Emerging MRI Methods in Translational Cardiovascular Research

Cardiac magnetic resonance imaging (CMR) has become a reference standard modality for imaging of left ventricular (LV) structure and function and, using late gadolinium enhancement, for imaging myocardial infarction. Emerging CMR techniques enable a more comprehensive examination of the heart, making CMR an excellent tool for use in translational cardiovascular research. Specifically, emerging CMR methods have been developed to measure the extent of myocardial edema, changes in ventricular mechanics, changes in tissue composition as a result of fibrosis, and changes in myocardial perfusion as a function of both disease and infarct healing. New CMR techniques also enable the tracking of labeled cells, molecular imaging of biomarkers of disease, and changes in calcium flux in cardiomyocytes. In addition, MRI can quantify blood flow velocity and wall shear stress in large blood vessels. Almost all of these techniques can be applied in both pre-clinical and clinical settings, enabling both the techniques themselves and the knowledge gained using such techniques in pre-clinical research to be translated from the lab bench to the patient bedside.     

Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies.

Non-ischaemic cardiomyopathies (NICMs) are chronic, progressive myocardial diseases with distinct patterns of morphological, functional, and electrophysiological changes. In the setting of cardiomyopathy (CM), determining the exact aetiology is important because the aetiology is directly related to treatment and patient survival. Determining the exact aetiology, however, can be difficult using currently available imaging techniques, such as echocardiography, radionuclide imaging or X-ray coronary angiography, since overlap of features between CMs may be encountered. Cardiovascular magnetic resonance (CMR) imaging has recently emerged as a new non-invasive imaging modality capable of providing high-resolution images of the heart in any desired plane. Delayed contrast enhanced CMR (DE-CMR) can be used for non-invasive tissue characterization and may hold promise in differentiating ischaemic from NICMs, as the typical pattern of hyperenhancement can be classified as 'ischaemic-type' or 'non-ischaemic type' on the basis of pathophysiology of ischaemia. This article reviews the potential of DE-CMR to distinguish between ischaemic and NICM as well as to differentiate non-ischaemic aetiologies. Rather than simply describing various hyperenhancement patterns that may occur in different disease states, our goal will be (i) to provide an overall imaging approach for the diagnosis of CM and (ii) to demonstrate how this approach is based on the underlying relationships between contrast enhancement and myocardial pathophysiology.     

Early evolution from ischemia to myocardial necrosis

The presence, age, and extent of myocardial ischemic injury can be determined with some precision using pathologic techniques. Electron microscopic studies can detect very early ischemic injury, only minutes old, even before irreversible injury (i.e., necrosis) is present; however, because of the small amount of tissue sampled, ultrastructural studies are not very useful for quantifying the size of the ischemic zone. Histologic studies can detect irreversible injury only hours old, and because large samples can be studied, the necrotic zone can be measured quite efficiently. In addition, the age of the infarct can be determined. The knowledge gleaned from such morphologic studies continues to contribute to the development of new diagnostic tests and therapies for patients with ischemic heart disease.     

Diagnostic value of contrast-enhanced magnetic resonance imaging and single-photon emission computed tomography for detection of myocardial necrosis early after acute myocardial infarction.

OBJECTIVES: This study sought to evaluate the diagnostic value of contrast-enhanced magnetic resonance imaging (CMR) and single-photon emission computed tomography (SPECT) for detection of myocardial necrosis after acute myocardial infarction (AMI). BACKGROUND: Single-photon emission computed tomography is widely accepted in the clinical setting for detection and estimation of myocardial infarction. Contrast-enhanced magnetic resonance imaging offers technical advantages and is therefore a promising new method for identification of infarcted tissue. METHODS: Seventy-eight patients with AMI were examined by CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced magnetic resonance imaging and SPECT images were scored for presence and location of infarction using a 17-segment model. Results were compared with the peak troponin T level, electrocardiographic, and angiographic findings. RESULTS: Acute myocardial infarction was detected significantly more often by CMR than SPECT (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to SPECT in detecting small infarction as assessed by the peak troponin T level <3.0 ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs. 84%; p = 0.03). Non-Q-wave infarctions were more likely to be detected by CMR (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for detection of AMI irrespective of the infarct-related artery, SPECT was less sensitive, particularly within the left circumflex artery territory. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging is superior to SPECT in detecting myocardial necrosis after reperfused AMI because CMR detects small infarcts that were missed by SPECT independent of the infarct location. Thus, CMR is attractive for accurate detection and assessment of the myocardial infarct region in patients early after AMI.     

Current clinical applications of cardiovascular magnetic resonance imaging

Cardiovascular magnetic resonance (CMR) imaging is unsurpassed in the evaluation of myocardial anatomy, function and mass. Myocardial perfusion pre- and post-stress, as well as late enhancement is increasingly used in the work-up for ischaemic heart disease, especially in establishing the presence of myocardial viability. Late enhancement patterns can contribute substantially to the diagnosis of myocarditis and various cardiomyopathies as well as infiltrative diseases and tumours. With their high incidence of cardiovascular disease, patients on the African continent could potentially benefit enormously from the proper utilisation of this exciting, continually evolving and versatile technique, via thorough didactic and clinical training as well as interdisciplinary co-operation.     

The emerging clinical role of cardiovascular magnetic resonance imaging

Starting as a research method little more than a decade ago, cardiovascular magnetic resonance (CMR) imaging has rapidly evolved to become a powerful diagnostic tool used in routine clinical cardiology. The contrast in CMR images is generated from protons in different chemical environments and, therefore, enables high-resolution imaging and specific tissue characterization in vivo, without the use of potentially harmful ionizing radiation.CMR imaging is used for the assessment of regional and global ventricular function, and to answer questions regarding anatomy. State-of-the-art CMR sequences allow for a wide range of tissue characterization approaches, including the identification and quantification of nonviable, edematous, inflamed, infiltrated or hypoperfused myocardium. These tissue changes are not only used to help identify the etiology of cardiomyopathies, but also allow for a better understanding of tissue pathology in vivo. CMR tissue characterization may also be used to stage a disease process; for example, elevated T2 signal is consistent with edema and helps differentiate acute from chronic myocardial injury, and the extent of myocardial fibrosis as imaged by contrast-enhanced CMR correlates with adverse patient outcome in ischemic and nonischemic cardiomyopathies.The current role of CMR imaging in clinical cardiology is reviewed, including coronary artery disease, congenital heart disease, nonischemic cardiomyopathies and valvular disease.     

Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study

Objectives

Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients.

Design

The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study.

Setting

Coronary care units in the Stockholm metropolitan area.

Subjects

Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded.

Results

In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6–28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified.

Conclusion

In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.     

Ischemic heart disease: comprehensive evaluation by cardiovascular magnetic resonance

Considerable technical advances over the past decade have increased the clinical application of cardiovascular magnetic resonance (CMR) imaging. A comprehensive CMR examination can accurately measure left and right ventricular size and function, identify the presence and extent of reversible versus irreversible myocardial injury, and detect inducible ischemia. Streamlined protocols allow such a CMR examination to be a time-efficient diagnostic tool in patients with coronary artery disease. Moreover, edema imaging with T2-weighted CMR allows the detection of acute coronary syndromes. In this review, we present the relevant CMR methods and discuss practical uses of CMR in acute and chronic ischemic heart disease.     

Role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis of acute and chronic myocarditis

The aetiopathogenesis of acute and chronic myocarditis is rather complex as a great variety of infectious agents can induce cardiac inflammation. Moreover, many systemic and autoimmune diseases such as sarcoidosis, giant cell myocarditis and systemic lupus erythematodes, drugs and toxins have been described as non-infectious causes of inflammatory heart disorders. Myocarditis may cause sudden death and lead to dilated cardiomyopathy. The correct and timely diagnosis of myocarditis is still a difficult clinical challenge, since the clinical spectrum of myocarditis is broad and comprises (amongst others) even those patients with no symptoms or those presenting with acute cardiogenic shock. Although endomyocardial biopsy still represents the gold standard for the diagnosis of myocarditis, new non-invasive imaging techniques such as cardiovascular magnetic resonance (CMR) imaging promise the non-invasive diagnosis of myocarditis. Considering the hallmarks of acute and chronic myocarditis (accumulation of inflammatory cells; swelling, necrosis and/or apoptosis of cardiomyocytes; increase in extracellular space and water content; myocardial remodelling with fibrotic tissue replacement), an imaging modality such as CMR that enables non-invasive detection of changes in myocardial tissue composition is highly valuable and welcome. This review will focus on the ‘clinical role’ of CMR in the diagnosis of acute and chronic myocarditis.     

The role of cardiovascular magnetic resonance in patients with acute coronary syndromes

Cardiovascular magnetic resonance (CMR) imaging is a recognized technique for characterization of myocardial tissue in stable ischemic heart disease. In addition, CMR is emerging as a noninvasive imaging tool that can provide supporting information to guide treatment in acute coronary syndromes (ACSs). The advantages of using CMR acutely could potentially include triage/differential diagnosis in patients presenting with chest pain and troponin rise but without diagnostic electrocardiogram changes, assessment of severity of myocardial injury (irreversible vs reversible damage) in patients with ST-elevation myocardial infarction and non–ST-elevation myocardial infarction, and risk stratification and assessment of prognosis in patients with ACS. This review evaluates a potential clinical role of CMR in the acute setting, highlighting its advantages and limitations. This critical approach emphasizes areas of uncertainty and ongoing controversies but aims to equip the reader to evaluate the potential clinical application and the practicalities of CMR in patients presenting with ACS.     

Safety and diagnostic accuracy of stress cardiac magnetic resonance imaging vs exercise tolerance testing early after acute ST elevation myocardial infarction

Objective

To determine the safety and diagnostic accuracy of adenosine‐stress cardiac magnetic resonance (CMR) perfusion imaging early after acute ST elevation myocardial infarction (STEMI) compared with standard exercise tolerance testing (ETT).

Design and setting

Cross sectional observational study in a university teaching hospital.

Patients

35 patients admitted with first acute STEMI.

Interventions

All patients underwent a CMR imaging protocol which included rest and adenosine‐stress perfusion, viability, and cardiac functional assessment. All patients also had an ETT (modified Bruce protocol) and x ray coronary angiography.

Main outcome measures

Safety and diagnostic accuracy of adenosine‐stress perfusion CMR vs ETT early after STEMI in identifying patients with significant coronary stenosis (⩾70%) and the need for coronary revascularisation. Also, to determine if CMR can distinguish between ischaemia in the peri‐infarct zone and ischaemia in remote myocardium.

Results

CMR imaging was well tolerated (all patients completed the protocol) and no complications occurred. CMR was more sensitive (86% vs 48%, p = 0.0074) and more specific than ETT (100% vs 50%, p<0.0001) for detecting significant coronary stenosis, and more sensitive for predicting revascularisation (94% vs 56%, p = 0.039). Inducible ischaemia in the infarct related artery territory was seen in 21 of 35 patients and was associated with smaller infarct size and less transmurality of infarction.

Conclusions

Adenosine‐stress CMR imaging is safe early after acute STEMI and identifies patients with significant coronary stenosis more accurately than ETT.     

Late gadolinium-enhanced magnetic resonance imaging in acute and chronic myocardial infarction. Improved prediction of regional myocardial contraction in the chronic state by measuring thickness of nonenhanced myocardium

OBJECTIVES: We sought to determine serial changes of enhanced and nonenhanced tissue on late gadolinium-enhanced cardiac magnetic resonance (CMR) imaging in patients with a myocardial infarction (MI) and to assess whether thickness of nonenhanced myocardium can improve the detection of preserved contractile function in the chronic state. BACKGROUND: Previous studies demonstrated that enhancement on late gadolinium-enhanced CMR images indicates myocardial necrosis, and nonenhancement shows the presence of viable myocardium. METHODS: The CMR studies were performed within one week (scan 1) and more than five months (scan 2) after the onset of MI in 18 patients. The area and mean thickness of enhanced tissue and nonenhanced myocardium were measured by using a 30-segment model. Systolic wall thickening on cine CMR at scan 2 was assessed for evaluating regional contractile function. RESULTS: The amount of enhanced tissue significantly decreased from scan 1 to 2 (22.1 +/- 14.0 ml vs. 15.0 +/- 9.3 ml, p < 0.001). The averaged thickness of nonenhanced myocardium in the infarct segments significantly increased from scan 1 to 2 (5.2 +/- 3.0 mm vs. 6.6 +/- 3.2 mm, p < 0.001). Receiver operating characteristic analysis demonstrated that the measurement of thickness of nonenhanced myocardium, compared with measurement of percent transmural enhancement, had better diagnostic accuracy for predicting improved systolic wall thickening form scan 1 to 2 in dysfunctional segments (Az 0.650 vs. 0.594, p < 0.05). CONCLUSIONS: The amounts of enhanced tissue and nonenhanced myocardium significantly altered from the acute to chronic state in MI patients. The diagnostic performance of CMR imaging for detection of preserved contractile function can be significantly improved by measuring thickness of nonenhanced myocardium in MI patients.     

Magnetic resonance imaging in the assessment of valvular heart disease

Although Doppler echocardiography remains the most frequently used imaging modality for assessing valvular heart disease, the technique has a number of limitations that could affect the quality of imaging studies and make the results difficult to interpret. Cardiac magnetic resonance (CMR) imaging could be superior to echocardiography in a number of ways: for example, for assessing ventricular dimensions, volumes, function and mass, for quantifying valvular regurgitation, and for investigating areas of myocardial fibrosis and extracardiac structures. In carrying out these tasks, CMR uses a variety of pulse sequences that are specially created to obtain information on specific tissue characteristics or on particular aspects of blood flow through heart valves. This general review article focuses on the usefulness of CMR in the clinical diagnosis of valvular heart disease and reviews how the data acquired using the technique can be incorporated into algorithms for the clinical management of patients with significant valvular heart lesions.     

Midwall myocardial fibrosis in Becker-Kiener muscular dystrophy

Summary We report on a 38- year-old man with Becker-Kiener muscular dystrophy (BMD) and dilated cardiomyopathy without clinical symptoms of congestive heart failure who was referred for risk evaluation of sudden cardiac death. The degree of cardiac involvement in BMD varies greatly from no or hardly any cardiac abnormality to severe arrhythmias, dilatative cardiomyopathy and heart failure to heart transplantation or sudden cardiac death. These cardiac abnormalities have been related to replacement of the cardiomyocytes by connecting tissue or fat. In the clinical setting, cardiovascular magnetic resonance (CMR) has been proved to be a valid non-invasive method for obtaining anatomical and structural information of the heart. Furthermore, gadolinium-enhanced CMR can also characterize areas of myocardial fibrosis. Demonstration of extensive areas of fibrosis in an early stage of the disease might be a surrogate marker for an impaired clinical outcome. Therefore, serial CMR examinations starting upon diagnosis of the disease should be considered, as this may lead to an earlier recognition of cardiac involvement and may affect further management of the patient.     

Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction

BACKGROUND: Transplanting cord blood-derived cells has been shown to augment neovascularization in ischaemic tissue. AIM: To test whether sustained delivery of basic fibroblast growth factor (bFGF) enhances the efficacy of angiogenic cord blood mononuclear cell (CBMNC) transplantation therapy in treating myocardial infarction. METHODS: Three weeks after myocardial infarction, Sprague-Dawley rats were randomised to either injection of medium only (control), CBMNC transplantation, sustained bFGF delivery, or combined CBMNC transplantation and sustained bFGF delivery. Six weeks after treatment, tissue formation, neovascularization, and apoptotic activity in the infarct regions were evaluated by histology and immunohistochemistry. Left ventricular (LV) dimensions and function were evaluated by magnetic resonance imaging. RESULTS: Combined bFGF delivery and CBMNC transplantation significantly enhanced neovascularization in the ischaemic myocardium, as compared with either therapy alone. The enhanced neovascularization was likely due to increased VEGF and bFGF expression. The combined therapy also exhibited a reduced infarct area and apoptosis in the ischaemic myocardium, as compared with either individual therapy. The combined therapy did not attenuate LV dilation or increase ejection fraction significantly over either individual therapy. CONCLUSION: This study demonstrates that sustained bFGF delivery enhances the angiogenic efficacy of CBMNC transplantation in rat myocardial infarction models.     

Gewebedifferenzierung mittels Kontrast-MRT („late enhancement“)

Cardiovascular MR (CMR) is a new diagnostic technique that not only provides morphologic and functional information about the entire cardiovascular system, but also allows non-invasive tissue characterization of the myocardium. Myocardial tissue characterization is mainly based on contrast-enhanced CMR. The main principle of contrast-enhanced CMR is the accumulation of gadolinium-based MR contrast agents in myocardial areas with enlarged extracellular space, such as regions of necrosis, fibrosis or deposits of abnormal proteins (e.g., amyloid), in the absence of contrast enhancement in normal myocardium. Based on the evidence presented in this review article, it is safe to conclude that contrast CMR can reliably detect acute and chronic myocardial infarcts in clinical routine, and that contrast CMR is capable of predicting recovery of wall motion after revascularization with a high degree of accuracy. In addition, contrast CMR is a valuable tool for the work up of new-onset heart failure, since the myocardial distribution of contrast enhancement often points to the underlying disease by providing insight into the myocardium in vivo that could previously only be obtained by postmortem examination. This information about the distribution of abnormal myocardial regions is also important for improving the sensitivity of endomyocardial biopsies that may be necessary in certain myocardial diseases, e.g., myocarditis.     

Gadolinium delayed enhancement cardiovascular magnetic resonance correlates with clinical measures of myocardial infarction

OBJECTIVES: The current study tested the hypothesis that gadolinium delayed enhancement assessment of infarct size correlates with clinical indices of myocardial infarction (MI) in humans. Acute infarct mass by cardiac magnetic resonance (CMR) was compared with peak troponin I, acute and chronic left ventricular (LV) systolic function, and chronic infarct mass in patients imaged after recent acute MI. BACKGROUND: Cardiac magnetic resonance accurately determines myocardial viability in patients with chronic ischemic heart disease but is not well validated for recent MI. METHODS: Patients with first acute MI (n = 33) or chronic MI (n = 10) underwent cine CMR followed by gadolinium delayed enhancement imaging. A follow-up CMR scan was performed on 20 of the 33 acute MI patients and all of the chronic MI patients. RESULTS: In patients with acute percutaneous coronary intervention, acute MI mass correlated with peak troponin I (r = 0.83, p < 0.001, n = 23). In the 20 acute infarct patients with follow-up CMR scans, the acute infarct size correlated well with the follow-up LV ejection fraction (r = 0.86, p < 0.001). The transmural extent of delayed enhancement imaged acutely correlated inversely with wall thickening measured acutely (p < 0.001) and at follow-up (p < 0.001). Although chronic infarct size was reproducible (11 +/- 4% vs. 12 +/- 7%, p = NS), acute infarct size decreased from 16 +/- 12% to 11 +/- 9% (p < 0.003). CONCLUSION: In humans imaged shortly after acute MI, gadolinium delayed enhancement acute CMR infarct size correlates with acute and chronic indices of infarct size but will appear to diminish in size on follow-up.     

Measuring myocardial salvage

The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by biochemical ischaemic markers or imaging modalities such as cardiovascular magnetic resonance (CMR). Angiographical methods may overestimate AAR and since methodological differences may exist between different modalities, the use of different modalities for estimating AAR and FIS may not be recommended. (99m)Technetium (Tc)-Sestamibi single-photon emission tomography (SPECT) allows quantification of AAR and FIS by tracer injection prior to revascularization and after 1 month, respectively. SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomized clinical trials. However, SPECT is logistically challenging, expensive, and includes radiation exposure. More recently, a large number of studies have suggested that CMR can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement. The T1- and T2-weighted CMR approaches for quantification of AAR utilize non-contrast, early and late gadolinium enhancement techniques. The technical progress, high spatial resolution and the potential for retrospective quantification of the AAR makes CMR the most appropriate technique for assessment of myocardial salvage. However, the optimum CMR technique for assessment of myocardial AAR remains to be defined. Consequently, we recommend a comprehensive CMR protocol to ensure reliable assessment of myocardial salvage.