Deep image prior cine MR fingerprinting with B1 + spin history correction.

PURPOSE: To develop a deep image prior (DIP) reconstruction for B1 + -corrected 2D cine MR fingerprinting (MRF). METHODS: The proposed method combines low-rank (LR) modeling with a DIP to generate cardiac phase-resolved parameter maps without motion correction, employing self-supervised training to enforce consistency with undersampled spiral k-space data. Two implementations were tested: one approach (DIP) for cine T1 , T2 , and M0 mapping, and a second approach (DIP with effective B1 + estimation [DIP-B1]) that also generated an effective B1 + map to correct for errors due to RF transmit inhomogeneities, through-plane motion, and blood flow. Cine MRF data were acquired in 14 healthy subjects and four reconstructions were compared: LR, low-rank motion-corrected (LRMC), DIP, and DIP-B1. Results were compared to diastolic ECG-triggered MRF, MOLLI, and T2 -prep bSSFP. Additionally, bright-blood and dark-blood images calculated from cine MRF maps were used to quantify ventricular function and compared to reference cine measurements. RESULTS: DIP and DIP-B1 outperformed other cine MRF reconstructions with improved noise suppression and delineation of high-resolution details. Within-segment variability in the myocardium (reported as the coefficient of variation for T1 /T2 ) was lowest for DIP-B1 (2.3/8.3%) followed by DIP (2.7/8.7%), LRMC (3.5/10.5%), and LR (15.3/39.6%). Spatial homogeneity improved with DIP-B1 having the lowest intersegment variability (2.6/4.1%). The mean bias in ejection fraction was -1.1% compared to reference cine scans. CONCLUSION: A DIP reconstruction for 2D cine MRF enabled cardiac phase-resolved mapping of T1 , T2 , M0 , and the effective B1 + with improved noise suppression and precision compared to LR and LRMC.

Synthetic multi-contrast late gadolinium enhancement imaging using post-contrast magnetic resonance fingerprinting.

Late gadolinium enhancement (LGE) MRI is the non-invasive reference standard for identifying myocardial scar and fibrosis but has limitations, including difficulty delineating subendocardial scar and operator dependence on image quality. The purpose of this work is to assess the feasibility of generating multi-contrast synthetic LGE images from post-contrast T1 and T2 maps acquired using magnetic resonance fingerprinting (MRF). Fifteen consecutive patients with a history of prior ischemic cardiomyopathy (12 men; mean age 63  ±  13 years) were prospectively scanned at 1.5 T between Oct 2020 and May 2021 using conventional LGE and MRF after injection of gadolinium contrast. Three classes of synthetic LGE images were derived from MRF post-contrast T1 and T2 maps: bright-blood phase-sensitive inversion recovery (PSIR), black- and gray-blood T2 -prepared PSIR (T2 -PSIR), and a novel "tissue-optimized" image to enhance differentiation among scar, viable myocardium, and blood. Image quality was assessed on a 1-5 Likert scale by two cardiologists, and contrast was quantified as the mean absolute difference (MAD) in pixel intensities between two tissues, with different methods compared using Kruskal-Wallis with Bonferroni post hoc tests. Per-patient and per-segment scar detection rates were evaluated using conventional LGE images as reference. Image quality scores were highest for synthetic PSIR (4.0) and reference images (3.8), followed by synthetic tissue-optimized (3.3), gray-blood T2 -PSIR (3.0), and black-blood T2 -PSIR (2.6). Among synthetic images, PSIR yielded the highest myocardium/scar contrast (MAD = 0.42) but the lowest blood/scar contrast (MAD = 0.05), and vice versa for T2 -PSIR, while tissue-optimized images achieved a balance among all tissues (myocardium/scar MAD = 0.16, blood/scar MAD = 0.26, myocardium/blood MAD = 0.10). Based on reference mid-ventricular LGE scans, 13/15 patients had myocardial scar. The per-patient sensitivity/accuracy for synthetic images were the following: PSIR, 85/87%; black-blood T2 -PSIR, 62/53%; gray-blood T2 -PSIR, 100/93%; tissue optimized, 100/93%. Synthetic multi-contrast LGE images can be generated from post-contrast MRF data without additional scan time, with initial feasibility shown in ischemic cardiomyopathy patients.

Midterm follow-up after computed tomography angiography planned left atrial appendage closure.

BACKGROUND: While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™ legacy and FLX devices, there has been no reported long-term data for this approach. OBJECTIVES: We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device. METHODS: A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively. RESULTS: From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively. CONCLUSIONS: CTA-based preprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years.

Incidence, progression, and predictors of left atrial appendage sealing after Watchman FLX device implantation with computed tomographic assessment.

BACKGROUND: Limited data exists regarding incidence, progression, and predictors of left atrial appendage (LAA) sealing after transcatheter LAA closure. We aimed to evaluate the incidence, progression, and predictive factors associated with LAA sealing after LAA closure. METHODS: This study includes patients who underwent successful LAA closure with Watchman FLX device and had both pre- and postprocedural computed tomography (CT). Postprocedural CT was performed 45 days after LAA closure and used to evaluate residual LAA patency. Patient who had residual LAA patency at 45 days underwent 1-year follow-up CT. RESULTS: A total of 105 patients (mean age: 75.2 ± 9.6 years; 53.3% female) who underwent successful LAA closure with Watchman FLX device and had pre- and postprocedural CT at 45 days were included. Residual patency was observed in 35 (33.3%) patients: 21 (20.0%) patients showed complete contrast opacification in LAA (complete LAA patency) while 14 (13.3%) patients showed contrast opacification only in the distal LAA (distal LAA patency). Among patients with residual LAA patency at 45 days, the rate of LAA sealing at 1 year was significantly higher in the distal LAA patency group than in the complete LAA patency group (75.0% vs. 16.7%; p = 0.019). Increased depth oversizing was associated with both distal LAA patency and complete LAA patency. CONCLUSION: Postprocedural CT at 45 days detected patent LAA in one-third of patients after LAA closure. LAA sealing was more frequently observed at 1 year among the distal LAA patency group than the complete LAA patency group.

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. AIMS: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. METHODS: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. RESULTS: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). CONCLUSION: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

Efficacy of 3D-multidetector computed tomography and fluoroscopy fusion for percutaneous left atrial appendage occlusion procedures.

INTRODUCTION: We studied the impact of the use of three-dimensional multidetector computed tomography (3D-MDCT) and fluoroscopy fusion on percutaneous left atrial appendage occlusion (LAAO) procedures in relation to procedure time, contrast volume, fluoroscopy time, and total radiation. METHODS: This was a single-center, prospective, single-blinded, randomized control trial. Patients meeting criteria for LAAO were randomized to undergo LAAO with the WATCHMAN FLXTM device with and without 3D-MDCT-fluoroscopy fusion guidance using a prespecified protocol using computed tomography angiography for WATCHMAN FLXTM sizing, moderate sedation, and intracardiac echocardiography for procedural guidance. RESULTS: Overall, 59 participants were randomly assigned to the fusion (n = 33) or no fusion (n = 26) groups. The median (interquartile range) age was 79 (75-83) years, 24 (41%) were female, and 55 (93%) were Caucasian. The median CHA2 DS2 VASc and HASBLED scores were 5 (4-6) and 3 (3-4), respectively. At the time of the study, 51 (53%) patients were on a direct acting oral anticoagulant. There were no significant differences between the fusion and no fusion groups in procedure time (52.4 ± 15.4 vs. 56.8 ± 19.5 min, p = .36), mean contrast volume used (33.8 ± 12.0 vs. 29.6 ± 11.5 mls, p = .19), mean fluoroscopy time (31.3 ± 9.9 vs. 28.9 ± 8.7 min, p = .32), mean radiation dose (1177 ± 969 vs. 1091 ± 692 mGy, p = .70), and radiation dose product curve (23.9 ± 20.5 vs. 35.0 ± 49.1 Gy cm2 , p = .29). There was no periprosthetic leak in the two groups in the immediate 1-month postprocedure follow-up periods. CONCLUSIONS: There was no significant difference with and without 3D-MDCT-fluoroscopy fusion in procedure time, contrast volume use, radiation dose, and radiation dose product.

Cardiac MR Fingerprinting: Overview, Technical Developments, and Applications.

Cardiovascular magnetic resonance (CMR) is an established imaging modality with proven utility in assessing cardiovascular diseases. The ability of CMR to characterize myocardial tissue using T1 - and T2 -weighted imaging, parametric mapping, and late gadolinium enhancement has allowed for the non-invasive identification of specific pathologies not previously possible with modalities like echocardiography. However, CMR examinations are lengthy and technically complex, requiring multiple pulse sequences and different anatomical planes to comprehensively assess myocardial structure, function, and tissue composition. To increase the overall impact of this modality, there is a need to simplify and shorten CMR exams to improve access and efficiency, while also providing reproducible quantitative measurements. Multiparametric MRI techniques that measure multiple tissue properties offer one potential solution to this problem. This review provides an in-depth look at one such multiparametric approach, cardiac magnetic resonance fingerprinting (MRF). The article is structured as follows. First, a brief review of single-parametric and (non-Fingerprinting) multiparametric CMR mapping techniques is presented. Second, a general overview of cardiac MRF is provided covering pulse sequence implementation, dictionary generation, fast k-space sampling methods, and pattern recognition. Third, recent technical advances in cardiac MRF are covered spanning a variety of topics, including simultaneous multislice and 3D sampling, motion correction algorithms, cine MRF, synthetic multicontrast imaging, extensions to measure additional clinically important tissue properties (proton density fat fraction, T2 *, and T1ρ ), and deep learning methods for image reconstruction and parameter estimation. The last section will discuss potential clinical applications, concluding with a perspective on how multiparametric techniques like MRF may enable streamlined CMR protocols. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Magnetization Transfer BOOST Noncontrast Angiography Improves Pulmonary Vein Imaging in Adults With Congenital Heart Disease.

BACKGROUND: Cardiac MRI plays an important role in the diagnosis and follow-up of patients with congenital heart disease (CHD). Gadolinium-based contrast agents are often needed to overcome flow-related and off-resonance artifacts that can impair the quality of conventional noncontrast 3D imaging. As serial imaging is often required in CHD, the development of robust noncontrast 3D MRI techniques is desirable. PURPOSE: To assess the clinical utility of noncontrast enhanced magnetization transfer and inversion recovery prepared 3D free-breathing sequence (MTC-BOOST) compared to conventional 3D whole heart imaging in patients with CHD. STUDY TYPE: Prospective, image quality. POPULATION: A total of 27 adult patients (44% female, mean age 30.9 ± 14.8 years) with CHD. FIELD STRENGTH/SEQUENCE: A 1.5 T; free-breathing 3D MTC-BOOST sequence. ASSESSMENT: MTC-BOOST was compared to diaphragmatic navigator-gated, noncontrast T2 prepared 3D whole-heart imaging sequence (T2prep-3DWH) for comparison of vessel dimensions, lumen-to-myocardium contrast ratio (CR), and image quality (vessel wall sharpness and presence and type of artifacts) assessed by two experienced cardiologists on a 5-point scale. STATISTICAL TESTS: Mann-Whitney test, paired Wilcoxon signed-rank test, Bland-Altman plots. P < 0.05 was considered statistically significant. RESULTS: MTC-BOOST significantly improved image quality and CR of the right-sided pulmonary veins (PV): (CR: right upper PV 1.06 ± 0.50 vs. 0.58 ± 0.74; right lower PV 1.32 ± 0.38 vs. 0.81 ± 0.73) compared to conventional T2prep-3DWH imaging where the PVs were not visualized in some cases due to off-resonance effects. MTC-BOOST demonstrated resistance to degradation of luminal signal (assessed by CR) secondary to accelerated or turbulent flow conditions. T2prep-3DWH had higher image quality scores than MTC-BOOST for the aorta and coronary arteries; however, great vessel dimensions derived from MTC-BOOST showed excellent agreement with standard T2prep-3DWH imaging. DATA CONCLUSION: MTC-BOOST allows for improved contrast-free imaging of pulmonary veins and regions characterized by accelerated or turbulent blood flow compared to standard T2prep-3DWH imaging, with excellent agreement of great vessel dimensions. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

DOCUMENTATION OF TRYPANOSOMA EVANSI IN CAPTIVE TIGERS AND LIONS IN PUNJAB (2016-2018), PAKISTAN.

Trypanosoma evansi is an important hemoparasite of a variety of animal species worldwide. This parasite is a threat to the health of domestic animals as well as wild animals, particularly those managed in captivity. The current study investigated the presence of T. evansi in captive tigers (Panthera tigris tigris) and lions (Panthera leo) in Pakistan. In total, 24 blood samples from 11 tigers and 3 lions (n = 14) were collected during the course of roughly 3 yr (2016-2018). Eighteen samples were subjected to both microscopic and molecular evaluation for the presence of T. evansi; the remaining 6 samples were processed for PCR only. Of the 18 samples tested by both methods, 3 (16%) and 8 (44%) were positive by microscopy and PCR, respectively. This highlights the higher sensitivity of PCR over microscopy for detection of trypanosomes. Of the 24 total samples evaluated by PCR, 12 (50%) were positive. The three sequences obtained showed 99% identity with variant surface glycoprotein genes of the different isolates of T. evansi. The sensitivity, specificity, positive predictive value, and negative predictive value of microscopy in identifying T. evansi was 37.5, 100, 100, and 66.7%, respectively, considering PCR as the gold standard. We recommend rigorous monitoring of captive tigers and lions for hemoparasites, particularly in winter and early spring in areas with high infection rate of this parasite, preferably via PCR.

Novel computed tomography angiography-based sizing methodology for WATCHMAN FLX device in left atrial appendage closure.

BACKGROUND: While there is recent data suggesting an advantage of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) for preprocedural left atrial appendage closure (LAAC) planning, there is limited published experience for sizing strategies. Device sizing for LAAC may be challenging and noninvasive algorithms that improve this selection process are warranted. OBJECTIVES: We sought to evaluate the safety and the feasibility for the implementation of a novel CTA-based sizing methodology for WATCHMAN™ FLX device in a series of patients undergoing LAAC using the TruPlan™ software package. METHODS: A prospective analysis of 136 consecutive patients who underwent LAAC over a 12-month period in a single, large academic hospital in the United States was conducted. CTA-guided preprocedural planning and intracardiac echocardiography (ICE) was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. RESULTS: A total of 136 patients who underwent LAAC procedure with WATCHMAN™ FLX platform between October 1, 2020 until September 30, 2021 were included. The pre-specified protocol using CTA and ICE was implemented in all patients (100%). Mean CHA2 DS2 VASc score was 4.4 ± 1.3 and the mean HAS-BLED score was 3.9 ± 0.8. ICE-guided 100% transseptal puncture success rate was 100% with 98.5% of overall procedural success rate. Preprocedural CTA sizing strategy accurately predicted the implanted size in 91.1% of patients. Ten patients (7.4%) required another sized device and 2 cases were aborted. At 45-day follow-up, only 1 patient (0.7%) had significant peri-device leak (≥5 mm) on TEE. CONCLUSIONS: CTA-based preprocedural sizing methodology for WATCHMAN™ FLX in LAAC was safe, feasible and associated with excellent procedural outcomes. Further studies are warranted to confirm if the features specific to TruPlan™ may reduce the number of deployment attempts, the number of devices utilized in the procedure, and the risk of complications.

Quantitative magnetization transfer imaging for non-contrast enhanced detection of myocardial fibrosis.

PURPOSE: To develop a novel gadolinium-free model-based quantitative magnetization transfer (qMT) technique to assess macromolecular changes associated with myocardial fibrosis. METHODS: The proposed sequence consists of a two-dimensional breath-held dual shot interleaved acquisition of five MT-weighted (MTw) spoiled gradient echo images, with variable MT flip angles (FAs) and off-resonance frequencies. A two-pool exchange model and dictionary matching were used to quantify the pool size ratio (PSR) and bound pool T2 relaxation ( T2B ). The signal model was developed and validated using 25 MTw images on a bovine serum albumin (BSA) phantom and in vivo human thigh muscle. A protocol with five MTw images was optimized for single breath-hold cardiac qMT imaging. The proposed sequence was tested in 10 healthy subjects and 5 patients with myocardial fibrosis and compared to late gadolinium enhancement (LGE). RESULTS: PSR values in the BSA phantom were within the confidence interval of previously reported values (concentration 10% BSA = 5.9 ± 0.1%, 15% BSA = 9.4 ± 0.2%). PSR and T2B in thigh muscle were also in agreement with literature (PSR = 10.9 ± 0.3%, T2B = 6.4 ± 0.4 us). In 10 healthy subjects, global left ventricular PSR was 4.30 ± 0.65%. In patients, PSR was reduced in areas associated with LGE (remote: 4.68 ± 0.70% vs. fibrotic: 3.12 ± 0.78 %, n = 5, P < .002). CONCLUSION: In vivo model-based qMT mapping of the heart was performed for the first time, with promising results for non-contrast enhanced assessment of myocardial fibrosis.

Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries.

OBJECTIVE: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE-/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level. CONCLUSIONS: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.

CD73 Promotes Age-Dependent Accretion of Atherosclerosis.

OBJECTIVE: CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; (cd73-/-/apoE-/-) were generated, and the extent of aortic atherosclerotic plaque was compared with apoE-/- controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, cd73-/-/apoE-/- mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in apoE-/- controls, P<0.005). By 20 weeks of age, this difference disappeared (2.9±0.4% versus 3.3±0.7%). A significant reversal in phenotype emerged at 32 weeks (9.8±1.2% versus 18.3±1.4%; P<0.0001) and persisted at the 52 week timepoint (22.4±2.1% versus 37.0±2.1%; P<0.0001). The inflammatory response to aging was found to be comparable between cd73-/-/apoE-/- mice and apoE-/- controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels (cd73-/-/apoE-/- versus apoE-/- at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], P<0.001). CONCLUSIONS: At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.

Clinical comparison of sub-mm high-resolution non-contrast coronary CMR angiography against coronary CT angiography in patients with low-intermediate risk of coronary artery disease: a single center trial.

BACKGROUND: The widespread clinical application of coronary cardiovascular magnetic resonance (CMR) angiography (CMRA) for the assessment of coronary artery disease (CAD) remains limited due to low scan efficiency leading to prolonged and unpredictable acquisition times; low spatial-resolution; and residual respiratory motion artefacts resulting in limited image quality. To overcome these limitations, we have integrated highly undersampled acquisitions with image-based navigators and non-rigid motion correction to enable high resolution (sub-1 mm3) free-breathing, contrast-free 3D whole-heart coronary CMRA with 100% respiratory scan efficiency in a clinically feasible and predictable acquisition time. OBJECTIVES: To evaluate the diagnostic performance of this coronary CMRA framework against coronary computed tomography angiography (CTA) in patients with suspected CAD. METHODS: Consecutive patients (n = 50) with suspected CAD were examined on a 1.5T CMR scanner. We compared the diagnostic accuracy of coronary CMRA against coronary CTA for detecting a ≥ 50% reduction in luminal diameter. RESULTS: The 50 recruited patients (55 ± 9 years, 33 male) completed coronary CMRA in 10.7 ± 1.4 min. Twelve (24%) had significant CAD on coronary CTA. Coronary CMRA obtained diagnostic image quality in 95% of all, 97% of proximal, 97% of middle and 90% of distal coronary segments. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were: per patient (100%, 74%, 55%, 100% and 80%), per vessel (81%, 88%, 46%, 97% and 88%) and per segment (76%, 95%, 44%, 99% and 94%) respectively. CONCLUSIONS: The high diagnostic image quality and diagnostic performance of coronary CMRA compared against coronary CTA demonstrates the potential of coronary CMRA as a robust and safe non-invasive alternative for excluding significant disease in patients at low-intermediate risk of CAD.

Inhibition of MPO (Myeloperoxidase) Attenuates Endothelial Dysfunction in Mouse Models of Vascular Inflammation and Atherosclerosis.

Objective- Inflammation-driven endothelial dysfunction initiates and contributes to the progression of atherosclerosis, and MPO (myeloperoxidase) has been implicated as a potential culprit. On release by circulating phagocytes, MPO is thought to contribute to endothelial dysfunction by limiting NO bioavailability via formation of reactive oxidants including hypochlorous acid. However, it remains largely untested whether specific pharmacological inhibition of MPO attenuates endothelial dysfunction. We, therefore, tested the ability of a mechanism-based MPO inhibitor, AZM198, to inhibit endothelial dysfunction in models of vascular inflammation. Approach and Results- Three models of inflammation were used: femoral cuff, the tandem stenosis model of plaque rupture in Apoe-/- mice, and C57BL/6J mice fed a high-fat, high-carbohydrate diet as a model of insulin resistance. Endothelial dysfunction was observed in all 3 models, and oral administration of AZM198 significantly improved endothelial function in the femoral cuff and tandem stenosis models only. Improvement in endothelial function was associated with decreased arterial MPO activity, determined by the in vivo conversion of hydroethidine to 2-chloroethidium, without affecting circulating inflammatory cytokines or arterial MPO content. Mechanistic studies in Mpo-/- mice confirmed the contribution of MPO to endothelial dysfunction and revealed oxidation of sGC (soluble guanylyl cyclase) as the underlying cause of the observed limited NO bioavailability. Conclusions- Pharmacological inhibition of MPO is a potential strategy to limit endothelial dysfunction in vascular inflammation. Visual Overview- An online visual overview is available for this article.

Accelerated high-resolution free-breathing 3D whole-heart T2-prepared black-blood and bright-blood cardiovascular magnetic resonance.

BACKGROUND: The free-breathing 3D whole-heart T2-prepared Bright-blood and black-blOOd phase SensiTive inversion recovery (BOOST) cardiovascular magnetic resonance (CMR) sequence was recently proposed for simultaneous bright-blood coronary CMR angiography and black-blood late gadolinium enhancement (LGE) imaging. This sequence enables simultaneous visualization of cardiac anatomy, coronary arteries and fibrosis. However, high-resolution (< 1.4 × 1.4 × 1.4 mm3) fully-sampled BOOST requires long acquisition times of ~ 20 min. METHODS: In this work, we propose to extend a highly efficient respiratory-resolved motion-corrected reconstruction framework (XD-ORCCA) to T2-prepared BOOST to enable high-resolution 3D whole-heart coronary CMR angiography and black-blood LGE in a clinically feasible scan time. Twelve healthy subjects were imaged without contrast injection (pre-contrast BOOST) and 10 patients with suspected cardiovascular disease were imaged after contrast injection (post-contrast BOOST). A quantitative analysis software was used to compare accelerated pre-contrast BOOST against the fully-sampled counterpart (vessel sharpness and length of the left and right coronary arteries). Moreover, three cardiologists performed diagnostic image quality scoring for clinical 2D LGE and both bright- and black-blood 3D BOOST imaging using a 4-point scale (1-4, non-diagnostic-fully diagnostic). A two one-sided test of equivalence (TOST) was performed to compare the pre-contrast BOOST images. Nonparametric TOST was performed to compare post-contrast BOOST image quality scores. RESULTS: The proposed method produces images from 3.8 × accelerated non-contrast-enhanced BOOST acquisitions with comparable vessel length and sharpness to those obtained from fully- sampled scans in healthy subjects. Moreover, in terms of visual grading, the 3D BOOST LGE datasets (median 4) and the clinical 2D counterpart (median 3.5) were found to be statistically equivalent (p < 0.05). In addition, bright-blood BOOST images allowed for visualization of the proximal and middle left anterior descending and right coronary sections with high diagnostic quality (mean score > 3.5). CONCLUSIONS: The proposed framework provides high-resolution 3D whole-heart BOOST images from a single free-breathing acquisition in ~ 7 min.

3D whole-heart isotropic sub-millimeter resolution coronary magnetic resonance angiography with non-rigid motion-compensated PROST.

BACKGROUND: To enable free-breathing whole-heart sub-millimeter resolution coronary magnetic resonance angiography (CMRA) in a clinically feasible scan time by combining low-rank patch-based undersampled reconstruction (3D-PROST) with a highly accelerated non-rigid motion correction framework. METHODS: Non-rigid motion corrected CMRA combined with 2D image-based navigators has been previously proposed to enable 100% respiratory scan efficiency in modestly undersampled acquisitions. Achieving sub-millimeter isotropic resolution with such techniques still requires prohibitively long acquisition times. We propose to combine 3D-PROST reconstruction with a highly accelerated non-rigid motion correction framework to achieve sub-millimeter resolution CMRA in less than 10 min. Ten healthy subjects and eight patients with suspected coronary artery disease underwent 4-5-fold accelerated free-breathing whole-heart CMRA with 0.9 mm3 isotropic resolution. Vessel sharpness, vessel length and image quality obtained with the proposed non-rigid (NR) PROST approach were compared against translational correction only (TC-PROST) and a previously proposed NR motion-compensated technique (non-rigid SENSE) in healthy subjects. For the patient study, image quality scoring and visual comparison with coronary computed tomography angiography (CCTA) were performed. RESULTS: Average scan times [min:s] were 6:01 ± 0:59 (healthy subjects) and 8:29 ± 1:41 (patients). In healthy subjects, vessel sharpness of the left anterior descending (LAD) and right (RCA) coronary arteries were improved with the proposed non-rigid PROST (LAD: 51.2 ± 8.8%, RCA: 61.2 ± 9.1%) in comparison to TC-PROST (LAD: 43.8 ± 5.1%, P = 0.051, RCA: 54.3 ± 8.3%, P = 0.218) and non-rigid SENSE (LAD: 46.1 ± 5.8%, P = 0.223, RCA: 56.7 ± 9.6%, P = 0.50), although differences were not statistically significant. The average visual image quality score was significantly higher for NR-PROST (LAD: 3.2 ± 0.6, RCA: 3.3 ± 0.7) compared with TC-PROST (LAD: 2.1 ± 0.6, P = 0.018, RCA: 2.0 ± 0.7, P = 0.014) and non-rigid SENSE (LAD: 2.3 ± 0.5, P = 0.008, RCA: 2.5 ± 0.7, P = 0.016). In patients, the proposed approach showed good delineation of the coronaries, in agreement with CCTA, with image quality scores and vessel sharpness similar to that of healthy subjects. CONCLUSIONS: We demonstrate the feasibility of combining high undersampling factors with non-rigid motion-compensated reconstruction to obtain high-quality sub-millimeter isotropic CMRA images in ~ 8 min. Validation in a larger cohort of patients with coronary artery disease is now warranted.

Evaluation of dyspnea of unknown etiology in HIV patients with cardiopulmonary exercise testing and cardiovascular magnetic resonance imaging.

AIM: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. METHODS AND RESULTS: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). CONCLUSION: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

The influence of humic and fulvic acids on Cd bioavailability to wheat cultivars grown on sewage irrigated Cd-contaminated soils.

The soil cadmium (Cd) contamination is a ubiquitous environmental problem that has resulted from intense irrigation with wastewater. This pot trial was conducted with aim to produce safe food with Cd tolerant wheat cultivar in wastewater irrigated soils. For this purpose, two wheat cultivars NARC-2011 (Cd tolerant) and Shafaq-2006 (Cd sensitive) were screened out and selected, after conducting a pilot trial of twelve local wheat cultivars against Cd stress. Both cultivars were grown in naturally contaminated soils with Cd concentrations (4.18, 3.23, 2.29 and 1.25 mg kg-1). After harvesting, NARC-2011 showed significant photosynthetic attributes, grain biochemical parameters and yield. Additionally, Cd concentrations in edible grains of NARC-2011 cultivars were found within standard limits (200 mg kg-1), in all contaminated soils. Furthermore, a marked decrease in Cd bioavailability was noted with cultivar NARC-2011, where contribution of mobile Cd fractions (exchangeable and reducible) percentage was decreased, while immobile Cd fractions percentage increased (oxidizable and residual). Fourier transform infrared (FTIR) spectroscopy reflects the maturity and stability of humic and fulvic like acid fractions and revealed that humification of these compounds after prolonged sludge enriched wastewater irrigation lowered the Cd availability. The wheat cultivar NARC-2011 (Cd tolerant) could be opted to grow on soils irrigated with wastewater for a long time, as Cd bioavailability decreased with ageing due to stabilized humic substances and varietal tolerance.

Five-minute whole-heart coronary MRA with sub-millimeter isotropic resolution, 100% respiratory scan efficiency, and 3D-PROST reconstruction.

PURPOSE: To enable whole-heart 3D coronary magnetic resonance angiography (CMRA) with isotropic sub-millimeter resolution in a clinically feasible scan time by combining respiratory motion correction with highly accelerated variable density sampling in concert with a novel 3D patch-based undersampled reconstruction (3D-PROST). METHODS: An undersampled variable density spiral-like Cartesian trajectory was combined with 2D image-based navigators to achieve 100% respiratory efficiency and predictable scan time. 3D-PROST reconstruction integrates structural information from 3D patch neighborhoods through sparse representation, thereby exploiting the redundancy of the 3D anatomy of the coronary arteries in an efficient low-rank formulation. The proposed framework was evaluated in a static resolution phantom and in 10 healthy subjects with isotropic resolutions of 1.2 mm3 and 0.9 mm3 and undersampling factors of ×5 and ×9. 3D-PROST was compared against fully sampled (1.2 mm3 only), conventional parallel imaging, and compressed sensing reconstructions. RESULTS: Phantom and in vivo (1.2 mm3 ) reconstructions were in excellent agreement with the reference fully sampled image. In vivo average acquisition times (min:s) were 7:57 ± 1:18 (×5) and 4:35 ± 0:44 (×9) for 0.9 mm3 resolution. Sub-millimeter 3D-PROST resulted in excellent depiction of the left and right coronary arteries including small branch vessels, leading to further improvements in vessel sharpness and visible vessel length in comparison with conventional reconstruction techniques. Image quality rated by 2 experts demonstrated that 3D-PROST provides good image quality and is robust even at high acceleration factors. CONCLUSION: The proposed approach enables free-breathing whole-heart 3D CMRA with isotropic sub-millimeter resolution in <5 min and achieves improved coronary artery visualization in a short and predictable scan time.