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Background: Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Methods: Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. Results: All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p < 0.001) and controls (from 1194 ± 26 ms to 1273 ± 44 ms, p < 0. 001). T2DM patients showed blunted relative stress non-contrast T1 response (T2DM: ΔT1 = 4.1 ± 2.9% vs. controls: ΔT1 = 6.6 ± 2.6%, p = 0.007) due to a blunted maximal T1 during adenosine stress (T2DM 1244 ± 44 ms vs. controls 1273 ± 44 ms, p = 0.045). Conclusions: Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). Methods: 42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE). Results: AS patients had increased resting myocardial T1 (1196 ± 47 ms vs. 1168 ± 27 ms, p = 0.037), reduced MPRI (0.92 ± 0.31 vs. 1.74 ± 0.32, p < 0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240 ± 51 ms vs. 1238 ± 54 ms, p = 0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (AT1 3.7 ± 2.7% vs. 6.0 ± 4.2% in controls, p = 0.013). Seven months after AVR (n = 16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI. Conclusions: Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values. [ABSTRACT FROM AUTHOR]

Background Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds. Methods We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including:(1) dark-blood T2W imaging; (2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE. Results Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis. Conclusion Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In addition, T1-mapping offers significant incremental diagnostic value, detecting additional areas of myocardial involvement beyond T2W and LGE imaging and identified extra cases when these conventional methods failed to identify abnormalities. In the future, it may be possible to perform gadolinium-free CMR using cine and T1-mapping for tissue characterization and may be particularly useful for patients in whom gadolinium contrast is contraindicated. [ABSTRACT FROM AUTHOR]

Background Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc. Methods 19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification. Results Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices. Conclusions Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc. [ABSTRACT FROM AUTHOR]

Background: Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique. Methods: A large cohort of healthy volunteers (n = 342, 50% females, age 11-69 years) from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate. Results: Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent "midwall myocardial" T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intraindividual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average. Conclusion: Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of "myocardial midwall" T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping. [ABSTRACT FROM AUTHOR]

Objectives. The lumbar infusion test is an invasive technique for quantifying cerebrospinal dynamics in patients with hydrocephalus. However, some patients have difficulty tolerating the duration of this procedure. Therefore, we investigated the limits of shortening the test by examining the reliability of cerebrospinal fluid (CSF) compensatory parameters as a function of time. Methods. We analysed recordings of the intracranial cerebral pressure (ICP) response to a constant, high-rate infusion of saline (2 ml/min) lasting 5.7-20 (12 ± 10) min in 30 patients with a preliminary diagnosis of hydrocephalus (13 men, aged 37-81 [65 ± 10] years). We performed computerised identification of CSF outflow resistance ( Rout), intracranial compliance parameters: elastance index ( E) and reference pressure ( P0), based on the truncated ICP response (20-100% of the available test length), estimating either all three parameters (3p method) or only Rout and E (2p method) assuming P0 as the regression between the ICP and its amplitude. Results. Following considerable variation during the initial rise of ICP, Rout typically converged within ± 10% of their final values within 10-15 min. Final Rout values were 4-40 (12 ± 6) mmHg/ml/min, and were method independent (R2 == 0.97). Compliance parameters ( E, typically 0.1-0.5/ml; P0: - 10 to ++ 20 mmHg) agreed poorly between methods (R2 == 0.3-0.7) and varied considerably within the observed infusion periods. Conclusion. The lumbar infusion test may be shortened to 10-15 min using a rapid infusion rate of 2 ml/min that fulfils the primary objective of obtaining reliable estimates of Rout. This may benefit patients who do not tolerate the full procedure. [ABSTRACT FROM AUTHOR]

Background: T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR. Methods: We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium. Results: All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p<0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p<0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p<0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %. Conclusions: Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis. [ABSTRACT FROM AUTHOR]

Background: T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients. Materials and methods: The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms

Abstract: Changes in cerebral blood flow (f) and vascular volume (v) are of major interest in mapping cerebral activity and metabolism, but the relation between them currently lacks a sufficient theoretical basis. To address this we considered three models: a uniform reactive tube model (M1); an extension of M1 that includes passive arterial inflow and venous volume (M2); and a more anatomically plausible model (M3) consisting of 19 compartments representing the whole range of vascular sizes and respective CO2 reactivities, derived from literature data. We find that M2 cannot be described as the simple scaling of a tube law, but any divergence from a linear approximation is negligible within the narrow physiological range encountered experimentally. In order to represent correctly the empirically observed slope of the overall v–f relationship, the reactive bed should constitute about half of the total vascular volume, thus including a significant fraction of capillaries and/or veins. Model M3 demonstrates systematic variation of the slope of the v–f relationship between 0.16 and 1.0, depending on the vascular compartment under consideration. This is further complicated when other experimental approaches such as flow velocity are used as substitute measurements. The effect is particularly large in microvascular compartments, but when averaged with larger vessels the variations in slope are contained within 0.25 to 0.55 under conditions typical for imaging methods. We conclude that the v–f relationship is not a fixed function but that both the shape and slope depend on the composition of the reactive volume and the experimental methods used. [Copyright &y& Elsevier]

Background: Cholesterol and triglycerides are among the most well-known risk factors for cardiovascular disease.Objectives: This study investigated whether higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol level are causal risk factors for changes in prognostically important left ventricular (LV) parameters.Methods: One-sample Mendelian randomization (MR) of 17,311 European individuals from the UK Biobank with paired lipid and cardiovascular magnetic resonance data was performed. Two-sample MR was performed by using summary-level data from the Global Lipid Genetics Consortium (n = 188,577) and UK Biobank Cardiovascular Magnetic Resonance substudy (n = 16,923) for sensitivity analyses.Results: In 1-sample MR analysis, higher LDL cholesterol was causally associated with higher LV end-diastolic volume (β = 1.85 ml; 95% confidence interval [CI]: 0.59 to 3.14 ml; p = 0.004) and higher LV mass (β = 0.81 g; 95% CI: 0.11 to 1.51 g; p = 0.023) and triglycerides with higher LV mass (β = 1.37 g; 95% CI: 0.45 to 2.3 g; p = 0.004). High-density lipoprotein cholesterol had no significant association with any LV parameter. Similar results were obtained by using 2-sample MR. Observational analyses were frequently discordant with those derived from MR.Conclusions: MR analysis demonstrates that LDL cholesterol and triglycerides are associated with adverse changes in cardiac structure and function, in particular in relation to LV mass. These findings suggest that LDL cholesterol and triglycerides may have a causal effect in influencing cardiac morphology in addition to their established role in atherosclerosis. [ABSTRACT FROM AUTHOR]

A quiz related to a case study of a 38-year-old man with acute chest pain and left ventricular hypertrophy is presented.

An abstract of the article "The diagnostic performance of novel techniques for the detection of acute myocarditis: a clinical study using cardiovascular magnetic resonance imaging," by Vanessa Ferreira and colleagues is presented.

An abstract of the conference paper "T1-mapping accurately detects acute myocardial edema: A comparison to T2-weighted cardiovascular magnetic resonance imaging," by Daniel Messroghli and colleagues is presented.

An abstract of the conference paper "Single breath-hold Vd(m) calculation as good as multi breath-hold technique in Equilibrium Contrast CMR," by Daniel Sado and colleagues is presented.

An abstract of the conference paper "Age and gender dependence of pre-contrast T1-relaxation times in normal human myocardium at 1.5T using ShMOLLI," by Stefan K. Piechnik and colleagues is presented.

An abstract of the article " The diagnostic performance of non-contrast T1-mapping in patients with acute myocarditis on cardiovascular magnetic resonance imaging," by Vanessa Ferreira and colleagues is presented.

An abstract of the conference paper "Characterization of acute myocardial infarction by pre-contrast T1 mapping," by Stefan K. Piechnik and colleagues is presented.

An abstract of the conference paper "Histological validation of ShMOLLI equilibrium contrast CMR for the measurement of diffuse myocardial fibrosis," by Steven K. White and colleagues is presented.

An abstract of the paper "Gaussian Modelling for Operator-independent and Threshold-free Volumetric Segmentation of Phase Sensitive Inversion Recovery Late Gadolinium Enhanced Images," by Stefan K. Piechnik and colleagues, from the 2011 SCMR/Euro CMR Joint Scientific Sessions, held in Nice, France, from February 3-6, 2011, is presented.

An abstract of the paper "Quantification of Acute Myocardial Injury by ShMOLLI T1-Mapping, T2-Weighted and Late Gadolinium Imaging in Patients Presenting With Chest Pain, Positive Troponins and Non-Obstructive Coronary Arteries," by Vanessa M. Ferreira and colleagues is presented.

An abstract of the paper "Quantification of Acute Myocardial Injury in STEMI Patients Post Revascularization at 3Tesla. Comparison of T1-Mapping, Late Gadolinium and Edema Imaging," by Stefan K. Piechnik and colleagues is presented.

BACKGROUND: T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients. MATERIALS AND METHODS: The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms

Background: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems.Methods: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed.Results: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction.Conclusions: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized.Objectives: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR).Methods: A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]).Results: Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups.Conclusions: This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations. [ABSTRACT FROM AUTHOR]

Concentric left ventricular (LV) remodeling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodeling in diabetes per se is unclear, but it may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship between myocardial metabolic changes and LV remodeling in T2DM. Forty-six nonhypertensive patients with T2DM and 20 matched control subjects underwent cardiovascular magnetic resonance to assess LV remodeling (LV mass-to-LV end diastolic volume ratio), function, tissue characterization before and after contrast using T1 mapping, and (1)H and (31)P magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine-to-ATP ratio, respectively. When compared with BMI- and blood pressure-matched control subjects, subjects with diabetes were associated with concentric LV remodeling, higher MTG, impaired myocardial energetics, and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodeling and systolic strain. Extracellular volume fraction was unchanged, indicating the absence of fibrosis. In conclusion, cardiac steatosis may contribute to concentric remodeling and contractile dysfunction of the LV in diabetes. Because cardiac steatosis is modifiable, strategies aimed at reducing MTG may be beneficial in reversing concentric remodeling and improving contractile function in the hearts of patients with diabetes. [ABSTRACT FROM AUTHOR]

Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced. [ABSTRACT FROM AUTHOR]

Background Aortic stenosis (AS) leads to diffuse fibrosis in the myocardium, which is linked to adverse outcome. Myocardial T1 values change with tissue composition. Objective To test the hypothesis that our recently developed non-contrast cardiac magnetic resonance (CMR) T1 mapping sequence could identify myocardial fibrosis without contrast agent. Design, setting and patients A prospective CMR non-contrast T1 mapping study of 109 patients with moderate and severe AS and 33 age- and gendermatched controls. Methods CMR at 1.5 T, including non-contrast T1 mapping using a shortened modified Look-Locker inversion recovery sequence, was carried out. Biopsy samples for histological assessment of collagen volume fraction (CVF%) were obtained in 19 patients undergoing aortic valve replacement. Results There was a significant correlation between T1 values and CVF% (r=0.65, p=0.002). Mean T1 values were significantly longer in all groups with severe AS (972±33 ms in severe asymptomatic, 1014 ±38 ms in severe symptomatic) than in normal controls (944±16 ms) ( p<0.05). The strongest associations with T1 values were for aortic valve area (r=-0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008), and these were the only independent predictors on multivariate analysis. Conclusions Non-contrast T1 values are increased in patients with severe AS and further increase in symptomatic compared with asymptomatic patients. T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future. [ABSTRACT FROM AUTHOR]

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans.Methods: A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC.Results: A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second.Conclusions: VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality. [ABSTRACT FROM AUTHOR]

Adenosine stress T1-mapping on cardiovascular magnetic resonance (CMR) can differentiate between normal, ischemic, infarcted, and remote myocardial tissue classes without the need for contrast agents. Regadenoson, a selective coronary vasodilator, is often used in stress perfusion imaging when adenosine is contra-indicated, and has advantages in ease of administration, safety profile, and clinical workflow. We aimed to characterize the regadenoson stress T1-mapping response in healthy individuals, and to investigate its ability to differentiate between myocardial tissue classes in patients with coronary artery disease (CAD). Eleven healthy controls and 25 patients with CAD underwent regadenoson stress perfusion CMR, as well as rest and stress ShMOLLI T1-mapping. Native T1 values and stress T1 reactivity were derived for normal myocardium in healthy controls and for different myocardial tissue classes in patients with CAD. Healthy controls had normal myocardial native T1 values at rest (931 ± 22 ms) with significant global regadenoson stress T1 reactivity (δT1 = 8.2 ± 0.8% relative to baseline; p < 0.0001). Infarcted myocardium had significantly higher resting T1 (1215 ± 115 ms) than ischemic, remote, and normal myocardium (all p < 0.0001) with an abolished stress T1 response (δT1 = −0.8% [IQR: −1.9–0.5]). Ischemic myocardium had elevated resting T1 compared to normal (964 ± 57 ms; p < 0.01) with an abolished stress T1 response (δT1 = 0.5 ± 1.6%). Remote myocardium in patients had comparable resting T1 to normal (949 ms [IQR: 915–973]; p = 0.06) with blunted stress reactivity (δT1 = 4.3% [IQR: 3.1–6.3]; p < 0.0001). Healthy controls demonstrate significant stress T1 reactivity during regadenoson stress. Regadenoson stress and rest T1-mapping is a viable alternative to adenosine and exercise for the assessment of CAD and can distinguish between normal, ischemic, infarcted, and remote myocardium. • Regadenoson has advantages over adenosine in terms of administration, safety profile, and clinical workflow. • There are distinct tissue characteristics for normal, ischemic, infarcted, and remote myocardium. • Healthy controls demonstrate significant stress T1 reactivity during vasodilator stress. • Regadenoson stress T1-mapping can distinguish between different myocardial tissue classes. • Regadenoson stress T1-mapping is a viable alternative to adenosine and exercise for the assessment of coronary artery disease. [ABSTRACT FROM AUTHOR]

Cardiovascular magnetic resonance T1-mapping is increasingly used for tissue characterization, commonly based on Modified Look-Locker Inversion recovery (MOLLI). However, there are numerous MOLLI variants with differing normal ranges. This lack of standardization presents confusion and difficulty in inter-center comparisons, hindering widespread adoption of T1-mapping. To address this, we performed a structured literature search for native left ventricular myocardial T1-mapping in healthy humans measured using MOLLI variants at 1.5 and 3 Tesla, across scanner vendors. We then used k-means clustering to structure normal MOLLI-T1 values according to magnetic field strength, and investigated correlations between common imaging parameters: repetition time (TR), echo time (TE), flip angle (FA). We analyzed data from 2207 healthy controls in 76 independent reports. Normal MOLLI-T1 standard deviations varied by 11-fold, and dependencies on TE, TR, and FA differed between 1.5 T and 3 T, thwarting meaningful T1 standardization even within a single field strength, including the use of Z-score. However, divergent MOLLI-T1 norms may be structured using data clustering. For 1.5 T, two clusters emerged: Cluster1 1.5T : T1 = 958 ± 16 ms (n = 1280); Cluster2 1.5T : T1 = 1027 ± 19 ms (n = 386). For 3 T, three clusters emerged: Cluster1 3T : T1 = 1160 ± 21 ms (n = 330); Cluster2 3T : T1 = 1067 ± 18 ms (n = 178); Cluster3 3T : T1 = 1227 ± 19 ms (n = 41). We then propose the concept of an online calculator for assigning local norms to a known MOLLI-T1 cluster, allowing benchmarking against published norms. Clustered structuring allows T1 standardization of widely-divergent MOLLI variants, benchmarking local norms (usually based on smaller samples) against published norms (larger samples). This may increase confidence and quality control in method implementation, facilitating wider clinical adoption of T1-mapping. • Normal myocardial T1 values vary widely across different MOLLI T1-mapping methods. • Clustered structuring via an online calculator is practical for T1 standardization. • Clustered structuring allows benchmarking of local norms against published norms. • Clustered structuring increases confidence and quality in T1-mapping implementation. [ABSTRACT FROM AUTHOR]

Background: Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults.Methods: 5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45–54, 55–64, 65–74 years).Results: Overall, 721 (14.2%) truly healthy participants aged 45–74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97.Conclusions: We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.Objectives: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.Methods: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.Results: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).Conclusions: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality. [ABSTRACT FROM AUTHOR]

Myocardial T1-mapping is increasingly used in multicentre studies and trials. Inconsistent image analysis introduces variability, hinders differentiation of diseases, and results in larger sample sizes. We present a systematic approach to standardize T1-map analysis by human operators to improve accuracy and consistency. We developed a multi-step training program for T1-map post-processing. The training dataset contained 42 left ventricular (LV) short-axis T1-maps (normal and diseases; 1.5 and 3 Tesla). Contours drawn by two experienced human operators served as reference for myocardial T1 and wall thickness (WT). Trainees (n = 26) underwent training and were evaluated by: (a) qualitative review of contours; (b) quantitative comparison with reference T1 and WT. The mean absolute difference between reference operators was 8.4 ± 6.3 ms (T1) and 1.2 ± 0.7 pixels (WT). Trainees' mean discrepancy from reference in T1 improved significantly post-training (from 8.1 ± 2.4 to 6.7 ± 1.4 ms; p < 0.001), with a 43% reduction in standard deviation (SD) (p = 0.035). WT also improved significantly post-training (from 0.9 ± 0.4 to 0.7 ± 0.2 pixels, p = 0.036), with 47% reduction in SD (p = 0.04). These experimentally-derived thresholds served to guide the training process: T1 (±8 ms) and WT (±1 pixel) from reference. A standardized approach to CMR T1-map image post-processing leads to significant improvements in the accuracy and consistency of LV myocardial T1 values and wall thickness. Improving consistency between operators can translate into 33–72% reduction in clinical trial sample-sizes. This work may: (a) serve as a basis for re-certification for core-lab operators; (b) translate to sample-size reductions for clinical studies; (c) produce better-quality training datasets for machine learning. • T1-mapping MRI is increasingly being employed as a Cardiovascular MRI technique in clinical studies and trials. • Standardisation of T1 mapping post-processing is still limited, hindering reproducibility and consistency across centres. • High-quality manual contouring of T1 maps is crucial to ensure good quality training data for machine learning algorithms. • Our training programme shows statistically significant reduction in discrepancy between operators analysing T1 maps. [ABSTRACT FROM AUTHOR]

Background: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.Objectives: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.Methods: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.Results: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.Conclusions: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk. Pregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40–69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors. Data were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1). Women who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear at present.Methods: The LV parameters were measured from the cardiovascular magnetic resonance studies of the UK Biobank. Genotyping was done using Affymetrix arrays, augmented by imputation. We performed genome-wide association studies of 6 LV traits-LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction, LV mass, and LV mass to end-diastolic volume ratio. The replication analysis was performed in the MESA study (Multi-Ethnic Study of Atherosclerosis). We identified the candidate genes at genome-wide significant loci based on the evidence from extensive bioinformatic analyses. Polygenic risk scores were constructed from the summary statistics of LV genome-wide association studies to predict the heart failure events.Results: The study comprised 16 923 European UK Biobank participants (mean age 62.5 years; 45.8% men) without prevalent myocardial infarction or heart failure. We discovered 14 genome-wide significant loci (3 loci each for LV end-diastolic volume, LV end-systolic volume, and LV mass to end-diastolic volume ratio; 4 loci for LV ejection fraction, and 1 locus for LV mass) at a stringent P<1×10-8. Three loci were replicated at Bonferroni significance and 7 loci at nominal significance (P<0.05 with concordant direction of effect) in the MESA study (n=4383). Follow-up bioinformatic analyses identified 28 candidate genes that were enriched in the cardiac developmental pathways and regulation of the LV contractile mechanism. Eight genes (TTN, BAG3, GRK5, HSPB7, MTSS1, ALPK3, NMB, and MMP11) supported by at least 2 independent lines of in silico evidence were implicated in the cardiac morphogenesis and heart failure development. The polygenic risk scores of LV phenotypes were predictive of heart failure in a holdout UK Biobank sample of 3106 cases and 224 134 controls (odds ratio 1.41, 95% CI 1.26 - 1.58, for the top quintile versus the bottom quintile of the LV end-systolic volume risk score).Conclusions: We report 14 genetic loci and indicate several candidate genes that not only enhance our understanding of the genetic architecture of prognostically important LV phenotypes but also shed light on potential novel therapeutic targets for LV remodeling. [ABSTRACT FROM AUTHOR]

Background and aims: Non-invasive assessment of portal hypertension is an area of unmet need. This proof of concept study aimed to evaluate the diagnostic accuracy of a multi-parametric magnetic resonance technique in the assessment of portal hypertension. Comparison to other non-invasive technologies was a secondary aim. Methods: T1 and T2* maps through the liver and spleen were acquired prior to trans-jugular liver biopsy and hepatic vein pressure gradient (HVPG) measurement. T1 measurements reflect changes in tissue water content, but this relationship is confounded by the presence of iron, which in turn can be quantified accurately from T2* maps. Data were analysed using LiverMultiScan (Perspectum Diagnostics, Oxford, UK) which applies an algorithm to remove the confounding effect of iron, yielding the "iron corrected T1" (cT1). Sensitivity, specificity, diagnostic values and area under the curve were derived for spleen cT1, liver cT1, transient elastography, and serum fibrosis scores. HVPG was the reference standard. Results: Nineteen patients (15 men) with median age 57 years were included. Liver disease aetiologies included non-alcoholic fatty liver disease (n = 9; 47%) and viral hepatitis (n = 4; 21%). There was strong correlation between spleen cT1 and HVPG (r = 0.69; p = 0.001). Other non-invasive biomarkers did not correlate with HVPG. Spleen cT1 had excellent diagnostic accuracy for portal hypertension (HVPG >5 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) with an area under the receiver operating characteristic curve of 0.92 for both. Conclusion: Spleen cT1 is a promising biomarker of portal pressure that outperforms other non-invasive scores and should be explored further. [ABSTRACT FROM AUTHOR]

Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk. Such studies pose new challenges requiring automatic image analysis. To date, few large-scale population-level cardiac imaging studies have been conducted. One such study stands out for its sheer size, careful implementation, and availability of top quality expert annotation; the UK Biobank (UKB). The resulting massive imaging datasets (targeting ca. 100,000 subjects) has put published approaches for cardiac image quantification to the test. In this paper, we present and evaluate a cardiac magnetic resonance (CMR) image analysis pipeline that properly scales up and can provide a fully automatic analysis of the UKB CMR study. Without manual user interactions, our pipeline performs end-to-end image analytics from multi-view cine CMR images all the way to anatomical and functional bi-ventricular quantification. All this, while maintaining relevant quality controls of the CMR input images, and resulting image segmentations. To the best of our knowledge, this is the first published attempt to fully automate the extraction of global and regional reference ranges of all key functional cardiovascular indexes, from both left and right cardiac ventricles, for a population of 20,000 subjects imaged at 50 time frames per subject, for a total of one million CMR volumes. In addition, our pipeline provides 3D anatomical bi-ventricular models of the heart. These models enable the extraction of detailed information of the morphodynamics of the two ventricles for subsequent association to genetic, omics, lifestyle habits, exposure information, and other information provided in population imaging studies. We validated our proposed CMR analytics pipeline against manual expert readings on a reference cohort of 4620 subjects with contour delineations and corresponding clinical indexes. Our results show broad significant agreement between the manually obtained reference indexes, and those automatically computed via our framework. 80.67% of subjects were processed with mean contour distance of less than 1 pixel, and 17.50% with mean contour distance between 1 and 2 pixels. Finally, we compare our pipeline with a recently published approach reporting on UKB data, and based on deep learning. Our comparison shows similar performance in terms of segmentation accuracy with respect to human experts. [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance (CMR) images play a growing role in the diagnostic imaging of cardiovascular diseases. Full coverage of the left ventricle (LV), from base to apex, is a basic criterion for CMR image quality and is necessary for accurate measurement of cardiac volume and functional assessment. Incomplete coverage of the LV is identified through visual inspection, which is time consuming and usually done retrospectively in the assessment of large imaging cohorts. This paper proposes a novel automatic method for determining LV coverage from CMR images by using Fisher-discriminative three-dimensional (FD3D) convolutional neural networks (CNNs). In contrast to our previous method employing 2-D CNNs, this approach utilizes spatial contextual information in CMR volumes, extracts more representative high-level features, and enhances the discriminative capacity of the baseline 2-D CNN learning framework, thus, achieving superior detection accuracy. A two-stage framework is proposed to identify missing basal and apical slices in measurements of CMR volume. First, the FD3D CNN extracts high-level features from the CMR stacks. These image representations are then used to detect the missing basal and apical slices. Compared to the traditional 3-D CNN strategy, the proposed FD3D CNN minimizes within-class scatter and maximizes between-class scatter. We performed extensive experiments to validate the proposed method on more than 5000 independent volumetric CMR scans from the UK Biobank study, achieving low error rates for missing basal/apical slice detection (4.9%/4.6%). The proposed method can also be adopted for assessing LV coverage for other types of CMR image data. [ABSTRACT FROM AUTHOR]

Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia.Objectives: This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia.Methods: A total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T.Results: Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036).Conclusions: DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor. [ABSTRACT FROM AUTHOR]

Introduction: Aortic distensibility can be calculated using semi-automated methods to segment the aortic lumen on cine CMR (Cardiovascular Magnetic Resonance) images. However, these methods require visual quality control and manual localization of the region of interest (ROI) of ascending (AA) and proximal descending (PDA) aorta, which limit the analysis in large-scale population-based studies. Using 5100 scans from UK Biobank, this study sought to develop and validate a fully automated method to 1) detect and locate the ROIs of AA and PDA, and 2) provide a quality control mechanism. Methods: The automated AA and PDA detection-localization algorithm followed these steps: 1) foreground segmentation; 2) detection of candidate ROIs by Circular Hough Transform (CHT); 3) spatial, histogram and shape feature extraction for candidate ROIs; 4) AA and PDA detection using Random Forest (RF); 5) quality control based on RF detection probability. To provide the ground truth, overall image quality (IQ = 0–3 from poor to good) and aortic locations were visually assessed by 13 observers. The automated algorithm was trained on 1200 scans and Dice Similarity Coefficient (DSC) was used to calculate the agreement between ground truth and automatically detected ROIs. Results: The automated algorithm was tested on 3900 scans. Detection accuracy was 99.4% for AA and 99.8% for PDA. Aorta localization showed excellent agreement with the ground truth, with DSC ≥ 0.9 in 94.8% of AA (DSC = 0.97 ± 0.04) and 99.5% of PDA cases (DSC = 0.98 ± 0.03). AA×PDA detection probabilities could discriminate scans with IQ ≥ 1 from those severely corrupted by artefacts (AUC = 90.6%). If scans with detection probability < 0.75 were excluded (350 scans), the algorithm was able to correctly detect and localize AA and PDA in all the remaining 3550 scans (100% accuracy). Conclusion: The proposed method for automated AA and PDA localization was extremely accurate and the automatically derived detection probabilities provided a robust mechanism to detect low quality scans for further human review. Applying the proposed localization and quality control techniques promises at least a ten-fold reduction in human involvement without sacrificing any accuracy. [ABSTRACT FROM AUTHOR]

Background: Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders.Methods: Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders.Results: The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter <2.5 μm concentration was significantly associated with larger left ventricular end-diastolic volume and end-systolic volume (effect size = 0.82%, 95% CI, 0.09-1.55%, P=0.027; and effect size = 1.28%, 95% CI, 0.15-2.43%, P=0.027, respectively, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm) and right ventricular end-diastolic volume (effect size = 0.85%, 95% CI, 0.12-1.58%, P=0.023, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm). Likewise, higher nitrogen dioxide concentration was associated with larger biventricular volume. Distance from the major roads was the only metric associated with lower left ventricular mass (effect size = -0.74%, 95% CI, -1.3% to -0.18%, P=0.01, per interquartile range increment). Neither left and right atrial phenotypes nor left ventricular geometric remodeling patterns were influenced by the ambient pollutants.Conclusions: In a large asymptomatic population with no prevalent cardiovascular disease, higher past exposure to particulate matter with an aerodynamic diameter <2.5 μm and nitrogen dioxide was associated with cardiac ventricular dilatation, a marker of adverse remodeling that often precedes heart failure development. [ABSTRACT FROM AUTHOR]

Abstract Background Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are common disorders associated with increased rates of cardiovascular disease (CVD), but the contribution of cytokine-induced inflammation to impaired cardiovascular function in these conditions remains poorly understood. Objectives We assessed the effect of anti-TNF therapy on myocardial and vascular function, myocardial tissue characteristics and perfusion in inflammatory arthropathy and systemic rheumatic disease (IASRD) patients, using cardiovascular magnetic resonance (CMR). Methods 20 RA patients, 7 AS patients, 5 PsA patients without previously known CVD scheduled to commence anti-TNF therapy and 8 RA patients on standard disease modifying antirheumatic drugs underwent CMR at 1.5 T, including cine, tagging, pulse wave velocity (PWV), T2-weighted, native and postcontrast T1 mapping, ECV quantification, rest and stress perfusion and late gadolinium enhancement (LGE) imaging. Results Following anti-TNF therapy, there was significant reversal of baseline subclinical cardiovascular dysfunction, as evidenced by improvement in peak systolic circumferential strain (p < 0.001), peak diastolic circumferential strain rate (p < 0.001), and total aortic PWV, (p < 0.001). This was accompanied by a reduction in myocardial inflammation, as assessed by T2-weighted imaging (p = 0.005), native T1 mapping (p = 0.009) and ECV quantification (p = 0.001), as well as in serum inflammatory markers like CRP (p < 0.001) and ESR (p < 0.001), and clinical measures of disease activity (DAS28-CRP, p = 0.001; BASDAI, p < 0.001). A trend towards improvement in myocardial perfusion was observed (p = 0.07). Focal myocardial fibrosis, as detected by LGE CMR was not altered by anti-TNF therapy (p = 0.92). Conclusions Anti-TNF therapy reduces subclinical myocardial inflammation and improves cardiovascular function in RA, AS and PsA. CMR may be used to track disease progression and response to therapy. Future CMR-based studies to demonstrate effect of anti-TNF therapy modulation of vascular structure and function on hard clinical events and outcomes would be useful. Highlights • We hypothesized that anti-TNF therapy would result in an improvement in myocardial and vascular characteristics in patients with IASRDs. • We show that CMR can detect subclinical cardiovascular involvement and track response to anti-TNF therapy in asymptomatic RA, AS and PsA patients. • Anti-TNF therapy improves strain, diastolic strain rate, aortic stiffness, and myocardial edema (T2-weighted, T1 and ECV quantification). • While a trend towards improvement in myocardial perfusion was observed, this did not reach statistical significance. • These novel observations were supported by parallel improvements in inflammatory parameters (CRP and ESR) and in disease activity indices. [ABSTRACT FROM AUTHOR]

Background: Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung function and cardiovascular structure in individuals with pulmonary disease, but the relationships in those free from diagnosed cardiorespiratory disease have not been fully explored. Methods: UK Biobank is a prospective cohort study of community participants in the United Kingdom. Individuals self-reported demographics and co-morbidities, and a subset underwent cardiovascular magnetic resonance (CMR) imaging and spirometry. CMR images were analysed to derive ventricular volumes and mass. The relationships between CMR-derived measures and spirometry and age were modelled with multivariable linear regression, taking account of the effects of possible confounders. Results: Data were available for 4,975 individuals, and after exclusion of those with pre-existing cardiorespiratory disease and unacceptable spirometry, 1,406 were included in the analyses. In fully-adjusted multivariable linear models lower FEV1 and FVC were associated with smaller left ventricular end-diastolic (−5.21ml per standard deviation (SD) change in FEV1, −5.69ml per SD change in FVC), end-systolic (−2.34ml, −2.56ml) and stroke volumes (−2.85ml, −3.11ml); right ventricular end-diastolic (−5.62ml, −5.84ml), end-systolic (−2.47ml, −2.46ml) and stroke volumes (−3.13ml, −3.36ml); and with lower left ventricular mass (−2.29g, −2.46g). Changes of comparable magnitude and direction were observed per decade increase in age. Conclusions: This study shows that reduced FEV1 and FVC are associated with smaller ventricular volumes and reduced ventricular mass. The changes seen per standard deviation change in FEV1 and FVC are comparable to one decade of ageing. [ABSTRACT FROM AUTHOR]

Background: Handgrip strength, a measure of muscular fitness, is associated with cardiovascular (CV) events and CV mortality but its association with cardiac structure and function is unknown. The goal of this study was to determine if handgrip strength is associated with changes in cardiac structure and function in UK adults. Methods and results: Left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), mass (M), and mass-to-volume ratio (MVR) were measured in a sample of 4,654 participants of the UK Biobank Study 6.3 ± 1 years after baseline using cardiovascular magnetic resonance (CMR). Handgrip strength was measured at baseline and at the imaging follow-up examination. We determined the association between handgrip strength at baseline as well as its change over time and each of the cardiac outcome parameters. After adjustment, higher level of handgrip strength at baseline was associated with higher LVEDV (difference per SD increase in handgrip strength: 1.3ml, 95% CI 0.1–2.4; p = 0.034), higher LVSV (1.0ml, 0.3–1.8; p = 0.006), lower LVM (-1.0g, -1.8 –-0.3; p = 0.007), and lower LVMVR (-0.013g/ml, -0.018 –-0.007; p<0.001). The association between handgrip strength and LVEDV and LVSV was strongest among younger individuals, while the association with LVM and LVMVR was strongest among older individuals. Conclusions: Better handgrip strength was associated with cardiac structure and function in a pattern indicative of less cardiac hypertrophy and remodeling. These characteristics are known to be associated with a lower risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The effect of menopausal hormone therapy (MHT)–previously known as hormone replacement therapy–on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort. Methods: Post-menopausal women who had never used MHT and those who had used MHT ≥3 years participating in the UK Biobank who had undergone cardiovascular magnetic resonance (CMR) imaging and free of known cardiovascular disease were included. Multivariable linear regression was performed to examine the relationship between cardiac parameters and MHT use ≥3 years. To explore whether MHT use on each of the cardiac outcomes differed by age, multivariable regression models were constructed with a cross-product of age and MHT fitted as an interaction term. Results: Of 1604 post-menopausal women, 513 (32%) had used MHT ≥3 years. In the MHT cohort, median age at menopause was 50 (IQR: 45–52) and median duration of MHT was 8 years. In the non-MHT cohort, median age at menopause was 51 (IQR: 48–53). MHT use was associated with significantly lower LV end-diastolic volume (122.8 ml vs 119.8 ml, effect size = -2.4%, 95% CI: -4.2% to -0.5%; p = 0.013) and LA maximal volume (60.2 ml vs 57.5 ml, effect size = -4.5%, 95% CI: -7.8% to -1.0%; p = 0.012). There was no significant difference in LV mass. MHT use significantly modified the effect between age and CMR parameters; MHT users had greater decrements in LV end-diastolic volume, LV end-systolic volume and LA maximal volume with advancing age. Conclusions: MHT use was not associated with adverse, subclinical changes in cardiac structure and function. Indeed, significantly smaller LV and LA chamber volumes were observed which have been linked to favourable cardiovascular outcomes. These findings represent a novel approach to examining MHT’s effect on the cardiovascular system. [ABSTRACT FROM AUTHOR]

Background: In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD).Objectives: The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography.Methods: Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements.Results: In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value.Conclusions: In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation. [ABSTRACT FROM AUTHOR]

Background: Novel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow.Objectives: This study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.8 and the index of microcirculatory resistance (IMR ≥25 U), compared with first-pass perfusion imaging.Methods: Ninety subjects (60 patients with angina; 30 healthy control subjects) underwent CMR (1.5- and 3-T) to assess left ventricular function (cine), ischemia (adenosine stress/rest T1 mapping and perfusion), and infarction (late gadolinium enhancement). FFR and IMR were assessed ≤7 days post-CMR. Stress and rest images were analyzed blinded to other information.Results: Normal myocardial T1 reactivity (ΔT1) was 6.2 ± 0.4% (1.5-T) and 6.2 ± 1.3% (3-T). Ischemic viable myocardium downstream of obstructive CAD showed near-abolished T1 reactivity (ΔT1 = 0.7 ± 0.7%). Myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction showed less-blunted T1 reactivity (ΔT1 = 3.0 ± 0.9%). Stress T1 mapping significantly outperformed gadolinium-based first-pass perfusion, including absolute quantification of myocardial blood flow, for detecting obstructive CAD (area under the receiver-operating characteristic curve: 0.97 ± 0.02 vs. 0.91 ± 0.03, respectively; p < 0.001). A ΔT1 of 1.5% accurately detected obstructive CAD (sensitivity: 93%; specificity: 95%; p < 0.001), whereas a less-blunted ΔT1 of 4.0% accurately detected microvascular dysfunction (area under the receiver-operating characteristic curve: 0.95 ± 0.03; sensitivity: 94%; specificity: 94%: p < 0.001).Conclusions: CMR stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation. [ABSTRACT FROM AUTHOR]

Aims: The UK Biobank is a large-scale population-based study utilising cardiovascular magnetic resonance (CMR) to generate measurements of atrial and ventricular structure and function. This study aimed to quantify the association between modifiable cardiovascular risk factors and cardiac morphology and function in individuals without known cardiovascular disease. Methods: Age, sex, ethnicity (non-modifiable) and systolic blood pressure, diastolic blood pressure, smoking status, exercise, body mass index (BMI), high cholesterol, diabetes, alcohol intake (modifiable) were considered important cardiovascular risk factors. Multivariable regression models were built to ascertain the association of risk factors on left ventricular (LV), right ventricular (RV), left atrial (LA) and right atrial (RA) CMR parameters. Results: 4,651 participants were included in the analysis. All modifiable risk factors had significant effects on differing atrial and ventricular parameters. BMI was the modifiable risk factor most consistently associated with subclinical changes to CMR parameters, particularly in relation to higher LV mass (+8.3% per SD [4.3 kg/m2], 95% CI: 7.6 to 8.9%), LV (EDV: +4.8% per SD, 95% CI: 4.2 to 5.4%); ESV: +4.4% per SD, 95% CI: 3.5 to 5.3%), RV (EDV: +5.3% per SD, 95% CI: 4.7 to 5.9%; ESV: +5.4% per SD, 95% CI: 4.5 to 6.4%) and LA maximal (+8.6% per SD, 95% CI: 7.4 to 9.7%) volumes. Increases in SBP were associated with higher LV mass (+6.8% per SD, 95% CI: 5.9 to 7.7%), LV (EDV: +4.5% per SD, 95% CI: 3.6 to 5.4%; ESV: +2.0% per SD, 95% CI: 0.8 to 3.3%) volumes. The presence of diabetes or high cholesterol resulted in smaller volumes and lower ejection fractions. Conclusions: Modifiable risk factors are associated with subclinical alterations in structure and function in all four cardiac chambers. BMI and systolic blood pressure are the most important modifiable risk factors affecting CMR parameters known to be linked to adverse outcomes. [ABSTRACT FROM AUTHOR]