Intracoronary Near-Infrared Spectroscopy (NIRS) Imaging for Detection of Lipid Content of Coronary Plaques: Current Experience and Future Perspectives

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).

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 mm 2 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]. 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][17][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][20][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].

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 lipidrich coronary atherosclerotic plaques [25].   [23] 2012 69 To compare the target lesion length using NIRS combined with angiography vs. angiography alone Patients undergoing stent implantation could have LCP extending beyond the intended treatment margins as defined using QCA alone

Am J Cardiol
Brugaletta, S. et .al [27] 2012 202 To explore a relationship between lipid plaque composition by NIRS and angiographic severity of coronary artery disease Patients with highest Syntax score have a higher LCBI JACC Cardiovasc Imaging Brilakis, E.S. et .al [16] 2012 9 To investigate whether use of an embolic protection device might prevent complications of LCP interventions Use of embolic protection devices frequently resulted in embolized material retrieval after stenting of native coronary artery lesions with large LCP

Catheter Cardiovasc Interv
Brugaletta, S. et .al [28] 2012 68 To assess LCP distribution in nonculprit coronary arteries using NIRS LCP were mainly located in proximal portions of the LAD and LCX, and more uniformly distributed in the RCA;

JACC Cardiovasc Imaging
Kini, A.S. et .al [15] 2013 87 To determine the impact of short-term intensive statine treatment on intracoronary plaque lipid content Short-term intensive treatment with statine may reduce lipid content in obstructive coronary lesions JACC Papayannis, A.C. et .al [24] 2013 9 To examine the association between presenting LCP (by NIRS) and poststenting thrombus formation (by OCT) 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.
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