Validating Intravascular Imaging with Serial Optical Coherence Tomography and Confocal Fluorescence Microscopy

Abstract

Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology.

In Vivo Near-Infrared Fluorescence Imaging of Atherosclerosis Using Local Delivery of Novel Targeted Molecular Probes

“…3d). Specific binding of the labeled nanobodies to ICAM-1 at the surface of cellular membranes rather than in the cytoplasm in tumor-necrosis factor alpha (TNF-α) activated human umbilical vein endothelial cells (HUVEC) was previously demonstrated 24 . Diffuse staining of collagen with the collagen-binding peptide was observed in both the intima and media of rabbit atherosclerotic aorta (Fig.…”

Whole mouse brain imaging using optical coherence tomography: reconstruction, normalization, segmentation, and comparison with diffusion MRI

“…Also, the attenuation contrast combined with local image texture analysis can be used to measure various fiber properties (e.g., orientation, density, and dispersion), which could feed tractography algorithms designed to obtain structural connectomes in ex vivo brains. Also, the reconstruction algorithm developed can stitch other types of tissue (such as aorta 54 or heart) and other optical modalities (e.g., multiphotons microscopy, CARS microscopy, and fluorescence confocal microscopy).…”

Molecular Imaging and Non-molecular Imaging of Atherosclerotic Plaque Thrombosis

“…IVUS yields cross-sectional and vertical axis images of the vascular walls and lumen, enabling the accurate assessment of thrombosis and atherosclerosis based on the quantification of luminal area, vessel size, non-protruding plaques, thrombosis, calcification, and the degree of positive vascular remodeling and plaque burden. Traditional grayscale IVUS images, however, are of relatively low resolution (axial resolution of 150–200 μm), restricting their utility as a tool for the evaluation of thrombosis ( 35 ). These IVUS images are particularly limited in their ability to detect acute and non-obstructive thrombi with high erythrocyte concentrations and low fibrin deposition.…”