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In patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease. In this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used 99mTc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133. In the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8–90·1), specificity 83·4% (79·5–86·7), positive predictive value 77·2%, (72·1–81·6) and negative predictive value 90·5% (87·1–93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4–72·1), specificity 82·6% (78·5–86·1), positive predictive value 71·4% (65·3–76·9), and negative predictive value 79·1% (74·8–82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively). CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR's high diagnostic accuracy in coronary heart disease and CMR's superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease. British Heart Foundation.

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

This is the second of two reviews that is intended to cover the essential aspects of cardiovascular magnetic resonance (CMR) physics in a way that is understandable and relevant to clinicians using CMR in their daily practice. Starting with the basic pulse sequences and contrast mechanisms described in part I, it briefly discusses further approaches to accelerate image acquisition. It then continues by showing in detail how the contrast behaviour of black blood fast spin echo and bright blood cine gradient echo techniques can be modified by adding rf preparation pulses to derive a number of more specialised pulse sequences. The simplest examples described include T2-weighted oedema imaging, fat suppression and myocardial tagging cine pulse sequences. Two further important derivatives of the gradient echo pulse sequence, obtained by adding preparation pulses, are used in combination with the administration of a gadolinium-based contrast agent for myocardial perfusion imaging and the assessment of myocardial tissue viability using a late gadolinium enhancement (LGE) technique. These two imaging techniques are discussed in more detail, outlining the basic principles of each pulse sequence, the practical steps required to achieve the best results in a clinical setting and, in the case of perfusion, explaining some of the factors that influence current approaches to perfusion image analysis. The key principles of contrast-enhanced magnetic resonance angiography (CE-MRA) are also explained in detail, especially focusing on timing of the acquisition following contrast agent bolus administration, and current approaches to achieving time resolved MRA. Alternative MRA techniques that do not require the use of an endogenous contrast agent are summarised, and the specialised pulse sequence used to image the coronary arteries, using respiratory navigator gating, is described in detail. The article concludes by explaining the principle behind phase contrast imaging techniques which create images that represent the phase of the MR signal rather than the magnitude. It is shown how this principle can be used to generate velocity maps by designing gradient waveforms that give rise to a relative phase change that is proportional to velocity. Choice of velocity encoding range and key pitfalls in the use of this technique are discussed.

Background Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping. Methods This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2. Results Twenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (− 25 ml, p = 0.002), LV stroke volume (− 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (− 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters. Conclusions Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

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

Background Cardiovascular magnetic resonance (CMR) can through the two methods 3D FLASH and diffusion tensor imaging (DTI) give complementary information on the local orientations of cardiomyocytes and their laminar arrays. Methods Eight explanted rat hearts were perfused with Gd-DTPA contrast agent and fixative and imaged in a 9.4T magnet by two types of acquisition: 3D fast low angle shot (FLASH) imaging, voxels 50 × 50 × 50 μm, and 3D spin echo DTI with monopolar diffusion gradients of 3.6 ms duration at 11.5 ms separation, voxels 200 × 200 × 200 μm. The sensitivity of each approach to imaging parameters was explored. Results The FLASH data showed laminar alignments of voxels with high signal, in keeping with the presumed predominance of contrast in the interstices between sheetlets. It was analysed, using structure-tensor (ST) analysis, to determine the most ( v 1 ST ), intermediate ( v 2 ST ) and least ( v 3 ST ) extended orthogonal directions of signal continuity. The DTI data was analysed to determine the most ( e 1 DTI ), intermediate ( e 2 DTI ) and least ( e 3 DTI ) orthogonal eigenvectors of extent of diffusion. The correspondence between the FLASH and DTI methods was measured and appraised. The most extended direction of FLASH signal ( v 1 ST ) agreed well with that of diffusion ( e 1 DTI ) throughout the left ventricle (representative discrepancy in the septum of 13.3 ± 6.7°: median ± absolute deviation) and both were in keeping with the expected local orientations of the long-axis of cardiomyocytes. However, the orientation of the least directions of FLASH signal continuity ( v 3 ST ) and diffusion ( e 3 ST ) showed greater discrepancies of up to 27.9 ± 17.4°. Both FLASH ( v 3 ST ) and DTI ( e 3 DTI ) where compared to directly measured laminar arrays in the FLASH images. For FLASH the discrepancy between the structure-tensor calculated v 3 ST and the directly measured FLASH laminar array normal was of 9 ± 7° for the lateral wall and 7 ± 9° for the septum (median ± inter quartile range), and for DTI the discrepancy between the calculated v 3 DTI and the directly measured FLASH laminar array normal was 22 ± 14° and 61 ± 53.4°. DTI was relatively insensitive to the number of diffusion directions and to time up to 72 hours post fixation, but was moderately affected by b-value (which was scaled by modifying diffusion gradient pulse strength with fixed gradient pulse separation). Optimal DTI parameters were b = 1000 mm/s 2 and 12 diffusion directions. FLASH acquisitions were relatively insensitive to the image processing parameters explored. Conclusions We show that ST analysis of FLASH is a useful and accurate tool in the measurement of cardiac microstructure. While both FLASH and the DTI approaches appear promising for mapping of the alignments of myocytes throughout myocardium, marked discrepancies between the cross myocyte anisotropies deduced from each method call for consideration of their respective limitations.

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. 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. 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). 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.

We develop a curvilinear invariant set of the diffusion tensor which may be applied to Diffusion Tensor Imaging measurements on tissues and porous media. This new set is an alternative to the more common invariants such as fractional anisotropy and the diffusion mode. The alternative invariant set possesses a different structure to the other known invariant sets; the second and third members of the curvilinear set measure the degree of orthotropy and oblateness/prolateness, respectively. The proposed advantage of these invariants is that they may work well in situations of low diffusion anisotropy and isotropy, as is often observed in tissues such as cartilage. We also explore the other orthogonal invariant sets in terms of their geometry in relation to eigenvalue space; a cylindrical set, a spherical set (including fractional anisotropy and the mode), and a log-Euclidean set. These three sets have a common structure. The first invariant measures the magnitude of the diffusion, the second and third invariants capture aspects of the anisotropy; the magnitude of the anisotropy and the shape of the diffusion ellipsoid (the manner in which the anisotropy is realised). We also show a simple method to prove the orthogonality of the invariants within a set.

Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness. This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness. The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT. Current Controlled Trials ISRCTN77246133.

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