It is recognized by many in the field of nuclear cardiology that in order to thrive and advance, the discipline needs to go beyond myocardial perfusion imaging (MPI). The high diagnostic and risk stratification utilities of radionuclide single-photon emission computed tomography (SPECT) and positron emission tomography (PET) MPI are well established,1–4 with observational studies5–7 strongly suggesting that performing and properly acting upon the results of MPI can lead to improved patient outcome, with a study in progress designed to firmly establish this.8 Nevertheless, there is an increased focus on developing radionuclide techniques that rely on a unique strength of the modality, that is, the ability to image the underlying molecular processes of cardiac disease.9 Among such nonperfusion radionuclide imaging methods of current interest is assessment of cardiac autonomic innervation.10,11
Neurohormonal regulation of the cardiovascular system is crucial for maintaining body function. One major component is circulating hormones that include epinephrine, norepinephrine (NE), arginine vasopressin, B-type natriuretic peptide (BNP), and substances of the renin-angiotensin aldosterone system (RAAS).12 Another component, working in conjunction with the hormonal mediators, is direct innervation via the sympathetic and parasympathetic autonomic nervous system. Together, these neurohormonal (sometimes also referred to as "neurohumoral") processes control cardiac output (CO), vascular tone, and blood volume, serving to maintain proper perfusion to body organs as needed for normal conditions and activities. In response to stressors or insults, such as volume depletion or diminished CO from cardiac dysfunction, neurohormonal mechanisms compensate with vasoconstriction, augmentation of myocardial contractility, increased heart rate, and expansion of extracellular volume.13 In many situations, such adaptations are necessary and beneficial, but in other circumstances neurohormonal activation can be excessive and persist beyond what is needed, thus maladaptive and potentially harmful.14 The ability to directly visualize these mechanisms via radionuclide imaging provides important insights into the pathophysiology of various cardiac diseases. Much recent work shows a robust ability of cardiac autonomic innervation imaging to effectively assess a patient's condition beyond other commonly used methods. There is much promise that such imaging will lead to improved disease management, thus a reduction of adverse events and improved patient outcome and well-being.
CARDIAC AUTONOMIC INNERVATION
The heart is richly innervated by sympathetic and parasympathetic fibers which are controlled by regulatory centers in the brain that integrate input signals from other parts of the brain and from receptors throughout the body. Efferent sympathetic signals from the regulatory centers follow descending pathways in the spinal cord, and synapse with preganglionic fibers that leave the spinal cord at levels T1–L3, subsequently synapsing with paravertebral stellate ganglia, and eventually innervating the right ventricle, and the anterior and lateral left ventricle. In the heart sympathetic nerves follow the coronary arteries in the subepicardium, and then penetrate the myocardium. Adrenergic output from this sympathetic innervation increases HR (chronotropic effect), augments contractility (inotropic effect), and enhances atrioventricular (AV) conduction ...