Acute coronary syndromes are frequently caused by “vulnerable” coronary plaques with a lipid-rich core. In 1993 near-infrared spectroscopy (NIRS) was first used to detect the lipid (cholesterol) content of atherosclerotic plaques in an experimental animal study. NIRS was then carefully validated using human atherosclerotic plaques (ex vivo), and has subsequently been developed for intracoronary imaging in humans, for which now an FDA-approved catheter-based NIRS system is available. NIRS provides a “chemogram” of the coronary artery wall and is used to detect lipid-rich plaques. Using this technology, recent studies have shown that lipid-rich plaques are very frequent in the culprit lesion of patients with an acute coronary syndrome, and are also common in non-culprit coronary lesions in these patients as compared to patients with stable coronary disease. First studies are evaluating the impact of statin therapy on coronary NIRS-detected lipid cores. Intracoronary NIRS imaging represents a highly interesting method for coronary plaque characterization in humans and may become a valuable tool for the development of novel therapies aiming to impact on the biology of human coronary artery plaques, likely in combination with other intracoronary imaging techniques, such as optical coherence tomography.
Introduction
Atherosclerotic plaques with a large lipid core are a frequent cause of acute coronary syndromes [1]. In 1993 near-infrared spectroscopy (NIRS) was first used for atherosclerotic plaque imaging in an experimental animal model [2]. In further ex vivo validation studies, NIRS was found to accurately detect the lipid (cholesterol) content of human atherosclerotic plaques [3]. In 2001, a device prototype for intracoronary imaging was developed [4]. Recently, NIRS received US Food and Drug Administration approval [5]. NIRS provides a “chemogram” of the wall of the coronary artery and aims to detect lipid-rich plaques [6].
NIRS Catheter
A commercially available catheter-based NIRS imaging system has been developed. This NIRS imaging system consists of a 3.2 French catheter (InfraReDx, Burlington, Massachusetts, USA), a pullback, rotation device, and a dedicated console comprising a laser light source and a computer for algorithmic data processing [7]. The catheter comprises the rotating core with optical fibers that deliver and collect near-infrared light [7]. The light is emitted into a sample by the NIR spectrometer, which subsequently measures the proportion of light that is returned over the range of optical wavelength [6]. The NIRS system uses wave lengths of 800 to 2500 nm, converting a diffuse reflectance signal from an object to produce a spectrum. Subsequently, a computer analyzes the spectra and produces an algorithm to demonstrate a chemogram, that corresponds strongly to the lipid content [5] (Figs. 1 and 2).
Fig. 1
An example of near-infrared spectroscopy (NIRS). A ‘chemogram’ is shown detecting a colour map of the artery wall and indicates the location and intensity of coronary lipid content. The horizontal-axis of the chemogram represents the pullback position and the vertical-axis represents the circumferential position in degrees (0–360°). Adapted and modified from: Choi B et al. Eur Heart J 2013;34:2047–2054
Fig. 2
Near-infrared spectroscopy (NIRS) imaging indicates the lipid-core containing plaques are substantially more frequent in human coronary arteries with endothelial dysfunction. Adapted and modified from: Choi B et al. Eur Heart J 2013;34:2047–2054
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Experience Using NIRS for Coronary Plaque Imaging in Humans in Vivo
Non-invasive imaging modalities including computed tomography or magnetic resonance have a limited resolution for precise plaque characterization [5]. Therefore, catheter-based intravascular imaging methods, such as optical coherence tomography (OCT) and NIRS are highly valuable for detailed characterization of coronary atherosclerotic plaques, and have become available within the last years.
As described above, the NIRS imaging system allowing for plaque assessment was carefully validated against atherosclerotic plaque autopsy specimens, and can nowadays be used in humans in vivo [7, 8]. A summary of recent clinical investigations is outlined in Table 1. NIRS provides excellent spectra through blood and despite heart movement by using short scanning acquisition cycles [7]. The PROSPECT study suggested, that a plaque burden of >70 %, thin-cap fibroatheroma, and minimal luminal area ≤4.0 mm2 are predictors of overall long-term adverse cardiovascular events [9]. NIRS has been established as a very accurate modality to characterize plaques with different lipid content [8]. Madder et al. have shown, that target lesions responsible for acute coronary syndrome are frequently composed of lipid core plaque with a high lipid core burden index (LCBI) [10]. The presence of lipid core plaque may address the high-risk setting for subsequent coronary events, which needs to be further investigated in future studies [11, 12]. Interestingly, both culprit and non-culprit lesions contained lipid core plaque more frequently in ACS patients as compared to patients with stable angina [10].
To determine whether catheter-based NIRS signals from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device
Spectral data were safely obtained by NIRS similarly to those from autopsy specimens; results demonstrated the feasibility of invasive detection of coronary LCP
To compare the findings of NIRS, IVUS virtual histology and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography
Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH necrotic core or LCP by NIRS
To determine the frequency of LCP at target and remote sites in ACS vs. stable angina
Target lesion responsible for ACS were frequently composed of LCP; LCPs often were found in remote, non-target areas; LCPs were more common in patients with ACS vs. stable angina patients
To evaluate LCP modification with coronary revascularization and its correlation with periprocedural MI
Plaque modification may be performed successfully using interventional methods and can be evaluated with NIRS; axial plaque shifting is an acute prognostic marker for postprocedure MI
Moreover, the study by Pu et al. have recently supported the notion, that combining NIRS with IVUS can lead to a better plaque characterization [13]. In addition, the three-dimensional reconstruction of coronary anatomy by ANGIOCARE Software permits the identification of the lipid core plaque location and therefore the association among vessel geometry, endothelial shear stress and plaque composition [14].
Implications for Guiding Therapy
The impact of short-term intensive statin treatment on a lipid plaque content has been investigated in a first study using NIRS demonstrating changes in lipid composition [15]. Several small studies have examined the potential impact of plaque evaluation by NIRS for interventional coronary therapy [16‐18]. It is well known, that 3-15 % of percutaneous coronary interventions (PCIs) are complicated by periprocedural myocardial infarction (MI) due to the distal embolization by intraluminal thrombus and/or lipid-core plaque content [19‐21]. First studies suggest that edge dissections or plaque disruptions may be more common when stents end within a lipid core plaque [22]. Dixon et al. have documented, that in 16 % of lesions lipid core plaque may extend beyond the margins of the lesion as assessed by angiography [23]. This further points to limitations of QCA alone in the evaluation of lesion- and subsequently stent length [23]. Notably, the NIRS-identified lipid core plaque has been described to be strongly associated with a high risk of thrombus formation or periprocedural myocardial infarction [17, 18, 24].
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Future Perspectives
NIRS is likely to become a sensitive modality for coronary plaque characterization. NIRS could be an interesting tool to investigate novel lipid-modulating and other cardiovascular therapies aiming to prevent adverse coronary events [17, 23]. However, a potential limitation of NIRS may be its inability to assess the depth of a lipid core and the measurement of lipid volume has not been validated so far [5]. NIRS may therefore be used in combination with other imaging modalities, such as IVUS or OCT. In this respect, a combined imaging catheter has recently been developed (TVC Imaging System, MC 7 system, InfraReDx, Burlington, Massachusetts, USA), combining both, an IVUS probe and NIRS light source. This catheter is being used in the IBIS-3 (Integrated Biomarker and Imaging Study 3) to investigate the effects of rosuvastatin therapy on the lipid-rich coronary atherosclerotic plaques [25].
Compliance with ethics Guidelines
Conflicts of Interest
Dr. Milosz Jaguszewski and Dr. Roland Klingenberg reported no conflicts of interest relevant to this article.
Dr. Ulf Landmesser serves as a Section Editor for Current Cardiovascular Imaging Reports.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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