Cardiac magnetic resonance imaging characterization of acute rejection in a porcine heterotopic heart transplantation model.

Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.

Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial.

AIMS: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection. METHODS AND RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group. CONCLUSION: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04883528.

Video analysis of ex vivo beating hearts during preservation on the TransMedics® organ care system.

Background: Reliable biomarkers for assessing the viability of the donor hearts undergoing ex vivo perfusion remain elusive. A unique feature of normothermic ex vivo perfusion on the TransMedics® Organ Care System (OCS™) is that the donor heart is maintained in a beating state throughout the preservation period. We applied a video algorithm for an in vivo assessment of cardiac kinematics, video kinematic evaluation (Vi.Ki.E.), to the donor hearts undergoing ex vivo perfusion on the OCS™ to assess the feasibility of applying this algorithm in this setting. Methods: Healthy donor porcine hearts (n = 6) were procured from Yucatan pigs and underwent 2 h of normothermic ex vivo perfusion on the OCS™ device. During the preservation period, serial high-resolution videos were captured at 30 frames per second. Using Vi.Ki.E., we assessed the force, energy, contractility, and trajectory parameters of each heart. Results: There were no significant changes in any of the measured parameters of the heart on the OCS™ device over time as judged by linear regression analysis. Importantly, there were no significant changes in contractility during the duration of the preservation period (time 0-30 min, 918 ± 430 px/s; time 31-60 min, 1,386 ± 603 px/s; time 61-90 min, 1,299 ± 617 px/s; time 91-120 min, 1,535 ± 728 px/s). Similarly, there were no significant changes in the force, energy, or trajectory parameters. Post-transplantation echocardiograms demonstrated robust contractility of each allograft. Conclusion: Vi.Ki.E. assessment of the donor hearts undergoing ex vivo perfusion is feasible on the TransMedics OCS™, and we observed that the donor hearts maintain steady kinematic measurements throughout the duration.

Reference values of myocardial native T1 and extracellular volume in patients without structural heart disease and had negative 3T cardiac magnetic resonance adenosine stress test.

Background: To establish the reference values of native T1 and extracellular volume (ECV) in patients without structural heart disease and had a negative adenosine stress 3T cardiac magnetic resonance. Methods: Short-axis T1 mapping images were acquired using a modified Look-Locker inversion recovery technique before and after administration of 0.15 mmol/kg gadobutrol to calculate both native T1 and ECV. To compare the agreement between measurement strategies, regions of interest (ROI) were drawn in all 16 segments then averaged to represent mean global native T1. Additionally, an ROI was drawn in the mid-ventricular septum on the same image to represent the mid-ventricular septal native T1. Results: Fifty-one patients (mean 65 years, 65 % women) were included. Mean global native T1 averaged from all 16 segments and a mid-ventricular septal native T1 were not significantly different (1221.2 ± 35.2 vs 1228.4 ± 43.7 ms, p = 0.21). Men had lower mean global native T1 (1195 ± 29.8 vs 1235.5 ± 29.4 ms, p < 0.001) than women. Both mean global and mid-ventricular septal native T1 were not correlated with age (r = 0.21, p = 0.13 and r = 0.18, p = 0.19, respectively). The calculated ECV was 26.6 ± 2.7 %, which was not influenced by either gender or age. Conclusions: We report the first study to validate the native T1 and ECV reference ranges, factors influencing T1, and the validation across measurement methods in older Asian patients without structural heart disease and had a negative adenosine stress test. These references allow for better detection of abnormal myocardial tissue characteristics in clinical practice.

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) isolated from zebrafish can direct targeted, injury-associated gene expression from viral DNA vectors delivered systemically in small and large adult mammalian species. When employed in combination with CRISPR-based epigenome editing tools in mice, zebrafish TREEs stimulated or repressed the expression of endogenous genes after ischemic myocardial infarction. Intravenously delivered recombinant AAV vectors designed with a TREE to direct a constitutively active YAP factor boosted indicators of cardiac regeneration in mice and improved the function of the injured heart. Our findings establish the application of contextual enhancer elements as a potential therapeutic platform for spatiotemporally controlled tissue regeneration in mammals.

Native T1 Mapping for the Diagnosis of Myocardial Fibrosis in Patients With Chronic Myocardial Infarction.

BACKGROUND: Myocardial fibrosis is a fundamental process in cardiac injury. Cardiac magnetic resonance native T1 mapping has been proposed for diagnosing myocardial fibrosis without the need for gadolinium contrast. However, recent studies suggest that T1 measurements can be erroneous in the presence of intramyocardial fat. OBJECTIVES: The purpose of this study was to investigate whether the presence of fatty metaplasia affects the accuracy of native T1 maps for the diagnosis of myocardial replacement fibrosis in patients with chronic myocardial infarction (MI). METHODS: Consecutive patients (n = 312) with documented chronic MI (>6 months old) and controls without MI (n = 50) were prospectively enrolled. Presence and size of regions with elevated native T1 and infarction were quantitatively determined (mean + 5SD) on modified look-locker inversion-recovery and delayed-enhancement images, respectively, at 3.0-T. The presence of fatty metaplasia was determined using an out-of-phase steady-state free-precession cine technique and further verified with standard fat-water Dixon methods. RESULTS: Native T1 mapping detected chronic MI with markedly higher sensitivity in patients with fatty metaplasia than those without fatty metaplasia (85.6% vs 13.3%) with similar specificity (100% vs 98.9%). In patients with fatty metaplasia, the size of regions with elevated T1 significantly underestimated infarct size and there was a better correlation with fatty metaplasia size than infarct size (r = 0.76 vs r = 0.49). In patients without fatty metaplasia, most of the modest elevation in T1 appeared to be secondary to subchronic infarcts that were 6 to 12 months old; the T1 of infarcts >12 months old was not different from noninfarcted myocardium. CONCLUSIONS: Native T1 mapping is poor at detecting replacement fibrosis but may indirectly detect chronic MI if there is associated fatty metaplasia. Native T1 mapping for the diagnosis and characterization of myocardial fibrosis is unreliable.

Assessment of Papillary Muscle Infarction with Dark-Blood Delayed Enhancement Cardiac MRI in Canines and Humans.

Background The relationship between papillary muscle infarction (papMI) and the culprit coronary lesion has not been fully investigated. Delayed enhancement cardiac MRI may detect papMI, yet its accuracy is unknown. Flow-independent dark-blood delayed enhancement (FIDDLE) cardiac MRI has been shown to improve the detection of myocardial infarction adjacent to blood pool. Purpose To assess the diagnostic performance of delayed enhancement and FIDDLE cardiac MRI for the detection of papMI, and to investigate the prevalence of papMI and its relationship to the location of the culprit coronary lesion. Materials and Methods A prospective canine study was used to determine the accuracy of conventional delayed enhancement imaging and FIDDLE imaging for detection of papMI, with pathology-based findings as the reference standard. Participants with first-time myocardial infarction with a clear culprit lesion at coronary angiography were prospectively enrolled at a single hospital from 2015 to 2018 and compared against control participants with low Framingham risk scores. In canines, diagnostic accuracy was calculated for delayed enhancement and FIDDLE imaging. Results In canines (n = 27), FIDDLE imaging was more sensitive (100% [23 of 23] vs 57% [13 of 23], P < .001) and accurate (100% [54 of 54] vs 80% [43 of 54], P = .01) than delayed enhancement imaging for detection of papMI. In 43 participants with myocardial infarction (mean age, 56 years ± 16 [SD]; 28 men), the infarct-related artery was the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery in 47% (20 of 43), 26% (11 of 43), and 28% (12 of 43), respectively. The prevalence of anterior papMI was lower than posterior papMI (37% [16 of 43 participants] vs 44% [19 of 43 participants]) despite more LAD culprit lesions. Culprits leading to papMI were restricted to a smaller "at-risk" portion of the coronary tree for anterior papMI (subtended first diagonal branch of the LAD or first marginal branch of the LCX) compared with posterior (subtended posterior descending artery or third obtuse marginal branch of the LCX). Culprits within these at-risk portions were predictive of papMI at a similar rate (anterior, 83% [15 of 18 participants] vs posterior, 86% [18 of 21 participants]). Conclusion Flow-independent dark-blood delayed enhancement cardiac MRI, unlike conventional delayed enhancement cardiac MRI, was highly accurate in the detection of papillary muscle infarction (papMI). Anterior papMI was less prevalent than posterior papMI, most likely due to culprit lesions being restricted to a smaller portion of the coronary tree rather than because of redundant, dual vascular supply. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Assessment of myocardial lipomatous metaplasia using an optimized out-of-phase cine steady-state free-precession sequence: Validation and clinical implementation.

Myocardial lipomatous metaplasia, which can serve as substrate for ventricular arrhythmias, is usually composed of regions in which there is an admixture of fat and nonfat tissue. Although dedicated sequences for the detection of fat are available, it would be time-consuming and burdensome to routinely use these techniques to image the entire heart of all patients as part of a typical cardiac MRI exam. Conventional steady-state free-precession (SSFP) cine imaging is insensitive to detecting myocardial regions with partial fatty infiltration. We developed an optimization process for SSFP imaging to set fat signal consistently "out-of-phase" with water throughout the heart, so that intramyocardial regions with partial volume fat would be detected as paradoxically dark regions. The optimized SSFP sequence was evaluated using a fat phantom, through simulations, and in 50 consecutive patients undergoing clinical cardiac MRI. Findings were validated using standard Dixon gradient-recalled-echo (GRE) imaging as the reference. Phantom studies of test tubes with diverse fat concentrations demonstrated good agreement between measured signal intensity and simulated values calculated using Bloch equations. In patients, a line of signal cancellation at the interface between myocardium and epicardial fat was noted in all cases, confirming that SSFP images were consistently out-of-phase throughout the entire heart. Intramyocardial dark regions identified on out-of-phase SSFP images were entirely dark throughout in 33 patients (66%) and displayed an India-ink pattern in 17 (34%). In all cases, dark intramyocardial regions were also seen in the same locations on out-of-phase GRE and were absent on in-phase GRE, confirming that these regions represent areas with partial fat. In conclusion, if appropriately optimized, SSFP cine imaging allows for consistent detection of myocardial fatty metaplasia in patients undergoing routine clinical cardiac MRI without the need for additional image acquisitions using dedicated fat-specific sequences.

Targeted Delivery for Cardiac Regeneration: Comparison of Intra-coronary Infusion and Intra-myocardial Injection in Porcine Hearts.

BACKGROUND: The optimal delivery route to enhance effectiveness of regenerative therapeutics to the human heart is poorly understood. Direct intra-myocardial (IM) injection is the gold standard, however, it is relatively invasive. We thus compared targeted IM against less invasive, catheter-based intra-coronary (IC) delivery to porcine myocardium for the acute retention of nanoparticles using cardiac magnetic resonance (CMR) imaging and viral vector transduction using qPCR. METHODS: Ferumoxytol iron oxide (IO) nanoparticles (5 ml) were administered to Yorkshire swine (n = 13) by: (1) IM via thoracotomy, (2) catheter-based IC balloon-occlusion (BO) with infusion into the distal left anterior descending (LAD) coronary artery, (3) IC perforated side-wall (SW) infusion into the LAD, or (4) non-selective IC via left main (LM) coronary artery infusion. Hearts were harvested and imaged using at 3T whole-body MRI scanner. In separate Yorkshire swine (n = 13), an adeno-associated virus (AAV) vector was similarly delivered, tissue harvested 4-6 weeks later, and viral DNA quantified from predefined areas at risk (apical LV/RV) vs. not at risk in a potential mid-LAD infarct model. Results were analyzed using pairwise Student's t-test. RESULTS: IM delivery yielded the highest IO retention (16.0 ± 4.6% of left ventricular volume). Of the IC approaches, BO showed the highest IO retention (8.7 ± 2.2% vs. SW = 5.5 ± 4.9% and LM = 0%) and yielded consistent uptake in the porcine distal LAD territory, including the apical septum, LV, and RV. IM delivery was limited to the apex and anterior wall, without septal retention. For the AAV delivery, the BO was most efficient in the at risk territory (Risk: BO = 6.0 × 10-9, IM = 1.4 × 10-9, LM = 3.2 × 10-10 viral copies per µg genomic DNA) while all delivery routes were comparable in the non-risk territory (BO = 1.7 × 10-9, IM = 8.9 × 10-10, LM = 1.2 × 10-9). CONCLUSIONS: Direct IM injection has the highest local retention, while IC delivery with balloon occlusion and distal infusion is the most effective IC delivery technique to target therapeutics to a heart territory most in risk from an infarct.

Double spectral attenuated inversion recovery (DSPAIR)-an efficient fat suppression technique for late gadolinium enhancement at 3 tesla.

Despite clinical use of late gadolinium enhancement (LGE) for two decades, an efficient, robust fat suppression (FS) technique still does not exist for this CMR mainstay. In ischemic and non-ischemic heart disease, differentiating fibrotic tissue from infiltrating and adjacent fat is crucial. Multiple groups have independently developed an FS technique for LGE, double spectral attenuated inversion recovery (DSPAIR), but no comprehensive evaluation was performed. This study aims to fill this gap. DSPAIR uses two SPAIR pulses and one non-selective IR pulse to enable FS LGE, including compatibility with phase sensitive inversion recovery (PSIR). We implemented a magnitude (MAGN) and a PSIR variant and compared them with LGE without FS (CONTROL) and with spectral presaturation with inversion recovery (SPIR) in simulations, phantoms, and patients. Fat magnetization by SPIR, MAGN DSPAIR, and PSIR DSPAIR was simulated as a function of pulse B1 , readout (RO) pulse number, and fat TI . A phantom with fat, fibrosis, and myocardium compartments was imaged using all FS methods and modifying pulse B1 , RO pulse number, and heart rate. Signal was measured in SNR units. Fat, myocardium, and fibrosis SNR and fibrosis-to-fat CNR were obtained. Patient images were acquired with all FS techniques. Fat, myocardium, and fibrosis SNR, fibrosis-to-fat CNR, and image and FS quality were assessed. In the phantom, both DSPAIR variants provided superior FS compared with SPIR, independent of heart rate and RO pulse number. MAGN DSPAIR reduced fat signal by 99% compared with CONTROL, PSIR DSPAIR by 116%, and SPIR by 67% (25 RO pulses). In patients, both DSPAIR variants substantially reduced fat signal (MAGN DSPAIR by 87.1% ± 10.0%, PSIR DSPAIR by 130.5% ± 36.3%), but SPIR did not (35.8% ± 25.5%). FS quality was good to excellent for MAGN and PSIR DSPAIR, and moderate to poor for SPIR. DSPAIR provided highly effective FS across a wide range of parameters. PSIR DSPAIR performed best.

Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination.

Importance: Vaccine-associated myocarditis is an unusual entity that has been described for the smallpox vaccine, but only anecdotal case reports have been described for other vaccines. Whether COVID-19 vaccination may be linked to the occurrence of myocarditis is unknown. Objective: To describe a group of 7 patients with acute myocarditis over 3 months, 4 of whom had recent messenger RNA (mRNA) COVID-19 vaccination. Design, Setting, and Participants: All patients referred for cardiovascular magnetic resonance imaging at Duke University Medical Center were asked to participate in a prospective outcomes registry. Two searches of the registry database were performed: first, to identify patients with acute myocarditis for the 3-month period between February 1 and April 30 for 2017 through 2021, and second, to identify all patients with possible vaccine-associated myocarditis for the past 20 years. Once patients with possible vaccine-associated myocarditis were identified, data available in the registry were supplemented by additional data collection from the electronic health record and a telephone interview. Exposures: mRNA COVID-19 vaccine. Main Outcomes and Measures: Occurrence of acute myocarditis by cardiovascular magnetic resonance imaging. Results: In the 3-month period between February 1 and April 30, 2021, 7 patients with acute myocarditis were identified, of which 4 occurred within 5 days of COVID-19 vaccination. Three were younger male individuals (age, 23-36 years) and 1 was a 70-year-old female individual. All 4 had received the second dose of an mRNA vaccine (2 received mRNA-1273 [Moderna], and 2 received BNT162b2 [Pfizer]). All presented with severe chest pain, had biomarker evidence of myocardial injury, and were hospitalized. Coincident testing for COVID-19 and respiratory viruses provided no alternative explanation. Cardiac magnetic resonance imaging findings were typical for myocarditis, including regional dysfunction, late gadolinium enhancement, and elevated native T1 and T2. Conclusions and Relevance: In this study, magnetic resonance imaging findings were found to be consistent with acute myocarditis in 7 patients; 4 of whom had preceding COVID-19 vaccination. Further investigation is needed to determine associations of COVID-19 vaccination and myocarditis.

A short form of the Recovery Assessment Scale-Domains and Stages: Development and validation among adults with anxiety disorders.

The Recovery Assessment Scale-Domains and Stages (RAS-DS) is a 38-item self-report instrument measuring recovery from serious mental illness. We explored the suitability of the RAS-DS for individuals with anxiety disorders. A parsimonious short form of the scale was developed. Participants with anxiety disorder symptoms (N = 295) completed the RAS-DS, DASS-21 and GAD-7. Confirmatory factor analysis supported the expected four-factor structure. Associations with related scales exhibited the expected pattern supporting construct validity in this population. The Recovery Assessment Scale-Short Form (RAS-SF) was derived by inspection of factor loadings and modification indices, yielding a 20-item scale with five items per subscale. Strong correlations between subscales confirmed the total score represented a valid overarching measure of recovery. The present study indicates that recovery is pertinent to individuals with anxiety disorders. Development of the short-form RAS-SF affords opportunity for routine measurement of recovery in populations with anxiety and other high prevalence conditions.

ECG-gated MR angiography provides better reproducibility for standard aortic measurements.

OBJECTIVE: Cardiac motion and aortic pulsatility can affect the image quality of 3D contrast-enhanced MR angiography (CE-MRA). The addition of ECG gating improves image quality; however, no studies have directly linked image quality improvements to clinically used measures. In this study, we directly compared diameter measurements in the same patient from ECG-gated to non-gated CE-MRA to evaluate the impact of ECG gating upon measurement reproducibility. METHODS: Fifty-three patients, referred for thoracic aortic angiography, were enrolled and underwent both non-gated and ECG-gated CE-MRA. Two readers independently measured vessel diameter, image quality, and vessel sharpness at the sinus of Valsalva (SOV), sinotubular junction (STJX), ascending aorta (AAO), distal aortic arch (DLSA), and descending aorta (DAO). Measurement reliability and reproducibility were compared between methods. RESULTS: Image quality with ECG gating was rated significantly higher at the SOV (3.2 ± 0.9 vs 1.2 ± 1.0, p < 0.0001), STJX (3.4 ± 0.7 vs 1.8 ± 1.0, p < 0.0001), AAO (3.5 ± 0.6 vs 1.7 ± 1.1 p < 0.0001), DLSA (4.0 ± 0.1 vs 3.6 ± 0.7, p = 0.006), and DAO (4.0 ± 0.1 vs 3.4 ± 0.9 p < 0.0001) than for non-gated studies. Bland-Altman analyses demonstrated that inter- and intra-observer variability was significantly smaller for ECG-gated MRA at the SOV and AAO. For the non-gated images at the SOV, the 95% limits of agreement for both inter- and intra-observer variability exceeded the growth-rate cutoff for surgical repair (0.5 cm). At the DAO, variability was similar between the two techniques. CONCLUSION: ECG-gated CE-MRA resulted in improved reproducibility in aortic root and ascending aortic measurements. These data suggest that ECG-gated CE-MRA should be used for the serial assessment of the ascending thoracic aorta. KEY POINTS: • ECG-gated CE-MRA improves the reproducibility and repeatability of measurements of the ascending aorta. • With non-gated CE-MRA, pulsatile motion in the proximal aorta results in significant variability in measurement reproducibility.

Comparison of magnetization transfer-preparation and T2-preparation for dark-blood delayed-enhancement imaging.

Recently developed dark-blood techniques such as Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE) allow simultaneous visualization of tissue contrast-enhancement and blood-pool suppression. Critical to FIDDLE is the magnetization preparation, which accentuates differences between myocardium and blood-pool. Here, we compared magnetization transfer (MT)-preparation and T2-preparation for use with FIDDLE. Variants of FIDDLE were developed with MT- or T2-preparation modules and tested in 35 patients (11 at 1.5 T, 24 at 3 T). Images were acquired with each FIDDLE variant in an interleaved fashion 10 minutes after gadolinium administration with otherwise identical acquisition parameters. Images were visually and quantitatively assessed for artifacts and differences in right ventricle to left ventricle (RV-to-LV) blood-pool suppression. Bright artifacts, reflecting incomplete blood-pool suppression, were frequently observed in the left atrium with T2-preparation FIDDLE at 1.5 and 3 T (82% and up to 100% of patients, respectively). MT-preparation FIDDLE resulted in fewer patients with artifacts (0% at 1.5 T, 22% at 3 T; P < .01). Left atrial blood-pool signal was significantly more homogeneous with MT-preparation than with T2-preparation at 1.5 and 3 T (P < .001 for all comparisons). Visibly different RV-to-LV blood-pool suppression was observed with T2-preparation in 36% of patients at 1.5 T and up to 94% at 3 T. In these patients, RV blood-pool signal was elevated, reducing the conspicuity of the myocardial-RV blood-pool border. Conversely, there were no visible differences in RV-to-LV blood-pool suppression with MT-preparation. Quantitative assessment of differences in blood-pool suppression and blood-pool artifacts was consistent with visual analyses. We conclude that for dark blood-blood delayed-enhancement imaging of the heart, MT-preparation results in fewer bright blood-pool artifacts and more uniform blood-pool suppression than T2-preparation.

Effectiveness of biosurfactant for the removal of trihalomethanes by biotrickling filter.

In this study, the biodegradation of a mixture of two trihalomethane (THM) compounds, chloroform (CF) and dichlorobromomethane (DCBM), was evaluated using two laboratory-scale biotrickling filters (BTFs). The two BTFs, hereby designated as "BTF-A" and "BTF-B," were run parallel and used ethanol as co-metabolite at different loading rates (LRs), and a lipopeptide-type biosurfactant that was generated by the gram-positive bacteria, Surfactin, respectively. The results using BTF-A showed that adding ethanol at a higher rate of 4.59 g/(m3 h) resulted in removal efficiencies of 85% and 87% for CF and DCBM, respectively. Conversely, for the same LR, the use of Surfactin without ethanol (BTF-B) showed comparable removal efficiencies of 85% and 80% for CF and DCBM, respectively. The maximum rate constant for CF and DCBM for the BTF-A was 0.00203 s-1 and 0.0022 s-1, respectively. For the same THMs LR, similar reaction rate constants resulted for the BTF-B. Further studies were conducted to investigate and understand the microbial diversity within both BTFs. The result indicated that for BTF with co-metabolite, Fusarium sp. was the most dominant fungi over 98% followed by F. Solani with less than 2%. F. oxysporum and Fusarium sp. were instead the dominant fungi for the BTF with Surfactin. Before introducing the Surfactin into the BTF, the batch experiment was conducted to evaluate the effectiveness of synthetic surfactant as compared to a biosurfactant (Surfactin). In this regard, vials with Surfactin showed better performance than vials with Tomadol 25-7 (synthetic surfactant).

Solar photo-Fenton treatment of microcystin-LR in aqueous environment: Transformation products and toxicity in different water matrices.

Transformation products and toxicity patterns of microcystin-LR (MC-LR), a common cyanotoxin in freshwaters, during degradation by solar photo-Fenton process were studied in the absence and presence of two major water components, namely fulvic acid and alkalinity. The transformation products m/z 795, 835, 515/1030 and 532 can be formed through attack of OH on the conjugated carbon double bonds of Adda. Transformation products with m/z 1010, 966 and 513 can be generated through the attack of OH on the methoxy group of Adda. The transformation products m/z 783, 508 and 1012 can be originated from the attack of OH on the cyclic structure of MC-LR. Transformation products (m/z 522, 1028, 1012, 1046 and 514) formed after hydroxylation of the aromatic ring with OH were also identified in this study. The toxicity study revealed that fulvic acid and alkalinity strongly influence the toxicity profiles of solar photo-Fenton treated MC-LR. Fulvic acid enhanced the detoxification whereas low level total alkalinity (1.8 mg L-1 CaCO3) inhibited the detoxification of MC-LR by solar photo-Fenton process as assessed by protein phosphatase-1 (PP-1) inhibition assay. This work provides insights on the utility of solar photo-Fenton destruction of MC-LR in water based on transformation products and toxicity data.

Dark-Blood Delayed Enhancement Cardiac Magnetic Resonance of Myocardial Infarction.

OBJECTIVES: This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal. BACKGROUND: The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible. METHODS: A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31). RESULTS: In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p < 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03). CONCLUSIONS: The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI.

Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.

BACKGROUND: Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. MATERIALS AND METHODS: Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. RESULTS: LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. CONCLUSIONS: The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective.