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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.

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.

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

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.

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.

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.

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.

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.

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.

The significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) depicts left ventricular (LV) dimension and pathology. Native T1 quantified by CMR (T1 proton relaxation time, milliseconds) is a fundamental tissue property determined by water

Methods This was a retrospective study using a 128 patient subsample of patients, selected from the CE-MARC study such that the distribution of risk factors and disease status within the sample was representative of the full study population. Both visual and quantitative analysis were carried out using the AHA standardised 16 segment model. Visual analysis was part of the original CE-MARC study and was performed by 2 expert reviewers in consensus. To obtain qMBF estimates, manual contouring of the myocardium was carried out and individual qMBF estimates were obtained for each AHA segment using Fermi-constrained deconvolution. The arterial input function was taken from the left ventricular blood pool of the basal slice. Myocardial perfusion reserve values were calculated on a segment by segment basis by dividing the stress by the rest qMBF. The reference standard for myocardial ischaemia was a quantitative coronary X-ray angiogram (QCA) score of ≥70% in any of the coronary territories, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver operator characteristic (ROC) curve analysis. For visual analysis the summed score from all AHA segments was used as the diagnostic measure. For quantitative analysis the minimum MPR value from the AHA segments was used. A DeLong, DeLong, ClarkePearson analysis was performed to test for a statistically significant difference in the area under the curve (AUC) values between visual and quantitative analysis.

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

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

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

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 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.

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.

Introduction Dynamic contrast enhanced myocardial perfusion MRI (DCE-MRI) has the potential to be superior to other currently available imaging techniques for the assessment of myocardial ischaemia. Quantitative analysis of cardiac perfusion is currently not routinely carried out because of the time consuming process of manually segmenting the myocardium from large DCE-MRI datasets. A range of automated segmentation algorithms have been proposed which quote results in terms of distance error or estimated myocardial blood flow (MBF). However, the relationship between these two evaluation measures is not clear, making objective comparisons of algorithm performance difficult.

Introduction First pass cardiac magnetic resonance (CMR) myocardial perfusion imaging (MPI) requires the acquisition of large amounts of image data in a short time. Acceleration techniques like k-t SENSE exploit spatiotemporal correlations to speed up data acquisition. In myocardial perfusion CMR k-t SENSE has been used to improve spatial resolution, temporal resolution or slice coverage with improvements of endocardial dark rim artefacts reported. To date, there has been no direct comparison between these strategies.

Introduction Reperfusion of severely ischaemic myocardium can lead to interstitial haemorrhage due to irreversible vascular injury. Haemorrhagic infarction can be detected in vivo by cardiovascular magnetic resonance (CMR) as hypointense signal on T2-weighted and T2* imaging. However, the clinical implications of myocardial haemorrhage following acute myocardial infarction (AMI) remain undetermined.

Objectives: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFa) blocking therapy. Methods: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. Results: Sixteen patients (13 women) were studied; all had previously failed TNFa-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p,0.01 indicating a significant treatment effect), with particular reduction in IFNc of 252% (95% CI 273 to 215, p,0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE–MRI showed a reduction of 15– 40% in MRI parameters. Conclusion: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA. Understanding of disease pathogenesis in rheumatoid arthritis (RA) has led to novel approaches in targeted drug development. Despite the demonstrated success of tumour necrosis factor (TNF) antagonists, up to 50% of patients have an inadequate response to TNF blockade therapy. 1–4

Animal experiments using labelled microspheres have shown that at rest, blood flow to the subendocardial layer is higher than to the subepicardium. With increasing levels of stress this transmural gradient of myocardial blood flow is reduced, so that the endocardium has a lower perfusion reserve than the epicardium [1]. The causes for this observation include higher compressive forces and higher resting metabolic activity in the endocardium. If microvascular function is impaired, endocardial perfusion reserve is reduced further [2]. Myocardial perfusion-CMR is usually performed with coverage of several myocardial sections to allow detection of ischemic perfusion defects. Consequently, compromises regarding image quality and motion artefact are made. For the study of global physiological phenomena and diffuse myocardial disease, optimised acquisition of a single section may be more useful.

Background The presence and extent of microvascular obstruction (MO) after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR) or after gadolinium injection with early or late enhancement (EGE/LGE) imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE. Methods 34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI), underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm × 1.5 mm × 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA), EGE (1-4 minutes after injection with a fixed TI of 440 ms) and LGE images (10-12 minutes after injection, TI determined by a Look-Locker scout) were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology. Results k-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively). The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7) was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002) and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003). The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p < 0.001). Conclusion The extent of MO following acute myocardial infarction appears larger on high-resolution first-pass perfusion CMR than on EGE and LGE. Given the inevitable time delay between gadolinium administration and acquisition of either EGE or LGE images, high resolution first-pass perfusion imaging may be the most accurate method to quantify MO.

Dynamic contrast-enhanced MRI (DCE-MRI) has demonstrated high sensitivity for detection of breast cancer. Analysis of correlation between quantitative DCE-MRI findings and prognostic factors (such as histological tumour grade) is\ud important for defining the role of this technique in the diagnosis of breast cancer as well as the monitoring of neoadjuvant therapies. This paper presents a practical clinical application of a quantitative pharmacokinetic model to study histologically confirmed and graded invasive human breast tumours. The hypothesis is that, given a\ud documented difference in capillary permeability between benign and malignant breast tumours, a relationship between permeability-related DCE-MRI parameters and tumour\ud aggressiveness persists within invasive breast carcinomas. In addition, it was hypothesized that pharmacokinetic parameters may demonstrate stronger correlation with prognostic factors than the more conventional black-box techniques, so a comparison was undertaken. Significant correlations were found between pharmacokinetic and black-box parameters in 59 invasive breast carcinomas. However,\ud statistically significant variation with tumour grade was demonstrated in only two permeability-related pharmacokinetic parameters: kep (p,0.05) and Ktrans (p,0.05), using one-way analysis of variance. Parameters kep and Ktrans were significantly higher in Grade 3 tumours than in low-grade tumours. None of the measured DCE-MRI parameters varied significantly between Grade 1 and Grade 2 tumours. Measurement of kep and Ktrans might therefore be used to monitor the effectiveness of neoadjuvant\ud treatment of high-grade invasive breast carcinomas, but is unlikely to demonstrate remission in low-grade tumours.