Magnetic resonance imaging (MRI) has become an important non-invasive imaging modality in the evaluation of cardiovascular diseases because of advances in scanner hardware, coil technology, parallel-imaging techniques and MRI sequences, all of which facilitate the rapid acquisition of high-quality images. Several scientific studies validated the use of MRI in cardiovascular diseases and showed good correlation with histological and clinical outcome data.1 MRI has spatio-temporal resolution, wide field-of-view and multiplanar reconstruction capabilities. MRI does not require ionising radiation and can be used safely in most patients, except those with contraindications such as metallic devices or pacemakers. Intravenous gadolinium-based contrast agents should be used with caution in patients with severe renal dysfunction, because of the risk of nephrogenic systemic fibrosis.
The clinical cardiac MRI scan is performed using magnets of high field strength (1.5 or 3 Tesla), multichannel phased-array coils, parallel imaging techniques and echocardiogram gating. Cine steady-state free precession (SSFP) sequences are used in the evaluation of cardiac morphology and function and are acquired in several dimensions, such as the short axis and horizontal long axis planes and the two-chamber, three-chamber and four-chamber projections. Phase-contrast images are used in the evaluation of flow. T1- and T2-weighted black-blood spin-echo images are used in the evaluation of cardiac and pericardiac morphology. Following intravenous gadolinium administration, early and delayed (10–15 minutes) post-contrast images are acquired using fast spin-echo and inversion recovery sequences, respectively. Angiography can be performed either with intravenous contrast using a T1-weighted spoiled gradient-echo sequence, or without contrast using a 3D navigator-gated SSFP sequence. In this article, we discuss the current role and applications of cardiovascular MRI.
Cardiac Function
MRI is now considered the gold standard in the evaluation of myocardial function because of its high accuracy as well as inter- and intra-observer reproducibility.1,2 Left ventricular (LV) and right ventricular (RV) function is quantified using SSFP images in the short axis and horizontal long axis planes, respectively. Endocardial and epicardial contours are drawn manually or automatically. Several parameters, such as ejection fraction, chamber volumes and cardiac mass, can be quantified. MRI is the ideal technique in the longitudinal follow-up of patients undergoing therapeutic interventions or participating in clinical trials. The high reproducibility of MRI means that the sample size required for clinical trials is smaller than that required if using echocardiography. Regional myocardial function can be estimated visually in an SSFP sequence, but can be quantified more accurately using myocardial tagging techniques such as spatial modulation of magnetisation. Abnormalities in regional function generally precede global functional changes. MRI can accurately estimate diastolic function using either tagging technique or phase-contrast images acquired at the level of the mitral valve leaflets (E, A values), basal lateral LV myocardium (E¹, A¹ values) and pulmonary vein (X, Y, Z values). An E/E¹ ratio of greater than 15 is diagnostic of diastolic dysfunction and correlates with an elevated LV filling pressure and poor prognosis.3
Ischaemic Heart Disease
MRI has clinical applications at all stages of ischaemic heart disease. yocardial perfusion is evaluated following intravenous injection of gadolinium, both at rest and after exercise-induced or pharmacological stress (adenosine or dipyridamole). In myocardial ischaemia, a perfusion defect is seen as a dark band in the stressimages, but the rest images are normal. MRI perfusion imaging has igh sensitivity and accuracy in the evaluation of myocardial ischaemia and has good correlation with nuclear scintigraphy and coronary and fractional flow reserves.4 In the acute setting, after exclusion of myocardial infarction (MI) by serial troponin assays, MRI has high prognostic value, detecting 100 % of patients with adverse cardiovascular outcomes.5 Blood oxygenation level-dependent MRI is a novel technique, in which myocardial ischaemia can be determined without using intravenous contrast, through differences in signal intensity between oxygenated and deoxygenated haemoglobin. MRIalso has high sensitivity and specificity, comparable to those of echocardiography, in detecting wall-motion abnormalities following dobutamine-induced stress.6
MRI is the most valuable imaging technique in the evaluation of myocardial viability because of its high sensitivity and accuracy.7 Indelayed-enhancement images, normal myocardium appears dark while scar appears bright. Scar can be assessed either qualitatively or quantitatively using several scoring techniques, such as the summed scar score and transmurality index. In MI, delayed enhancement is seen in the acute stage because of myocardial necrosis and loss of cell membrane integrity, and in the chronicstage because of increased uptake and retention in the scar. Scar is seen in a subendocardial or transmural distribution, confined to a vascular territory (see Figure 1). Excellent correlation has been shown between the quantity of scar seen on MRI and histology, while there is an inverse correlation between the amount of scarand the potential for functional restoration following myocardial revascularisation procedures.7 While segments with scar >75 % of myocardial thickness have a less than 5 % chance of functional improvement, segments with scar <50 % of myocardial thickness have a greater than 70 % chance of functional improvement.7
In acute MI, myocardial oedema is seen in T2-weighted MRI equences as a high myocardial signal. Potentially, this technique can be used in the emergency room to diagnose, with a high degree of accuracy, MI in patients with typical and atypical chest pain.8 The extent of myocardial oedema is generally larger than that of delayed enhancement, and this difference is considered the ‘area at risk’ salvageable following revascularisation. In both the acute and chronic settings, MRI can be used to distinguish MI from other pathologies with similar presentation, which has major therapeutic implications. In acute MI, microvascular obstruction is seen as a non-enhanced area within an enhanced scar, and is considered an adverse prognostic determinant because of the association with adverse LV remodelling. Haemorrhage within the infarct is also associated with adverse prognosis. MRI can be used to evaluate other complications of MI such as aneurysm, pseudoaneurysm, ventricular rupture, septal rupture, mitral regurgitation, pericarditis and thrombus.9
Non-ischaemic Cardiomyopathies
MRI plays an important role in the evaluation of cardiomyopathies. MRI can distinguish restrictive cardiomyopathies from constrictive disease and can determine the specific cardiomyopathy phenotype based on the morphology and delayed-enhancement patterns. A mid-myocardial pattern of enhancement may be seen in dilated cardiomyopathy, hypertrophic cardiomyopathy (HCM), myocarditis, sarcoidosis, Fabry disease and Chagas disease. A subepicardial pattern of enhancement can be seen in myocarditis, sarcoidosis, Fabry disease and Chagas disease. Scarring at RV insertion sites is seen in HCM, pulmonary hypertension and systemic sclerosis. A global subendocardial pattern of enhancement is seen in amyloidosis, systemic sclerosis and uraemia as well as following cardiac transplant. In dilated non-ischaemic cardiomyopathy, the left ventricle is dilated with systolic dysfunction, and a linear band of mid-myocardial pattern enhancement may be seen in the interventricular septum. HCM has a heterogeneous phenotypical expression, which can be superbly demonstrated with MRI. MRI can quantify the hypertrophy and LV outflow tract gradients and evaluate the mitral valve for systolic anterior motion and regurgitation. Scarring may be seen in hypertrophied and non-hypertrophied segments, typically in a patchy mid-myocardial distribution (see Figure 2), most commonly at the RV insertion sites. MRI is invaluable in the assessment of papillary muscle abnormalities such as abnormal thickening, attachments and mobility, which can cause LV obstruction without significant myocardial hypertrophy. Acute myocarditis demonstrates a high myocardial T2 signal and early and delayed contrast enhancement, most commonly in the basal inferolateral wall. Involvement of the anteroseptum is seen in herpesvirus infection. Regional wall-motion abnormalities may be seen. Fabry disease is characterised by diffuse myocardial thickening, which is sometimes mistaken for a sign of HCM, and patchy mid-myocardial enhancement in the basal inferolateral wall. Cardiac sarcoidosis may show myocardial thickening and oedema in the acute phase and scarring in the chronic phase, usually in a mid-myocardial or subepicardial distribution.
In cardiac amyloidosis, diffuse thickening of the myocardium, atria and interatrial septum is seen. Delayed enhancement is observed in a global subendocardial distribution in the early stages, progressing to transmural distribution in the advanced stages. Rapid contrastwashout and abnormal T1 kinetics are seen, which can be demonstrated using a T1 scout sequence (e.g., the Look-Locker sequence). A T1 difference of less than 23 ms between the subepicardium and subendocardium at two minutes following contrastis associated with poor prognosis.10 In LV non-compaction, prominent trabeculations are seen in the LV myocardium, more commonly in themid and apical regions, with an end-diastolic non-compacted to compacted myocardial ratio of greater than 2.3:1.0. Delayed enhancement may be seen in the trabecula.
In arrhythmogenic RV dysplasia, fat infiltration may be seen in the RV wall in T1 or T2 black-blood images. Global or regional RV wall-motion abnormalities, such as akinesis, dyskinesis and aneurysms, may be seen and fulfil the criteria for diagnosing arrhythmogenic RV dysplasia.11 In haemochromatosis, a low signal intensity is seen in T1- and T2-weighted images. Myocardial iron load can be quantified byevaluating the T2 * value using black-blood T2-weighted images acquired at different echo times. Abnormal T2* values may be seen in the early stages of the disease, which provides a window of opportunity for initiating chelation therapy. Endomyocardial fibrosis is characterised by subendocardial enhancement and apical thrombus formation. Scarring is also seen in other disorders, such as Chagas disease, systemic sclerosis, Churg–Strauss syndrome, pulmonary hypertension and post-partum cardiomyopathy. In Takosubo cardiomyopathy, hyperkinesis of basal and akinesis of apical segments are seen, along with reversible global systolic dysfunction. Myocardial oedema may be seen, but not delayed enhancement. Scar is a substrate for arrhythmia. Regardless of the underlying aetiology, the degree of delayed enhancement has been shown to predict all-cause mortality or cardiac transplantation after adjustment of traditional, well-known prognosticators.12 In patients with arrhythmia, MRI helps to detecting a scar, which can then be ablated.
Pericardial Disease
MRI is used in the morphological and functional evaluation of pericardial disease. MRI can detect congenital pericardial abnormalities, such as absence, cysts and diverticula. In pericarditis, thickened pericardium (>4 mm) is seen in both the acute and chronic phases. MRI is the ideal imaging modality for determining pericardial inflammation, which is demonstrated by enhancement both in early and delayed post-contrast sequences (see Figure 3). Knowledge of inflammation is essential to tailor the treatment for patients with pericarditis. Calcification in chronic stages of pericarditis may be seen as a dark signal, which is indistinguishable from fibrosis, making MRI less suited for determining it. However, MRI is valuable in the detection of pericardial constriction. In addition to morphological abnormalities, such as conical deformity of ventricles, biatrial dilation and inferior vena cava (IVC) dilation, MRI can also demonstrate diastolic septal bounce, abrupt diastolic cessation and tethering. Exaggerated septal flattening or inversion during inspirationcan be demonstrated using real-time cine images, which have high sensitivity and specificity in the diagnosis of constriction, sometimesseen without pericardial thickening. Real-time imaging of the IVC can also distinguish constrictive from restrictive cardiac disease. MRI is useful in the evaluation of pericardial effusions, particularly when they are small and loculated. MRI can distinguish between transudative and exudative effusions based on signal characteristics.13
Cardiac and Paracardiac Masses
MRI is the ideal modality for the evaluation of cardiac and pericardial masses, largely because of its tissue characterisation capabilities. In patients with suspected masses, several MRI sequences are performed for tissue characterisation, such as T1-weighting, T2-weighting, fat saturation, early post-contrast and delayed post-contrast images. MRI can distinguish a real cardiac mass from normal variants (e.g., crista terminalis, Chiari network and Coumadin ridge) and other pseudomasses. Thrombus is seen as a low-signal lesion in T2 and post-contrast sequences, and typically does not show contrast enhancement, except in the chronic vascularised stage. Lipomatous hypertrophy of the interatrial septum may be confused with a lipoma, but it has a ‘dumbbell’ configuration with sparing of the fossa ovalis. MRI can distinguish a benign from a malignant mass based on several characteristics. Benign masses are more common on the left side, have well-defined margins and may be pedunculated, but they do not show infiltration of the myocardium, pericardium or adjacent structures. Malignant tumours are more common on the right side, have ill-defined margins and infiltrate the cardiac and paracardiac structures. Myxoma (see Figure 4), lipoma, fibroelastoma, haemangioma, paraganglioma, rhabdomyoma and fibroma are the benign cardiac tumours, while metastasis, sarcoma, lymphoma and mesothelioma are the malignant tumours. MRI can evaluate the extent and infiltration of cardiac masses and complications, such as valvular obstruction and thromboemboli.14
Valvular Disease
Although echocardiography is the first-line imaging modality in the evaluation of valvular disease because of its high temporal resolution and wide availability, MRI is also increasingly used, particularly when echocardiography is technically challenging or indeterminate. MRI is as good as echocardiography in evaluating the valve morphology. MRI can qualitatively estimate the severity of regurgitation or stenosis by using the area, duration and extent of the dark jet, because of the spin dephasing – although this depends on several technical and hysiological parameters (see Figure 5). Regurgitation and stenosis can also be quantified using phase-contrast images. Regurgitation through the aortic and pulmonary valves can be directly estimated using through-plane phase-contrast images through the ascending aorta and main pulmonary artery. Direct estimation of tricuspid and mitral valve flow is technically challenging because of the through-plane motion of these valves, which may necessitate 3D valve-motion tracking. Indirect estimation of atrioventricular regurgitation can be made using the stroke volume of the left ventricle and right ventricle and forward flow through the aorta and pulmonary valve for mitral and tricuspid regurgitations, respectively. MRI has been shown to have high sensitivity (98 %), specificity (95 %) and accuracy (97 %) in diagnosing aortic and mitral regurgitation.15 Phase-contrast images can also be used to estimate the velocity of jet through a stenotic valve, from which peak and mean pressure gradients can be calculated based on Bernoulli’s equation. Generally,MRI tends to underestimate the peak velocities, since flow velocities are averaged in the sample plane. The valve orifice can be directly measured using planimetry, although this does not take into account the complex, jagged 3D shape in stenosis and the fact that the anatomical valve area is larger than the physiological valve area. The strength of MRI is its capability to evaluate the consequences of valvular disease, such as chamber dilation and hypertrophy, ventricular function and aortic dilation, all of which have prognostic implications and determine the type and timing of treatment.1 Our understanding of flow patterns and vascular function in several cardiovascular disorders has improved thanks to 3D and 4D phase-contrast sequences. MRI can also be used in the evaluation of valvular abnormalities, such as thrombus, vegetations and masses.
Vascular Disease
MRI is useful in the evaluation of large- and medium-sized vessels. Congenital aortic anomalies and acquired aortic lesions, such as aneurysm, dissection, intramural haematoma, penetrating therosclerotic ulcer and rupture, can be evaluated with similar accuracy to that of computed tomography (CT), with the added benefit of the lack of radiation. In aneurysm, MRI is used to detect, measure and assess the morphology of and relationship to branch vessels. MRI is useful in serial follow-up and pre-surgical and interventional planning. In aortic dissection, MRI can assess the type, extent and involvement of branch vessels, and evaluate complications, such as aortic regurgitation and haemopericardium. Penetrating atherosclerotic ulcer is seen as focal outpouching from the aortic wall. High-resolution MRI of the aortic walls has been used for detecting and characterising atherosclerotic plaques, particularly for serial follow-up and response to therapeutic regimens.Studies showed the utility of T1-weighted images in determining a vulnerable plaque based on a necrotic core, haemorrhage and complex signal, particularly in aorta and carotid arteries.16 MRI is useful in assessing the activity of arteritis. In the active phase of arteritis, a high T2 signal is seen in the arterial wall and there may be delayed contrast enhancement, while in the chronic phase there is no oedema or contrast enhancement, although a thick wall may be seen.17 MRI can evaluate various pulmonary arterial abnormalities, such as congenital abnormalities, dilation, aneurysm and masses, and is increasingly used in the evaluation of thromboembolism.
Coronary artery imaging is performed using 3D whole-heart SSFPsequences. MRI is the ideal modality for evaluating coronary arterial origins. MRI has been shown to have good sensitivity (100 %), specificity (85 %) and accuracy (87 %) in the detection of left mainartery or three-vessel disease,18 although it does not provide diagnostic information comparable to that of CT or catheterisation inthe evaluation of distal disease, because of spatial resolution limitations, cardiac and respiratory motion and a high signal from epicardial fat. Coronary arterial wall is imaged using black-blood images. Coronary artery flow can be estimated by phase-contrast MRI, with good correlation with Doppler ultrasound wire.19 MRI is also useful in assessing the patency of coronary artery bypass grafts. MRI is also used in the evaluation of pulmonary veins, both before and after a catheter-ablation procedure for atrial fibrillation, mainly for the evaluation of pulmonary venous anatomy and also to detect pulmonary venous stenosis and atrial thrombosis, which are contraindications for the procedure and can be seen as complications following it. Delayed-enhancement images through the left atrium can be used to determine the success of atrial ablation procedures based on the scar pattern around the ostia.20 Complete circumferential pulmonary venous scarring indicates a successful procedure, although this is difficult to achieve. Breaks inscar lesions can be used as targets for repeat ablation.20 Coronary veins can be evaluated prior to transvenous procedures, such as cardiac resynchronisaton therapy, which would not be feasible if the veins were occluded or absent. Systemic veins can be evaluated for abnormal and variant anatomy, including anomalous pulmonary venous drainage.
Congenital Heart Disease
MRI is the ideal modality for the evaluation of congenital heart disease, because of its unrivalled capability in evaluating not only the heart but also the vessels and other structures in the thorax (see Figure 6). The bsence of radiation makes it an ideal tool in the evaluation of patients with congenital heart disease, who often require serial follow-up. MRI is used in several congenital abnormalities to evaluate the anatomy of the heart and great vessels and to quantify the ventricular and valvular functions. Shunts can be evaluated morphologically and can be quantified by using either the pulmonary-to-systemic blood flow ratio obtained with phase-contrast images through the pulmonary artery and the aorta, or images acquired directly through the shunt. MR angiography is used in the evaluation of vascular anatomy and connections. MRI is ideal in the evaluation of surgical procedures and their complications.1
Emerging Applications
Several experimental MRI techniques and applications are currently being evaluated for clinical use in cardiovascular diseases.T1 mapping is a technique in which the myocardial T1 value is quantified using either the Look–Locker sequence or its modification. Delayed-enhancement imaging is limited in diffuse cardiomyopathies when there is patchy disease with no regionality and when nulling of normal myocardium becomes problematic because of the difficulty in selecting inversion time due to patchy infiltration. T1 mapping hasa higher sensitivity than delayed-enhancement technique in the evaluation of diffuse cardiomyopathies and has shown good correlation with histology.21 The coronary arterial wall can be imaged with and without contrast. Hyperintense plaque in non-contrast T1-weighted sequences indicates an unstable plaque caused by intra-plaque haemorrhage and correlates with positive remodelling, ultrasound attenuation, lower Hounsfield units in CT and transient flow after percutaneous intervention – which thus indicates a complex plaque.22 Coronary arterial wall enhancement has been demonstrated during acute MI caused by oedema or inflammation with resolution during the delayed phase (six months later).23 Intravascular MRI has been used in experimental models for high-resolution imaging of the arterial wall and, along with MRI fluoroscopy, can be used to guide coronary catheter interventions. Interventional MRI is used in specialised institutes to guide percutaneous procedures for valvular and congenital diseases.24
MRI is also increasingly used as a molecular imaging technique to probe cardiovascular disease at a molecular level. Several contrast agents have been developed to target molecules involved in various stages of the atherosclerosis and cardiovascular disease. For example, macrophage activity in an inflamed plaque can be demonstrated with the use of superparamagnetic iron-oxide particles, which are phagocytosed by macrophages. Gadolinium bound to the enzyme that metabolises matrix metalloproteinase can be used to assess inflammation. Iron particles bound to endothelial molecules, such as vascular cell adhesion molecule 1 and P-selectin, can be used to evaluate endothelial injury.25 Iron-oxide microparticles tagged to antibody that binds to activated glycoprotein 2b/3a receptor can be used for detecting thrombus. Fibrin can be detected using EP-2104R, which is a fibrin-targeted gadolinium-containing peptide.26 Post-mortem MRI has potential applications in the evaluation of MI and cardiac trauma.27
Conclusion
MRI has evolved into a powerful and valuable tool for the non-invasive evaluation of cardiovascular diseases, both through technological advances that facilitate the rapid acquisition of high-quality images and through scientific studies that have validated it against histology and clinical outcomes. The role of cardiac MRI is likely to continue to expand with the translation of ongoing experimental techniques into clinical applications in the near future.