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We describe the transcatheter management of severe aortic regurgitation in a middle-aged patient with a porcelain aorta who underwent implantation of an apicoaortic valved conduit 12 years ago. Instantaneous relief of heart failure symptoms was achieved by restoring antegrade blood flow to the ascending aorta. (Level of Difficulty: Advanced.), Graphical abstract

We present not‐yet‐seen multimodal images of a 55‐year‐old female patient with isolated atrial amyloidosis (IAA) who clinically suffered from multiple atrial arrhythmias and heart failure symptoms with preserved left ventricular ejection fraction. We aim to show structural and functional abnormalities detected by electrophysiological voltage mapping, cardiac magnetic resonance imaging (MRI) [cMRI; atrial strain measurements, late gadolinium enhancement (LGE) visualization], and 99mTc‐DPD scintigraphy. Bipolar voltage mapping performed during two electrophysiological procedures showed diffuse left atrial low‐voltage areas (bipolar

Introduction Persistent cardiopulmonary symptoms after COVID-19 are reported in a large number of patients and the underlying pathology is still poorly understood. (1) Histopathologic studies revealed myocardial macrophage infiltrates in deceased patients, likely an unspecific finding of severe illness, and increased prevalence of micro- and macrovascular thrombi. (2) We examined whether microvascular perfusion, measured by quantitative cardiac magnetic resonance under vasodilator stress, was altered post COVID-19. Methods Our population consisted of 12 patients from the Pa-COVID-19-Study of the Charité Berlin, which received a cardiac MRI as part of a systematic follow up post discharge, 10 patients that presented at the German Heart Center Berlin with persistent cardiac symptoms post COVID-19 and 12 patients from the Kings College London referred for stress MRI and previous COVID-19. The scan protocol included standard functional, edema and scar imaging and quantitative stress and rest perfusion to assess both macro- and microvascular coronary artery disease. The pharmacological stress agent was regadenosone in 20 and adenosine in 13 of the patients. To control for the higher heart rate increase under regadenosone compared to adenosine, we calculated the myocardial blood flow per heartbeat (MBF_HRi) under stress. Results The median time between first positive PCR for COVID-19 and the CMR exam was 2 months (Range 0 to 12). None of the 33 patients exhibited signs of myocardial edema. One patient with a previous history of myocarditis had focal fibrosis. Three patients with known coronary artery disease showed ischemic Late Enhancement. Five patients had a small pericardial effusion; one of these four patients showed slight focal pericardial edema and LGE, consistent with mild focal pericarditis. Five Patients had a stress-induced focal perfusion deficit. Mean Stress MBF_HRi was 32.5±6.5 μl/beat/g. Stress MBF_HRi was negatively correlated with COVID-19 severity (rho=−0.361, P=0.039) and age (r=−0.452, P=0.009). The correlation with COVID-19 severity remained significant after controlling for age (rho=−0.390, P=0.027). There was no apparent difference in stress MBF_HRi between patients with and without persistent chest pain (34.5 vs. 31.5 μl/beat/g, P=0.229) Conclusion While vasodilator-stress myocardial blood flow after COVID-19 was negatively correlated to COVID-19 severity, it was not correlated to the presence of chest pain. The etiology of persistent cardiac symptoms after COVID-19 remains unclear. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Philips Figure 1. A) Quantitative regadenosone stress myocardial blood flow (MBF) map, medial short axis slice, in a patient with persistent cardiac symptoms after COVID-19. B) Boxplot of stress MBF per heart beat by COVID-19 severity, showing decreasing MBF with increasing COVID-19 severity.

Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty‐nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10‐year mean phenylalanine concentration, 924±330 µmol/L) and 39 age‐ and sex‐matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten‐year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end‐diastolic thickness, 7.0±17 versus 8.8±1.7 mm [ P P =0.004]), more dilated left ventricular cavity (end‐diastolic volume, 87±14 versus 80±14 mL/m 2 [ P =0.0178]; end‐systolic volume, 36±9 versus 29±8 mL/m 2 [ P P P =0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m 2 [ P P 1200 µmol/L (909±48 ms). Both mean phenylalanine ( P =0.013) and tyrosine ( P =0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early‐stage cardiomyopathy. Regular cardiology follow‐up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

This case report describes the contributions of multimodality imaging, cardiac biopsy, and genetic sequencing to the diagnosis and management of heart transplant rejection in a 23-year old patient with dilated cardiomyopathy.

Background: Aim of this study was to review current literature and data regarding the effects of MRI-examination post stent implantation on re-occlusion rates. Methods: We focused on representative...

Introduction: While cardiac tumors are rare, their identification and differentiation has wide clinical implications. Recent cardiac magnetic resonance (CMR) parametric mapping techniques allow for quantitative tissue characterization. Our aim was to examine the range of values encountered in cardiac myxomas in correlation to histological measurements.Methods and Results: Nine patients with histologically proven cardiac myxomas were included. CMR (1.5 Tesla, Philips) including parametric mapping was performed in all patients pre-operatively. All data are reported as mean ± standard deviation. Compared to myocardium, cardiac myxomas demonstrated higher native T1 relaxation times (1,554 ± 192 ms vs. 1,017 ± 58 ms, p < 0.001), ECV (46.9 ± 13.0% vs. 27.1 ± 2.6%, p = 0.001), and T2 relaxation times (209 ± 120 ms vs. 52 ± 3 ms, p = 0.008). Areas with LGE showed higher ECV than areas without (54.3 ± 17.8% vs. 32.7 ± 18.6%, p = 0.042), with differences in native T1 relaxation times (1,644 ± 217 ms vs. 1,482 ± 351 ms, p = 0.291) and T2 relaxation times (356 ± 236 ms vs. 129 ± 68 ms, p = 0.155) not reaching statistical significance.Conclusions: Parametric CMR showed elevated native T1 and T2 relaxation times and ECV values in cardiac myxomas compared to normal myocardium, reflecting an increased interstitial space and fluid content. This might help in the differentiation of cardiac myxomas from other tumor entities.

Background: Phenylketonuria (PKU) is the most common inborn error of amino-acid metabolism, which, when untreated results to severe neuropsychological complications. . New born screenings programs and immediate beginning of phenylalanine-restricted diet, greatly ameliorate the prognosis. However, previous studies have shown that PKU patients have elevated levels of oxidative stress and collateral metabolic abnormalities such as dyslipidemia, predisposing to cardiovascular disease. The purpose of this study was to characterize the cardiac phenotype of adult subjects with PKU using advanced cardiac imaging. Methods: Thirty-nine adult patients with PKU (age 30.5±8.7 year old, median 10 year phenylalanine concentration (Phe) 924±330 µmol/L) and thirty-nine age- and gender- matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance imaging (CMR) and echocardiography examination to determine systolic and diastolic left (LV) and right (RV) ventricular function, LV mass, ventricular fibrosis, left atrial function and aortic distensibility. CMR parametric mapping was used to characterize structural tissue modification. All available quarterly plasma levels of Phe and tyrosine (Tyr) levels were averaged for 10 years prior to the CMR scan to evaluate therapeutic efficacy and compliance. Results: PKU patients had thinner LV walls (Septal end-diastolic (ED) thickness 7.0±17 vs 8.8±1.7 mm, p 1200µmol/L (909±48 ms). Both mean Phe (p=0.013) and Tyr (p=0.035) concentration levels were independently predictive for lower T1 values in a regression model. Conclusion: Taken together our findings indicate an early stage LV dysfunction in patients with PKU which associates lower T1 native levels probably reflecting an infiltration with lipids of the myocardium. These results suggest the importance of regular cardiac follow-up in clinical monitoring of the adult subjects with PKU. Funding Statement: Sebastian Kelle is supported by a grant from Philips Healthcare and received funding from the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). Declaration of Interests: None of the other authors reports a relationship with industry and other relevant entities – financial or otherwise – that might pose a conflict of interest in connection with the submitted article. The following authors report financial activities outside the submitted work: Radu Tanacli reports no conflict of interest. Burkert Pieske reports having received consultancy and lecture honoraria from Bayer Daiichi Sankyo, MSD, Novartis, Sanofi-Aventis, Stealth Peptides and Vifor Pharma; and editor honoraria from the Journal of the American College of Cardiology. Radu Tanacli and the other co-authors report no conflict of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of the Charite University of Medicine in Berlin, complied with the Declaration of Helsinki and was registered at the German Register for Clinical Studies (DRKS00001120).

Oncolytic virotherapy with vaccine viruses employs replicative vectors, which quite selectively infect tumor cells leading to massive virus replication followed by subsequent profound tumor cell death (oncolysis). Measles vaccine virus (MeV) has already shown great oncolytic activity against different types of cancers, including pancreatic cancer. Gemcitabine is a first line chemotherapeutic drug used for pancreatic cancer in palliative treatment plans. Furthermore, this drug can be used to induce senescence, a permanent cell cycle arrest, in tumor cells. In our preclinical work, three well-characterized immortalized human pancreatic cancer cell lines were used to investigate the combinatorial effect of MeV-based virotherapy together with the chemotherapeutic compound gemcitabine. Viability assays revealed that the combination of only small amounts of MeV together with subtherapeutic concentrations of gemcitabine resulted in a tumor cell mass reduction of >50%. To further investigate the replication of the oncolytic MeV vectors under these distinct combinatorial conditions, viral growth curves were generated. As a result, viral replication was found to be only slightly diminished in the presence of gemcitabine. As gemcitabine induces senescence, the effect of MeV on that phenomenon was explored using a senescence-associated β-galactosidase assay. Notably, gemcitabine-induced tumor cell senescence was not impaired by MeV. Accordingly, the chemovirotherapeutic combination of gemcitabine plus oncolytic MeV constitutes a novel therapeutic option for advanced pancreatic carcinoma that is characterized by the mutual improvement of the effectiveness of each therapeutic component.

Purpose To prospectively assess the feasibility, image quality, and diagnostic accuracy of high-dose dobutamine stress magnetic resonance imaging (DSMR) using steady-state free precession (SSFP) cine imaging at 3T applying a dual-source radiofrequency (RF) excitation magnetic resonance imaging (MRI) system with parallel transmission and patient adaptive local RF shimming. Materials and Methods DSMR using SSFP cine imaging was performed in 44 patients at 3T scheduled for a clinically indicated coronary angiography. The effect of conventional versus dual-source RF transmission was assessed regarding homogeneity of the B1 field, contrast-to-noise ratios (CNRs) at rest, image quality, and diagnostic accuracy of DSMR using long and short axis. Results The mean percentage of the intended flip angle within the heart increased from 88 ± 9.1% with single-source to 103 ± 5.6% (P < 0.001) dual-source RF transmission. CNR increased for dual-source particularly at the apex (63.4 ± 24.2 vs. 36.5 ± 16.5, P < 0.001) but also at the base of the left ventricle (LV) (50.1 ± 14.8 vs. 39.3 ± 15.8, P < 0.001). Image quality of dual-source was higher both at rest (2.8 ± 0.5 vs. 2.6 ± 0.7, P < 0.001) and stress (2.5 ± 0.7 vs. 2.0 ± 1.0, P < 0.001). The number of segments with severe artifacts or nondiagnostic image quality at stress was lower with dual-source RF transmission (8% vs. 27%, P < 0.001). The diagnostic accuracy of DSMR in coronary territories using dual-source RF transmission was significantly higher (77% vs. 65%, P = 0.04). Conclusion Patient adaptive local RF shimming using dual-source RF transmission provided significantly improved image quality and higher diagnostic accuracy of SSFP during DSMR at 3T compared to conventional RF transmission. J. Magn. Reson. Imaging 2015;42:746–753.

Objective This study aimed to investigate the advantages of recently developed cardiac imaging techniques of fat–water separation and feature tracking to characterize better individuals with chronic myocardial infarction (MI). Materials and methods Twenty patients who had a previous MI underwent CMR imaging. The study protocol included routine cine and late gadolinium enhancement (LGE) technique. In addition, mDixon LGE imaging was performed in every patient. Left ventricular (LV) circumferential (EccLV) and radial (ErrLV) strain were calculated using dedicated software (CMR42, Circle, Calgary, Canada). The extent of global scar was measured in LGE and fat–water separated images to compare conventional and recent CMR imaging techniques. Results The infarct size derived from conventional LGE and fat–water separated images was similar. However, detection of lipomatous metaplasia was only possible with mDixon imaging. Subjects with fat deposition demonstrated a significantly smaller percentage of fibrosis than those without fat (10.68 ± 5.07% vs. 13.83 ± 6.30%; p = 0.005). There was no significant difference in EccLV or ErrLV between myocardial segments containing fibrosis only and fibrosis with fat. However, EccLV and ErrLV values were significantly higher in myocardial segments adjacent to fibrosis with fat deposition than in those adjacent to LGE only. Conclusions Advanced CMR imaging ensures more detailed tissue characterization in patients with chronic MI without a relevant increase in imaging and post-processing time. Fatty metaplasia may influence regional myocardial deformation especially in the myocardial segments adjacent to scar tissue. A simplified and shortened myocardial viability CMR protocol might be useful to better characterize and stratify patients with chronic MI.

Over the past years dobutamine stress magnetic resonance imaging (DSMR) has matured into a highly valuable clinical tool for the assessment of myocardial ischemia and viability. Furthermore, the results of DSMR can be utilized to direct clinical management and to determine cardiac prognosis. This article gives an update on recently published data regarding the performance of DSMR including technical developments, diagnostic accuracy, prognosis, and the implications on clinical management in patients with coronary artery disease (CAD).

Die isolierte linksventrikulare Noncompaction-Kardiomyopathie (LVNC) gehort zu den seltenen Kardiomyopathien. Bei der LVNC bestehen typischerweise prominente Trabekel und tiefe Rezessus, die insgesamt als ein 2-schichtig verdicktes Myokard erscheinen. Dabei dominiert eine Schicht als nicht kompaktiertes und eine als kompaktiertes Myokard. Klinischer Standard zur Diagnostik der LVNC ist die Echokardiographie, wobei es verschiedene diagnostische Kriterien gibt. In schwierigen Fallen ist die kardiale Magnetresonanztomographie wegen ihres ausgezeichneten nativen Kontrastes zwischen Blut und Myokard hilfreich. Die meisten Patienten weisen Symptome einer chronischer Herzinsuffizienz auf. Haufig werden im Verlauf Thrombembolien und Arrhythmien beobachtet. Eine kausale Therapie gibt es nicht, daher sind Therapieansatze auf die Behandlung der Herzinsuffizienz und die Pravention von Thrombembolien begrenzt.

Wir berichten uber einen 34-jahrigen Mann, der aufgrund einer Prasynkope stationar aufgenommen wurde. In der Vorgeschichte ist eine Myokarditis vor 5 Jahren und eine Infektion mit Echinococcus granulosus vor 4 Jahren ohne Beteiligung abdomineller Organe bekannt, die medikamentos mittels Albendazol behandelt wurde. Im EKG zeigte sich ein bereits bekannter Linksschenkelblock. Echokardiographisch wurden 2 Zysten in der posterolateralen Wand des linken Ventrikels mit echodichtem Randwall dargestellt. Die kardiale Magnetresonanztomographie zeigte in den Perfusionsuntersuchungen nach Kontrastmittelgabe eine Verbindung des Zysteninhalts mit der linken Herzkammer sowie in den Spataufnahmen nach Kontrastmittelgabe ein die Zysten umgebendes fibrotisches Gewebe. Es wurde die Diagnose einer kardialen zystischen Echinokokkose gestellt. Bei fehlender klinischer Symptomatik und negativer Serologie erfolgte keine weitere Therapie. Die kardiale Magnetresonanztomographie stellt bei dieser Erkrankung eine exzellente Moglichkeit der Bildgebung dar, da neben der Anatomie, der Zysteninhalt sowie die Beziehung zum Myokard zur Darstellung kommen.

Purpose To assess the distribution and regional differences of flow and vessel wall parameters such as wall shear stress (WSS) and oscillatory shear index (OSI) in the entire thoracic aorta. Materials and Methods Thirty-one healthy volunteers (mean age = 23.7 ± 3.3 years) were examined by flow-sensitive four-dimensional (4D)-MRI at 3T. For eight retrospectively positioned 2D analysis planes distributed along the thoracic aorta, flow parameters and vectorial WSS and OSI were assessed in 12 segments along the vascular circumference. Results Mean absolute time-averaged WSS ranged between 0.25 ± 0.04 N/m2 and 0.33 ± 0.07 N/m2 and incorporated a substantial circumferential component (–0.05 ± 0.04 to 0.07 ± 0.02 N/m2). For each analysis plane, a segment with lowest absolute WSS and highest OSI was identified which differed significantly from mean values within the plane (P < 0.05). The distribution of atherogenic low WSS and high OSI closely resembled typical locations of atherosclerotic lesions at the inner aortic curvature and supraaortic branches. Conclusion The normal distribution of vectorial WSS and OSI in the entire thoracic aorta derived from flow-sensitive 4D-MRI data provides a reference constituting an important perquisite for the examination of patients with aortic disease. Marked regional differences in absolute WSS and OSI may help explaining why atherosclerotic lesions predominantly develop and progress at specific locations in the aorta. J. Magn. Reson. Imaging 2009;30:77–84. © 2009 Wiley-Liss, Inc.

Background and Objectives It can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance. Methods All investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed. Results Using the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton. Conclusions We showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.

A 48-year-old male patient was admitted with palpitations and presyncopes due to new onset ventricular extrasystole following respiratory tract infection. On admission the patient presented with symptomatic sustained ventricular tachycardia ( Panel A ) which was terminated by amiodarone. Initial blood tests showed mild leucocytosis, no increase in C-reactive …

This paper identifies trends within and relationships between the amount of participation and the quality of contributions in three crowdsourced surveys. Participants were asked to perform a collective problem solving task that lacked any explicit incentive: they were instructed not only to respond to survey questions but also to pose new questions that they thought might-if responded to by others-predict an outcome variable of interest to them. While the three surveys had very different outcome variables, target audiences, methods of advertisement, and lengths of deployment, we found very similar patterns of collective behavior. In particular, we found that: the rate at which participants submitted new survey questions followed a heavy-tailed distribution; the distribution in the types of questions posed was similar; and many users posed non-obvious yet predictive questions. By analyzing responses to questions that contained a built-in range of valid response we found that less than 0.2% of responses lay outside of those ranges, indicating that most participants tend to respond honestly to surveys of this form, even without explicit incentives for honesty. While we did not find a significant relationship between the quantity of participation and the quality of contribution for both response submissions and question submissions, we did find several other more nuanced participant behavior patterns, which did correlate with contribution in one of the three surveys. We conclude that there exists an optimal time for users to pose questions early on in their participation, but only after they have submitted a few responses to other questions. This suggests that future crowdsourced surveys may attract more predictive questions by prompting users to pose new questions at specific times during their participation and limiting question submission at non-optimal times.

The purpose of this study is to explore the experience of being disconnected while traveling for technologically savvy travelers. This paper will explore how new technologies ‘separate’ travelers from the physical and embodied travel experience, and how experiences and tensions caused by being disconnected or unplugged are negotiated. For this study, travelers’ experiences were elicited through a series of online interviews conducted primarily through email and Facebook. Pearce and Gretzel’s (Int J Tourism Sci 12(2):1–20, 2012) technology-induced tensions and recent literature on internet/technology addiction provide a conceptual framework for the analysis.

In this clinical study, we tested the hypothesis that a marked systolic blood pressure decrease35% (DeltaSBP35%) from preanesthetic baseline during the induction and maintenance of anesthesia is associated with more postoperative nausea and vomiting (PONV). In 300 ASA physical status I and II women undergoing elective gynecological surgery with general anesthesia, the maximum DeltaSBP during the induction as well as maintenance of general anesthesia were calculated. Observers blinded to hemodynamic variables assessed the incidence of PONV. The overall incidence of nausea (visual analog scale4) and vomiting within the immediate observation period (0-2 h) was 39% and 25%, respectively. Frequency of nausea and vomiting in the late observation period was 21% and 9%, respectively. Women with a DeltaSBP35% during the induction of anesthesia suffered from a more frequent incidence of PONV within the immediate (57% versus 35% and 41% versus 22%, respectively; P0.01) and within the late observation period (33% versus 18% and 19% versus 7%, respectively; Por = 0.01). In women with a DeltaSBP35% during maintenance of anesthesia, a more frequent incidence of nausea within the immediate observation period (53% versus 36%; P0.05) was found. We conclude that a maximum DeltaSBP35% during the anesthetic induction is associated with an increased incidence of PONV after gynecological surgery during general anesthesia.A prospective clinical investigation revealed that a marked systolic blood pressure decrease35% (DeltaSBP35%) during the induction of general anesthesia is associated with an increased incidence of postoperative nausea and vomiting (PONV). The association between a DeltaSBP35% during maintenance of general anesthesia and PONV is less pronounced.

Background Dobutamine stress cardiovascular magnetic resonance (DS-CMR) has been established for the detection of coronary artery disease (CAD). The novel technique feature tracking (FT) analyses left ventricular circumferential strain (Ecc) thus offering detailed information about myocardial deformation. The purpose of this study was to evaluate FT based Ecc for the detection of myocardial ischemia during DS-CMR. Methods A total of 25 patients (18 males; mean age 64 ± 10 years) with suspected or known CAD underwent a standardized high-dose DS-CMR protocol at 1.5 T. For FT analysis cine short axis (SAX) views (apical, medial, basal) at rest and during maximum dobutamine stress were used. None of the patients had wall motion abnormalities (WMAs) or impaired left ventricular function at rest or scar tissue. For analysis of Ecc the three SAX planes were divided into 16 segments (n = 400 segments). During stress 15 patients (34 segments) developed WMAs as assessed by visual analysis. All patients underwent x-ray coronary angiography for clinical reasons which served as the reference standard. Patients without WMAs during DS-CMR and exclusion of stenotic CAD were defined as normal (10 patients, 160 segments). In patients with significant CAD segments that were supplied by a vessel of >70% narrowing were defined as stenotic (n = 64). The remaining segments in patients with significant CAD were considered as remote (n = 176). Results At rest no differences in Ecc were observed between normal, stenotic and remote segments. High-dose dobutamine stress revealed highly significant differences between Ecc of normal and stenotic segments (p

Background Phenylketonuria (PKU) is one of the most common inherited metabolic disorders. The molecular pathway of neurological damage is not yet sufficiently understood. To date, there is a lack information about cardiac involvement related to the disease. This study aims to characterize cardiac morphology and function in adult patients with PKU using cardiovascular magnetic resonance (CMR).

Background Renal Denervation (RDN) is a novel therapy for patients with resistant hypertension. Its cardiac effects at followup are currently unknown. On the other hand, T1 mapping permits the assessment of myocardial extracellular volume (ECV), a parameter proposed to quantify diffuse myocardial fibrosis and independently associated with mortality and hard cardiovascular events. Our aim was to study the effects of RDN on ECV at 6-month follow-up. Methods 14 patients with resistant hypertension undergoing RD (RD group) and 4 resistant hypertensive patients not undergoing RD (control group) were prospectively included. A 1.5T cardiac MR including T1 mapping preand post-contrast was performed before the RD procedure and at 6-month follow-up in both groups. Blood hematocrit was determined at both time points. Images were post-processed using commercial software (Qmass, Medis

There was an error in the article title. The correct title is: Resveratrol as a Pan-HDAC Inhibitor Alters the Acetylation Status of Histone Proteins in Human-Derived Hepatoblastoma Cells The correct citation is: Venturelli S, Berger A, Bocker A, Busch C, Weiland T, et al. (2013) Resveratrol as a Pan-HDAC Inhibitor Alters the Acetylation Status of Histone Proteins in Human-Derived Hepatoblastoma Cells. PLoS ONE 8(8): e73097. doi:10.1371/journal.pone.0073097

Background Dobutamine stress magnetic resonance (DSMR-wall motion) has been established as a valuable tool for the detection of inducible wall motion abnormalities. Additional perfusion imaging during DSMR (DSMR-perfusion) was shown to improve sensitivity for the detection of myocardial ischemia. Current experience is based on 1.5T only, mainly due to insufficient image quality of steady state free precession (SSFP) cine imaging at higher field strengths. Recently, image quality and diagnostic accuracy of SSFP sequences was significantly improved by dual-source parallel radiofrequency (RF) transmission for 3.0T. We examined whether the addition of myocardial perfusion imaging during DSMR at 3.0T is feasible and whether it provides incremental benefit for the evaluation of CAD.

Background Several studies have demonstrated the consistently high diagnostic and prognostic value of adenosine stress perfusion imaging with cardiovascular magnetic resonance (CMR). The feasibility and diagnostic accuracy of CMR stress perfusion in patients with atrial fibrillation is unknown. The purpose of this study was to assess the utility of CMR stress perfusion imaging in patients with atrial fibrillation who had suspected and known coronary artery disease (CAD).

To the Editor: In the present study we sought to investigate the predictive value of resting and inducible wall motion abnormalities (WMA) and of late gadolinium enhancement (LGE) for hard cardiac outcomes and for revascularization procedures in 3,138 patients undergoing dobutamine cardiac magnetic

BACKGROUND: Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD. METHODS: We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34-45 minutes after low-dose gadolinium administration. RESULTS: No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474). CONCLUSION: Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.

Melanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2'-Deoxy-5-fluorouridylyl-(3'-5')-3'-C-ethynylcytidine [5-FdU(3'-5')ECyd] and 3'-C-ethynylcytidinylyl-(5' → 1-O)-2-O-octadecyl-sn-glycerylyl-(3-O → 5')-2'-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5-FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient-derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real-time)-proliferation assays demonstrated that 5-FdU(3'-5')ECyd and ECyd-lipid-5-FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range. Cytotoxicity was conducted by induction of DNA cleavage indicating apoptotic cells. Chicken embryotoxicity demonstrated that the duplex drugs were less toxic than 5-FdU at 0.01 μM. In vivo the duplex drug 5-FdU(3'-5')ECyd was efficacious in the murine LOX IMVI melanoma xenograph model on administration of 11.2 mg/kg/injection every fourth day. Both duplex drugs are promising novel cytostatic agents for the treatment of malignant melanoma meriting clinical evaluation.

Whether the aim is to slow global warming, reduce poverty, or improve urban education, social entrepreneurs and philanthropists seek scalable solutions to the pressing social problems of our time. More recently, however, academics, nonprofit leaders, and consultants have questioned the emphasis on scale on two counts. First, a number of scholars have shown that organizations can significantly grow their impact without growing in size (Dees et al., 2004; Uvin et al., 2000; Wei-Skillern and Marciano, 2008). Second, social entrepreneurs and their observers have documented the challenges associated with scaling social change organizations.

We present preliminary data of the vascular hemodynamics in a novel, anatomically shaped ascending aortic graft in comparison to non-operated individuals by use of 3D magnetic resonance (MR) flow measurements. We examined a 72-year-old male patient after Tiron David I valve sparing aortic root reconstruction and replacement of the ascending aorta (AAo) with an anatomically curved prosthesis. Results from flow-sensitive MR at 3T were compared to 12 age-matched individuals with comparable diameters of the AAo. For 3D flow visualization, streamlines and time-resolved particle traces were applied. A visual analysis of hemodynamic properties including blood flow helicity, vorticity and retrograde flow was performed. In contrast to reported highly disturbed flow of straight aortic grafts in the literature, the patient analysis revealed smooth blood flow through the graft which gave rise to a right-handed helical flow in the reconstructed aorta. In comparison to non-operated volunteers, blood flow helicity was more pronounced. Flow jets or vortices were not encountered. While physiological retrograde flow was seen in the volunteers, it was absent in the patient which may be explained by the altered aortic compliance and thus reduced Windkessel effect. This promising finding will have to prove its validity in further comparative studies.

Objectives In light of the ongoing discussion about flow-mediated arterial remodeling, it was the aim of this report to demonstrate the detailed assessment of 3-dimensional vascular hemodynamics by high-field magnetic resonance imaging in healthy volunteers and to illustrate its potential in comparison with results in a patient with stenosis. Materials and Methods All examinations consisted of flow-sensitive 4-dimensional magnetic resonance imaging at 3 Tesla. Retrospective blood flow visualization and segmental quantification of wall shear stress and oscillatory shear index were performed. The results from 11 healthy individuals were compared with a 13-year-old patient with aortic stenosis who received a combined protocol with time-resolved 3-dimensional magnetic resonance angiography before and 5 and 9 months after intervention. Results Evaluation of normal blood flow characteristics demonstrated predominantly right-handed helical flow in the ascending aorta. Vortex formation was observed in 1 of 11 volunteers. Consistently high segmental wall shear stress was found along the circumference of the ascending aorta (average wall shear stress = 0.191 ± 0.06 N/m2) and descending aorta (average 0.191 ± 0.06 N/m2). Compared with volunteers, the patient revealed substantial flow changes proximal and distal to the stenosis. Blood flow alterations in the ascending aorta were also observed associated with changes in velocities and wall shear stress that gradually normalized after intervention. Conclusion Flow-sensitive 4-dimensional magnetic resonance imaging at 3 Tesla can provide deeper insights into hemodynamic alterations in the diagnosis and follow-up of aortic pathologies. These findings indicate the potential of the methodology for the evaluation of effects of localized pathologies on the entire vascular system, which will have to be confirmed in future studies.

Background Left ventricular myocardial motion analysis and the assessment of regional dysfunction are crucial for the detection and prognosis in different cardiac pathologies. Myocardial tagging (MT) is a cardiac magnetic resonance (CMR) based method for tracking myocardial motion, which has been established as reference standard for assessment of strain. Currently, strain can also be assessed by CMR using feature tracking (FT) or by echocardiography with speckle tracking (ST). Aim of our study was to evaluate intraindividually and compare myocardial circumferential strain (Ecc) using MT, FT and ST.

Current underwater protection systems are complex expensive devices consisting of multiple electronic sensing elements. The detection and identification of divers and small submerged watercraft requires very high image resolution. The high price of an array of conventional piezoelectric transducers and associated electronic components makes this solution feasible for localized implementations, but the protection of large stretches of coastline requires a different approach. We present a novel multichannel sonar design that augments current active sonar transducers with a passive fiber-optic multichannel acoustic emission sensing array. The system provides continuous monitoring of the acoustic wave reflections emitted by a single projector, yielding information about the size and shape of approaching objects. A novel fiber hydrophone enclosure is utilized to dramatically enhance the sensor response to the sonar frequency, while suppressing out-of-band sound sources and noise. The ability of a fiber hydrophone to respond to acoustic emissions is based on established fiber Bragg grating sensing techniques. In this approach, the energy of an acoustic wave is converted into the modulation of the in-fiber optical transducer's optical properties. The obtained results demonstrate significant response of the designed fiber optic hydrophone to the incident acoustic wave over the frequency domain from 1-80 kHz. Our approach allows selective tuning of the sensor to a particular acoustic frequency, as well as potential extension of the spectral response to 300- 400kHz. 2

For almost 30 years, Red Flag has given relatively inexperienced aircrew-Blue 4-a chance to experience eight to ten realistic combat missions in a high threat, but safe environment. It has also given more experienced pilots the chance to serve as package commanders and learn how to best employ an integrated large-force package to achieve a tactical objective. However, as the complexity of air operations has increased-with the advent of network-centric warfare, precision-guided munitions, stealth technology, and the integration of special operations, space, and information warfare into the Combat Air Forces-so has the pressure to change Red Flag to include more platforms and expand its training focus. The Air Force now has an historic opportunity to foster a new era of realistic training. More importantly, the expansion of Red Flag-without corresponding improvements in the range, aggressor, and assessment capabilities-will actually decrease the training value of Red Flag. Transforming Red Flag will not come "on the cheap" as did the original Red Flag exercise that simply combined pre-existing Aggressor capabilities and range space. This paper reviews the origins of Red Flag, highlights recent changes in the exercise, and provides recommendations on how to guide the transformation of Red Flag.

Background Adenosine stress magnetic resonance is highly accurate for the detection of myocardial perfusion abnormalities. Visual assessment of inducible wall motion abnormalities (IWMA) during adenosine has low sensitivity but high specificity since only high-grade perfusion defects are associated with detectable IWMAs. The novel technique Feature Tracking (FT) measures myocardial strain and gives detailed information about regional myocardial deformation. The aim of this study was to investigate FT for the detection of myocardial ischemia during adenosine stress.

Background Dobutamine stress magnetic resonance (DSMR) has been established for the detection of coronary artery disease (CAD) due to its high diagnostic accuracy and prognostic value. The novel technique feature tracking (FT) analyses regional myocardial strain and thereby offers detailed information about myocardial deformation. The purpose of this study was to examine how FT based circumferential strain (CS) compares to visually detected wall motion abnormalities (WMA) during DSMR and whether it adds beneficial information for detecting CAD. Methods A total of 25 patients (72% male; mean age 64 ± 8) with suspected or known CAD underwent a standardized high-dose DSMR protocol at 1.5 T. CMR images were acquired at rest and during stress in three short-axis views (SAX; apical, medial, basal). None of the patients had evidence for WMAs or impaired left ventricular function at rest or scar tissue based on late gadolinium enhancement (LGE). For strain analysis the SAX planes were divided into 16 segments (n = 400 segments). All patients underwent x-ray coronary angiography for clinical reasons. Patients without WMA during DSMR and exclusion of CAD by coronary angiography were defined as normal and served as control (10 patients, 160 segments). 15 patients developed WMA during DSMR (34 segments). Additionally, based on angiographic findings, segments that were supplied by a vessel with >75% were defined as stenotic (64 segments). The remaining segments, which did not develop a WMA or were supplied by a vessel

Summary We sought to assess late gadolinium enhancement (LGE) of the coronary artery wall and ascending aorta in patients with Takayasu arteritis (TA) compared to patients with stable CAD. Our findings suggest that LGE of the coronary artery wall can be demonstrated in patients with TA and seems to be similarly pronounced as in CAD patients. The observed coronary LGE seems rather unspecific and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.

8570 Background: Melanoma is increasingly common and currently no cure exists for patients with stage IV disease. There is an urgent need for noval drugs in order to effectively treat this potentia...