Intravascular Frequency-Domain Optical Coherence Tomography Assessment of Atherosclerosis and Stent-Vessel Interactions in Human Carotid Arteries

Discussion

Ischemic stroke is largely an embolic disease. Nonetheless, current standard-of-practice guidelines suggesting that carotid revascularization with endarterectomy or a stent procedure¹⁹ is beneficial in asymptomatic patients are largely based on North American²⁰ and European²¹ trials. Both trials, limiting enrollment to patients with at least 60% angiographic stenosis, reported only modest benefit of an operation over medical management, with a 3-year absolute risk reduction of approximately 3% and no definite correlation between the degree of stenosis and outcomes.

Indeed, several investigators have reported data suggesting that risk of stroke is poorly defined by the degree of stenosis but strongly related to histopathologic findings in carotid plaques. Spangoli et al²² examined surgically removed plaques from patients without symptoms versus those with transient ischemic attack or cerebrovascular accident. They stressed that the presence and severity of clinical events was significantly correlated with thrombus and cap inflammation in ruptured plaques, after assessing endarterectomy specimens in a cohort with similar degrees of angiographic stenosis. Similarly, in another histopathologic evaluation, a higher percentage of macrophage-rich areas and number of T-cells per square millimeter in symptomatic-versus-asymptomatic patients with similar degrees of carotid narrowing was described.²³

Moreover, using multidetector CT angiography to examine symptomatic atherosclerotic plaques in patients with anterior circulation disease, Homburg et al²⁴ found that culprit plaque ulcerations were equally distributed between patients with more than and less than 50% carotid stenosis. Further evidence that symptoms from carotid artery disease are correlated with plaque histopathology has been provided by a report that established correlation between plaque ulceration, intraluminal thrombus, symptoms, and cerebral microemboli as detected by transcranial Doppler in patients with similar degrees of angiographic stenosis.²⁵ Redgrave et al,²⁶ in the histopathologic study of 526 carotid endarterectomy specimens from recently symptomatic stenosis, found a high prevalence of cap rupture, large lipid core, and attenuated macrophage infiltration, highlighting the fact that these markers for plaque instability were similar to those previously described in unstable coronary artery plaques.

OCT is an emerging technology in the cardiac catheterization laboratory. Its accuracy in measurements of vascular dimensions,²⁷ in the characterization of atherosclerotic plaques,^11,28 and in the identification of thrombus¹⁶ and plaque inflammation^15,29 has been well demonstrated; therefore, it enables imaging of structures that have a potential causative role in cerebrovascular ischemia (eg, thrombus, TCFA with plaque rupture, and inflammation).

In this case series, we report the use of FDOCT to assist in the management of 4 asymptomatic patients in whom a proper course of action was not readily apparent after diagnostic studies that included conventional angiography. Patient A underwent OCT evaluation to clarify abnormal but nonspecific findings on a carotid angiogram following carotid stent placement, with resultant findings that included marked tissue prolapse through the stent struts and the presence of an otherwise undetectable ruptured TCFA. The 3500-patient CAPTURE (Carotid Acculink/Accunet Post-approval Trial to Uncover unanticipated or Rare Events) carotid stent registry, reporting a 30-day stroke rate of 4.8%, found that only 23% of strokes occurred intraprocedurally,³⁰ raising the possibility that at least some of the ipsilateral postprocedural strokes following carotid artery stent placement might be related to issues surrounding tissue prolapse through stent cell struts. In patient A, OCT findings resulted in a decision to place a second (closed cell) stent in the target lesion to treat tissue prolapse. Moreover, another change in procedural strategy, specifically stent length, could have been considered to achieve full coverage of the segment containing the ruptured TCFA had OCT been performed before stent deployment in this case.

Intervention was, however, deferred in patient B, despite inexplicably high ICA velocities that could otherwise justify revascularization, on the basis of OCT documentation of <60% stenosis and the absence of any features thought to suggest plaque instability by pathologic criteria. Revascularization was recommended for patient D, after an OCT evaluation of “borderline” carotid duplex and angiographic data demonstrated findings that have been associated with higher risk in the pathology literature.³¹ Patient C, despite the presence of “low-risk” clinical (restenosis) and angiographic (60% stenosis) markers, was treated with carotid stent placement when an unanticipated large thrombus burden was detected by OCT. This case as well demonstrates the ability of OCT to differentiate normal- and abnormal-appearing tissue on the basis of signal intensity coupled with homogeneity and smoothness of tissue contour. Although these findings have not been previously described in the carotid arteries or validated by OCT, echolucent tissue, described as a “black hole” in intravascular sonography studies after intracoronary brachytherapy and drug-eluting stent implantation,³² is composed of acellular/hypocellular necrotic tissue, scattered in an extracellular matrix rich in proteoglycans but also containing T lymphocytes and foam cells.³³ On the basis of known optical properties of different materials, tissue depicting poor signals on OCT images is likely composed of fibrin or organized thrombus,³⁴ though highly organized proteoglycan could also provide similar images.³⁵

Yoshimura et al³⁶ initially described the use of carotid OCT with balloon occlusion to clarify an ambiguous carotid angiogram in 2010. More recently, the use of OCT to evaluate carotid artery stent placement was reported in 7 patients for whom the authors emphasized the necessity of proximal balloon occlusion (complicated by symptomatic cerebral ischemia in 1 patient) to obtain acceptable images.³⁷ Furthermore, an early experience with OCT in carotid plaque characterization was reported in a brief communication that compared OCT with other imaging modalities.³⁸ Most recently, a 30-patient cohort undergoing scheduled carotid artery stent placement was studied before and following stent placement with TDOCT.³⁹ Again, all patients were imaged after proximal balloon occlusion. Conversely, our group acquired OCT images with hand injections of contrast without proximal balloon occlusion. FDOCT technology, with a much faster pullback speed (up to 25 mm/s) compared with TDOCT, enables adequate blood clearance, without the necessity of proximal balloon occlusion. Furthermore, its wider FOV (∼10 mm) allows imaging of larger arteries.¹⁰ In our series, only 13% of all the cross-sections were not suitable for analysis because of blood clearance artifacts or inadequate FOV.

In contrast to these earlier studies, our group also reports the use of data obtained by preintervention FDOCT in clinical decision-making in patients with ambiguous angiographic or noninvasive data. No complications were reported in this case series.

The present cases, although not conclusive, provide important clinical insights. First, the feasibility of interrogating the carotid vasculature by using high-resolution FDOCT imaging without the need for complex technical adaptations for blood displacement or interruption of carotid flow is shown. Second, these cases are, to the best of our knowledge, the first use of FDOCT to assess plaque morphology and guide, albeit empirically, decision-making before planned intervention in human carotid arteries in vivo. Finally, this report also describes the use of “next -generation” analytical imaging software with automated detection and quantification of vascular disease that capitalizes on the 3D nature of FDOCT images.

Several points of caution should be noted in the interpretation and use of data presented in this case series. First, carotid artery instrumentation may carry a risk of embolization. While no signals of safety issues in excess of those associated with diagnostic carotid angiography have been reported to date in small series of carotid intravascular sonography and OCT patients,^{9,36⇓⇓⇓–40} the risk versus benefit of this technique will remain uncertain until studies that are appropriately powered to assess safety and efficacy end points are available. Second, we assumed that OCT histopathologic correlations that have been extensively validated outside of the carotid circulation^{11⇓⇓⇓⇓–16,34,35} are also valid in the carotid circulation. Finally, limited tissue penetration, particularly in lipid-rich plaques, precludes the interpretation and quantification of underlying tissue layers.

In this case series, FDOCT revealed unexpected findings in virtually all patients including marked tissue prolapse through an open-cell carotid stent and the demonstration of ruptured TCFAs and thrombus in lesions defined as “low-risk” according to current clinical criteria. These unexpected findings suggest that further studies are needed to evaluate the role of FDOCT in the assessment of asymptomatic carotid artery disease.