From Thallium Scan to Molecular Imaging

Abstract

The diagnostic and prognostic evaluation of cardiovascular diseases has been improved considerably by the application of imaging procedures. Among many, scintigraphic procedures have emerged as important diagnostic tools to assess extent, severity, and prognosis in patients with coronary artery disease (CAD). For more than the last 30 years, however, the application of perfusion imaging has been extended to allow the combined evaluation of perfusion, perfusion reserve, and ventricular function. With positron emission tomography (PET), quantitative assessment of perfusion has become possible. In combination with pharmacological stress agents, the coronary flow reserve (CFR) can be quantitatively assessed as an early marker of endothelial dysfunction. PET in combination with metabolic tracers has added the evaluation of cardiac substrate metabolism, which has become an important clinical marker for ischemically jeopardized myocardium. The PET information is widely considered as the gold standard for tissue viability in the management of patients with advanced CAD and impaired left ventricular function (LVF). New tracer approaches include the assessment of cardiac innervation, which plays an increasingly recognized role in the pathophysiology of cardiac diseases. Radiolabeled catecholamine analogues provide visualization of sympathetic nerve terminals that are functionally altered in patients with diabetes mellitus and cardiomyopathy. In addition, this scintigraphic information allows the monitoring of physiological processes such as reinnervation of the transplanted heart. New methods, such as imaging of apoptosis and gene expression, are of interest in cardiology. Combining the therapeutic gene with a reporter gene, the transfection of cardiac tissue can be monitored noninvasively. First results employing the herpes simplex virus thymidine kinase reporter gene (HSV1-tk) are encouraging and represent an attractive approach for the use of PET imaging in the control of cardiac gene therapy.

Introduction

I

n-vivo imaging has become an important tool in medicine, not only to detect the disease process but also to quantify extent and severity, as well as to follow the time course of disease. Starting from the application of X-ray technology to measure the density distribution within the body, new techniques have been introduced during the last century to assess—besides anatomic details—the functional aspects of the disease process. The introduction of dynamic data acquisition allows for the description of organ function (Figure 1). Examples, such as the noninvasive assessment of cardiac pump function using computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography are widely applied clinical tests. In addition to the dynamic data acquisition, the use of contrast agents has improved the diagnostic information obtainable from imaging. X-ray contrast agents not only provide enhancement of vascular structures, but also the estimation of tissue perfusion. With the introduction of tracer techniques, physiological and biochemical processes can be directly visualized. Tracer approaches excel by their high sensitivity and specificity for a given physiological process. The fact that only small amounts of radiolabeled molecules are needed offers the advantage that biological processes are not disturbed. Combining the tracer approach with tracer kinetic modeling, quantitative parameters not only of perfusion but also other tissue function such as metabolism can be derived for diagnosis and prognosis.¹ These advances in the area of imaging are paralleled by a change in our understanding of the disease process. Rapid advances in molecular biology led to an improved understanding of the pathophysiology and the hope to identify patients at risk prior to developing disease with clinical manifestations. It can be foreseen that patients at genetic risk will undergo imaging to define the phenotype using early markers of disease, such as endothelial dysfunction in the case of coronary artery disease (CAD).

In this article, we will review the progress of nuclear cardiology as an example of how imaging technologies adapted to the changing understanding of cardiovascular diseases. We will also try to define future challenges for imaging technologies in a clinical setting, as well as in a research environment.