperative TBV, perioperative BIS, CHD complexity, length of hospital stay, and SES as covariates.CHD diagnoses included univentricular heart defect (n = 15), transposition of the great arteries (n = 33), and acyanotic CHD (n = 9). Perioperative moderate-to-severe brain injury was detected in 15 (26%) patients. The total IQ was similar to test norms (P = .11), whereas the total motor score (P .001) was lower. Neither postoperative TBV nor perioperative BIS predicted the total IQ, but SES (P .001) and longer hospital stay (P = .004) did. No factor predicted the motor outcome.Although the predictive value of neonatal conventional MRIs for long-term neurodevelopment is low, duration of hospital stay and SES better predict the outcome in this CHD sample. These findings should be considered in initiating early therapeutic support.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero., Comment: Results from FeTA Challenge 2021, held at MICCAI; Manuscript submitted

A kardiális autonóm neuropathia (CAN) a cukorbetegség gyakori mikrovaszkuláris szövődménye, amely összefüggést mutat a kardiovaszkuláris betegségekkel. A CAN diagnosztikájára a Ewing-féle kardiovaszkuláris reflextesztek használatosak. A paraszimpatikus beidegzés működését a mélylégzéses vizsgálat, a Valsalva-manőver és a felálláskor bekövetkező szívfrekvencia-változás mérésével értékeljük. Az ortosztatikus hipotenzió és a kézizom-szorító erő (handgrip teszt) vizsgálata a szimpatikus idegrendszer működéséről nyújt tájékoztatást. Azonban a Ewing-tesztek elvégzése időigényes folyamat és a beteg részéről is nagyfokú kooperációt igényel. A CAN legtöbbször tünetszegényen jelentkezik és késői stádiumban kerül felismerésre, ezért felmerült az igény egy egyszerű, kérdőíves szűrőmódszer kidolgozására. A Composite Autonomic Symptom Score 31 (COMPASS-31) kérdőív 6 vegetatív tünetcsoportot ölel fel, és a válaszokra adott pontértékek megfelelő súlyozásával megbízható módszernek bizonyult az autonóm neuropathia korai felimerésében. Célkitűzésünk a COMPASS-31 kérdőív alkalmazhatóságának vizsgálata diabeteses neuropathiás betegeink körében. Betegek és módszerek: A vizsgálatunk során a debreceni Diabeteses Neuropathia Centrumban 36 diabeteses neuropathiás beteg (24 nő/12 férfi) töltötte ki a kérdőívet, amelyek pontértékeit a Ewing-teszteken elért eredményeikkel hasonlítottunk össze, ROC analízist végeztünk, és meghatároztuk azt a pontszámot, amelyet határértékként használva a legkedvezőbb diagnosztikai szenzitivitás és specificitás érhető el. Eredmények: A paraszimpatikus és szimpatikus kardiovaszkuláris reflexteszteket együttesen összehasonlítva a COMPASS-31 teszt eredményeivel, a ROC görbe alatti terület (AUC) 0,83 (95%-os CI: 0,69–0,97, p=0,002), a kérdőív szenzitivitása 88%, specificitása 73%, ha a kérdőíven elért 14 feletti pontszámot tekintettük diagnosztikusnak. Ha a CAN diagnózisát a handgrip teszt megbízhatatlansága miatt a paraszimpatikus reflextesztek és az ortosztatikus hipotenzió fennállása alapján állítottuk fel, akkor a ROC-AUC 0,92 (95%-os CI: 0,81–1,03, p

Cardiosphere-derived cells (CDCs) are progenitor cells derived from heart tissue and have shown promising results in preclinical models. APOSEC, the secretome of irradiated peripheral blood mononuclear cells, has decreased infarct size in acute and chronic experimental myocardial infarction (MI). We enhanced the effect of CDCs with APOSEC preconditioning (apoCDC) and investigated the reparative effect in a translational pig model of reperfused MI. Supernatants of CDCs, assessed by proteomic analysis, revealed reduced production of extracellular matrix proteins after in vitro APOSEC preconditioning. In a porcine model of catheter-based reperfused anterior acute MI (AMI), CDCs with (apoCDC, n = 8) or without APOSEC preconditioning (CDC, n = 6) were infused intracoronary, 15 min after the start of reperfusion. Untreated AMI animals (n = 7) and sham procedures (n = 5) functioned as controls. 2-deoxy-2-(18 F)-fluoro-D-glucose-positron emission tomography-magnetic resonance imaging ([18F]FDG-PET-MRI), with late enhancement after 1 month, showed reduced scar volume and lower transmurality of the infarcted area in CDC and apoCDC compared to AMI controls. Segmental quantitative PET images displayed indicated more residual viability in apoCDC. The left-ventricle (LV) ejection fraction was improved nonsignificantly to 45.8% ± 8.6% for apoCDC and 43.5% ± 7.1% for CDCs compared to 38.5% ± 4.4% for untreated AMI. Quantitative hybrid [18F]FDG-PET-MRI demonstrated improved metabolic and functional recovery after CDC administration, whereas apoCDCs induced preservation of viability of the infarcted area.

Absztrakt: Bevezetés: Világszerte jelentősen növekszik a cukorbetegség előfordulása. A distalis típusú szenzomotoros polyneuropathia (DSPN) a leggyakrabban előforduló és a legkorábban kimutatható microvascularis szövődmény, mely változatos klinikai megjelenése és sokszor atípusos tünetei miatt gyakran csak a cukorbetegség előrehaladott stádiumában kerül felismerésre. Célkitűzés és módszer: Munkánk során 431 beteg adatait dolgoztuk fel, akiket 2011 és 2018 között a Debreceni Egyetem Diabeteses Neuropathia Centrumában vizsgáltunk Neurometer® segítségével, és összefüggéseket kerestünk a különböző szív-ér rendszeri és microvascularis szövődmények (retinopathia, microalbuminuria), a laboratóriumi paraméterek és a DSPN súlyossága között. Eredmények: A betegek átlagéletkora 63,4 év, 62%-uk nő volt, 92%-uk 2-es típusú cukorbetegségben szenvedett. A cukorbetegség fennállásának átlagos ideje 13,7 év volt. Cardiovascularis betegség a betegek 42%-ánál volt ismert. A microvascularis szövődmények közül a retinopathia előfordulása 12% volt, perzisztáló microalbuminuria a betegek 16%-ánál volt igazolva. A vizsgált betegek 19%-ánál a típusos DSPN-panaszok ellenére sem tudtunk idegi károsodást kimutatni; 49%-ban enyhe fokú, 19%-ban közepes fokú és 13%-ban súlyos fokú neuropathia volt kimutatható Neurometer® segítségével. A cukorbetegséggel összefüggő idegi károsodás kifejezettebb volt diabeteses retinopathia (pKövetkeztetés: Eredményeink alapján a diabeteses neuropathia progressziója előre jelezheti az egyéb microvascularis szövődmények megjelenését 2-es típusú cukorbetegségben, adataink azonban nem mutattak összefüggést a cardiovascularis betegségek kialakulásával. A Neurometer® segítségével végzett perifériás idegrendszeri vizsgálat alkalmas a DSPN követésére és a neuropathia súlyosságának megállapítására. A cardiovascularis kockázatot az autonóm idegrendszeri funkciót vizsgáló Ewing-féle reflextesztek segítségével jobban meg tudjuk ítélni cukorbetegeinknél. Orv Hetil. 2020; 161(30): 1243–1251.

Magnetic resonance imaging (MRI) has become an essential diagnostic modality for congenital disorders of the central nervous system. Recent advancements have transformed foetal MRI into a clinically feasible tool, and in an effort to find predictors of clinical outcomes in spinal dysraphism, foetal MRI began to unveil its potential. The purpose of our review is to introduce MRI techniques to experts with diverse backgrounds, who are involved in the management of spina bifida. We introduce advanced foetal MRI postprocessing potentially improving the diagnostic work-up. Importantly, we discuss how postprocessing can lead to a more efficient utilisation of foetal or neonatal MRI data to depict relevant anatomical characteristics. We provide a critical perspective on how structural, diffusion and metabolic MRI are utilised in an endeavour to shed light on the correlates of impaired development. We found that the literature is consistent about the value of MRI in providing morphological cues about hydrocephalus development, hindbrain herniation or outcomes related to shunting and motor functioning. MRI techniques, such as foetal diffusion MRI or diffusion tractography, are still far from clinical use; however, postnatal studies using these methods revealed findings that may reflect early neural correlates of upstream neuronal damage in spinal dysraphism.

Funding Acknowledgements Type of funding sources: None. Purpose We sought to retrospectively evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession MRI sequences. Methods We retrospectively assessed the visibility of cardiovascular anatomy in 66 fetuses without suspicion of congenital heart defect (mean gestational age 27+/- 4, range 21-38 weeks). Non-gated dynamic balanced steady-state free precession (SSFP) sequences were acquired in three planes (axial, coronal and sagittal) of the fetal thorax (slice thickness 4-5mm, FOV 400, FA 60°, matrix 256x256). The images were analysed following a segmental approach in consensus reading by an experienced paediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure. Basic diagnostic structures included the atria, ventricles, systemic veins, right and left ventricular outflow tracts (RVOT/LVOT), aortic arch, descending aorta (DAO), ductus arteriosus and thymus (12 points); advanced diagnostic features included the atrioventricular (AV) valves, pulmonary arteries and veins, supraaortic arteries and trachea, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (good). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. Results 34 scans were performed at 1.5 T, 32 at 3 T. Heart position, atria and ventricles could be seen in all 66 fetuses. Basic diagnosis (>12 points) was achieved in 60 (90%) cases, with visualization of the IVC and SVC in 65 (98%) and 63 (95%), RVOT in 62 (94%), LVOT in 61 (92%), aortic arch in 60 (91%), DAO in 64 (97%), ductus arteriosus in 59 (89%) and thymus in 50 (76%) fetuses. The AV valves were recognised in 55 (83%), the pulmonary arteries in 35 (53%), at least one pulmonary vein in 46 (70%), the supraaortic arteries in 42 (64%), and the trachea in 59 (89%) fetuses. The mean imaging score was 16.8 +/- 3.7. Maternal panniculus (r -0.3; p 0.01) and gestational age (r 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5 T being better than 3T images (p 0.04), but not the total imaging score. Imaging score or quality were independent from placenta position. Conclusions Fetal heart MRI with a non-gated SSFP sequence in multiple planes enables recognition of basic cardiovascular anatomy. Advanced diagnostics may be limited by thick maternal panniculus, lower GA and higher field strength.

It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open datasets of segmented fetal brains. Here we introduce a publicly available dataset of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the dataset for the development of automatic algorithms., Scientific Data, 8 (1), ISSN:2052-4463

The quantitative assessment of the developing human brain in utero is crucial to fully understand neurodevelopment. Thus, automated multi-tissue fetal brain segmentation algorithms are being developed, which in turn require annotated data to be trained. However, the available annotated fetal brain datasets are limited in number and heterogeneity, hampering domain adaptation strategies for robust segmentation. In this context, we use FaBiAN, a Fetal Brain magnetic resonance Acquisition Numerical phantom, to simulate various realistic magnetic resonance images of the fetal brain along with its class labels. We demonstrate that these multiple synthetic annotated data, generated at no cost and further reconstructed using the target super-resolution technique, can be successfully used for domain adaptation of a deep learning method that segments seven brain tissues. Overall, the accuracy of the segmentation is significantly enhanced, especially in the cortical gray matter, the white matter, the cerebellum, the deep gray matter and the brain stem., Comment: 4 pages, 4 figures. This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

There is emerging evidence for delayed brain development in neonates with congenital heart disease. We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to post-operative changes in the connectome in congenital heart disease neonates relative to healthy term newborns and assess factors contributing to disturbed perioperative network development. In this prospective cohort study, 114 term neonates with congenital heart disease underwent cardiac surgery at the University Children’s Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and post-operative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion MR tractography. Graph theory parameters calculated across a proportional cost threshold range were compared between groups by multi-threshold permutation correction adjusting for confounders. Network-based statistic was calculated for edgewise network comparison. White-matter injury volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) cardiac subtype and (ii) injury volume with post-menstrual age at MRI, respectively, were built to assess modifying effects on network development. Pre- and post-operatively, at the global level, efficiency, indicative of network integration, was lower in heart disease neonates than controls. In contrast, local efficiency and transitivity, indicative of network segregation, were higher compared to controls (all P, Graphical Abstract, Feldmann et al. demonstrate a delayed maturation of the structural whole-brain network in neonates with congenital heart disease, with a pattern of lower structural integration and higher segregation compared to healthy controls. The degree of white-matter injury burden negatively impacts network strength and integration.

Inhibition abilities are often impaired in children born very preterm. In typically-developing individuals, inhibition has been associated with structural brain connectivity (SC). As SC is frequently altered following preterm birth, this study investigated whether aberrant SC underlies inhibition deficits in school-aged children born very preterm. In a group of 67 very preterm participants aged 8–13 years and 69 term-born peers, inhibition abilities were assessed with two tasks. In a subgroup of 50 very preterm and 62 term-born participants, diffusion tensor imaging (DTI) data were collected. Using network-based statistics (NBS), mean fractional anisotropy (FAmean) was compared between groups. Associations of FAmean and inhibition abilities were explored through linear regression. The composite score of inhibition abilities was lower in the very preterm group (M ​= ​−0.4, SD ​= ​0.8) than in the term-born group (M ​= ​0.0, SD ​= ​0.8) but group differences were not significant when adjusting for age, sex and socio-economic status (β ​= ​−0.13, 95%-CI [-0.30, 0.04], p ​= ​0.13). In the very preterm group, FAmean was significantly lower in a network comprising thalamo-frontal, thalamo-temporal, frontal, cerebellar and intra-hemispheric connections than in the term-born group (t ​= ​5.21, lowest p-value ​= ​0.001). Irrespective of birth status, a network comprising parietal, cerebellar and subcortical connections was positively associated with inhibition abilities (t ​= ​4.23, lowest p-value ​= ​0.02). Very preterm birth results in long-term alterations of SC at network-level. As networks underlying inhibition abilities do not overlap with those differing between the groups, FAmean may not be adequate to explain inhibition problems in very preterm children. Future studies should combine complementary measures of brain connectivity to address neural correlates of inhibition abilities.

Introduction The thalamus is a key hub for regulating cortical connectivity. Dysmaturation of thalamocortical networks that accompany white matter injury has been hypothesized as neuroanatomical correlate of late life neurocognitive impairment following preterm birth. Our objective was to find a link between thalamocortical connectivity measures at term equivalent age and two‐year neurodevelopmental outcome in preterm infants. Methods Diffusion tensor MRI data of 58 preterm infants (postmenstrual age at birth, mean (SD), 29.71 (1.47) weeks) were used in the study. We utilized probabilistic diffusion tractography to trace connections between the cortex and thalami. Possible associations between connectivity strength, the length of the probabilistic fiber pathways, and developmental scores (Bayley Scales of Infant Development, Second Edition) were analyzed using multivariate linear regression models. Results We found strong correlation between mental developmental index and two complementary measures of thalamocortical networks: Connectivity strength projected to a cortical skeleton and pathway length emerging from thalamic voxels (partial correlation, R = .552 and R = .535, respectively, threshold‐free cluster enhancement, corrected p‐value, Our purpose was to find a link between thalamocortical connectivity measures at term equivalent age and two‐year neurodevelopmental outcome in 58 infants following preterm birth. Using probabilistic diffusion tractography, we found that injury or dysmaturation of tracts emerging from ventral‐specific and various nonspecific thalamus projecting to late‐maturing cortical regions is predictive of mental, but not psychomotor developmental outcomes

Background In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. Purpose To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. Study type Retrospective, cross-sectional study. Subjects Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). Field strength/sequence In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. Assessment Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. Statistical tests Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). Results Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. Data conclusion Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

The design methods of the load bearing glass columns developed extremely in the last years. Numerous glass researchers have been trying to optimize the glass structures in terms of cost-effectiveness and safety. The authors carried out several laboratory experiments to analyze the key factors of the glass column design. Factors are investigated in the present article for example the influence of the fixing at the end of the glass columns, which essentially modifies the load bearing capacity of structures. The efficiency of the gluing of the interlayer foil (the coupling parameter) was analyzed based on the individual laboratory experiments.

Open spina bifida (SB) is one of the most common congenital defects and can lead to impaired brain development. Emerging fetal surgery methods have shown considerable success in the treatment of patients with this severe anomaly. Afterwards, alterations in the brain development of these fetuses have been observed. Currently no longitudinal studies exist to show the effect of fetal surgery on brain development. In this work, we present a fetal MRI neuro-imaging analysis pipeline for fetuses with SB, including automated fetal ventricle segmentation and deformation-based morphometry, and demonstrate its applicability with an analysis of ventricle enlargement in fetuses with SB. Using a robust super-resolution algorithm, we reconstructed fetal brains at both pre-operative and post-operative time points and trained a U-Net CNN in order to automatically segment the ventricles. We investigated the change of ventricle shape post-operatively, and the impacts of lesion size, type, and GA at operation on the change in ventricle shape. No impact was found, except for moderately larger ventriculomegaly progression in myeloschisis patients. Prenatal ventricle volume growth was also investigated. Our method allows for the quantification of longitudinal morphological changes to fully quantify the impact of prenatal SB repair and could be applied to predict postnatal outcomes., Comment: Pre-print version, published in MICCAI PIPPI 2019

Developmental pathoconnectomics is an emerging field that aims to unravel the events leading to and outcome from disrupted brain connectivity development. Advanced magnetic resonance imaging (MRI) technology enables the portrayal of human brain connectivity before birth and has the potential to offer novel insights into normal and pathological human brain development. This review gives an overview of the currently used MRI techniques for connectomic imaging, with a particular focus on recent studies that have successfully translated these to the in utero or postmortem fetal setting. Possible mechanisms of how pathologies, maternal, or environmental factors may interfere with the emergence of the connectome are considered. The review highlights the importance of advanced image post processing and the need for reproducibility studies for connectomic imaging. Further work and novel data-sharing efforts would be required to validate or disprove recent observations from in utero connectomic studies, which are typically limited by low case numbers and high data drop out. Novel knowledge with regard to the ontogenesis, architecture, and temporal dynamics of the human brain connectome would lead to the more precise understanding of the etiological background of neurodevelopmental and mental disorders. To achieve this goal, this review considers the growing evidence from advanced fetal connectomic imaging for the increased vulnerability of the human brain during late gestation for pathologies that might lead to impaired connectome development and subsequently interfere with the development of neural substrates serving higher cognition.

Background The disturbance of cardiac energy substrate metabolism has a decisive role in the pathogenesis of adverse cardiac remodeling and heart failure. Under normoxic conditions, the free fatty acid metabolism is the predominant pathway by providing the highest energy per substrate molecule. Severe myocardial hypoxia leads to a switch from beta-oxidation to glucose metabolism to increase the ATP production per oxygen molecule. This metabolic disorder appears as perfusion-metabolism mismatch in 18F-fluorodeoxyglucose (18F-FDG) PET images, as increased 18F-FDG uptake in the under-perfused hypoxic myocardial area. Purpose The aim of our study was to evaluate the simultaneous perfusion, metabolism and function of the ischemic heart by hybrid 18F-FDG-PET-cMRI with late enhancement images in a translation animal model of heart failure. Methods Under general anesthesia, closed chest reperfused acute myocardial infarction (AMI) was induced in 36 domestic pigs by 90 min occlusion of the mid left anterior descending artery with a percutaneous intracoronary balloon, followed by reperfusion. Three days and 1 month after AMI, after 12h fasting, 18F-FDG-PET-cMRI were performed by using standardized acquisition protocols (n=30). Cardiac functional parameter, such as ejection fraction (EF), end-diastolic volume (EDV), infarct size, and mean tracer uptake of the infarcted area were quantitatively assessed. Six animals were euthanized after the 3-day 18F-FDG-PET-cMRI images to elaborate the differences in gene expression patterns in animals with perfusion-metabolic mismatch by using next generation sequencing (NGS) and pathway network analyses. Results Eight (group Mismatch) of the 30 animals (group Match) with 1-month follow-up showed high 18F-FDG uptake in the infarcted area (perfusion-metabolism mismatch) at the 3-day 18F-FDG-PET-cMRI-LE images (Figure). The animals in the Mismatch group had significantly lower EF at 3 days (34±8.8 vs 42±3%) and at the 1-month follow-up (35.8±6 vs 43±6.6%) and larger infarct size at day 3 (26.6±6.6 vs 22.1±4.4%) and 1 month (28±5.4 vs 20.3±4.3%) with higher EDV at 1 month. Mean tracer uptake of the infarcted area was significantly reduced in the Mismatch group at 1 month (56±23.1 vs 64.7±13.2%). NGS revealed downregulation of the cholesterol metabolism pathway, and upregulation of carbohydrate derivative catabolism pathway with highly activated innate immune system and genes responsible for cytokine activation in the infarcted area 3 days post-AMI in the Mismatch group, which explains the paradox high 18F-FDG tracer uptake in the infarction zone. Accordingly, the high energy demand of the severe hypoxic area led to “glucose steel phenomenon” at the molecular level, subtracting the 18F-FDG from the normally perfused non-ischemic myocardial regions. Conclusions 18F-FDG-glucose perfusion-metabolism mismatch early after AMI visualized by hybrid 18F-FDG-PET-MRI images predict development of LV adverse remodeling. Acknowledgement/Funding Fibrotarget EU Grant Nr 602904

Children with congenital heart disease (CHD) remain at risk for neurodevelopmental impairment despite improved peri- and intraoperative care. Our prospective cohort study aimed to determine the relationship between perioperative brain volumes and neurodevelopmental outcome in neonates with severe CHD. Pre- and postoperative cerebral MRI was acquired in term born neonates with CHD undergoing neonatal cardiopulmonary bypass surgery. Brain volumes were measured using an atlas prior based automated method. One-year outcome was assessed with the Bayley-III. CHD infants (n=77) had lower pre- and postoper-ative total and regional brain volumes compared to controls (n=44, all p

We investigated the antiarrhythmic effects of ischemic preconditioning (IPC) and postconditioning (PostC) by intracardiac electrocardiogram (ECG) and measured circulating microRNAs (miRs) that are related to cardiac conduction. Domestic pigs underwent 90-min. percutaneous occlusion of the mid left anterior coronary artery, followed by reperfusion. The animals were divided into three groups: acute myocardial infarction (AMI, n = 7), ischemic preconditioning-acute myocardial infarction (IPC-AMI) (n = 9), or AMI-PostC (n = 5). IPC was induced by three 5-min. episodes of repetitive ischemia/reperfusion cycles (rI/R) before AMI. PostC was induced by six 30-s rI/R immediately after induction of reperfusion 90 min after occlusion. Before the angiographic procedure, a NOGA endocardial mapping catheter was placed again the distal anterior ventricular endocardium to record the intracardiac electrogram (R-amplitude, ST-Elevation, ST-area under the curve (AUC), QRS width, and corrected QT time (QTc)) during the entire procedure. An arrhythmia score was calculated. Cardiac MRI was performed after one-month. IPC led to significantly lower ST-elevation, heart rate, and arrhythmia score during ischemia. PostC induced a rapid recovery of R-amplitude, decrease in QTc, and lower arrhythmia score during reperfusion. Slightly higher levels of miR-26 and miR-133 were observed in AMI compared to groups IPC-AMI and AMI-PostC. Significantly lower levels of miR-1, miR-208, and miR-328 were measured in the AMI-PostC group as compared to animals in group AMI and IPC-AMI. The arrhythmia score was not significantly associated with miRNA plasma levels. Cardiac MRI showed significantly smaller infarct size in the IPC-AMI group when compared to the AMI and AMI-PostC groups. Thus, IPC led to better left ventricular ejection fraction at one-month and it exerted antiarrhythmic effects during ischemia, whereas PostC exhibited antiarrhythmic properties after reperfusion, with significant downregulaton of ischemia-related miRNAs.

Austria and Hungary share a complicated common past. After the collapse of Austria-Hungary, Austria developed into a liberal democratic republic and Hungary into a monarchy, and yet the B-VG, like the theories of its founding father Hans Kelsen, was received in Hungary. On the one hand, this article sheds light on the legal theoretical influence of the B-VG and the reactions to it in the interwar period. On the other hand, there are concrete influences of the Austrian administrative and constitutional courts on their Hungarian counterparts. Our result is that the potential for Austrian influence remained unfulfilled.

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI.

Aims The clinical application of doxorubicin (DOX) is severely compromised by its cardiotoxic effects, which limit the therapeutic index and the cumulative dose. Liposomal encapsulation of DOX (Myocet®) provides a certain protective effect against cardiotoxicity by reducing myocardial drug accumulation. We aimed to evaluate transcriptomic responses to anthracyclines with different cardiotoxicity profiles in a translational large animal model for identifying potential alleviation strategies. Methods and results We treated domestic pigs with either DOX, epirubicin (EPI), or liposomal DOX and compared the cardiac, laboratory, and haemodynamic effects with saline-treated animals. Cardiotoxicity was encountered in all groups, reflected by an increase of plasma markers N-terminal pro-brain-natriuretic peptide and Troponin I and an impact on body weight. High morbidity of EPI-treated animals impeded further evaluation. Cardiac magnetic resonance imaging with gadolinium late enhancement and transthoracic echocardiography showed stronger reduction of the left and right ventricular systolic function and stronger myocardial fibrosis in DOX-treated animals than in those treated with the liposomal formulation. Gene expression profiles of the left and right ventricles were analysed by RNA-sequencing and validated by qPCR. Interferon-stimulated genes (ISGs), linked to DNA damage repair and cell survival, were downregulated by DOX, but upregulated by liposomal DOX in both the left and right ventricle. The expression of cardioprotective translocator protein (TSPO) was inhibited by DOX, but not its liposomal formulation. Cardiac fibrosis with activation of collagen was found in all treatment groups. Conclusions All anthracycline-derivatives resulted in transcriptional activation of collagen synthesis and processing. Liposomal packaging of DOX-induced ISGs in association with lower cardiotoxicity, which is of high clinical importance in anticancer treatment. Our study identified potential mechanisms for rational development of strategies to mitigate anthracycline-induced cardiomyopathy.

Intravoxel incoherent motion (IVIM) imaging allows contrast-agent free in vivo perfusion quantification with magnetic resonance imaging (MRI). However, its use is limited by typically low accuracy due to low signal-to-noise ratio (SNR) at large gradient encoding magnitudes as well as dephasing artefacts caused by subject motion, which is particularly challenging in fetal MRI. To mitigate this problem, we propose an implicit IVIM signal acquisition model with which we learn full posterior distribution of perfusion parameters using artificial neural networks. This posterior then encapsulates the uncertainty of the inferred parameter estimates, which we validate herein via numerical experiments with rejection-based Bayesian sampling. Compared to state-of the-art IVIM estimation method of segmented least-squares fitting, our proposed approach improves parameter estimation accuracy by 65% on synthetic anisotropic perfusion data. On paired rescans of in vivo fetal MRI, our method increases repeatability of parameter estimation in placenta by 46%.

Congenital heart diseases (CHD) are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits of higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. 44 newborns were included in our study, out of whom 33 were diagnosed with dextro-transposition of the great arteries (d-TGA) and 11 with other forms of severe CHD. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation based morphometry, we calculated brain growth rate maps that reflected the rate of non-linear deformation that occurs between pre- and post-operative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the left planum temporale and the posterior operculum of the left frontal lobe and language score at 12 months of age, corrected for demographic variables (p=0.018, t=5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacts with this correlation with longer hospitalization stay results in faster enlargement of the internal cerebro-spinal fluid spaces. Our study provides evidence to the early importance of left-dominant perisylvian regions in language development even before the direct postnatatal exposure to native language. In CHD patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at one year of age.