Cardiovascular magnetic resonance native T-2 and T-2* quantitative values for cardiomyopathies and heart transplantations:a systematic review and meta-analysis

Background: The clinical application of cardiovascular magnetic resonance (CMR) T2 and T2* mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T2 and T2* mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated. Methods: The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T2 or T2* values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data. Results: One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T2 values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P < 0.01) compared with controls. T2 values in iron overload patients (SMD =-0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T2* values were lower in patients with MI and iron overload (SMD of-1.99 and-2.39, respectively, P < 0.01) compared with controls. T2* values in HCM patients (SMD =-0.61, P = 0.22), DCM patients (SMD =-0.54, P = 0.06) and hypertension patients (SMD =-1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies. Conclusions: The clinical utility of T2 and T2* mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T2 and T2* values of most cardiomyopathies are similar

Validation of thoracic aortic dimensions on ECG-triggered SSFP as alternative to contrast-enhanced MRA

Objectives: Assessment of thoracic aortic dimensions with non-ECG-triggered contrast-enhanced magnetic resonance angiography (CE-MRA) is accompanied with motion artefacts and requires gadolinium. To avoid both motion artefacts and gadolinium administration, we evaluated the similarity and reproducibility of dimensions measured on ECG-triggered, balanced steady-state free precession (SSFP) MRA as alternative to CE-MRA. Methods: All patients, with varying medical conditions, referred for thoracic aortic examination between September 2016 and March 2018, who underwent non-ECG-triggered CE-MRA and SSFP-MRA (1.5 T) were retrospectively included (n = 30). Aortic dimensions were measured after double-oblique multiplanar reconstruction by two observers at nine landmarks predefined by literature guidelines. Image quality was scored at the sinus of Valsalva, mid-ascending aorta and mid-descending aorta by semi-automatically assessing the vessel sharpness. Results: Aortic dimensions showed high agreement between non-ECG-triggered CE-MRA and SSFP-MRA (r = 0.99, p < 0.05) without overestimation or underestimation of aortic dimensions in SSFP-MRA (mean difference, 0.1 mm; limits of agreement, − 1.9 mm and 1.9 mm). Intra- and inter-observer variabilities were significantly smaller with SSFP-MRA for the sinus of Valsalva and sinotubular junction. Image quality of the sinus of Valsalva was significantly better with SSFP-MRA, as fewer images were of impaired quality (3/30) than in CE-MRA (21/30). Reproducibility of dimensions was significantly better in images scored as good quality compared to impaired quality in both sequences. Conclusions: Thoracic aortic dimensions measured on SSFP-MRA and non-ECG-triggered CE-MRA were similar. As expected, SSFP-MRA showed better reproducibility close to the aortic root because of lesser motion artefacts, making it a feasible non-contrast imaging alternative. Key Points: • SSFP-MRA provides similar dimensions as non-ECG-triggered CE-MRA. • Intra- and inter-observer reproducibilities improve for the sinus of Valsalva and sinotubular junction with SSFP-MRA. • ECG-triggered SSFP-MRA shows better image quality for landmarks close to the aortic root in the absence of cardiac motion

Genotoksičnost metalnih nanočestica: osvrt na podatke istraživanja In vivo

With increasing production and application of a variety of nanomaterials (NMs), research on their cytotoxic and genotoxic potential grows, as the exposure to these nano-sized materials may potentially result in adverse health effects. In large part, indications for potential DNA damaging effects of nanoparticles (NPs) originate from inconsistent in vitro studies. To clarify these effects, the implementation of in vivo studies has been emphasised. This paper summarises study results of genotoxic effects of NPs, which are available in the recent literature. They provide indications that some NP types cause both DNA strand breaks and chromosomal damages in experimental animals. Their genotoxic effects, however, do not depend only on particle size, surface modifi cation (particle coating), and exposure route, but also on exposure duration. Currently available animal studies may suggest differing mechanisms (depending on the duration of exposure) by which living organisms react to NP contact. Nevertheless, due to considerable inconsistencies in the recent literature and the lack of standardised test methods - a reliable hazard assessment of NMs is still limited. Therefore, international organisations (e.g. NIOSH) suggest utmost caution when potential exposure of humans to NMs occurs, as long as evidence of their toxicological and genotoxic effect(s) is limited.S povećanjem proizvodnje i primjene niza različitih nanomaterijala (NM) raste i potreba istraživanja njihovih mogućih citotoksičnih i genotoksičnih učinaka kao i drugih štetnih učinaka na zdravlje u uvjetima profesionalne ili opće izloženost ljudi. Indikacije potencijanog oštećenja DNA kojeg uzrokuju nanočestice u velikoj mjeri proizlaze iz nedosljednih in vitro ispitivanja. Kako bi se razjasnili ti učinci, naglašena je potreba provedbe in vivo ispitivanja. Ovaj pregledni rad sažima rezultate procjene genotoksičnih učinaka nanočestica koji su objavljeni u novijoj stručnoj i znanstvenoj literaturi. Navedeni rezultati pokazuju da određene nanočestice uzrokuju lomove u molekuli DNA i oštećuju kromosome u eksperimentalnim životinjama. Njihovi genotoksični učinci ne ovise samo o veličini čestice, modifi kaciji površine (oblaganje čestice) i načinu izlaganja, već i o trajanju izloženosti nanočesticama. Postojeća istraživanja provedena na životinjama upućuju na različite mehanizme koji ovise o trajanju izlaganja i pomoću kojih živi organizmi reagiraju na doticaj s nanočesticama. Međutim postoje brojne nedosljednosti u novijoj literaturi, a standardne testne metode nisu dostupne pa je stoga pouzdanija procjena opasnosti od izlaganja nanomaterijalima u ljudi još uvijek veoma ograničena. Stoga se u međunarodnim dokumentima savjetuje oprez prilikom svakog izlaganja ljudi nanomaterijalima kako bi se spriječili mogući opći toksični genotoksični učinci

Neutrophils incite and macrophages avert electrical storm after myocardial infarction

Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2−/− mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36−/− and Mertk−/− mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death

Advances in MRI-Based Detection of Cerebrovascular Changes after Experimental Traumatic Brain Injury

Traumatic brain injury is a heterogeneous and multifaceted neurological disorder that involves diverse pathophysiological pathways and mechanisms. Thorough characterization and monitoring of the brain’s status after neurotrauma is therefore highly complicated. Magnetic resonance imaging (MRI) provides a versatile tool for in vivo spatiotemporal assessment of various aspects of central nervous system injury, such as edema formation, perfusion disturbances and structural tissue damage. Moreover, recent advances in MRI methods that make use of contrast agents have opened up additional opportunities for measurement of events at the level of the cerebrovasculature, such as blood–brain barrier permeability, leukocyte infiltration, cell adhesion molecule upregulation and vascular remodeling. It is becoming increasingly clear that these cerebrovascular alterations play a significant role in the progression of post-traumatic brain injury as well as in the process of post-traumatic brain repair. Application of advanced multiparametric MRI strategies in experimental, preclinical studies may significantly aid in the elucidation of pathomechanisms, monitoring of treatment effects, and identification of predictive markers after traumatic brain injury

Differential Development of Human Brain White Matter Tracts

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted ‘U-shape’), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples