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Aims: Uncertainty exists over the importance of device-detected short-duration atrial arrhythmias. Continuous atrial diagnostics, through home monitoring (HM) technology (BIOTRONIK, Berlin, Germany), provides a unique opportunity to assess frequency and quantity of atrial fibrillation (AF) episodes defined as atrial high-rate events (AHRE).Methods and Results: Prospective data from 560 heart failure (HF) patients (age 67 ± 10 years, median ejection fraction 27%) patients with a cardiac resynchronization therapy (CRT) device capable of HM from two multi-centre studies were analysed. Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of >180 beats for at least 1% or total of 14 min per day. The primary endpoint was incidence of a thromboembolic (TE) event. Secondary endpoints were cardiovascular death, hospitalization because of AF, or worsening HF. Over a median 370-day follow-up AHRE occurred in 40% of patients with 11 (2%) patients developing TE complications and mortality rate of 4.3% (24 deaths, 16 with cardiovascular aetiology). Compared with patients without detected AHRE, patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications (P= 0.006). The majority of patients (73%) did not show a temporal association with the detected atrial episode and their adverse event, with a mean interval of 46.7 ± 71.9 days (range 0-194) before the TE complication.Conclusion: In a high-risk cohort of HF patients, device-detected atrial arrhythmias are associated with an increased incidence of TE events. A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate. Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients. [ABSTRACT FROM AUTHOR]

For the quantification of rotating frame relaxation times, the T 2ρ relaxation pathway plays an essential role. Nevertheless, T 2ρ imaging has been studied only to a small extent compared with T 1ρ , and preparation techniques for T 2ρ have so far been adapted from T 1ρ methods. In this work, two different preparation concepts are compared specifically for the use of T 2ρ mapping. The first approach involves transferring the balanced spin-locking (B-SL) concept of T 1ρ imaging. The second and newly proposed approach is a continuous-wave Malcolm-Levitt (CW-MLEV) pulse train with zero echo times and was motivated from T 2 preparation strategies. The modules are tested in Bloch simulations for their intrinsic sensitivity to field inhomogeneities and validated in phantom experiments. In addition, myocardial T 2ρ mapping was performed in mice as an exemplary application. Our results demonstrate that the CW-MLEV approach provides superior robustness and thus suggest that established methods of T 1ρ imaging are not best suited for T 2ρ experiments. In the presence of field inhomogeneities, the simulations indicated an increased banding compensation by a factor of 4.1 compared with B-SL. Quantification of left ventricular T 2ρ time in mice yielded more consistent results, and values in the range of 59.2-61.1 ms (R 2  = 0.986-0.992) were observed at 7 T., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range., Methods: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields. The REX detection approach was validated under controlled conditions in phantom experiments at 3 T. Gaussian and sinc-shaped stimuli were investigated. In addition, the detection of artificial fields resembling a cardiac QRS complex, which is the most prominent peak visible on a magnetocardiogram, was tested., Results: Bloch simulations demonstrated that the REX method has a high sensitivity to pulsed fields in the resonance case, which is met when the spin-lock frequency coincides with a non-zero Fourier component of the stimulus field. In the experiments, we found that magnetic stimuli of different durations and waveforms can be distinguished by their characteristic REX response spectrum. The detected REX amplitude was proportional to the stimulus peak amplitude (R 2  > 0.98) and the lowest field detection was 1 nT. Furthermore, the detection of QRS-like fields with varying QRS durations yielded significant results in a phantom setup (p < 0.001)., Conclusion: REX detection can be transferred to non-sinusoidal pulsed magnetic fields and could provide a non-invasive, quantitative tool for spatially resolved assessment of cardiac biomagnetism. Potential applications include the direct detection and characterization of cardiac conduction., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: 7 T cardiac magnetic resonance imaging (MRI) studies may enable higher precision in clinical metrics like cardiac function, ventricular mass, and more. Higher precision may allow early detection of functional impairment and early evaluation of treatment responses in clinical practice and pre-clinical studies., Methods: Seven female German Landrace pigs were scanned prior to and at three time points (3-4 days, 7-10 days, and ~60 days) post myocardial infarction using a whole body 7 T system and three radiofrequency (RF) coils developed and built in-house to accompany animal growth., Results: The combination of dedicated RF hardware and 7 T MRI enables a longitudinal study in a pig model of acute and chronic infarction, providing consistent blood tissue contrast and high signal-to-noise ratio (SNR) in measurements of cardiac function, as well as low coefficients of variation (CoV) for ejection fraction (CoV intra-observer : 2%, CoV inter-observer : 3.8%) and infarct size (CoV intra-observer : 8.4%, CoV inter-observer : 3.8%), despite drastic animal growth., Conclusions: Best results are achieved via manual segmentation. We define state-of-the-art procedures for large animal studies at 7 T., (© 2024. The Author(s).)

CMR at 3.0T in the presence of active cardiac implants remains a challenge due to susceptibility artifacts. Beyond a signal void that cancels image information, magnetic field inhomogeneities may cause distorted appearances of anatomical structures. Understanding influencing factors and the extent of distortion are a first step towards optimizing the image quality of CMR with active implants at 3.0T. All measurements were obtained at a clinical 3.0T scanner. An in-house designed phantom with a 3D cartesian grid of water filled spheres was used to analyze the distortion caused by four representative active cardiac devices (cardiac loop recorder, pacemaker, 2 ICDs). For imaging a gradient echo (3D-TFE) sequence and a turbo spin echo (2D-TSE) sequence were used. The work defines metrics to quantify the different features of distortion such as changes in size, location and signal intensity. It introduces a specialized segmentation technique based on a reaction-diffusion-equation. The distortion features are dependent on the amount of magnetic material in the active implants and showed a significant increase when measured with the 3D TFE compared to the 2D TSE. This work presents a quantitative approach for the evaluation of image distortion at 3.0T caused by active cardiac implants and serves as foundation for both further optimization of sequences and devices but also for planning of imaging procedures., (© 2024. The Author(s).)

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium., (© 2024. The Author(s).)

Cardiac myocyte sodium (Na + ) homoeostasis is pivotal in cardiac diseases and heart failure. Intracellular Na + ([Na + ] i ) is an important regulator of excitation-contraction coupling and mitochondrial energetics. In addition, extracellular Na + ([Na + ] e ) and its water-free storage trigger collagen cross-linking, myocardial stiffening and impaired cardiac function. Therefore, understanding the allocation of tissue Na + to intra- and extracellular compartments is crucial in comprehending the pathophysiological processes in cardiac diseases. We extrapolated [Na + ] e using a three-compartment model, with tissue Na + concentration (TSC) measured by in vivo 23 Na-MRI, extracellular volume (ECV) data calculated from T1 maps, and [Na + ] i measured by in vitro fluorescence microscopy using Na + binding benzofuran isophthalate (SBFI). To investigate dynamic changes in Na + compartments, we induced pressure overload (TAC) or myocardial infarction (MI) via LAD ligation in mice. Compared to SHAM mice, TSC was similar after TAC but increased after MI. Both TAC and MI showed significantly higher [Na + ] i compared to SHAM (around 130% compared to SHAM). Calculated [Na + ] e increased after MI, but not after TAC. Increased TSC after TAC was primarily driven by increased [Na + ] i , but the increase after MI by elevations in both [Na + ] i and [Na + ] e ., (© 2024. The Author(s).)

Fluorine-19 ( 19 F) magnetic resonance imaging is a unique quantitative molecular imaging modality that makes use of an injectable fluorine-containing tracer that generates the only visible 19 F signal in the body. This hot spot imaging technique has recently been used to characterize a wide array of cardiovascular diseases and seen a broad range of technical improvements. Concurrently, its potential to be translated to the clinical setting is being explored. This review provides an overview of this emerging field and demonstrates its diagnostic potential, which shows promise for clinical translation. We will describe 19 F magnetic resonance imaging hardware, pulse sequences, and tracers, followed by an overview of cardiovascular applications. Finally, the challenges on the road to clinical translation are discussed., Competing Interests: Disclosures Dr Schwitter receives research support by Bayer Healthcare, Schweiz AG. Dr Schreiber receives research support from Siemens Healthineers. The other authors report no conflicts.

Recent technical advancements allow cardiac MRI (CMR) examinations in the presence of so-called MRI conditional active cardiac implants at 3.0 T. However, the artifact burden caused by susceptibility effects remain an obstacle. All measurements were obtained at a clinical 3.0 T scanner using an in-house designed cubic phantom and optimized sequences for artifact evaluation (3D gradient echo sequence, multi-slice 2D turbo spin echo sequence). Reference sequences according to the American Society for Testing and Materials (ASTM) were additionally applied. Four representative active cardiac devices and a generic setup were analyzed regarding volume and shape of the signal void. For analysis, a threshold operation was applied to the grey value profile of each data set. The presented approach allows the evaluation of the signal void and shape even for larger implants such as ICDs. The void shape is influenced by the orientation of the B0-field and by the chosen sequence type. The distribution of ferromagnetic material within the implants also matters. The void volume depends both on the device itself, and on the sequence type. Disturbances in the B0 and B1 fields exceed the visual signal void. This work presents a reproducible and highly defined approach to characterize both signal void artifacts at 3.0 T and their influencing factors., (© 2022. The Author(s).)

Background: Sodium homeostasis is disrupted in many cardiovascular diseases, which makes non-invasive sodium storage assessment desirable. In this regard, sodium MRI has shown its potential to reveal differences in sodium content between healthy and diseased tissues as well as treatment-related changes of sodium content. When different tissues are affected disparately, simultaneous assessment of these compartments is expected to provide better information about sodium distribution, reduce examination time, and improve clinical efficiency., Objectives: The objectives were (1) to investigate sodium storage levels in calf and pectoral muscle in healthy controls and patients and quantify changes following medical treatment and (2) to demonstrate homogeneous disruption in skeletal muscle sodium storage in patients with primary hyperaldosteronism (PHA)., Methods: We assessed sodium storage levels (relative sodium signal intensity, rSSI) in the calf and pectoral muscles of eight patients with PHA prior and after treatment and 12 age- and sex-matched healthy volunteers., Results: Calf and pectoral muscle compartments exhibited similar sodium content both in healthy subjects (calf vs pectoral rSSI: 0.14 ± 0.01 vs 0.14 ± 0.03) and PHA patients (calf vs pectoral rSSI: 0.19 ± 0.03 vs 0.18 ± 0.03). Further, we observed similar treatment-related changes in pectoral and calf muscles in the patients (proportional rSSI change calf: 26%; pectoral: 28%)., Conclusion: We found that sodium was distributed uniformly and behaved equally in different skeletal muscles in Conn's syndrome. This allows to measure both heart and skeletal muscle sodium signals simultaneously by a single measurement without repositioning the patient. This increases 23Na-MRI's clinical feasibility as an innovative technique to monitor sodium storage.

Long-term alteration of dopaminergic neurotransmission is known to modulate the D 2 /D 3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [ 11 C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient ( Apoe -/- , n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe -/- mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.

The role of the Na + /K + -ATPase (NKA) in heart failure associated with myocardial infarction (MI) is poorly understood. The elucidation of its precise function is hampered by the existence of two catalytic NKA isoforms (NKA-α1 and NKA-α2). Our aim was to analyze the effects of an increased NKA-α2 expression on functional deterioration and remodeling during long-term MI treatment in mice and its impact on Ca 2+ handling and inotropy of the failing heart. Wild-type (WT) and NKA-α2 transgenic (TG) mice (TG-α2) with a cardiac-specific overexpression of NKA-α2 were subjected to MI injury for 8 wk. As examined by echocardiography, gravimetry, and histology, TG-α2 mice were protected from functional deterioration and adverse cardiac remodeling. Contractility and Ca 2+ transients (Fura 2-AM) in cardiomyocytes from MI-treated TG-α2 animals showed reduced Ca 2+ amplitudes during pacing or after caffeine application. Ca 2+ efflux in cardiomyocytes from TG-α2 mice was accelerated and diastolic Ca 2+ levels were decreased. Based on these alterations, sarcomeres exhibited an enhanced sensitization and thus increased contractility. After the acute stimulation with the β-adrenergic agonist isoproterenol (ISO), cardiomyocytes from MI-treated TG-α2 mice responded with increased sarcomere shortenings and Ca 2+ peak amplitudes. This positive inotropic response was absent in cardiomyocytes from WT-MI animals. Cardiomyocytes with NKA-α2 as predominant isoform minimize Ca 2+ cycling but respond to β-adrenergic stimulation more efficiently during chronic cardiac stress. These mechanisms might improve the β-adrenergic reserve and contribute to functional preservation in heart failure. NEW & NOTEWORTHY Reduced systolic and diastolic calcium levels in cardiomyocytes from NKA-α2 transgenic mice minimize the desensitization of the β-adrenergic signaling system. These effects result in an improved β-adrenergic reserve and prevent functional deterioration and cardiac remodeling.

Purpose: Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement., Methods: Flow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE -/- mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification., Results: 4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE -/- mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m 2 in wildtype mice and (1.27 ± 0.10) N/m 2 in ApoE -/- mice., Conclusion: The post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements.

Since its beginning, 30 years ago, magnetic resonance imaging of the heart made tremendous progress. Starting from an almost experimental level in the 90 s it has now become a routine tool within cardiac diagnostics. This article presents a selection of present applications of cardiac magnetic resonance imaging. Besides it superiority in determining mass and volumes of the heart, structural imaging of myocardial tissue has become the domain of cardiac magnetic resonance imaging. This implies detection and quantification of scars and fibrosis, inflammatory and infiltrative processes in myocarditis and amyloidosis, and characterization of cardiac tumors. Perfusion imaging allows detection of ischemia, and measurement of blood flow quantifies cardiac shunts and valve disorders. In combination with Positron Emission Tomography, the relationship of molecular/cellular processes and functional, microstructural alterations become visible in myocarditis and amyloidosis. Recent contraindications of cMRI/MRI as cardiac devices MRI have been resolved; however, image quality of the heart is still a challenge., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients.

Background: Cardiac arrhythmias are a serious complication in patients admitted due to intoxication in suicidal attempts. Upon admission, detailed information about the specific kind of intoxication are frequently missing. The differential diagnoses of electrocardiogram (ECG) changes such as elevation of T-waves, prolongation of the QT-interval or elevation of ST-segments in this special subgroup of patients comprise drug-induced electrolyte disorders or direct toxic effects on cardiac excitation and repolarization., Case Summary: In this clinical report of a 27-year-old male patient, we present a case of unusual ECG alterations mimicking ST-elevation, high amplitude, biphasic T-waves and prolongation of QT-interval. These changes of surface ECG were induced by ingestion of cylindrical batteries in a suicidal attempt and immediately normalized after removal of batteries by esophagogastroduodenoscopy., Discussion: There is limited literature describing changes in surface ECG in patients having ingested cylindrical batteries. We propose two hypotheses for the occurrence of these changes after ingestion of cylindrical batteries: (i) Cardiac movement within the perturbation field induced by the batteries causes electrical changes on a time scale of the heart rate which are above the threshold of the high pass filter. (ii) The batteries' electrotonic potential affects the membrane currents of cardiac myocytes, not inducing an action potential but generating repolarization abnormalities. Individual factors, such as body constitution and localization of the batteries within the stomach, determine the interindividual characteristics of repolarization abnormalities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE-/- mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. All in vivo MR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE-/- mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis., Competing Interests: The authors have declared that no competing interests exist.

Understanding the function and control of channel transport is of paramount importance for cell physiology and nanotechnology. In particular, if several species are involved, the mechanisms of selectivity, competition, cooperation, pumping, and its modulation need to be understood. What lacks is a rigorous mathematical approach within the framework of stochastic thermodynamics, which explains the impact of interparticle in-channel interactions on the transport properties of the respective species. To achieve this, stochastic channel transport of two species is considered in a model, which different from mean field approaches, explicitly conserves the spatial correlation of the species within the channel by analysis of the stochastic dynamics within a state space, the elements of which are the channel's spatial occupation states. The interparticle interactions determine the stochastic transitions between these states. Local flow and entropy production in this state space reveal the respective particle flows through the channel and the intensity of the Brownian ratchet like rectifying forces, which these species exert mutually on each other, together with its thermodynamic effectiveness and costs. Perfect coupling of transport of the two species is realized by an attractive empty channel and strong repulsive forces between particles of the same species. This confines the state space to a subspace with circular topology, in which the concentration gradients as thermodynamic driving forces act in series, and channel flow of both species becomes equivalent. For opposing concentration gradients, this makes the species with the stronger gradient the driving, positive entropy producing one; the other is driven and produces negative entropy. Gradients equal in magnitude make all flows vanish, and thermodynamic equilibrium occurs. A differential interparticle interaction with less repulsive forces within particles of one species but maintenance of this interaction for the other species adds a bypass path to this circular subspace. On this path, which is not involved in coupling of the two species, a leak flow of the species with less repulsive interparticle interaction emerges, which is directed parallel to its concentration gradient and, hence, produces positive entropy here. Different from the situation with perfect coupling, appropriate strong opposing concentration gradients may simultaneously parallelize the flow of their respective species, which makes each species produce positive entropy. The rectifying potential of the species with the bypass option is diminished. This implies the existence of a gradient of the other species, above which its flow and gradient are parallel for any gradient of the less coupled species. The opposite holds for the less coupled species. Its flow may always be rectified and turned anti-parallel to its gradient by a sufficiently strong opposing gradient of the other one.

Magnetic resonance imaging (MRI) has long been contraindicated in patients with implanted pacemakers, defibrillators, and cardiac resynchronisation therapy (CRT) devices due to the risk of adverse effects through electromagnetic interference. Since many recipients of these devices will have a lifetime indication for an MRI scan, the implantable systems should be developed as 'MRI-conditional' (be safe for the MRI environment under predefined conditions). We evaluated the clinical safety of several Biotronik ProMRI ('MRI-conditional') defibrillator and CRT systems during head and lower lumbar MRI scans at 1.5 Tesla. The study enrolled 194 patients at 22 sites in Australia, Canada, and Europe. At ≥9 weeks after device implantation, predefined, non-diagnostic, specific absorption rate (SAR)-intensive head and lower lumbar MRI scans (total ≈30 minutes per patient) were performed in 146 patients that fulfilled pre-procedure criteria. Three primary endpoints were evaluated: freedom from serious adverse device effects (SADEs) related to MRI and defibrillator/CRT (leading to death, hospitalisation, life-threatening condition, or potentially requiring implanted system revision or replacement), pacing threshold increase, and sensing amplitude decrease, all at the 1-month post-MRI clinical visit. No MRI-related SADE occurred. Lead values remained stable, measured in clinic and monitored daily by the manufacturer home monitoring technology.

Purpose: 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice., Methods: 4D flow and WSS were measured in the aortic arch of 12-week-old wildtype C57BL/6 J mice (n = 7) with a radial 4D-phase-contrast (PC)-CMR sequence, which was validated in a flow phantom. Cardiac and respiratory motion signals were extracted from the radial CMR signal and were used for the reconstruction of 4D-flow data. Rigid motion correction and a first order B 0 correction was used to improve the robustness of magnitude and velocity data. The aortic lumen was segmented semi-automatically. Temporally averaged and time-resolved WSS and oscillatory shear index (OSI) were calculated from the spatial velocity gradients at the lumen surface at 14 locations along the aortic arch. Reproducibility was tested in 3 animals and the influence of subsampling was investigated., Results: Volume flow, cross-sectional areas, WSS and the OSI were determined in a measurement time of only 32 min. Longitudinal and circumferential WSS and radial stress were assessed at 14 analysis planes along the aortic arch. The average longitudinal, circumferential and radial stress values were 1.52 ± 0.29 N/m 2 , 0.28 ± 0.24 N/m 2 and - 0.21 ± 0.19 N/m 2 , respectively. Good reproducibility of WSS values was observed., Conclusion: This work presents a robust measurement of 4D flow and WSS in mice without the need of ECG trigger signals. The retrospective approach provides fast flow quantification within 35 min and a flexible reconstruction framework.

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Herein, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class-II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in mice. Transferred MYHCA614-629-specific CD4+ T (TCR-M) cells selectively accumulated in the myocardium and mediastinal lymph nodes (med-LN) of infarcted mice, acquired a Treg phenotype with a distinct pro-healing gene expression profile, and mediated cardioprotection. Myocardial Treg cells were also detected in autopsies from patients who suffered a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in MI-patients. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence showing that MI-context induces pro-healing T cell autoimmunity in mice and confirms the existence of an analogous heart/med-LN/T cell axis in MI patients.

Purpose: Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance of 18 F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18 F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed., Methods: Twenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwent 18 F-florbetaben-PET/CT for diagnostic work-up. Qualitative and quantitative assessment including calculation of myocardial tracer retention (MTR) was performed, and compared to echo (n = 20), CMR (n = 16), scintigraphy (n = 16) and serologic biomarkers (NT-proBNP, cTnT, free light chains). In four patients, follow-up PET/CT was available (after treatment initiation, n = 3; surveillance, n = 1)., Results: PET demonstrated myocardial 18 F-florbetaben retention consistent with CA in 14/22 patients. Suspicion of CA was subsequently dropped in all eight PET-negative patients. Amyloid subtypes showed characteristic retention patterns (AL > AA > ATTR; all p < 0.005). MTR correlated with morphologic and functional parameters, as measured by CMR and echo (all r| > 0.47|, all p < 0.05), but not with cardiac biomarkers. Changes in MTR from baseline to follow-up corresponded well to treatment response, as assessed by cardiac biomarkers and performance status., Conclusions: Imaging of cardiac amyloidosis (CA) with 18 F-florbetaben-PET/CT is feasible and might be useful in differentiating CA subtypes.

The combination of magnetic resonance imaging (MRI) and active cardiac implants, such as pacemakers and implantable cardioverter defibrillators (ICD) has been a challenge for electrophysiologists and imaging for many years. Diagnostic and therapeutic possibilities on the one hand and technical hazards on the other hand highlight the need for improvements and algorithms that enable a safe approach to these challenges. The advent of so-called MRI conditional implants provides safe procedures for at least some of the patients with an implant and the need for MRI. Recently published data encourage clinicians not to completely excluded an imaging modality as promising as MRI in clinically urgent cases in the presence of conventional implants. The interdisciplinary consensus paper of the German Society of Cardiology and the German Society of Radiology provides recommendations for these situations. This review article discusses these recommendations and provides an overview of the most recent publications with a focus on the long-term course of device parameters.

Aims: Sodium intake has been linked to left ventricular hypertrophy independently of blood pressure, but the underlying mechanisms remain unclear. Primary hyperaldosteronism (PHA), a condition characterized by tissue sodium overload due to aldosterone excess, causes accelerated left ventricular hypertrophy compared to blood pressure matched patients with essential hypertension. We therefore hypothesized that the myocardium constitutes a novel site capable of sodium storage explaining the missing link between sodium and left ventricular hypertrophy., Methods and Results: Using 23Na magnetic resonance imaging, we investigated relative sodium signal intensities (rSSI) in the heart, calf muscle, and skin in 8 PHA patients (6 male, median age 55 years) and 12 normotensive healthy controls (HC) (8 male, median age 61 years). PHA patients had a higher mean systolic 24 h ambulatory blood pressure [152 (140; 163) vs. 125 (122; 130) mmHg, P < 0.001] and higher left ventricular mass index [71.0 (63.5; 106.8) vs. 55.0 (50.3; 66.8) g/m2, P = 0.037] than HC. Compared to HC, PHA patients exhibited significantly higher rSSI in the myocardium [0.31 (0.26; 0.34) vs. 0.24 (0.20; 0.27); P = 0.007], calf muscle [0.19 (0.16; 0.22) vs. 0.14 (0.13; 0.15); P = 0.001] and skin [0.28 (0.25; 0.33) vs. 0.19 (0.17; 0.26); P = 0.014], reflecting a difference of +27%, +38%, and +39%, respectively. Treatment of PHA resulted in significant reductions of the rSSI in the myocardium, calf muscle and skin by -13%, -27%, and -29%, respectively., Conclusion: Myocardial tissue rSSI is increased in PHA patients and treatment of aldosterone excess effectively reduces rSSI, thus establishing the myocardium as a novel site of sodium storage in addition to skeletal muscle and skin., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients receiving dual-chamber implantable cardioverter-defibrillator (DR-ICD) therapy are at risk of developing atrial arrhythmia because of the increased rate of ventricular pacing and the progression of heart failure. Remote monitoring (RM) may identify the patients at highest risk of adverse events such as atrial arrhythmias. A total of 283 patients with 91,632 remote transmissions during a 15-month follow-up (FU) period enrolled in the LION registry were analysed. The parameters retrieved included the pacing mode, lower rate limit, percentage of atrial (%AP) and ventricular pacing (%VP), and percentage of atrial arrhythmia burden (%AB). In 92.7% of patients, the devices were initially programmed in DDD(R) or DDI(R), with changes of the pacing mode in 19.3% only. The lower rate limit remained stable in 80.4% of patients. At the first transmission, 8.7% of patients suffered from RM-detected atrial arrhythmia, which reached 36% during FU. The %AP was not associated with increased AB ( p = 0.67), but the %VP was different in patients developing RM-detected atrial arrhythmia (26.9% vs. 13.7%, p < 0.00001). The %VP increased in 105 patients (significance level of α = 0.05), and 11 patients crossed the border of 50% VP. The LION substudy supports the concept of using RM in a real-world DR-ICD population. Remote monitoring of DR-ICDs allows for the quantification of the course of the pacing parameters and AB. Based on these observations, device parameters can be adjusted and optimized.

Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a randomized placebo-controlled clinical trial, we contrasted pain relief (3-month treatment period), and anatomical (gray matter density [GMD], assessed by voxel-based morphometry) and functional connectivity (resting state fMRI nodal degree count [DC]) adaptations, in 39 knee osteoarthritis (OA) patients (22 females), randomized to duloxetine (DLX, 60 mg once daily) or placebo. Pain relief was equivalent between treatment types. However, distinct circuitry (GMD and DC) could explain pain relief in each group: up to 85% of variance for placebo analgesia and 49% of variance for DLX analgesia. No behavioral measures (collected at entry into the study) could independently explain observed analgesia. Identified circuitry were outside of nociceptive circuitry and minimally overlapped with OA-abnormal or placebo response predictive brain regions. Mediation analysis revealed that changes in GMD and DC can influence each other across remote brain regions to explain observed analgesia. Therefore, we can conclude that distinct brain mechanisms underlie DLX and placebo analgesia in OA. The results demonstrate that even in the absence of differences in subjective pain relief, pharmacological treatments can be differentiated from placebo based on objective brain biomarkers. This is a crucial step to untangling mechanisms and advancing personalized therapy approaches for chronic pain., (© 2018 Wiley Periodicals, Inc.)

Quantitative nuclear magnetic resonance imaging (MRI) shifts more and more into the focus of clinical research. Especially determination of relaxation times without/and with contrast agents becomes the foundation of tissue characterization, e.g. in cardiac MRI for myocardial fibrosis. Techniques which assess longitudinal relaxation times rely on repetitive application of readout modules, which are interrupted by free relaxation periods, e.g. the Modified Look-Locker Inversion Recovery = MOLLI sequence. These discontinuous sequences reveal an apparent relaxation time, and, by techniques extrapolated from continuous readout sequences, a putative real T 1 is determined. What is missing is a rigorous analysis of the dependence of the apparent relaxation time on its real partner, readout sequence parameters and biological parameters as heart rate. This is provided in this paper for the discontinuous balanced steady state free precession (bSSFP) and spoiled gradient echo readouts. It turns out that the apparent longitudinal relaxation rate is the time average of the relaxation rates during the readout module, and free relaxation period. Knowing the heart rate our results vice versa allow to determine the real T 1 from its measured apparent partner., (Copyright © 2018. Published by Elsevier GmbH.)

Contrast and non-contrast MRI based characterization of myocardium by T 1 -mapping will be of paramount importance to obtain biomarkers, e.g. fibrosis, which determines the risk of heart failure patients. T 1 -mapping by the standard post-processing of the modified look-locker inversion recovery (MOLLI) lacks of accuracy when trying to reduce its duration, which on the other hand, is highly desirable in patients with heart failure. The recently suggested inversion group fitting (IGF) technique, which considers more parameters for fitting, has a superior accuracy for long T 1 times despite a shorter duration. However, for short T 1 values, the standard method has a superior precision. A conditional fitting routine is proposed which ideally takes advantage of both algorithms., Materials and Methods: All measurements were performed on a 1.5T clinical scanner (ACHIEVA, Philips Healthcare, The Netherlands) using a MOLLI 5(n)3(n)3 prototype with n(heart beats) being a variable waiting time between inversion experiments. Phantom experiments covered a broad range of T 1 times, waiting times and heart rates. A saturation recovery experiment served as a gold standard for T 1 measurement. All data were analyzed with the standard MOLLI, the IGF fit and the conditional fitting routine and the obtained T 1 values were compared with the gold standard. In vivo measurements were performed in a healthy volunteer and a total of 34 patients with normal findings, dilative cardiomyopathy and amyloidosis., Results: Theoretical analysis and phantom experiments provided a threshold value for an apparent IGF T 1 * determining processing with IGF post processing for values above, or switching to the standard technique for values below. This was validated in phantoms and patients measurements. A reduction of the waiting time to 1 instead of 3 heart beats between the inversion experiments showed reliable results. The acquisition time was reduced from 17 to 13 heart beats. The in vivo measurements showed ECV values between 25% (18-33%; SD 0.03) in the healthy, 30% (22-40%; SD 0.04) in patients with DCM and 45% (30-60%; SD 0.9) in patients with amyloidosis., Conclusion: The adopted post-processing algorithm determines long T 1 values with high accuracy and short T 1 values while maintaining a high precision. Based on reduction of waiting time, and independence of heart rate, it shortens breath hold duration and allows fast T 1 -mapping, which is frequently a prerequisite in patients with cardiac diseases., (Copyright © 2017. Published by Elsevier GmbH.)

Flow of particles of two different species through a narrow channel with solely two discrete spatial positions is analyzed with respect to the species' capability to cooperate or compete for transport. The origin of the latter arises from particle-channel and interparticle interactions within the channel, i.e., blocking the position of a particle, and its interaction with its neighbors in the channel. The variety of occupation options within the channel defines the state space. The transition dynamics within is considered as a continuous Markov process, which, in contrast to mean-field approaches, conserves explicitly spatial correlations. A strong repulsive interaction between particles of the same kind and a very attractive empty channel imply a strong entanglement of transport of both species. In the limiting case of perfect coupling, flows in state space are restricted to a cyclic subspace, where they become all equivalent in the steady state. In particular, this implies equal particle flows of the two species. Entanglement of transport implies that the species mutually exert entropic forces on each other. For parallel directed concentration gradients this implies that the species' ability to cooperate increases with the degree of entanglement. Thus, the gradient of one species reciprocally induces a higher flow of the other species when compared to that in its absence. The opposite holds for antiparallel gradients where species mutually hamper their transport. For a sufficient strong coupling, the species under the influence of the stronger concentration gradient drives the other against its gradient, i.e., the positive mixing entropy production of the driving species becomes the motor for the negative mixing entropy production of the driven one. The degree of effectiveness by which negative entropy production emerges at the cost of positive entropy production increases with the coupling strength. This becomes evident from location and connectivity of the sources of entropy production in state space.

Purpose: The importance of the orientation of the selective inversion slice in relation to the anatomy in flow-sensitive alternating inversion recovery arterial spin labeling (FAIR ASL) kidney perfusion measurements is demonstrated by comparing the standard FAIR scheme to a scheme with an improved slice selective control experiment., Methods: A FAIR ASL method is used. The selective inversion preparation slice is set perpendicular to the measurement slice to decrease the unintended labeling of arterial spins in the control experiment. A T 1 * -based quantification method compensates for the effects of the imperfect inversion on the edge of the selective inversion slice. The quantified perfusion values are compared to the standard experiment with parallel orientation of imaging and selective inversion slice., Results: Perfusion maps acquired with the perpendicular inversion slice orientation show higher sensitivity compared to the parallel orientation. The T 1 * -based quantification method removes artifacts arising from imperfect inversion slice profiles. The stability is improved., Conclusion: Adjusting the labeling technique to the anatomy is of high importance. Improved sensitivity and reproducibility could be demonstrated. The proposed method provides a solution to the problem of FAIR ASL measurements of renal perfusion in coronal view., (Copyright © 2017. Published by Elsevier GmbH.)

Background: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities., Methods: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE (-/-) -mice) at 12 adjacent locations along the abdominal aorta., Results: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE (-/-) -group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE (-/-) -animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis., Conclusion: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE (-/-) -mice as a relevant model of atherosclerosis.

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in living cells, we provide direct experimental evidence that the cAMP concentration in the vicinity of an individual PDE molecule is below the detection limit of our FRET sensors (<100nM). This cAMP gradient persists in crude cytosol preparations. We developed mathematical models based on diffusion-reaction equations which describe the creation of nanocompartments around a single PDE molecule and more complex spatial PDE arrangements. The analytically solvable equations derived here explicitly determine how the capability of a single PDE, or PDE complexes, to create a nanocompartment depend on the cAMP degradation rate, the diffusive mobility of cAMP, and geometrical and topological parameters. We apply these generic models to our experimental data and determine the diffusive mobility and degradation rate of cAMP. The results obtained for these parameters differ by far from data in literature for free soluble cAMP interacting with PDE. Hence, restricted cAMP diffusion in the vincinity of PDE is necessary to create cAMP nanocompartments in cells.

Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE-/- and WT mice were determined for global and local PWV measurements (global PWV: ApoE-/-: 2.7±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE-/-: 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R2 = 0.75, P<0.01), implying a widely uniform arterial elasticity. In ApoE-/- animals, however, no significant correlation between individual local and global PWV was present (R2 = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.

Mild traumatic brain injury (mTBI) patients frequently experience emotion dysregulation symptoms, including post-traumatic stress. Although mTBI likely affects cortical activation and structure, resulting in cognitive symptoms after mTBI, early effects of mTBI on cortical emotion processing circuits have rarely been examined. To assess early mTBI effects on cortical functional and structural components of emotion processing, we assessed cortical activation to fearful faces within the first 2 weeks after motor vehicle collision (MVC) in survivors who did and did not experience mTBI. We also examined the thicknesses of cortical regions with altered activation. MVC survivors with mTBI (n = 21) had significantly less activation in left superior parietal gyrus (SPG) (-5.9, -81.8, 33.8; p = 10 -3.623 ), left medial orbitofrontal gyrus (mOFG) (-4.7, 36.1, -19.3; p = 10 -3.231 ), and left and right lateral orbitofrontal gyri (lOFG) (left: -16.0, 41.4, -16.6; p = 10 -2.573 ; right: 18.7, 22.7, -17.7; p = 10 -2.764 ) than MVC survivors without mTBI (n = 23). SPG activation in mTBI survivors within 2 weeks after MVC was negatively correlated with subsequent post-traumatic stress symptom severity at 3 months (r = -0.68, p = 0.03). Finally, the SPG region was thinner in the mTBI survivors than in the non-mTBI survivors (F = 11.07, p = 0.002). These results suggest that early differences in activation and structure in cortical emotion processing circuits in trauma survivors who sustain mTBI may contribute to the development of emotion-related symptoms., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Purpose: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs., Methods: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T 1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T 1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference., Results: Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T 1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference., Conclusion: The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T 1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR.15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUVmean) and maximum standardized uptake values (SUVmax) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity.SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up.In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUVmean and SUVmax in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUVmean and 2.0±0.3 and 1.7±0.3 for SUVmax, respectively.Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.