Introduction: Disruption of vulnerable atherosclerotic plaque is the precipitating factor that culminates in thrombosis and ischemia (1). Current technologies do not have sufficient power to identify subtle thrombogenic lesions (ie ulcers) in the arterial endoluminal surfaces nor reliably predict markers for future symptomatology (2). We developed an ultra-thin scanning fiber endoscope (SFE) to directly visualize the endoluminal surface of carotid arteries and identify structural, chemical and biological markers of vulnerable and complicated atherosclerotic plaques (3).
Methods: 1.2mm and 2.1mm endoscopes containing single optical fiber scanned by a piezoelectric drive mechanism were developed to illuminate tissue surfaces with red, blue, and green laser beams (RBG). Laser-induced backscattering (reflectance) and tissue fluorescence collected by a ring of optical fibers were then digitalized to reconstruct color videos with large fields-of-view. Then, SFE was studied ex-vivo in human carotid arteries and in-vivo in a rabbit model of atherosclerosis (4). After imaging, specimens were processed for histology, lesions independently reviewed by two pathologists and matched to endoscopic images with ANOVA.
Results: High definition structural and chemical images of 20 carotid arteries harvested during hospital autopsies revealed 42 lesions. Based on anatomical features and tissue fluorescence, we developed a classifier that enabled identification of: healthy endovascular regions (smooth surfaces with strong homogeneous fluorescence); early plaques (dot or streak-like elevated lesions with low fluorescence); advance plaques (irregular elevated lesions with minimal to absent fluorescence) and; complicated plaques (ulcers: punch-out dark-grey lesions with raised irregular bead-like borders and speckled fluorescence pattern; hematoma: absent reflection -black regions- and fluorescence). The image quality and validity of the classifier were reproduced in vivo in an atherogenic rabbit model.
Conclusions: Multimodal SFE generates high-definition structural and label-free chemical images, and detects with high sensitivity and specificity small intravascular thrombi and subtle surface thrombogenic lesions in non-stenosing complicated plaques, even in cases not detected by conventional diagnostic modalities. Therefore, it holds the potential for becoming a new imaging platform in cerebrovascular and cardiovascular disease.
Patient Care: SFE technology could reveal small intravascular thrombi and subtle thrombogenic lesions in non-stenosing complicated plaques, otherwise not identifiable by conventional imaging modalities. Therefore, patients suffering cryptogenic strokes secondary to non-stenosing complicated carotid atherosclerotic disease could be appropriately diagnosed, avoid further invasive workup and benefit from targeted treatment. In addition, the possibility offered by this new technology to analyze vulnerability features of individual plaques through high definition structural, chemical and molecular imaging and deliver specific treatments directly into vulnerable or complicated lesions could lead to a new catheter-based paradigm in atherosclerosis treatment, which is currently focus in risks factor management. This flourishing area of neurointerventional surgery, which interfaces with the departments of engineering and molecular biology, represents an exciting new domain that will lead to increased diversity of the field and could evolve into a novel and exciting platform for future endovascular interventions.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) understand the novel pathology paradigm of atherosclerosis; 2) identify the pitfalls of current diagnostic algorithms and technologies for atherosclerotic disease in carotid arteries, 3) recognized the value, potential and limitation of multimodal endovascular endoscopy as a novel platform for carotid atherosclerosis imaging.
References: 1. Fisher, Mark, et al. "Carotid plaque pathology thrombosis, ulceration, and stroke pathogenesis." Stroke 36.2 (2005): 253-257.
2. Brinjikji, Waleed, et al. "Contemporary carotid imaging: from degree of stenosis to plaque vulnerability." Journal of neurosurgery (2015): 1-16.
3. Lee, Cameron M., Christoph J. Engelbrecht, Timothy D. Soper, Fritjof Helmchen, and Eric J. Seibel. "Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging." Journal of biophotonics 3, no. 5-6 (2010): 385-407.
4. Fan, Jianglin, et al. "Rabbit models for the study of human atherosclerosis: From pathophysiological mechanisms to translational medicine." Pharmacology & therapeutics 146 (2015): 104-119.