Beyond the Lumen: Molecular Imaging to Unmask Vulnerable Coronary Plaques

Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden cardiac deaths. Early detection of vulnerable plaque is crucial for clinicians to implement appropriate risk-mitigation treatment strategies, offer timely interventions, and prevent potentially life-threatening events. There is an imperative clinical need to develop practical diagnostic pathways that utilize non-invasive means to risk-stratify symptomatic patients. Since the early 1990s, the identification of vulnerable plaque in clinical practice has primarily relied on invasive imaging techniques. In the last two decades, CT coronary angiogram (CTCA) has rapidly evolved into the prevalent non-invasive diagnostic modality for assessing coronary anatomy. There are now validated plaque appearances on CTCA correlating with plaque vulnerability. It is worth noting that in clinical practice, most CTCA reports omit mention of vulnerable plaque details because spatial resolution (0.3-0.5 mm) is often insufficient to reliably detect some crucial features of vulnerable plaques, such as thin fibrous caps. Additionally, accurately identifying vulnerable plaque features requires substantial expertise and time, which many cardiologists or radiologists may lack in routine reporting. Cardiac magnetic resonance imaging (cMRI) is also non-invasive and allows simultaneous anatomic and functional assessment of coronary plaques. Despite several decades of research and development, routine clinical application of cMRI in coronary plaque imaging remains hampered by complex imaging protocols, inconsistent image quality, and cost. Molecular imaging with radiotracers, specifically positron emission tomography (PET) with sodium fluoride (Na¹⁸F PET), have demonstrated significant potential as a sensitive and specific imaging procedure for diagnosing vulnerable coronary artery plaque. The study protocol is robust and brief, requiring minimal patient preparation. Compared to CTCA and cMRI, the diagnostic accuracy of this test is less dependent on the experience and expertise of the readers. Furthermore, validated automated quantitative algorithms complement the visual interpretation of the study, enhancing confidence in the diagnosis. This combination of factors makes Na¹⁸F PET a promising tool in cardiology for identifying high-risk coronary plaques.