formation is the consequence of inflammation and extracellular matrix formation as well as cholesterol deposition in the vasculature. Altered lipids attract proteolytic enzyme‐producing macrophages to their site, which engulf the lipids and leave behind a soft and unstable core that is highly abundant in foam cells and lipids. Cholesterol, whether esterified or unesterified, forms the major part of the lipid core. Histologic studies as well as studies with intravascular imaging have confirmed the association of the presence of lipid‐laden plaques with the risk of ACS and increased peri‐interventional complications. The ability to detect lipid‐rich plaques in patients is therefore of great clinical significance.
Near‐infrared spectroscopy (NIRS) is widely used in many disciplines to identify the chemical composition of unknown substances. It utilizes the absorbance and reflectance of near‐infrared light from an illuminated targeted area to derive the presence of the target substance. This method is a simple quick technique that provides multiconstituent analysis, and requires no sample preparation or manipulation with hazardous agents [121]. Studies have documented the ability of NIRS to accurately identify lipid‐core atherosclerotic plaques in animal models or autopsy specimens and finally, after in vivo and ex vivo validation studies [122,123], an intraluminal spectroscopy catheter was developed and released for clinical use.
System description
Initially, intracoronary NIRS was developed as an independent imaging modality, but a major drawback was the inability to provide spatial orientation to match the lipid content alongside the plaque distribution. However, current co‐registered NIRS‐IVUS catheters (TVC Imaging System, InfraReDx Inc, Burlington, MA, USA) provide data regarding both the vessel structure and the plaque composition.
After completion of an automatic pullback, data are processed displaying a two‐dimensional map of the vessel, revealing the probability of the presence of a lipid core plaque (LCP), with the pullback position in millimeters on the x‐axis and the circumferential position on the y‐axis. This display is known as the “chemogram.” For each pixel of 0.1 mm and 1°, length and angle respectively, the lipid core probability is calculated from the spectral data collected and semi‐quantitatively coded on a color scale from 0 for red and to 1 for yellow. Whenever a pixel lacks sufficient data, for instance the guidewire is shadowing, the pixel appears black.
The block chemogram, also created from the NIRS images, combines the results for each 2‐mm section of the artery to create a “virtual block” that summarizes and reflects the probability of LCP intervals. The numeric value of each block produced is the 90th percentile of all pixel values obtained in the corresponding 2‐mm section of the artery in the chemogram. Here, the red coloration indicates a low probability of an LCP, whereas yellow coloration determines a higher probability of an LCP, alongside the intensity of the color reflecting the amount of cholesterol present. In isolation, the block chemogram specifically adapts a four‐color scale method of analysis (red (p < 0.57), orange (0.57 ≤ p < 0.84), tan (0.84 ≤ p < 0.98) and yellow (p ≥ 0.98)) that reflects the probability of the existence of an LCP in each 2‐mm block of pullback which aids the overall visual interpretation. Spectral data are paired with corresponding IVUS frames, overall displayed as a ring around the IVUS image. The lipid core burden index (LCBI) measures the portion of pixels that exceed an LCP probability of 0.6, in all viable pixels within the scanned region, multiplied by 1000. This is a quantitative measure of the intensity of yellow pixels present on the chemogram. The LCBI values vary from 0 to 1000 and the maximum value of LCBI for any of the 4‐mm segments along the analyzed segment is defined as the maxLCBI4mm.
Potential clinical uses
Determination of high‐risk plaque
The necrotic core region has an abundance of lipid deposition and lacks mechanical stability due to the degradation of fibrous tissue and disappearance of cells. The size of the necrotic core has been significantly associated with the likelihood of plaque rupture. In a previous pathologic study of aortic plaques, ulceration, and thrombosis were characteristic of plaques with >40% of their volume occupied by extracellular lipids [124]. As the lipid core increases plaque vulnerability, the NIRS can potentially be used to identify high risk plaques (Figure 9.7). It has been shown that the target lesions responsible for ACS were in most cases lipid‐rich plaques; additionally, patients with ACS commonly harbored remote, nontarget lipid‐rich plaques [125]. In another study in patients with STEMI, maxLCBI4mm > 400 in NIRS accurately distinguished culprit from non‐culprit segments within the artery and from the lipidrich plaque‐free autopsy histology segments [126]. In a recently published prospective observational study, NIRS imaging was performed in a non‐culprit coronary artery in 203 patients referred for angiography due to stable angina pectoris or ACS. It was shown that the one year cumulative incidence of a cardiovascular event in patients with an LCBI equal to or above the median value (43.0) was significantly higher than those with an LBCI value below the median [127].
Figure 9.7 A 39‐year‐old man was admitted with unstable angina. Angiography showed significant lesions in right and left anterior descending arteries. After post‐dilatation, near‐infrared spectroscopy–intravenous ultrasound (NIRS‐IVUS) imaging was performed, which revealed lipid core plaque in the mid‐ and distal left anterior descending (LAD) (b and c). Proximal segments were relatively disease free (a). Right coronary artery (RCA) also harbored lipid core plaques.
The Lipid Rich Plaque (LRP) study enrolled 1241 patients with stable or unstable angina and myocardial infarction and studied more than 5000 lesions assessed with NIRS‐IVUS. The study demonstrated that the identification of non‐critical, untreated, lipid‐rich plaques by NIRS imaging is associated with adverse events following PCI for de novo culprit lesions. NIRS allows the assessment of atherosclerotic plaques by the analysis of reflected spectrum of near infrared light, providing a reliable chemogram of the wall lipid content. The lipid core burden index (LCBI) is reported along the entire acquisition segment, or within the 4 mm segment of highest accumulation (LCBI4mm). Commercially available systems allow the simultaneous acquisition of IVUS and NIRS signals, providing the assessment of lipid content, lumen stenosis severity and plaque burden. Four non‐randomized studies, the two largest ATHEROREMO‐NIRS and Spectrum NIRS‐IVUS registry enrolling more than 400 patients, demonstrated that an increased LCBI is associated with the development of subsequent MACE. In the LRP study, NIRS‐IVUS imaging was performed in non‐culprit arteries in 1563 patients with coronary artery disease (46.3% stable angina) who underwent PCI for an index event. Patient‐ and plaque‐level events were followed for two years among those with at least one maxLCBI4mm segment ≥ 250 and a randomly selected 50% of patients with all maxLCBI4mm segments < 250. A representative example is presented in Figure 9.8. The adjusted patient‐level analysis showed that for each 100 unit increase of maxLCBI4mm the risk of non‐culprit MACE increased by 18% and patient with maxLCBI4mm greater than 400 is at 87% higher risk of non‐culprit MACE. Also, the plaque‐level analysis demonstrated a 45% higher risk of events within 24 months with each 100‐unit increase in maxLCBI4mm in a coronary segment, with MACE rates of 3.7% versus 0.8% for plaques with maxLCBI4mm ≥ 400 and < 400, respectively. The results of this trial show that NIRS is a safe and feasible technique able to identify vulnerable plaque and vulnerable patients in whom strategies of tailored secondary prevention could be focused [128].
