Apoptosis Imaging in Diseased Myocardium

Abstract

In various myocardial disorders including myocardial ischemia, infarction and subsequent cardiac remodelling and heart failure, myocarditis, cardiomyopathy, cardiac allograft rejection, chemotherapy induced cardiotoxicity, both necrosis and apoptosis are considered to play an important role in the underling pathophysioloy. Molecular and cellular dysfunction has been widely investigated in cardiovascular fields using various modalities. Of particular, radionuclide imaging technique has advantage for quantitative assessment of molecular function in vivo in patients. Especially in patients with coronary artery disease, perfusion imaging agents such as 201Tl, 99mTc-MIBI and tetrofosmin with combination of stress testing and ECG-gated data acquisition have been used for the simultaneous assessment of the ventricular function and severity of myocardial perfusion abnormality including its location and size in stress and resting condition. From these data, status of myocardial ischemia or jeopardized myocardium, myocardial viability and reversibility of wall motion abnormality can be diagnosed to some extent but still insufficiently. Molecular imaging may play an important role for assessing the pathophysiology and its severity in these various cardiovascular diseases beyond perfusion imaging. This chapter focuses on the apoptosis imaging that is one of the most possible nuclear molecular imaging in-vivo at this stage, and its clinical application might permit more precise assessment of the pathophysiology in various myocardial abnormalities beyond perfusion imaging. Four decades ago, the term apoptosis has been introduced by Kerr et. al. as a special form of cell death different from necrosis (Kerr, et al., 1972). Necrosis is passive and unregulated form of cell death, characterized by irreversible loss of plasma membrane integrity with cell swelling and rupture after sudden severe insults which preclude adequate homeostatic energy-dependent cell functions, leading to release of intracellular contents and a subsequent inflammatory response. Apoptosis on the other hand is characterized morphologically by the condensation of nuclear chromatin, cytoplasmic condensation, cell shrinkage, followed by the nuclear and cellular fragmentation and phagocytosis of apoptotic bodies by neighboring cells in the absence of inflammation. Apoptosis is considered to be an active and highly regulated ATP dependent programmed cell daeth process and plays an important roles in embryonic developement and maintenace of postnatal tissues and contributes to both normal physiology and pathology. Dysregulation of apoptosis results in either too littel or too much cell death and implicated in various diseases. For instance, insufficient apoptosis may contribute carcinogenesis, on the otherhand, eccessive apoptosis