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Objectives Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response. Methods We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis. Cardiometabolic, anthropometric and disease activity assessments were performed at baseline (pre-apremilast) and at months 1, 3 and 6 of apremilast treatment in 60 patients. A subgroup underwent further assessment of endothelial function, body composition and adipocyte morphology. Results In patients (median age 54.5 years, 63% women, median BMI 33.2 kg/m2), apremilast was associated with a mean weight loss of 2.2 kg (95% CI 1.4, 3.0; P Conclusion Following apremilast treatment, we observed weight loss, principally abdominal subcutaneous fat, and improvement in psoriatic disease activity. The latter was independent of weight change, suggesting apremilast likely acts through direct immunological mechanisms.

Background Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. Purpose To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. Methods MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. Results T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. Conclusions The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Highlights • CMR T1 correlated with reference T1 and T2; this derives the QA model for T1-map. • The proposed QA model is robust to temperature variations and phantom aging. • This QA method requires no frequent phantom replacements. • The T1-map QA program can be readily deployed in multicenter trials.

Objective To assess interobserver reproducibility of different regions of interest (ROIs) on multi-parametric renal MRI using commercially available software. Materials and methods Healthy volunteers (HV), patients with heart failure (HF) and renal transplant recipients (Tx) were recruited. Localiser scans, T1 mapping and pseudo-continuous arterial spin labelling (pCASL) were performed. HV and Tx also underwent diffusion-weighted imaging to allow calculation of apparent diffusion coefficient (ADC). For T1, pCASL and ADC, ROIs were drawn for whole kidney (WK), cortex (Cx), user-defined representative cortex (rep-Cx) and medulla. Intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were assessed. Results Forty participants were included (10 HV, 10 HF and 20 Tx). The ICC for renal volume was 0.97 and CoV 6.5%. For T1 and ADC, WK, Cx, and rep-Cx were highly reproducible with ICC ≥ 0.76 and CoV 0.86, but CoV up to 14.2%). While reproducible, WK values were derived from a wide spread of data (ROI standard deviation 17% to 55% of the mean value for ADC and pCASL, respectively). Renal volume differed between groups (p p = 0.009) and HF (p = 0.02). Medullary T1 values were also higher in Tx than HV (p = 0.03), while medullary pCASL values were significantly lower in Tx compared to HV and HF (p = 0.03 for both). Discussion Kidney volume calculated by manually contouring a localiser scan was highly reproducible between observers and detected significant differences across patient groups. For T1, pCASL and ADC, Cx and rep-Cx ROIs are generally reproducible with advantages over WK values.

Objectives Ferumoxytol is an alternative to gadolinium-based compounds as a vascular contrast agent for magnetic resonance angiography (MRA), particularly for patients with chronic kidney disease (CKD). However, dose-related efficacy data are lacking. We aimed to determine the optimal (minimum effective) dose of ferumoxytol for MRA in patients with CKD. Methods Ferumoxytol-enhanced MRA (FeMRA) was performed at 3.0 T in patients with CKD after dose increments up to a total of 4 mg/kg. Image quality was assessed by contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) in the abdominal aorta and inferior vena cava. Quadratic regression analyses were performed to estimate the effects of dose increments on CNR and SNR. Results Twenty-three patients underwent FeMRA (mean age 60 [SD 13] years, 87% men, 48% had diabetic nephropathy) with cumulative doses of 0, 1, 2, 3 and 4 mg/kg of ferumoxytol. On regression analyses, a parabolic relationship was observed between ferumoxytol dose and signal with progressive signal loss using doses exceeding 4 mg/kg. A dose of 3 mg/kg achieved ≥ 75% of predicted peak CNR and SNR and images were deemed of excellent diagnostic quality. Conclusions In patients with CKD undergoing FeMRA, a dose of 3 mg/kg provides excellent arterial and venous enhancement. The benefits of increasing the dose to a theoretically optimal value of 4 mg/kg appear to be negligible and likely of minimal, if any, diagnostic value. Key Points • Ferumoxytol is used off-label as an MRI contrast agent but dose-related data are lacking. • In patients with CKD requiring MR angiography, a dose of 3 mg/kg provides excellent vascular enhancement. Electronic supplementary material The online version of this article (10.1007/s00330-019-06137-4) contains supplementary material, which is available to authorized users.

Computational Fluid Dynamics (CFD) and time‐resolved phase‐contrast magnetic resonance imaging (PC‐MRI) are potential non‐invasive methods for the assessment of the severity of arterial stenoses. Fractional flow reserve (FFR) is the current “gold standard” for determining stenosis severity in the coronary arteries but is an invasive method requiring insertion of a pressure wire. CFD derived FFR (vFFR) is an alternative to traditional catheter derived FFR now available commercially for coronary artery assessment, however, it can potentially be applied to a wider range of vulnerable vessels such as the iliac arteries. In this study CFD simulations are used to assess the ability of vFFR in predicting the stenosis severity in a patient with a stenosis of 77% area reduction (>50% diameter reduction) in the right iliac artery. Variations of vFFR, overall pressure drop and flow split between the vessels were observed by using different boundary conditions. Correlations between boundary condition parameters and resulting flow variables are presented. The study concludes that vFFR has good potential to characterise iliac artery stenotic disease.

Objectives To compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease. Methods Detailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls. Results PsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (s.d. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (s.d. 1.83 l)] (P Conclusion Individuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk.

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age ( Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, –10.8 to –1.2) mL/m 2 ( P =0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, –13.7 to –2.6) mL/m 2 ( P =0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%–47%), P =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03485092.

Aims The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). Methods and results In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of −9.6 mmHg (P = 0.01) and −13.5 mmHg (P = 0.0003) for systolic blood pressure and −5.2 mmHg (P = 0.02) and −8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (−0.24 vs. −0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. Conclusion In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

Background Vascular calcification is an independent predictor of cardiovascular disease in patients with chronic kidney disease. Computed tomography (CT) is the gold-standard for detecting vascular calcification. Radial volumetric-interpolated breath-hold examination (radial-VIBE), a free-breathing gradient-echo cardiovascular magnetic resonance (CMR) sequence, has advantages over CT as it is ionising radiation-free. However, its capability in detecting thoracic aortic calcification (TAC) has not been investigated. This study aims to compare radial-VIBE to CT for the detection of TAC in the descending aorta of patients with end-stage renal disease (ESRD) using semi-automated methods, and to investigate the association between TAC and coronary artery calcification (CAC). Methods Paired cardiac CT and radial-VIBE CMR scans from ESRD patients participating in 2 prospective studies were obtained. Calcification volume was quantified using semi-automated methods in a 9 cm segment of the thoracic aorta. Correlation and agreement between TAC volume measured on CMR and CT were assessed with Spearman’s correlation coefficient (ρ), linear regression, Bland–Altman plots and intraclass correlation coefficient (ICC). Association between CAC Agatston score and TAC volume determined by CT and CMR was measured with Spearman’s correlation coefficient. Results Scans from 96 participants were analysed. Positive correlation was found between CMR and CT calcification volume [ρ = 0.61, 95% confidence interval (CI) 0.45–0.73]. ICC for consistency was 0.537 (95% CI 0.378–0.665). Bland–Altman plot revealed that compared to CT, CMR volumes were systematically higher at low calcification volume, and lower at high calcification volume. CT did not detect calcification in 41.7% of participants, while radial-VIBE CMR detected signal which the semi-quantitative algorithm reported as calcification in all of those individuals. Instances of suboptimal radial-VIBE CMR image quality were deemed to be the major contributors to the discrepancy. Correlations between CAC Agatston score and TAC volume measured by CT and CMR were ρ = 0.404 (95% CI 0.214–0.565) and ρ = 0.211 (95% CI 0.008–0.396), respectively. Conclusion Radial-VIBE CMR can detect TAC with strong positive association to CT, albeit with the presence of proportional bias. Quantification of vascular calcification by radial-VIBE remains a promising area for future research, but improvements in image quality are necessary.

Background Duplex US is performed routinely for vascular mapping prior to arteriovenous fistula (AVF) creation for hemodialysis but cannot demonstrate the central vasculature. Ferumoxytol, an iron oxide nanoparticle, provides an alternative to gadolinium contrast material for MR angiography for safe use in chronic kidney disease (CKD). Purpose To assess the clinical utility of ferumoxytol-enhanced MR angiography compared with duplex US for vascular mapping before upper limb AVF creation in participants with CKD. Materials and Methods In a prospective comparative study (ClinicalTrials.gov: NCT02997046) from December 2016 to August 2018, participants with CKD underwent ferumoxytol-enhanced MR angiography and duplex US. Two independent readers evaluated vessels for diameter, stenosis or occlusion, arterial disease, and central stenosis. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess intra- and interreader variability. On the basis of accepted standards for AVF creation, an algorithm was developed to predict AVF outcome based on imaging findings. Multivariable regression models used AVF success as the dependent variable and age, sex, and duplex US or ferumoxytol-enhanced MR angiography findings as independent variables. Results Fifty-nine participants with CKD (mean age, 59 years ± 13 [standard deviation]; 30 women) were evaluated. A total of 51 fistulas were created, of which 24 (47%) were successful. Ferumoxytol-enhanced MR angiography showed excellent inter- and intrareader repeatability (ICC, 0.84-0.99) for all variables assessed. In addition to revealing 15 central vasculature stenoses, ferumoxytol-enhanced MR angiography resulted in characterization of 88 of 236 (37%) of the arterial sections examined as unsuitable for AVF creation compared with 61 of 236 (26%) sections with duplex US (

Background and Aims Existing methods of investigating renal transplant dysfunction do not provide reliable information regarding diagnosis nor prognosis. Multi-parametric magnetic resonance imaging (MRI) may provide novel biomarkers for evaluation of transplant dysfunction. We aim to determine how MRI parameters change over the first year of transplantation, and how these relate to future renal function. Method Patients receiving a kidney transplant attended for study visits at 6, 26 and 52 weeks post operatively, comprising measurement of clinical and biochemical parameters, together with research multi-parametric MRI. Imaging measurements comprised kidney volume, arterial spin labelling (ASL) perfusion, T1 relaxation time, T2*, apparent diffusion coefficient (ADC) and fractional anisotropy (FA). Imaging was performed at 3.0 Tesla using a Siemens MAGNETOM Prisma system. Regions of interest were drawn in whole kidney (WK), cortex (Cx) and medulla (Md) (figure 1). Results 20 patients were included: 16 were male, with age 55.5±12.8 years, baseline eGFR 54.0±23.6 ml/min/1.73m2, and blood pressure 146/80 ± 15/15 mmHg. 14 received deceased, and 6 received live, donor transplants. Patients were all managed with tacrolimus, mycophenolate and low dose prednisolone, following induction therapy with either basiliximab or anti-thymocyte globulin. 6 week ADC was 1.69±0.14 in WK, 1.65±0.08 in Cx, and 1.67±0.10 ×10-3 mm2/s in Md. FA was 0.19±0.04 in WK, 0.14 ± 0.04 in Cx and 0.22 ± 0.10 in Md. T2* was 57.6±9.4 in WK, 63.9±8.7 in Cx and 45.0±8.0 ms in Md. Over the 3 visits there was reduction in FA (p=0.008) and medullary T2* (p Over 1 year the median change in eGFR was -2ml/min/1.73m2. There was correlation between baseline eGFR and the following variables: volume (r=0.29, p=0.04), whole kidney ADC (r=0.36, p=0.01), cortical ADC (r=0.46, p=0.001), representative cortex ADC (r=0.48, p Conclusion Diffusion weighted MRI measurements correlate with eGFR and may allow improved prognostication regarding future renal function. Certain MRI parameters including FA and R2* vary depending on time point of transplantation which may reflect changes in transplant microstructure in the early postoperative period. Multi-parametric MRI provides a novel method of evaluating renal transplants non-invasively and may allow more accurate prediction of future transplant function than existing biochemical measures.

Supplemental Digital Content is available in the text., The rationale for our study was to investigate the pathophysiology of microvascular injury in patients with acute ST-segment–elevation myocardial infarction in relation to a history of hypertension. We undertook a cohort study using invasive and noninvasive measures of microvascular injury, cardiac magnetic resonance imaging at 2 days and 6 months, and assessed health outcomes in the longer term. Three hundred twenty-four patients with acute myocardial infarction (mean age, 59 [12] years; blood pressure, 135 [25] / 79 [14] mm Hg; 237 [73%] male, 105 [32%] with antecedent hypertension) were prospectively enrolled during emergency percutaneous coronary intervention. Compared with patients without antecedent hypertension, patients with hypertension were older (63 [12] years versus 57 [11] years; P

Although kidney transplantation is the treatment of choice for suitable patients with end-stage kidney disease, approximately 25% of chronic kidney disease (CKD) patients have peripheral arterial disease (PAD) ([1][1]). Computed tomography angiography (CTA) can identify patients requiring

BACKGROUND: Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. PURPOSE: To report multicenter safety data for off-label diagnostic ferumoxytol use. MATERIALS AND METHODS: The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1–5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs. RESULTS: Between January 2003 and October 2018, 3215 patients (median age, 58 years; range, 1 day to 96 years; 1897 male patients) received 4240 ferumoxytol injections for MRI. Ferumoxytol dose ranged from 1 to 11 mg per kilogram of body weight (≤510 mg iron; rate ≤45 mg iron/sec). There were no systematic changes in vital signs after ferumoxytol administration (P > .05). No severe, life-threatening, or fatal AEs occurred. Eighty-three (1.9%) of 4240 AEs were related or possibly related to ferumoxytol infusions (75 mild [1.8%], eight moderate [0.2%]). Thirty-one AEs were classified as allergiclike reactions using ACR criteria but were consistent with minor infusion reactions observed with parenteral iron. CONCLUSION: Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI. © RSNA, 2019 Online supplemental material is available for this article.

Background Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. Objectives This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. Methods This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (, Central Illustration

Objectives This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. Background Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. Methods This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. Results The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial blood flow values to generate a myocardial perfusion reserve did not significantly increase the quantitative analysis area under the curve (p = 0.79). Conclusions Quantitative perfusion has a high diagnostic accuracy for detecting coronary artery disease but is not superior to visual analysis. The incorporation of rest perfusion imaging does not improve diagnostic accuracy in quantitative perfusion analysis.

Traditional contrast-enhanced methods for scanning blood vessels using magnetic resonance imaging (MRI) or CT carry potential risks for patients with advanced kidney disease. Ferumoxytol is a superparamagnetic iron oxide nanoparticle preparation that has potential as an MRI contrast agent in assessing the vasculature. Twenty patients with advanced kidney disease requiring aorto-iliac vascular imaging as part of pre-operative kidney transplant candidacy assessment underwent ferumoxytol-enhanced magnetic resonance angiography (FeMRA) between December 2015 and August 2016. All scans were performed for clinical indications where standard imaging techniques were deemed potentially harmful or inconclusive. Image quality was evaluated for both arterial and venous compartments. First-pass and steady-state FeMRA using incremental doses of up to 4 mg/kg body weight of ferumoxytol as intravenous contrast agent for vascular enhancement was performed. Good arterial and venous enhancements were achieved, and FeMRA was not limited by calcification in assessing the arterial lumen. The scans were diagnostic and all patients completed their studies without adverse events. Our preliminary experience supports the feasibility and utility of FeMRA for vascular imaging in patients with advanced kidney disease due for transplant listing, which has the advantages of obtaining both arteriography and venography using a single test without nephrotoxicity. • Evaluation of vascular disease is important in planning kidney transplantation. • Standard vascular imaging methods are often problematic in kidney disease patients. • FeMRA has the advantage of arteriography and venography in a single test. • FeMRA is safe and non-nephrotoxic. • FeMRA is not limited by arterial calcification.

Supplemental Digital Content is available in the text., The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P

Aims: Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. Methods: We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and flow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. Results: T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. Conclusions: Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD.

Background— Although accelerated high-spatial-resolution cardiovascular MR (CMR) myocardial perfusion imaging has been shown to be clinically feasible, there has not yet been a direct comparison with standard-resolution methods. We hypothesized that higher spatial resolution detects more subendocardial ischemia and leads to greater diagnostic accuracy for the detection coronary artery disease. This study compared the diagnostic accuracy of high-resolution and standard-resolution CMR myocardial perfusion imaging in patients with suspected coronary artery disease. Methods and Results— A total of 111 patients were recruited to undergo 2 separate perfusion-CMR studies at 1.5 T, 1 with standard-resolution (2.5×2.5 mm in-plane) and 1 with high-resolution (1.6×1.6 mm in-plane) acquisition. High-resolution acquisition was facilitated by 8-fold k-t broad linear speed-up technique acceleration. Two observers visually graded perfusion in each myocardial segment on a 4-point scale. Segmental scores were summed to produce a perfusion score for each patient. All patients underwent invasive coronary angiography and coronary artery disease was defined as stenosis ≥50% luminal diameter (quantitative coronary angiography). CMR data were successfully obtained in 100 patients. In patients with coronary artery disease (n=70), more segments were determined to have subendocardial ischemia with high-resolution than with standard-resolution acquisition (279 versus 108; P P P =0.002) and overall (area under the curve, 0.93 versus 0.83; P Conclusions— High-resolution perfusion-CMR has greater overall diagnostic accuracy than standard-resolution acquisition for the detection of coronary artery disease in both single- and multivessel disease and detects more subendocardial ischemia.

The past 15 years has seen an exponential rise in the use of MRI for the assessment of rheumatoid arthritis (RA). In this Perspectives article, we review the current and potential future role of MRI in the diagnosis, prognosis and monitoring of RA. We also review the impact of MRI research on the understanding of disease mechanisms. In our view, the pivotal role of synovitis in RA and its predilection for sonographically accessible joints makes it likely that MRI will be used diagnostically in joints that are inaccessible to ultrasonography or where the differential diagnosis is unclear. Additionally, MRI will probably assume an even more prominent role in clinical trials where the aim of therapy is the complete ablation of synovitis. Given the ever-increasing sophistication of MRI, we anticipate that it will continue to be a key research tool in the coming years.

Myocardial blood flow varies during the cardiac cycle in response to pulsatile changes in epicardial circulation and cyclical variation in myocardial tension. First-pass assessment of myocardial perfusion by dynamic contrast-enhanced MRI is one of the most challenging applications of MRI because of the spatial and temporal constraints imposed by the cardiac physiology and the nature of dynamic contrast-enhanced MRI signal collection. Here, we describe a dynamic contrast-enhanced MRI method for simultaneous assessment of systolic and diastolic myocardial blood flow. The feasibility of this method was demonstrated in a study of 17 healthy volunteers at rest and under adenosine-induced vasodilatory stress. We found that myocardial blood flow was independent of the cardiac phase at rest. However, under adenosine-induced hyperemia, myocardial blood flow and myocardial perfusion reserve were significantly higher in diastole than in systole. Furthermore, the transmural distribution of myocardial blood flow and myocardial perfusion reserve was cardiac phase dependent, with a reversal of the typical subendocardial to subepicardial myocardial blood flow gradient in systole, but not diastole, under stress. The observed difference between systolic and diastolic myocardial blood flow must be taken into account when assessing myocardial blood flow using dynamic contrast-enhanced MRI. Furthermore, targeted assessment of systolic or diastolic perfusion using dynamic contrast-enhanced MRI may provide novel insights into the pathophysiology of ischemic and microvascular heart disease.

The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated.MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p0.0001) and tenosynovitis than PsA patients (p0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups.Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.

Objective The anatomic basis for joint disease localization in polymyalgia rheumatica (PMR) is poorly understood. This study used contrast-enhanced and fat suppression magnetic resonance imaging (MRI) to evaluate the relationship between synovial and extracapsular inflammation in PMR and early rheumatoid arthritis (RA). Methods Ten patients with new-onset PMR and 10 patients with early RA underwent dynamic contrast-enhanced MRI and conventional MRI of affected metacarpophalangeal (MCP) joints. Synovitis and tenosynovitis were calculated based on the number of enhancing voxels, initial rate of enhancement, and maximal enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone edema were scored according to the OMERACT (Outcome Measures in Rheumatology Clinical Trials) scoring system in both groups. The degree of extracapsular Gd-DTPA enhancement was assessed in both conditions using semiquantitative scoring. Results No significant differences were seen in the volume of synovitis (P = 0.294), degree of flexor tenosynovitis (P = 0.532), periarticular erosions (P = 0.579), or degree of bone edema (P = 0.143) between RA and PMR joints. However, despite comparable degrees of synovitis, the proportion of MCP joints showing extracapsular enhancement was higher in the PMR group (100%) than in the RA group (50%) (P = 0.030). One PMR patient, but none of the RA patients, had bone edema at the capsular insertion. Conclusion Despite degrees of synovitis and tenosynovitis comparable with those in RA, PMR-related hand disease is associated with prominent extracapsular changes, suggesting that inflammation in these tissues is more prominent than joint synovitis, which is common in both conditions. This suggests that the anatomic basis for joint disease localization differs between RA and PMR.

Background— The use of fractional flow reserve (FFR) in acute coronary syndromes is controversial. The British Heart Foundation Fractional Flow Reserve Versus Angiography in Guiding Management to Optimize Outcomes in Non-ST-Elevation Myocardial Infarction (FAMOUS-NSTEMI) study (NCT01764334) has recently demonstrated the safety and feasibility of FFR measurement in patients with non–ST-segment–elevation myocardial infarction. We report the findings of the cardiac magnetic resonance (CMR) substudy to assess the diagnostic accuracy of FFR compared with 3.0-T stress CMR perfusion. Methods and Results— One hundred six patients with non–ST-segment–elevation myocardial infarction who had been referred for early invasive management were included from 2 centers. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30%, and if percutaneous coronary intervention was performed, an FFR assessment was repeated. Myocardial perfusion was assessed with stress perfusion CMR at 3 T. The mean age was 56.7±9.8 years; 82.6% were men. Mean time from FFR evaluation to CMR was 6.1±3.1 days. The mean±SD left ventricular ejection fraction was 58.2±9.1%. Mean infarct size was 5.4±7.1%, and mean troponin concentration was 5.2±9.2 μg/L. There were 34 fixed and 160 inducible perfusion defects. There was a negative correlation between the number of segments with a perfusion abnormality and FFR ( r =−0.77; P P Conclusions— FFR in patients with recent non–ST-segment–elevation myocardial infarction showed high concordance with myocardial perfusion in matched territories as revealed by 3.0-T stress perfusion CMR. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02073422.

ObjectivesThe purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA).MethodsNormal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion.ResultsVascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%).ConclusionThe findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

Background: Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute STEMI patients is unknown. We aimed to assess the clinical significance of infarct tissue characteristics using native T1 cardiac magnetic resonance (CMR).\ud \ud Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The area-at-risk and infarct territory were depicted with T1 mapping and late gadolinium contrast enhancement imaging, respectively. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.\ud \ud Results: 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps and follow-up assessments (median duration 845 days). Infarct size was 18 ±14% of left ventricular mass. Microvascular obstruction occurred in 160 (55.6%) patients. Native T1 within the area-at-risk (1097 ±52 ms) was higher than in the remote zone (961 ±25 ms; p

Background:\ud Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of infarct core native T1.\ud Methods:\ud We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction (MVO) were depicted with late gadolinium enhancement CMR. Adverse remodeling was defined as an increase in LV end-diastolic volume (LVEDV) ≥ 20% at 6 months. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.\ud \ud Results:\ud 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps. Infarct size was 18 ±14% of LV mass. One hundred and forty five (50%) of 288 patients had late MVO, whereas 160 (56%) patients had infarct core pathology revealed by native T1. Native T1 within the infarct core (996.9±57.3; p

Purpose To evaluate the technical performance of sensitivity encoding (SENSE)-accelerated myocardial perfusion magnetic resonance (MR) imaging and prospectively assess the diagnostic accuracy of this examination for depiction of significant coronary artery disease (CAD). Materials and methods All 102 subjects provided written informed consent, and the local ethics committee approved the study. A saturation-recovery segmented k-space gradient-echo pulse sequence was combined with SENSE to allow dynamic acquisition of myocardial perfusion data on four parallel short-axis MR image sections at every heartbeat. This technique was evaluated in 10 healthy volunteers and in 92 patients scheduled to undergo conventional coronary angiography. Gadopentetate dimeglumine was peripherally injected at rest and during adenosine-induced stress. The maximal upslope of the signal intensity-time profiles was plotted for 16 myocardial segments defined on three MR image sections, and a myocardial perfusion reserve index (MPRI) between stress and rest, normalized to the input function from the blood pool of the most basal section, was calculated. Areas under receiver operating characteristic curves (AUCs) were used to assess the diagnostic performance of cardiac MR imaging for depiction of greater than 70% CAD seen at coronary angiography, the reference standard. Results In volunteers, the mean myocardial enhancement was 2.1 +/- 1.2 (standard deviation), with homogeneous signal intensity distribution across the segments. The diagnostic accuracy of MPRI measurements was high (AUC, 0.908; sensitivity, 88% [52 of 59 patients]; specificity, 82% [27 of 33 patients]). Diagnostic performance was similar among separate analyses of the three coronary territories and among separate analyses of data in the patients with diabetes mellitus, left ventricular hypertrophy, or myocardial infarction. Conclusion Multisection myocardial perfusion MR imaging with SENSE is feasible and has high diagnostic accuracy in the detection of CAD.

Background There are limited data on the cardiac effects of radiotherapy and chemo-radiotherapy on the heart in patients with non-small cell lung cancer (NSCLC). CART is a pilot study designed to investigate change in myocardial function and tissue properties where Patients will undergo cardiac magnetic resonance (CMR) at baseline, during treatment, at 6 weeks and at 6 months after treatment completion. Here we report our preliminary findings related to temporal changes in myocardial perfusion index (MPI). Methods CMR was performed on a Siemens MAGNETOM Verio (Erlangen, Germany) 3.0 Tesla scanner. First-pass myocardial perfusion was assessed by saturation recovery prepared dynamic contrast enhanced sequence during administration of 0.1 mmol/kg of gadoterate meglumine (Dotarem). Semiquantitative analysis was performed on segmented basal and mid-LV short axis slices to derive normalised upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The change in MPI over time was analysed statistically using a linear mixed effects model. Results 13 patients currently have undergone CMR at baseline and during treatment (mean age 66 years, SD: 9; 71% male), 8 patients have undergone CMR at 6 weeks post treatment initiation (5 patients lost to follow-up/ died), and 6 patients have undergone CMR at 6 months from baseline (n = 2 lost to follow-up/ died). Perfusion index (Figure 1) varies significantly with time (p = 0.0015). After adjustment for multiple testing, the increase from baseline is statistically significant at 6 weeks (p = 0.014) and approaches significance at 6 months (p = 0.074) post treatment. Conclusion Change in microvascular perfusion is most pronounced 6 weeks following the completion of treatment. This finding will be used in the design of future clinical studies, where measurement of MPI will provide a robust comparison of different existing and emerging treatment protocols for NSCLC with regard to their effects on myocardial physiology. Funding Beatson Oncology Centre Fund

Objective Ethical constraints on the conduct of placebo-controlled trials evaluating new therapies for serious chronic diseases, such as rheumatoid arthritis (RA), indicate the need for discerning methods to assess treatment effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic resonance imaging (DEMRI) is a sensitive technique for the detection of synovial inflammation in RA. Therefore, this investigation was undertaken to evaluate DEMRI as an efficacy assessment tool for differentiating treatment effect in a randomized, active-controlled trial comparing leflunomide and methotrexate. Methods Patients with active RA (n = 39) were randomized in a 2-center, prospective, double-blind clinical trial to receive either leflunomide (n = 18) or methotrexate (n = 21) therapy for 4 months. DEMRI scans were obtained at baseline and at 4 months, and the initial rate of enhancement (IRE) and the maximal signal intensity (SI) enhancement (ME) were calculated from the SI curves. Clinical improvement was assessed by conventional outcome measures. Results Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baseline and end point DEMRI scans. Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05). Average values of ME indicated reduction of inflammation with both leflunomide and methotrexate. The improvement in clinical signs and symptoms, as measured by traditional assessments, was comparable for both active treatments. Conclusion Results of this study validate the sensitivity of DEMRI in detecting inflammatory changes in active RA in response to treatment. Improvement in synovial inflammation as measured by IRE was significantly better with leflunomide than with methotrexate over 4 months of therapy.

Background: The pathophysiological basis of reperfusion injury in smokers is incompletely understood. Methods: Patients with acute STEMI were prospectively enrolled during emergency PCI, and categorized according to a current smoking status (yes/no). Contrast-enhanced MRI at 1.5T was acquired 2

Background In patients with myocardial infarction (MI), an important factor in determining the long-term prognosis is the degree of regional contractile dysfunction. DENSE (Displacement ENcoding with Stimulated Echoes) is a technique which allows quantification of myocardial strain[1], and which has been shown to be more sensitive to the presence of late gadolinium enhancement (LGE) than wall thickening measured from cine images[2]. The aim of this study was to further investigate the performance of DENSE for the diagnosis and assessment of myocardial infarction. Methods 50 male patients (age 56 ± 10 years) within 7 days of MI and 30 healthy male controls (age 45 ± 18 years) underwent CMR on a 1.5T Siemens Avanto. The protocol included DENSE and LGE (patients only) obtained from a single mid-ventricular short-axis slice, which was divided into 6 segments for analysis. The percentage of each segment which contained LGE was calculated using a threshold of mean+5SD of remote myocardium intensity. DENSE images were analysed to obtain a value for peak circumferential strain (Ecc). The following analyses were performed: (i) intra- and inter-operator and inter-scan repeatability, (ii) sensitivity and specificity for the detection of LGE, using a reference range established from control data, and ROC analysis and (iii) the ability to distinguish between non-infarcted, 50% infarction, and between remote, adjacent and infarcted segments. Results along with the percentages of segments correctly identified when grouped according to extent of LGE. The reference range was calculated to be (-11.8, -27.0). Inter-operator repeatability was assessed using Levene’s test (variance) and a paired t-test (mean), and no statistically significant differences were found. A paired t-test found no statistically significant difference for inter-scan repeatability. The results of (iii) are illustrated in Figure 1. Comparisons between categories were performed using a one-way ANOVA with Tukey’s post-hoc test. Conclusions DENSE can be successfully applied in a clinical setting, and provides repeatable results. The sensitivity and specificity of the technique for detecting the presence of LGE are good, and the number of segments with LGE correctly identified increases as the extent of LGE increases. Peak

OBJECTIVES—CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology. METHODS—Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site. RESULTS—12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated. CONCLUSIONS—SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.

To compare stepping-table digital subtraction gadolinium-enhanced magnetic resonance (MR) angiography of the distal aorta and lower extremity arteries with conventional catheter digital subtraction x-ray angiography in patients with arterio-occlusive disease.Twenty patients underwent both conventional catheter angiography and fast three-dimensional gadolinium-enhanced MR angiography of the aorta and outflow vessels at 1.5 T; the images were acquired in three consecutive imaging locations during a single infusion of a gadolinium chelate.Compared with catheter angiography, according to the findings of two blinded independent reviewers, MR angiography had sensitivities of 81% and 89% and specificities of 91% and 95%, respectively, for demonstration of insignificant (or = 50%) stenosis versus significant (51%-100%) stenosis. For demonstration of occlusion, the sensitivity and specificity were 94% and 97%, respectively, by consensus. There was good interobserver correlation between the two readers overall (kappa = 0.65 for reporting the degree of narrowing in all lesions; 0.86, for reporting of insignificant versus significant stenoses; and 0.928, for reporting of occluded versus patient segments).Stepping-table digital subtraction contrast material-enhanced MR angiography has high accuracy compared with catheter angiography in patients with arterio-occlusive disease of the aorta and outflow vessels. These preliminary study results suggest that this technique may ultimately provide a safe, noninvasive, and cost-effective alternative to catheter angiography.

It has been noted recently, initially in pathological specimens, that infarcted myocardium can be infiltrated by adipose cells, known as lipomatous metaplasia (LM). It has been suggested that the presence of myocardial fat may interfere with the conduction system of the heart, perhaps providing a

Background Displacement encoding with stimulated echoes (DENSE) encodes myocardial tissue displacement into the phase of the MRI image permitting direct quantification of myocardial displacement at multiple cardiac phases. Strain-encoded CMR with DENSE has high spatial (3.2 mm × 3.2 mm × 8 mm) and temporal resolution (TR= 27.34 ms). We aimed to measure myocardial strain values with DENSE in healthy adults across a broad age range at 3.0Tesla. Methods Healthy volunteers with no prior medical history or treatment were enrolled and underwent CMR at 3.0T (Magnetom Verio, Siemens, Erlangen, Germany). Mid-left ventricular short axis and horizontal long axis DENSE sequences were obtained, and analysed using CIM_DENSE2D software (University of Auckland, New Zealand and Siemens Healthcare). Segmental and global myocardial circumferential (Ecc) and longitudinal (Ell) strain were obtained with DENSE. Results 77 participants (mean (SD) age 43.0(16.9) years; range 18–78 years; 40 (52%) males;) were grouped into 3 tertiles according to age. Longitudinal strain differed according to age tertile with strain being greatest in individuals 35–55 years compared to younger or older subjects. There were no differences in Ecc according to age per tertile (Table 1). Conclusion Longitudinal myocardial strain, as revealed by strain-encoded CMR, is associated with chronological age in healthy adults. Funding Medical Research Scotland project grant. Professor Berry was supported by a Senior Clinical Fellowship from the Scottish Funding Council.

Background The clinical significance of infarct extracellular volume (ECV) post-STEMI is unknown. ECV can be estimated by cardiac magnetic resonance imaging (CMR) using T1 MOLLI maps. We measured infarct ECV in STEMI survivors, and assessed the relationships between ECV and markers of MI severity. Methods STEMI survivors were enrolled in a single-centre cohort study (BHF MR-MI study – NCT02072850). Culprit artery flow was described by thrombus in myocardial infarction (TIMI) classification. CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2-days and 6-months post-MI, including T1-mapping with MOLLI before and 15-minutes after contrast (0.15 mmol/kg gadoterate meglumine). ECV was analysed by outlining regions-of-interest (ROIs) in infarcted myocardium, including microvascular obstruction, and left ventricular (LV) blood pool. ECV was calculated as the relaxation rate (R1=1/T1) for myocardium and LV blood pool before vs. after contrast, corrected for haematocrit. ECV was compared with TIMI-flow pre- and post-percutaneous coronary intervention (PCI) and ST-segment resolution. A reduction in ST-segment voltage of ≥70% was considered complete ST-resolution and Results 201 STEMI patients (age 58 ± 11 years; 156 (77%) male) were enrolled. Infarct ECV was similar at baseline and follow-up (51.3 ± 9.5% vs. 50.3 ± 12.0%, p = 0.1). Pre-PCI, 131 (65%) patients had TIMI-flow 0 and 70 (35%) had TIMI-flow 1–3. Post-PCI, 3 (1.5%) patients had TIMI-flow 0 and 198 (98.5%) had TIMI-flow 2–3. TIMI-flow 0 pre-PCI was associated with higher infarct ECV at baseline (p Conclusion Preserved culprit artery flow and complete ST-resolution are associated with lower infarct ECV at baseline and follow-up. Clinical and electrocardiographic markers of MI severity are predictors of interstitial expansion in the infarct zone in STEMI patients.

Qualitative differences in synovitis between the cartilage-pannus junction (CPJ) region and the adjoining suprapatellar pouch (SPP) have been reported in rheumatoid arthritis and the spondyloarthropathies.To determine if the distribution of synovitis is the same in osteoarthritis (OA) using sensitive measures of inflammation derived from dynamic, contrast enhanced magnetic resonance imaging (DEMRI).20 subjects with established OA of the knee were recruited. Conventional MR images together with the DEMRI measurements were obtained. Areas of synovitis at the CPJ region and at a distant site in the SPP were calculated; differences in CPJ and SPP synovitis were determined using DEMRI parameters: the initial rate of contrast enhancement (IRE) and maximal enhancement (ME).The area of synovitis was significantly greater adjacent to the CPJ than in the SPP. IRE and ME measures were greater at the CPJ than the SPP.The magnitude of synovitis at the CPJ is not disease-specific and applies across the spectrum of degenerative disease as well as inflammatory diseases.

With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T(1), T(2) and T(1ρ) relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.

Background Myocardial haemorrhage is a prognostically important complication of acute ST-elevation myocardial infarction (STEMI). Persistence of haemoglobin degradation products within infarct scar tissue and the potential clinical significance have not been investigated. Methods and Results Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI; ClinicalTrials.gov: NCT02072850). 211 patients (mean (SD) age 57 (11) years, 77% male) had evaluable T2* cardiac magnetic resonance (CMR) imaging (1.5 Tesla) 2 days 6 months post-MI. Myocardial haemorrhage was defined as a hypointense infarct core with T2* signal de novo haemorrhage after the first CMR scan. Clinical associates of a persistent hypointense core at 6 months included hypertension (odds ratio (95% confidence interval) 0.28 (0.08, 0.95); p = 0.040), heart rate (1.08 (1.03, 1.13); p = 0.001), systolic blood pressure (1.06 (1.01, 1.12); p = 0.015), neutrophil count (2.19 (1.01, 4.74); p = 0.048), left anterior descending as culprit artery (9.26 (1.26, 67.99); p = 0.029), infarct size (1.10 (1.03, 1.17); p = 0.004) and initial haemorrhage size (1.34 (1.06, 1.66); p = 0.012). A hypointense infarct core with T2*-mapping at 6 months was associated with worsening LV end-diastolic volume (regression coefficient (95% confidence interval) 15.43 (1.35, 29.50); p = 0.032) and worsening left ventricular ejection fraction (-4.15 (-7.40, -0.89); p = 0.013). Conclusion Persistence of haemoglobin degradation products at 6 months post-STEMI is common and prognostically important.

Background The natural history of persistent myocardial oedema after ST-elevation myocardial infarction (STEMI) is uncertain. Methods and ResultsPatients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI; ClinicalTrials.gov: NCT02072850). Cardiac magnetic resonance (CMR) imaging with T2-mapping of myocardial oedema was performed at 1.5 Tesla 2 days and 6 months post-MI. Myocardial oedema was defined as infarct signal intensity (S. I.) >2 standard deviations from the mean S. I. within a remote reference region. 283 STEMI patients (mean (SD) age 59 (12) years, 75% male) were enrolled. Infarct size was 18 (13)% of left ventricular (LV) mass. At 2 days, infarct zone T2 (ms) was higher than remote zone T2 (62.9 (5.2) vs. 49.7 (2.1); p Conclusion Persistence of oedema within the infarct zone affected the majority of patients at 6 months post-STEMI, and was associated with the initial severity of STEMI and adverse LV remodelling.

Background Despite the success of emergency PCI for acute STEMI, failed myocardial reperfusion (microvascular obstruction) is common and prognostically important, but it commonly passes undetected in clinical practice. Purpose To investigate coronary flow reserve (CFR) and the index of microvascular resistance (IMR) in the culprit coronary artery in patients with acute reperfused STEMI. Methods CFR and IMR were measured at the end of PCI using guidewire-based thermodilution (n = 283; mean age 60 (12) years, 73% male). CMR imaging was used to assess left ventricular (LV) function and infarct pathology 2 days and 6 months post-MI (n = 264). All-cause death or first heart failure hospitalisation (ACD) was a pre-specified outcome that was assessed during follow-up (median duration 845 days). Results The median [IQR] CFR was 1.6 [1.1–2.1] and the median IMR was 25 [15–48]. Microcirculatory status was associated with Killip Heart Failure classification, ST-segment resolution, LV ejection fraction and infarct size and pathology revealed by CMR 2 days later. In multivariate analysis, the combination of a CFR 25 was associated with changes in both LV ejection fraction (-2.47 (95% CI: -4.45, -0.49); p = 0.015) and LV end-diastolic volume (8.49 (1.96, 15.92); p = 0.025), and a CFR median was a multivariable (2.96 (1.24, 7.08); p = 0.015) associate of ACD. Conclusions The combination of a reduced CFR and an increased IMR immediately identifies patients who have a substantially increased risk of adverse LV outcomes and all-cause death or heart failure.

Despite the success of emergency percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (STEMI), failed myocardial reperfusion (microvascular obstruction (MVO)) is common and prognostically important. Our aim was to compare coronary flow reserve (CFR), a measure of

To compare myocardial blood flow (MBF) at systole and diastole and determine the diagnostic accuracy of both phases in patients suspected of having coronary artery disease (CAD).The study was approved by the regional ethics committee, and all patients gave written informed consent. After coronary angiography, 40 patients (27 men; mean age, 64 years ± 8) underwent stress-rest perfusion magnetic resonance (MR) imaging at 1.5 T, with images aquired simultaneously at end systole and middiastole. Patients were classified as having CAD (stenosis .70%) or no significant CAD. In patients with CAD, myocardial segments were classified as stenosis-dependent (downstream of significant stenosis) or remote. MBF and myocardial perfusion reserve (MPR) were calculated for each segment, and mean values in each phase were compared with paired t tests. The diagnostic accuracy of each phase was determined with receiver operating characteristic (ROC) analysis.Twenty-one of the 40 patients (53%) had CAD. Resting MBF was similar in both phases for patients with and patients without CAD (P.05). Stress MBF was greater in diastole than systole in normal, remote, and stenosis-dependent segments (3.75 mL/g/min ± 1.50 vs 3.15 mL/g/min ± 1.10, respectively, for normal segments; 2.75 mL/g/min ± 1.20 vs 2.38 mL/g/min ± 0.99, respectively, for remote segments; 2.49 mL/g/min ± 1.07 vs 2.23 mL/g/min ± 0.90, respectively, for stenosis-dependent segments; P.01). MPR was greater in diastole than systole in all segment groups (P.05). The diagnostic accuracies at diastole and systole were similar (area under the ROC curve = 0.79 and 0.82, respectively; P = .30).Myocardial perfusion MR estimates of stress MBF and MPR were greater in diastole than systole in patients with and patients without CAD. However, both phases had similar diagnostic accuracy. These observations may be relevant to other dynamic perfusion methods, including computed tomography and echocardiography.

This study has shown that in patients with suspected and confirmed CAD, estimates of MBF by perfusion-CMR are significantly higher in diastole than systole during maximal hyperemic stress.

Background Myocardial fractional flow reserve (FFR) has uncertain validity in patients with recent myocardial infarction and the use of FFR in this setting is controversial. We performed a prospective study to assess the diagnostic accuracy of FFR in patients with a recent non-ST segment myocardial infarction (NSTEMI). Methods NSTEMI patients who had been referred for early invasive management were included. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30% severity. Where clinically appropriate, an FFR assessment following PCI was also performed. Patients were scheduled for a stress perfusion 3T MRI following discharge from hospital.In a subsetof patients MRI was performed prior to coronary angiography/PCI. Baseline stress (I.V. adenosine 140 µg/kg/min) and rest perfusion MRI images were analysed side-by-side using dedicated software (Argus Dynamic Signal, Siemens, Erlangen, Germany). The stress and rest perfusion scans were viewed simultaneously, areas of hypoperfusion were assigned to coronary territories using the American Heart Association coronary arterial segment model. The analyses were performed independently by two observers who were blinded to the FFR results. In each patient, the coronary artery territories with abnormal perfusion were recorded. In cases of disagreement between observers, a third blinded observer adjudicated. Results 106 NSTEMI patients (mean age 56.7 ± 9.8 years, 82.6% male) were included. The mean time between the FFR evaluation and MRI was 5.8 ± 3.1 days. The mean ± SD left ventricular ejection fraction was 58.2 ± 9.1%. Mean infarct size was 5.4 ± 7.1% and mean troponin was 5.2 ± 9.2 g/L. A total of 1696 segments were available for analysis. 34 segments were excluded from the analysis due to problematic image quality so 1664 segments were finally included.Of these, 824 segments were available for comparison with FFR. 156 coronary arteries were assessed 92 in the infarct-related arteries and 64 in the non-infarct-related arteries. Of these, 28(17.1%) and 33(21.1%) arteries had an FFR ≤ 0.75 and ≤0.80, respectively. There was a negative correlation between the number of ischaemic segments and FFR (r = -0.79, 0 ROC analysis defined the optimal FFR cut off value for identification of reversible ischaemia on MRI to be ≤0.8 (AUC 0.94 (0.89–0.99), p Conclusion FFR measured in patients with recent NSTEMI has a high level of accuracy for inducible perfusion abnormalities revealed by 3T stress MRI, a non-invasive reference method.