Shining light on neurovascular disease

Since Egas Moniz performed the first angiogram, ¹ imaging of intracranial arteries has been limited to angiographic techniques using a variety of contrast agents, providing flow-affected opacification of vascular anatomy. Although advancements in X-ray detectors have yielded improved submillimeter spatial resolution, the information provided is limited to the luminal confines of the vasculature. In parallel, advancements in noninvasive radiologic techniques, such as calcium and Hounsfield determinations for computed tomography (CT) and vessel wall imaging techniques using magnetic resonance (MR), have offered insights into ongoing pathophysiological processes. Despite these advancements, however, there remain severe inherent limitations to spatial resolution that limit therapeutic utility.

In the early 1990s, the interventional cardiology community faced challenges with high rates of coronary stent failures, leading to thrombosis and restenosis. A 1994 study revealed that more than 70% of implanted coronary stents that were deemed sufficiently positioned and expanded using X-ray angiography appeared under-expanded when examined with intravascular imaging. ² These findings led to improved techniques for better stent implantation, ultimately reducing post-percutaneous coronary intervention (PCI) adverse outcomes. ³ Additionally, intravascular imaging has helped identify which lesions require treatment, reducing the number of elective PCIs resulting in stents. ⁴ Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have become standard tools during peripheral vascular and coronary interventions. Finally, three decades later, intravascular imaging has entered the neurovascular space, promising to transform our understanding of cerebrovascular disease and the safety and effectiveness of our procedures.

OCT, a light-based imaging technique, provides detailed views from within the artery, offering extraordinary improvements in resolution and contrast over standard angiographic techniques. It enables precise and artifact-free visualization of arterial wall tissue, therapeutic devices, and their interactions. ⁵ These capabilities have been extensively validated in numerous histopathology studies over a span of more than 20 years.^6–10 During PCI, OCT is used for the assessment of coronary atherosclerosis, elucidating plaque composition and other characteristics, such as the presence of thin fibrous caps, lipid pools, calcifications, plaque neovascularization, and signs of inflammation (e.g. macrophage accumulations), as well as quantifying stent expansion, apposition, and iatrogenic dissections, thereby enabling the optimization of PCI. ¹¹ However, the size, stiffness, and characteristics of existing coronary catheters render them unsuitable for use in the tortuous vasculature of the human brain. Similarly, IVUS is routinely used in coronary and peripheral vasculatures but cannot be safely navigated within the intracranial anatomy.

This all changes with a new study published in Science Translational Medicine. ¹² Pereira, Lylyk, and colleagues presented their initial clinical experience using neuro OCT (nOCT). This technology features a miniaturized imaging probe, specifically designed for the tortuous anatomy of the human cerebral vasculature. ¹³ Offering a small profile (0.0155-inch) and a high degree of flexibility, the imaging probe was delivered without difficulty in tortuous intracranial arteries using standard 0.021-inch neurovascular microcatheters. This study firstly illustrates that nOCT imaging can be safely and effectively integrated into a wide variety of diagnostic and interventional neurovascular procedures. Those authors performed nOCT in both anterior and posterior circulations in 32 patients undergoing neurovascular procedures. nOCT data sets were rapidly acquired in just 2 s during a brief simultaneous injection of contrast media to clear the blood from the arterial lumen. This technology was successfully utilized in both anterior and posterior circulations as well as the largest and smaller vessels where they could easily deliver a 0.021-inch microcatheter. Notably, unlike most new technologies that run aground trying to navigate intracranial tortuosity, with nOCT, the degree of tortuosity did not impact either delivery or image quality. The most impressive aspect of this study is that the images provide a level of spatial detail previously reserved only for histopathology. With a resolution approaching 10 µm, nOCT provides visualization of neurovascular disease processes and device performances at an unprecedented level (Figure 1A to D), offering insights simply not achievable with angiography, MR, or CT. Furthermore, the study provided initial evidence that nOCT offers actionable information for the treatment of neurovascular disease, unattainable by other modalities.

In patients suffering from intracranial aneurysms, the authors demonstrated visualization of the aneurysmal wall, including quantification of dome thickness and microstructure. Such enhanced characterization of the disease could aid in a more precise diagnosis and risk assessment. During treatment procedures, nOCT aided in the selection of optimal landing zones and sizing of therapeutic devices (e.g. flow-diverting stents) as well as the assessment of device expansion and apposition to the arterial wall and the aneurysm neck following implantation. Furthermore, acute thrombus formation over therapeutic devices was readily identified, even when angiography appeared pristine, guiding further treatment. In complex and recurring aneurysms, interventionalists benefitted from a better understanding of the causes of the initial failure, informing an evidence-based treatment strategy. Such more precise assessments of pathology and treatment can lead to better procedural results, potentially avoiding complications and aiding improved long-term outcomes.

In the context of intracranial artery disease (ICAD), nOCT offered a comprehensive, three-dimensional assessment of the arterial wall pathology and the luminal narrowing. It characterized atherosclerotic plaque eccentricity and composition, including the presence of lipid and calcified tissue, and accumulation of macrophages as an indicator of inflammation, and offered accurate measurements of the luminal anatomy and disease extension. Together with an accurate depiction of perforating arteries and their location, nOCT offered actionable insights for the optimal sizing of intracranial balloons and stents. Post-implantation, nOCT enabled an accurate assessment of the treatment results, including quantification of device expansion, apposition to the arterial wall, and plaque prolapse, which can aid procedure optimization.

During diagnostic follow-up examinations, nOCT depicted in high-resolution neointimal tissue coverage over the struts of flow diverters and intracranial stents, in conjunction with a visualization of the device state, including its expansion, apposition, distortion, and interaction with the ostium of covered branches. Such accurate assessment could offer a better understanding of the healing progression, aiding decision-making in patient management, such as the duration of anti-aggregation therapy. In cases of in-stent restenosis, nOCT provided microstructural information of the newly formed restenotic tissue as well as accurate measurements of device configuration (e.g. underexpansion), offering a unique opportunity for a better understanding of this well-known complication and better informed patient management.

In acute ischemic stroke interventions, nOCT provided a clear picture of the underlying arterial wall conditions, as well as the shape, size, length, and composition of the thrombus (i.e. platelet/fibrin-rich vs. red blood cell-rich), and its interaction within the arterial lumen and side branches. Post-thrombectomy, nOCT enabled an accurate assessment of procedural results in situ, including residual thrombus and damage to the arterial wall. In challenging thrombectomy cases, where initial attempts fail or there is a tendency for reocclusion, the operator could benefit from an nOCT-mediated more accurate diagnosis of arterial wall conditions (e.g. presence of ICAD-plaques and dissections), as well as a better understanding of thrombus size, composition, and arterial interaction, which can inform optimal treatment selection. In arterial segments surrounded by cerebrospinal fluid (CSF), nOCT offered an accurate clinical visualization of extravascular structures (e.g. perforating arteries, subarachnoid trabeculae, and concomitant veins) and the presence of blood in high resolution for the first time.

In their study, Pereira et al. demonstrated that the insights provided by nOCT could lead to a more comprehensive assessment of neurovascular pathologies. When faced with ambiguous findings, neurointerventionalists will have access to a miniaturized imaging probe capable of safely performing an “optical biopsy” in vivo and directly visualizing the arterial wall microstructure, its pathology, and the effect of therapeutic devices in a comprehensive, three-dimensional manner. This study showed the great potential of intravascular imaging to address some of the unmet needs in the treatment of neurovascular diseases and for the adoption of nOCT in routine neurovascular practice. The availability of high-resolution imaging tools can massively impact our current understanding of neurovascular disease as well as open new lines of investigation borne out of visualization of extraluminal structures in the CSF. Further larger studies will certainly expand on this initial transformative experience. This study clearly opens the door to intravascular imaging with synergistic contemporaneous and complementary angiography to address longstanding unmet needs in endovascular surgery of the intracranial vasculature.