Search

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.

No abstract available.

BACKGROUND: Fractional myocardial blood volume (fMBV) estimated using ferumoxytol-enhanced MRI (FE-MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half-life and its use for steady-state MRI is off-label. PURPOSE: To optimize and evaluate a two-compartment model for estimation of fMBV based on FE-MRI. STUDY TYPE: Prospective ANIMAL MODEL: Nine healthy swine; one swine with artificially-induced single-vessel coronary stenosis. FIELD STRENGTH/SEQUENCE: 3.0T clinical magnet using the 5(3)3(3)3 Modified Look-Locker Inversion Recovery (MOLLI) sequence. ASSESSMENT: Myocardial longitudinal spin-lattice relaxation rate (R1) was measured using the MOLLI sequence before and at contrast steady state following seven ferumoxytol infusions (0.125 – 4.0 mg/kg). fMBV and water exchange were estimated using a two-compartment model. Model-fitted fMBV was compared to simple fast-exchange fMBV approximation and percent change in pre and post-ferumoxytol R1. Dose under-sampling schemes were investigated to reduce acquisition duration. STATISTICAL TESTS: Variation in fMBV was assessed with a one-way analysis of variance (ANOVA). Fast-exchange fMBV and ferumoxytol dose under-sampling were evaluated using Bland-Altman analysis. RESULTS: Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s(−1). There was inter-subject variation in fMBV (p

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.

PurposeThe aims of the current study, therefore, were to compare 1) free-living MPS and 2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults.MethodsEighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO2max and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of resistance exercise training. Results Free-living muscle protein synthesis was not different between South Asians (1.48 ± 0.09 %/day) and White Europeans (1.59 ± 0.15 %/day) (p=0.522). In response to resistance exercise training there were no differences, between South Asians and White Europeans, muscle mass, lower body strength or insulin sensitivity. However, there were differences between the ethnicities in response to resistance exercise training in body fat, resting carbohydrate and fat metabolism, blood pressure, VO2max and upper body strength with responses less favourable in South Asians. ConclusionIn this exploratory study there were no differences in muscle protein synthesis or anabolic and metabolic responses to resistance exercise, yet there were less favourable responses in several outcomes. These findings require further investigation.

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.

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.

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

Background Microvascular obstruction affects half of patients with acute ST-segment elevation myocardial infarction and confers an adverse prognosis. Purpose We aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intra-coronary alteplase infused early after coronary reperfusion associates with ischaemic time. Methods We conducted a prospective, multicentre, parallel group, 1:1:1 randomised, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischaemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified sub-group of interest. Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the UK were enrolled with follow up to 3 months. Patients with acute myocardial infarction due to occlusion of a major coronary artery presenting ≤6 hours from symptom onset were randomly assigned to treatment with placebo, alteplase 10mg or alteplase 20mg. The primary outcome was the amount of microvascular obstruction disclosed by cardiac magnetic resonance imaging at 2–7 days. Secondary outcomes included infarct size, myocardial haemorrhage, left ventricular ejection fraction, and troponin T area-under-the curve. Results 440 patients were randomized (figure), the primary endpoint was achieved in 396 (90%), seventeen (3.9%) withdrew and all other patients were followed up to 3 months. In the primary analysis, the amount of microvascular obstruction did not differ between the groups. Their ischaemic times were: ≤2 hours, n=98; ≥2– In patients with an ischaemic time ≥4 hours, treatment with alteplase (10 mg, n=26; 20 mg, n=30) was associated with a dose dependent increase in the amount (mean) of microvascular obstruction (% left ventricular mass) compared to placebo (n=27) 1.14 vs. 3.11 vs. 5.20; mean difference on square root scale 0.81 (95% CI 0.21, 1.42), p=0.009. The interaction test between ischaemic time and treatment (active vs. placebo) was not statistically significant p=0.06, however when the interaction was assessed for a trend across treatment groups this did reach statistical significance, p=0.018. Furthermore, a higher proportion of patients presenting ≥4–6 hours treated with 20 mg of alteplase had myocardial haemorrhage (59.3%) compared to the placebo group (28.0%), odds ratio 3.81 (95% CI 1.19, 12.25), p=0.025. The amount of haemorrhage was also greater; estimated mean difference 3.49 (95% CI 1.22, 5.75), p=0.0026. No between-treatment group differences for myocardial haemorrhage were observed in patients presenting with shorter ischaemic times. Study flow diagram Conclusions In patients presenting with an ischaemic time ≥4 hours, adjunctive treatment with low-dose intra-coronary alteplase during primary PCI was associated with increases in microvascular obstruction and myocardial haemorrhage. The mechanism may involve haemorrhagic transformation within the infarct core. Acknowledgement/Funding NIHR EME programme (reference: 12/170/45); British Heart Foundation (BHF reference FS/16/74/32573)

Medical imaging has revolutionised the practice of diagnostic medicine since Wilhelm Rontgen’s discovery of X-rays in 1895. The profound impact of conventional medical imaging on diagnostic medicine is currently being replicated in the domain of clinical research, where quantitative imaging methods provide a powerful and versatile tool for the investigation of disease aetiology, measurement of disease progression and assessment of response to therapy/intervention. Quantitative imaging also holds immense promise as a method for risk assessment, prognosis and treatment stratification.

The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

To compare the diagnostic performance of four tracer kinetic analysis methods to quantify myocardial perfusion from magnetic resonance (MR) imaging cardiac perfusion data sets in terms of their ability to lead to the diagnosis of myocardial ischemia.The study was approved by the regional ethics committee, and all patients gave written consent. A representative sample of 50 patients with suspected ischemic heart disease was retrospectively selected from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease trial data set. Quantitative myocardial blood flow (MBF) was estimated from rest and adenosine stress MR imaging perfusion data sets by using four established methods. A matching diagnosis of both an inducible defect as assessed with single photon emission computed tomography and a luminal stenosis of 70% or more as assessed with quantitative x-ray angiography was used as the reference standard for the presence of myocardial ischemia. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis for each method, with stress MBF and myocardial perfusion reserve (MPR) serving as continuous measures.Area under the ROC curve with stress MBF and MPR as the outcome measures, respectively, was 0.86 and 0.92 for the Fermi model, 0.85 and 0.87 for the uptake model, 0.85 and 0.80 for the one-compartment model, and 0.87 and 0.87 for model-independent deconvolution. There was no significant difference between any of the models or between MBF and MPR, except that the Fermi model outperformed the one-compartment model if MPR was used as the outcome measure (P = .02).Diagnostic performance of quantitative myocardial perfusion estimates is not affected by the tracer kinetic analysis method used.

Background Patients with recent non–ST‐segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. Methods and Results We prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2‐weighted short tau inversion recovery [T2W‐STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non–ST‐segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0‐T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct‐related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W‐STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct‐related artery were similar (P=0.125), and both were superior to T2W‐STIR (P

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.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.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 of2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis.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).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.

Objective.Hypervascularization in finger clubbing is recognized, but its microanatomical basis remains unclear. This pilot descriptive study used magnetic resonance imaging (MRI) to explore this further.Methods.High-resolution MRI acquired with contrast agent was carried out in 4 patients with finger clubbing and 4 healthy volunteers. The anatomy of the nail bed, capsular structures, and bony changes were described.Results.Marked nail bed thickening and contrast enhancement was noted in all clubbed fingers, with bone edema in 3 of the 4 patients. None of the healthy subjects had similar abnormalities.Conclusion.This confirms that hypervascularization of the nail bed observed in the microanatomy on high-resolution MRI is associated with clubbed appearances of the nails.

To determine if myocardial perfusion cardiac magnetic resonance (MR) imaging can show changes in myocardial blood flow (MBF) during the cold pressor test (CPT) and can allow identification of the differing endothelial function of smokers and nonsmokers when compared during adenosine stress.The study was approved by the institutional ethics review board and all participants gave informed written consent. Twenty-nine healthy volunteers (19 nonsmokers, 10 smokers; mean age ± standard deviation, 22 years ± 4) underwent 1.5-T MR imaging and analysis. Myocardial perfusion was assessed during rest, peak CPT, and adenosine hyperemia with a saturation-recovery gradient-echo pulse sequence (spatial resolution, 2.4 × 2.4 × 10 mm). Global, endocardial, and epicardial MBF were calculated by using Fermi-constrained deconvolution. Paired and independent t test statistical analyses were used to compare the responses between tests and groups. Regression analysis was performed to identify predictors of MBF change.MBF at rest was similar between the nonsmoking and smoking groups (0.97 mL/g/min ± 0.4 vs 0.96 mL/g/min ± 0.3, respectively; P = .96). Nonsmokers responded to CPT with a 47% increase in MBF (1.43 mL/g/min ± 0.5) and smokers responded with a 27% increase (1.22 mL/g/min ± 0.4; P.001). An endocardial-to-epicardial gradient existed at rest (nonsmokers, 1.10 [P = .002]; smokers, 1.30 [P = .01]) and CPT (nonsmokers, 1.19 [P.001] smokers, 1.28 [P = .04]) but reversed during adenosine stress (nonsmokers, 0.89 [P = .03]; smokers, 0.92 [P = .42]).Myocardial perfusion cardiac MR imaging during CPT can allow assessment of changes in MBF globally and in the separate myocardial layers in healthy smokers and nonsmokers. This allows the combined assessment of endothelium-dependent (CPT) and endothelium-independent (adenosine stress test) MBF reserve in a single study.

Purpose: To assess the reproducibility of semiquantitative and quantitative analysis of first-pass myocardial perfusion cardiovascular magnetic resonance (CMR) in healthy volunteers. Materials and Methods: Eleven volunteers underwent myocardial perfusion CMR during adenosine stress and rest on 2 separate days. Perfusion data were acquired in a single mid-ventricular section in two cardiac phases to permit cardiac phase reproducibility comparisons. Semiquantitative analysis was performed to derive normalized upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The quantitative analysis estimated absolute myocardial blood flow (MBF) using Fermi-constrained deconvolution. The perfusion reserve index was calculated by dividing stress by rest data. Two observers performed all the measurements independently. One observer repeated all first scan measurements 4 weeks later. Results: The reproducibility of perfusion CMR was highest for semiquantitative analysis with an intraobserver coefficient of variability (CoV) of 3%–7% and interobserver CoV of 4%–10%. Semiquantitative interstudy comparison was less reproducible (CoV of 13%–27%). Quantitative intraobserver CoV of 10%–18%, interobserver CoV of 8%–15% and interstudy CoV of 20%–41%. Reproducibility of systolic and diastolic phases and the endocardial and epicardial myocardial layer showed similar reproducibility on both semiquantitative and quantitative analysis. Conclusion: The reproducibility of CMR myocardial perfusion estimates is good, but varies between intraobserver, interobserver, and interstudy comparisons. In this study semiquantitative analysis was more reproducible than quantitative analysis. J. Magn. Reson. Imaging 2013;37:865–874. © 2013 Wiley Periodicals, Inc.

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

Purpose To assess myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults. Materials and Methods Healthy adults without any history of cardiovascular disease underwent magnetic resonance imaging (MRI) at 1.5T and 3.0T within 2 days. The MRI protocol included balanced steady‐state free‐precession (b‐SSFP), 2D cine‐echo planar imaging (EPI)‐DENSE, and late gadolinium enhancement in subjects >45 years. Acquisitions were divided into six segments; global and segmental peak longitudinal and circumferential strain were derived and analyzed by field strength, age, and gender. Results In all, 89 volunteers (mean age 44.8 ± 18.0 years, range: 18–87 years) underwent MRI at 1.5T, and 88 of these subjects underwent MRI at 3.0T (1.4 ± 1.4 days between the scans). Compared with 3.0T, the magnitudes of global circumferential (–19.5 ± 2.6% vs. –18.47 ± 2.6%; P = 0.001) and longitudinal (–12.47 ± 3.2% vs. –10.53 ± 3.1%; P = 0.004) strain were greater at 1.5T. At 1.5T, longitudinal strain was greater in females than in males: –10.17 ± 3.4% vs. –13.67 ± 2.4%; P = 0.001. Similar observations occurred for circumferential strain at 1.5T (–18.72 ± 2.2% vs. –20.10 ± 2.7%; P = 0.014) and at 3.0T (–17.92 ± 1.8% vs. –19.1 ± 3.1%; P = 0.047). At 1.5T, longitudinal and circumferential strain were not associated with age after accounting for sex (longitudinal strain P = 0.178, circumferential strain P = 0.733). At 3.0T, longitudinal and circumferential strain were associated with age (P < 0.05). Longitudinal strain values were greater in the apico‐septal, basal‐lateral, and mid‐lateral segments and circumferential strain in the inferior, infero‐lateral, and antero‐lateral LV segments. Conclusion Myocardial strain parameters as revealed by cine‐DENSE at different MRI field strengths were associated with myocardial region, age, and sex. J. Magn. Reson. Imaging 2016;44:1197–1205.

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.

Summary Objective Nuclear magnetic resonance (NMR) spin–lattice relaxation rates were measured in bovine and porcine articular cartilage as a function of water content. Methods Water content was varied by freeze-drying samples for short periods of time (up to 15min). The samples were weighed at all stages of drying so that water content could be quantified. Spin–lattice relaxation rates were measured using magnetic resonance imaging (MRI). Results Linear correlations were observed between relaxation rate and two measures of inverse water content: (1) solid-to-water ratio ( ρ ), expressed as a ratio of the mass of the solid component of the cartilage ( m s ) and the mass of water at each freeze-drying time point ( m w ), and (2) a ratio of the total mass of the fully-hydrated cartilage and m w (1/ w ). These correlations did not appear significantly different for the bovine and porcine data. However, fitting the data to a piecewise-linear model revealed differences between these two species. We interpret the first two segments of the piecewise model as the depletion of different water phases but conjecture that the third segment is partially caused by changes in relaxation rates as a result of a reduction in macromolecular mobilities. Conclusions Whilst we can produce linear correlations which broadly describe the dependence of the measured spin–lattice relaxation rate on (inverse) water content, the linear model seems to obscure a more complicated relationship which potentially provides us with more information about the structure of articular cartilage and its extracellular water.

This study aims to quantify subendocardial and subepicardial myocardial blood flow (MBF) from dynamic contrast-enhanced MRI and to compare semi-quantitative and quantitative analysis methods. 17 healthy volunteers (9 males, mean age 34 ± 8) were scanned during adenosine stress and at rest. A “semi-quantitative” myocardial perfusion index (MPI) was calculated based on maximal upslopes of signal intensity-time profiles for a mid-ventricular myocardial slice. In addition, absolute MBF (ml/g/min) was estimated using Fermi-constrained deconvolution. On semi-quantitative analysis, the ratio of subendocardial to subepicardial MPI was 0.98 ± 0.1 at stress and 1.16 ± 0.09 at rest, P < 0.0001. The MPRI (i.e. the ratio of stress over rest MPI) for the subendocardium was 1.54 ± 0.3 versus 1.81 ± 0.35 for the subepicardium, P = 0.03. For quantitative analysis, the ratio of subendocardial to subepicardial MBF was 0.91 ± 0.11 at stress versus 1.17 ± 0.16 at rest, P < 0.0001. The subendocardial MBF reserve was also lower than in the subepicardium (2.6 ± 0.75 vs. 3.32 ± 0.93, P = 0.027). In conclusion, semi-quantitative and quantitative analysis of dynamic contrast-enhanced MRI shows higher subendocardial blood flow at rest and reduced subendocardial perfusion reserve compared to the subepicardium.

Quantitative analysis of cardiac dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) perfusion datasets is dependent on the drawing (manually or automatically) of myocardial contours. The required accuracy of these contours for myocardial blood flow (MBF) estimation is not well understood. This study investigates the relationship between myocardial contour errors and MBF errors. Myocardial contours were manually drawn on DCE-MRI perfusion datasets of healthy volunteers imaged in systole. Systematic and random contour errors were simulated using spline curves and the resulting errors in MBF were calculated. The degree of contour error was also evaluated by two recognized segmentation metrics. We derived contour error tolerances in terms of the maximum deviation (MD) a contour could deviate radially from the 'true' contour expressed as a fraction of each volunteer's mean myocardial width (MW). Significant MBF errors were avoided by setting tolerances of MD ≤ 0.4 MW, when considering the whole myocardium, MD ≤ 0.3 MW, when considering six radial segments, and MD ≤ 0.2 MW for further subdivision into endo- and epicardial regions, with the exception of the anteroseptal region, which required greater accuracy. None of the considered segmentation metrics correlated with MBF error; thus, both segmentation metrics and MBF errors should be used to evaluate contouring algorithms.

Reaction–diffusion computational models of cardiac electrophysiology require both dynamic excitation models that reconstruct the action potentials of myocytes as well as datasets of cardiac geometry and architecture that provide the electrical diffusion tensor D , which determines how excitation spreads through the tissue. We illustrate an experimental pipeline we have developed in our laboratories for constructing and validating such datasets. The tensor D changes with location in the myocardium, and is determined by tissue architecture. Diffusion tensor magnetic resonance imaging (DT-MRI) provides three eigenvectors e i and eigenvalues λ i at each voxel throughout the tissue that can be used to reconstruct this architecture. The primary eigenvector e 1 is a histologically validated measure of myocyte orientation (responsible for anisotropic propagation). The secondary and tertiary eigenvectors ( e 2 and e 3 ) specify the directions of any orthotropic structure if λ 2 is significantly greater than λ 3 —this orthotropy has been identified with sheets or cleavage planes. For simulations, the components of D are scaled in the fibre and cross-fibre directions for anisotropic simulations (or fibre, sheet and sheet normal directions for orthotropic tissues) so that simulated conduction velocities match values from optical imaging or plunge electrode experiments. The simulated pattern of propagation of action potentials in the models is partially validated by optical recordings of spatio-temporal activity on the surfaces of hearts. We also describe several techniques that enhance components of the pipeline, or that allow the pipeline to be applied to different areas of research: Q ball imaging provides evidence for multi-modal orientation distributions within a fraction of voxels, infarcts can be identified by changes in the anisotropic structure—irregularity in myocyte orientation and a decrease in fractional anisotropy, clinical imaging provides human ventricular geometry and can identify ischaemic and infarcted regions, and simulations in human geometries examine the roles of anisotropic and orthotropic architecture in the initiation of arrhythmias.

Objective\ud To investigate the ability of high-field (9.4 T) magnetic resonance (MR) imaging to delineate porcine knee meniscal tissue structure and meniscal tears.\ud \ud Materials and methods\ud Porcine knees were obtained from a local abattoir, and eight medial menisci with no visible defects were dissected. Lesions simulating longitudinal tears were created on two of the menisci. MR images of the menisci were obtained at 9.4 T using a three-dimensional (3D)-FLASH sequence. A detailed 3D internal architecture of the intact and injured menisci was demonstrated on high-resolution MR images.\ud \ud Results\ud High-resolution 3D MR imaging allowed visualisation of internal architecture of the meniscus and disruption to the internal structural network in damage models. The architecture of the porcine knee meniscus revealed by the MR scans appeared similar to the structures visualised by histology in previously reported studies.\ud \ud Conclusion\ud High-field MRI is a non-destructive technique to examine the internal structural components and damage/wear of meniscal tissue. It has tremendous potential in the field of functional cartilage/meniscus biomechanics and biotribology.

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.