Cardiovascular imaging

Introduction

In recent years, numerous imaging modalities have been developed to diagnose cardiac disease noninvasively and to measure structural, functional, and bio chemical performance of cardiac tissue. Especially, applications of imaging procedures to assess myocardial perfusion under rest and stress conditions have substantially added to noninvasive diagnosis and assessment of prognosis in patients with suspected and documented coronary artery disease. With the advent of cardiac magnetic resonance imaging (CMR), high-resolution structural and functional imaging has become available. Biochemical and molecular tissue characterization with specific radiotracers has been enabled by the introduction of single photon emission computed tomography (SPECT) and positron emission tomography (PET). Driven by rapid acceptance of PET/CT in patients with oncological diseases, hybrid imaging systems have been developed to promote noninvasive multimodality characterization of disease processes. PET/CT has become a routine imaging procedure in oncology, while PET/MR plays an increasing clinical role in neuroimaging combining anatomic and functional measurements. Cardiac patients also benefitted from multimodality approaches such as PET/CT. PET/CT offers the integrated assessment of regional myocardial perfusion as well as coronary anatomy linking functional measurements with accurate delineation of individual vessel anatomy. This combined approach does not only optimize sensitivity and specificity of the diagnostic process but also guides the therapeutic approach of selective revascularization in patients with advanced disease ( ).

PET/MR on the other hand is currently considered as very attractive cardiovascular research instrumentation, which can provide unique biomarkers of tissue composition and molecular signatures specific to a given disease process. It is hoped that multimodal imaging biomarkers may not only support early diagnosis of disease but also individual selection of patients for possible therapeutic interventions. In this chapter, we will highlight some of the emerging concepts of clinical PET/MR and discuss technical challenges to exploit the full potential of combining two powerful imaging modalities to the benefit of patients with cardiovascular disease.

Finally, given the complexity and heterogeneity of cardiac diseases as well as the usage of different tracers, the specific as well as rather generic protocols will be briefly touched at the end.

Detection of coronary artery disease

Myocardial infarction remains a major cause of mortality in developed countries. However, in recent years there has been a marked decrease of sequels of ischemic heart disease due to the improved early diagnosis and prognostic information provided by modern imaging modalities. Now, coronary artery disease can be detected early by using a variety of imaging procedures. Measurements of left ventricular function, regional perfusion and wall motion allow sensitive and specific detection of impaired coronary flow reserve. Most prominent are the measurements of regional myocardial perfusion, using either contrast agents or radiopharmaceuticals by MR, CT or SPECT, PET. Assessing the homogeneity of myocardial perfusion under rest and stress condition, allows identification of regional impaired coronary flow reserve. Such functional measurements of coronary physiology support the anatomic delineation of regional coronary lesions and have been shown to provide an important adjunct in the decision-making process of regional coronary revascularization ( ). Measurements of coronary flow reserve by noninvasive imaging techniques are accepted gatekeepers for interventional procedures as documented in many guidelines for treating patients with coronary artery disease ( ). Myocardial perfusion imaging (MPI) employing PET provides very accurate delineation of regional perfusion. Several tracers are available for qualitative and quantitative assessment of regional tracer distribution ( ). Attenuation corrected images allow the quantification of blood flow under rest and stress condition in absolute units, which has been extensively validated in preclinical and clinical models. Myocardial perfusion PET imaging with the generator-produced radiopharmaceutical rubidium-82 has become a major diagnostic routine tool in nuclear cardiology ( ). In most clinical settings, the application of MPI has to be restricted to patients with “medium probability” of disease as gatekeeper for interventions. In patients with “low likelihood” of coronary artery disease, the risk of developing coronary artery disease will primarily be based on visualization of coronary calcification and CT-angiography (CTA) while in patients with “high likelihood” of disease invasive diagnostic procedures are indicated. This stepwise approach of applying imaging modalities has been very successful in managing patients with suspected and documented CAD ( ; ). The application of quantitative flow measurements is useful to follow patients under therapy and to assess the significance of a given anatomic coronary alteration in the context of high-risk interventions. The clinical utility of PET and MR in hybrid instrumentation for the assessment of regional perfusion is limited in contrast to PET/CT due to the lack of diagnostic coronary angiography by MR. However, PET, as the most quantitative and most accurate method to assess myocardial blood flow, can be used to cross-validate MR techniques, to assess coronary flow reserve, and help to optimize methods providing validation of advanced MR flow measurements kinetics ( ; ) ( Fig. 5.1 ).

Beyond this methodological aspects, examples for the synergetic use of both modalities can be found: Fig. 5.2 depicts an example of simultaneous PET and MR coronary blood flow measurements employing adenosine stress in a patient with left ventricular hypertrophy and subcritical 3-vessel coronary artery disease.

Assessment of tissue viability and infarct size

For many years, PET has been advocated and used for the identification of residual tissue viability in patients with advanced coronary artery disease ( ). By using 18F-fluorodeoxyglucose, the extent of viable tissue can be delineated even in the presence of severe functional impairment. Such measurements have shown to be predictive for functional recovery as well as long-term outcome of patients with advanced ischemic cardiomyopathy ( ). The signal of increased FDG-uptake in cardiac tissue has also been applied for detection of inflammatory reactions in patients with acute myocardial infarction since activated inflammatory cells display an up-regulated glycolytic metabolism. This metabolic imaging concept, however, requires standardization of intrinsic metabolic activity of the myocardium by providing a special diet suppressing glucose metabolism of myocardial cells such as specific lipid rich diets ( ; ).

With the advent of contrast-enhanced magnetic resonance imaging the delayed wash-out of contrast agents in the myocardium has been associated with expanded extracellular space ( ). In myocardial scar tissue, the extracellular space is significantly larger as compared to normal contracting myocardium. Therefore, late contrast enhancement (LGE) of cardiac tissue is indicative of injured and scarred myocardium and has been extensively validated as marker of myocardial infarction. Numerous studies have indicated that CMR technology offers very sensitive detection of small islands of myocardial infarction ( ). Such discrete areas of late enhancement in the presence of normal left ventricular function have shown to be predictive for increased cardiovascular risk ( ). Taking PET and MR measurements together, the extent of myocardial infarction and viable tissue can be assessed simultaneously ( Fig. 5.3 ). Several studies have indicated that in the presence of subendocardial scar the metabolism in epicardial tissue is upregulated, providing evidence of residual viable tissue ( ). The combination of both methodologies has been used to crossvalidate them but also to assess ventricular function as well as the extent of reversible and irreversible myocardial injury by one hybrid imaging modality. The combined identification of viable myocardium has been demonstrated to optimize the predictive information of imaging for functional recovery following revascularization. Rischpler et al. investigated 28 patients with recent acute myocardial infarction within 5–7 days after PCI. Follow-up MR was performed 6 months later. Concordant identification of viable myocardium was associated with better functional outcome. 18% of dysfunctional segments displayed discordant infarction on viability. “PET nonviable segments” recovered less than “PET viable segments” supporting the predictive role of residual metabolic activity ( ). Future prospective studies in larger patient population are needed to address the additional diagnostic or prognostic value by adding two imaging modalities together in patients with history of myocardial infarction and impaired left ventricular function.