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Intravascular imaging continues to play a vital role in advancing our understanding of the pathophysiology of coronary artery disease (CAD) and in the development of novel cardiovascular drugs and device therapies.1,2,3,4,5,6,7 Grayscale intravascular ultrasound (IVUS) was introduced more than 25 years ago and has been an integral component of the clinical decision-making process in the catheterization laboratory. Contemporary percutaneous coronary intervention (PCI) techniques mostly derived from initial IVUS observations showing that high-pressure balloon inflation was required to adequately appose metallic stents to the vessel wall and prevent thrombosis. Intravascular imaging has also evolved with time. IVUS technologies have added features such as tissue characterization by means of radiofrequency data analysis to facilitate evaluation of the atherosclerotic plaque. This technique allows a more sophisticated assessment of changes in plaque characteristics over time beyond simplistic measurements of plaque dimensions.8 However, the relative poor image resolution of IVUS and physical limitations of sound have hampered a broader clinical and research application of intravascular imaging. The introduction of infrared light-based imaging technologies such as optical coherence tomography (OCT), which offers image resolution 10 times greater than that of IVUS, has allowed interventional cardiologists to explore the vascular microenvironment for the first time, whereas near-infrared spectroscopy (NIRS) has enabled more reliable assessment of plaque composition and detection of the lipid component.9 Other emerging invasive imaging techniques, such as Raman spectroscopy photoacoustic imaging, near-infrared fluorescence imaging, and time-resolved fluorescence spectroscopy, are currently undergoing preclinical evaluation; they are expected to have clinical applications in the near future and provide additional information about plaque morphology and pathophysiology (Fig. 21–1). These intravascular imaging technologies and their clinical and research applications are discussed in more detail below.

FIGURE 21–1.

Emerging intravascular imaging techniques. A. Spread-out plots of the compositional characteristics of the plaque estimated by an intravascular Raman spectroscopy catheter. The first panel portrays the distribution of the total cholesterol (in y-axis the number of the sensors used to scan the vessel); the yellow-red color corresponds to increased cholesterol. The second panel provides estimation of the nonesterified cholesterol, which was measured when the total cholesterol was greater than 5%. B. Intravascular photoacoustic images of a diseased (I) and a normal (II) aorta. The unique photoacoustic characteristics of different tissues (eg, lipid tissue [1], normal vessel wall [2], and media-adventitia [3]) allow identification of the plaque’s composition (III). C. Fluorescence reflectance imaging (I) and near-infrared fluorescence (NIRF) images obtained by an intravascular NIRF catheter in a stented rabbit aorta (II). An activatable NIRF agent has been used to mark the cysteine protease activity before pullback. An increased activity was noted at the edges of the stent (indicated with a white-yellow color), suggesting inflammation of the vessel wall. D. A carotid atherosclerotic plaque assessed by time-resolved spectroscopy (TRFS) imaging. TRFS allows evaluation of the biochemical composition of superficial plaque that is portrayed in ...

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