Cardiology

Coronary angiography is the standard technique for the diagnosis of coronary artery disease and assessment of coronary plaques. Angiography also guides the vast majority of endovascular interventions. Unfortunately, angiography has significant limitations in assessing physically small but pathologically significant coronary lesions and identifying complications after implantation of endovascular stents.

As a result, there has been significant interest in the development of new intravascular imaging techniques.

Currently, the most commonly utilized method for endovascular imaging is IVUS. IVUS allows visualization of coronary artery to a depth of 10 mm with a resolution of 150 mcm.

Optical coherence tomography (OCT), the newest endovascular imaging technique, allows significantly more detailed imaging, but at lower tissue penetration. The function of OCT is analogous to IVUS with light as the imaging modality instead of sound. It uses near-infrared light and measures the magnitude and echo time delay of reflected light. As a result, tissue is imaged to a depth of 2 mm to 3 mm on a micrometric (ie, sub-cellular) scale.

OCT advantages, limitations

Although the use of light allows far clearer distinction of vessel lumen and wall, coronary plaque components and endovascular stents compared with sound, it also results in the main limitation of OCT — the lack of penetration into the vessel wall beyond 3 mm. The vessel adventitia cannot be imaged and total plaque burden cannot be determined. Because blood scatters light, the vessel being imaged must be flushed with either saline or contrast as images are obtained. Current OCT systems utilizing a rapid automated pull-back system can image vessels at a rate of 20 mm/second, minimizing the flush time required during image acquisition. They can readily be incorporated into catheterization procedures using a 6 French guiding catheter with low complication rates.

A singular advantage of OCT is the detailed characterization of superficial coronary plaque components. Features of plaques that are believed to predispose to rupture include a thin fibrous cap, a lipid core and accumulation of macrophages. The high resolution of OCT permits the identification of the plaques that contain these features.

Histological analysis of autopsy specimens has revealed three general plaque types: fibrous, fibro-calcific and lipid-rich. OCT has showed ex vivo to accurately identify the three plaque types (Figure 1). Sensitivity of OCT for fibro-calcific and lipid-rich plaques is notably higher than for fibrous plaques. Plaque rupture occurs most often at sites where the fibrous cap is thinnest. OCT is unique among intravascular imaging techniques at measuring cap thickness. Cadaveric studies have confirmed the ability of OCT to accurately measure the thickness of collagen caps. In vivo studies of patients presenting with either acute coronary syndrome or stable angina revealed thinner plaque caps (as measured by OCT) in ACS patients. As with thinner caps, increasing plaque lipid content tends to correlate with plaque instability and is more commonly seen in patients presenting with ACS.

Figure 2. A well-apposed stent.

OCT is also significantly more sensitive than IVUS for the detection of such lipid-rich plaques and allows identification of plaque macrophage density. Increased density of macrophages, especially near points of plaque rupture, has been seen in patients presenting with ACS. Because it can identify many of the key characteristics of vulnerable plaques, OCT is a promising tool both to study the pathobiology of atherosclerosis and potentially to guide treatment.

OCT and PCI

Besides its role in characterizing atherosclerotic plaques, OCT can provide significant information to guide coronary interventions. Before percutaneous coronary intervention, OCT can accurately determine the reference vessel diameter and minimal luminal diameter of the target vessel. The length of the lesion can be measured and the lesion characteristics (such as lipid and calcium content) can be defined before intervention. These plaque characteristics, as defined by OCT, can be predictive of post-procedural MI.

During intervention and immediately post-intervention, OCT can identify stent malapposition, tissue prolapsed and both in-stent and edge dissection with significantly higher sensitivity than IVUS (Figures 2 and 3). OCT is also beneficial in assessing stent apposition with overlapping stents.

Figure 3. A malapposed stent.

The clinical significance of malapposition and dissection as visualized by OCT has not been firmly established. In small studies, malapposition of stents appears to correlate with poor endothelialization of the stent and may be a risk factor for late stent thrombosis. During long-term follow-up after PCI, OCT can assess the degree of late-acquired malapposition, strut tissue coverage and neointimal hyperplasia. As a result, OCT has been utilized to compare various stent platforms in terms of stent deployment, endothelialization and in-stent restenosis. For example, paclitaxel-eluting (Taxus, Boston Scientific) and zotarolimus-eluting (Endeavor, Medtronic) stents have been shown to have lower rates of malapposition and fewer exposed stents at 9 months compared with sirolimus-eluting stents (Cypher, Cordis). OCT can characterize different pathological processes resulting in-stent restenosis and stent thrombosis.

Research needed

Recent studies have shown that late in-stent restenosis, unlike early in-stent restenosis, is a result of de novo atherosclerosis rather than neointimal hyperplasia. Although OCT is clarifying our understanding of coronary biology and intervention, outcome data showing the clinical significance of pathology seen by OCT is still lacking. Clinical trial and registry data showing clinical significance are needed to transform OCT from a research tool into a clinical tool.

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Farhad Abtahian, MD, PhD, is a cardiology fellow at Massachusetts General Hospital, Boston; Ik-Kyung Jang, MD, PhD, is the director of the Clinical Trials Program at Massachusetts General Hospital and is a board member of Cardiology Today Intervention; Koji Kato, MD, is a research fellow in the Cardiology Division of the Massachusetts General Hospital.

Disclosure: Drs. Abtahian and Kato report no relevant financial disclosures; Dr. Jang has received research grant and consulting fees from St. Jude Medical-LightLab.