Optical coherence tomography for coronary imaging

Optical coherence tomography (OCT) is a novel invasive imaging technique that produces high resolution intracoronary images. Its general principle of operation is similar to IVUS, however OCT uses infrared light, not ultrasound. In the last years, the need for more precise information regarding coronary artery disease to achieve optimal treatment has seen intravascular imaging becoming an area of primary importance in interventional cardiology. OCT in this area has grown and is spreading. It benefits both therapeutic and research purposes and is also proving able to fill gaps in conventional invasive coronary imaging.

Infrared light offers greater resolution but less tissue penetration

OCT catheters contain a single optical fiber that emits infrared light. OCTs measure the echo time delay and the signal intensity after its reflection or back-scattering from the coronary wall structures while simultaneously operating a pull-back along the coronary artery, and thus performing a scan of the segment of interest (1). The system then creates cross sections of the coronary artery allowing for real- and off-line analysis of each section. It uses light in the infrared spectrum with central wavelength between 1,250 and 1,350 nm (3,4). Speed of light being greater than  ultrasound, an interferometer is necessary to measure the backscattered light. Axial resolution with OCT is 10-20 micron whereas it is typically only 100-200 micron with intravascular ultrasounds. OCT resolution is also superior to non-invasive coronary imaging techniques such as computer tomography coronary angiography (CTCA) and cardiac magnetic resonance (CMR).

Nevertheless, current maximum tissue penetration with OCT is approximately 1.5 mm-3 mm and consequently, some vessel structures, including the external elastic lamina, cannot be visualised by OCT in cases of coexisting large atherosclerotic plaque. IVUS maximum tissue penetration, on the other hand, is 10 mm, thus allowing plaque volume measurement. 

Furthermore, red blood cells interfere with the propagation of infrared light, therefore it is necessary to displace the blood from vessel’s lumen during the OCT scan to avoid artifacts that may limit good visualisation of the coronary artery wall. This result was previously achieved by relatively complex techniques such as occluding the coronary lumen with an inflated balloon and simultaneously flushing the vessel with saline through the balloon catheter. Recently, non occlusive techniques that consist in flushing the coronary artery with contrast media to displace the blood pool during vessel’s scan that allow full vessel visualisation without occlusion have come forth (8).  OCT technology has been developing over time, moving from time domain to frequency domain OCT systems. Currently available frequency-domain OCT (FD-OCT) systems have much higher frame rates and scanning speeds, enabling the acquisition of long coronary segments very rapidly. With FD-OCT, 100 frames\sec can be obtained, with an automatic pullback of 20 mm/sec and a resolution of 500.000 pixel/frame during a single injection of contrast bolus. TD-OCT used a broadband light whereas FD-OCT employs a laser that emits near monochromatic light which allows higher frame rate and speed of data acquisition. Takarada et al. have recently shown that FD-OCT allows better image quality compared to TD-OCT for the assessment of atherosclerotic lesions. 

Safety and feasibility

Referring to Prati’s published data on the non-occlusive technique using TD-OCT adopted in 64 patients undergoing PCI, a success rate of around 94% was observed using an average amount of contrast of approximately 30 mL. Also, the reproducibility of OCT images is high and a high correlation was observed in the measurement of lumen size between OCT and IVUS. Energy applied during an OCT scan is low, in a 5.0-8.0 mW range, and it is unable to cause tissue damage. Additionally the brief interruption of blood flow, during the scan with both occlusive and non occlusive technique, does not involve significant ischemic phenomena. Another study conducted by Barlis et al in 468 patients with both occlusive and non occlusive technique, listed three classes of possible adverse events: 

• Self-limiting adverse events
• Major complications (arrhythmia, embolisation, coronary dissection or spasm).
• Mechanical OCT device failure. 

They concluded that there were no MACE during the 24 hours following OCT examination, major complications were highly uncommon, less than 2%, which could be minimised using a careful procedural scheme.

OCT applications

The main applications of the OCT system are:

1. Atherosclerotic plaque assessment
2. Stent struts coverage and apposition assessment, and in stent restenosis evaluation
3. PCI guide and optimisation

Atherosclerotic plaque assessment

Rupture of atherosclerotic plaque and the subsequent thrombosis is the most frequent cause of acute coronary syndromes (11,12). High resolution imaging of coronary atherosclerotic plaque morphology and composition is important to recognise the vulnerable plaques at high risk of acute modification which could cause acute coronary events and sudden death. From autopsy studies, it is well known that the vulnerable plaque has certain peculiar characteristics including: thin fibrous cap (<65 µm) (13), large lipid pool and inflammatory coxtest with activated macrophages near the fibrous cap. Indeed, the majority (about 80%) of plaques that cause acute coronary syndromes have a point of rupture at the level of an inflamed thin fibrous cap (14,15), thereby identifying an high risk area in the context of the plaque (16) (Fig.1). Several studies have shown that the shoulder region of atherosclerotic plaque is site of intense inflammatory cell infiltrate, especially macrophages. When this cells are activated, they produce and release metalloproteinases inside the coronary artery wall, and induce locus minoris resistentiae that have a potentially higher risk of rupture. Other factors also contributing to the vulnerability of this region include enhanced expression of adhesion molecules, increased biomechanical stress and neovascularisation. OCT is able to detect the sites of plaque vulnerability and distinguish the differences in its composition with a high degree of sensibility and specificity also compared to histopathology (17,18). It can also identify intraluminal thrombi that appear as irregular structures protruding into the coronary lumen, with different signal attenuation according to red blood cells content and thus allowing to differentiate between red thrombi which have high signal attenuation, and white thrombi that conversely appear like signal-rich protruding structures (19) (Fig. 2).

Table 1 and Fig. 3 summarise the OCT peculiarity of different types of plaque.

Tab. 1  
     

Fig. 1 Vulnerable lipid rich plaque with point of rupture at the level of thin fibrous cap (TFC) and intraluminal thrombus formation. White lines indicate the interface between the lipid pool and the fibrous cap.

Fig. 2 A - Red thrombus with typical high signal attenuation. B - White thrombus appear like signal-rich protruding structure.

Fig. 3 Example of various types of atherosclerotic plaque. A and B - Calcified plaques. C - Fibrous plaque. D - Lipid plaque and detail of  the fibrous cap with corresponding size.

Fig. 4 Spontaneous intimal dissection.

Fig. 5 Six month follow up after primary PCI with BMS. Complete stent struts coverage (A); Incomplete stent struts coverage with co-existing struts malapposition (B).

Fig. 6 Example of late stent thrombosis. A Thrombus at proximal stent edge with coexisting malapposed and uncovered struts (arrow). B -  Cross section close to subocclusion with uncovered stent struts (arrows). C Cross section at the level of the thrombotic subocclusion.

Fig. 7 Different patterns of in stent restenosis (ISR). A Eccentric critical in-DES restenosis on left main coronary artery with layered pattern. B - Microvessel (arrow) in the contest of homogeneous ISR with high backscatter. C - Concentric critical restenosis of a PET-covered stent and D - its quantification.

Fig. 8 Example of OCT assessment of an angiographically intermediate stenosis of ostial left descending artery. The OCT-derived MLA of 3.88 mm2  at the level of the stenosis cross-section indicates a significant stenosis.

Fig. 9 A Complete stent apposition. B and C - Examples of stent malapposition (white arrows) of a self-expandable coronary BMS (B) and of a balloon-expandable BMS. D - Stent malapposition after stent implantation on a thrombotic lesion in a patient with acute myocardial infarction.

Fig. 10 Thrombus protrusion into the stent lumen after primary PCI.

Fig.11 Two examples of plaque shift. A - Left descending artery (**) - Diagonal branch (*) bifurcation before PCI. B - Plaque shift (arrow) in the same diagonal branch after PCI.

Fig.12 Intimal dissection at distal stent edge after PCI.

Stent struts coverage and apposition, and in stent restenosis assessment

OCT, with its high resolution capability helps greatly with investigation of stent status after implantation. In particular, it can show and quantify stent struts coverage over time with high reliability (20). Several studies have demonstrated that incomplete neointimal coverage of stent struts is a powerful predictor of stent thrombosis and is the best surrogate indicator of endothelisation (21,22) (Fig. 5,6). Since it was first found that stent malapposition is a very common finding in patients with very late stent thrombosis after drug eluting stent (DES) implantation (23), the pivotal role of stent malapposition in the pathogenesis of very late stent thrombosis has been observed. A recent comparative study between OCT and IVUS showed that OCT can accurately detect and quantify in-stent coverage and strut healing with high reproducibility compared to IVUS, which instead tends to underestimate the percentage of in-stent tissue coverage because of its lower resolution and artifact close to metal struts (24). Considering the fundamental data derived from OCT analysis related to its high capability to detect tissue coverage of stent struts, this unique imaging system can early on become an indispensable tool for clinical research and development of new types of stents. This was demonstrated in the ATLANTA trial (Assessment of The LAtest Non-Thrombogenic Angioplasty stent) where OCT was used for the first time in a first-in-man trial to evaluate the vascular response to a newly developed coronary stent. Indeed, in the ATLANTA OCT-substudy, OCT allowed to demonstrate coverage in 99.5% of the stent struts analysed at six month follow-up, providing data on the safety and efficacy of this Polyzene-F® coated coronary stent as a potential alternative to both BMS and DES, without increased risk of stent thrombosis and no requirement for long-term dual antiplateled therapy (25).
In stent restenosis (ISR) is a phenomenon  related to exceeding neointimal proliferation and it was the main limitation of  BMS. In DES era, the incidence of this event is now sensibly reduced. There are different patterns of  ISR that can be easily identified by OCT analysis, as it has been described by Gonzalo N et al. who classified three types  of restenosis in 24 patients. Restenotic tissue structure was layered in 52%, homogeneous in 28%, and heterogeneous in 20% of analyzed stents, respectively. The predominant backscatter was high in 72% and microvessels were visible in the context of in stent tissue in 12% (Fig. 7). These findings may have important clinical implications (26).

PCI guide and optimisation

In the first phase, OCT can provide clear delineation of the coronary lumen with an accurate measurement of reference lumen diameters, especially the proximal reference, and the minimal lumen area (MLA) at the level of the plaque which is particularly useful for the assessment of intermediate angiographic stenosis (Fig. 8). OCT can characterise the culprit lesion, its length, and the presence of other vulnerable plaques at risk of rupture. It can show whether the culprit lesion is very hardly calcified, if there is plaque ulceration or rupture with intraluminal thrombus or if there is intimal dissection close to the plaque. Moreover, in the context of bifurcation lesions, it can provide important information regarding the status of the side branch, to decide whether or not to stent it and, eventually, the most appropriate technique to choose.

The second phase, following PCI, is important to assess the result of PCI and its possible complications. In this phase, OCT can provide important  information, in particular, luminal diameters and area of the stented coronary segment, which correlates with the risk of restenosis. It can reveal an incomplete coverage of the atherosclerotic lesion and therefore, the need for a second stent, or the status of an overlapping area if multiple stents are implanted (28). Several studies have showed that IVUS imaging can demonstrate stent strut malapposition in approximately 7% of cases (28,29). Since OCT can visualise the coronary wall with greater resolution than IVUS, OCT studies have showed a relatively higher proportion of malapposed struts (Fig. 9). For example, Tanigawa et al (29) found strut malapposition in 9.1±7.4% of stent implanted in their series. OCT can also show the presence of plaque protrusion into the stent or plaque shift after its implantation (Fig. 10, 11) and may suggest the need for post-dilatation in case of stent under-expansion or sub-optimal result of its deployment caused by highly calcified plaque or overlapping with other stents (30). Furthermore, OCT can visualise edge dissection after stent implantation better than IVUS (31) with the potential benefit of reducing the risk of acute or sub-acute stent thrombosis (Fig. 12).

Conclusion:

OCT provides in vivo information on atherosclerotic plaque morphology with near light microscopy resolution, thus opening the window to an unexplored world. The high resolution of this imaging technique enables detailed evaluation not only of coronary atherosclerotic plaques but also regarding the vascular response to coronary interventional devices, such as new generation coronary stents, providing important information on neointima formation and strut coverage over time in patients, with potentially significant clinical implications. Moreover, compared to conventional intravascular ultrasound coronary imaging, OCT can be used as a guide for coronary intervention with improved resolution.