ABSTRACT
This study aimed to evaluate the feasibility and accuracy of a technique for atherosclerosis imaging using local delivery of relatively small quantities (0.04-0.4 mg/kg) of labeled-specific imaging tracers targeting ICAM-1 and unpolymerized type I collagen or negative controls in 13 rabbits with atheroma induced by balloon injury in the abdominal aorta and a 12-week high-cholesterol diet. Immediately after local infusion, in vivo intravascular ultrasonography (IVUS)-NIRF imaging was performed at different time-points over a 40-minute period. The in vivo peak NIRF signal was significantly higher in the molecular tracer-injected rabbits than in the control-injected animals (P < 0.05). Ex vivo peak NIRF signal was significantly higher in the ICAM-1 probe-injected rabbits than in controls (P = 0.04), but not in the collagen probe-injected group (P = 0.29). NIRF signal discrimination following dual-probe delivery was also shown to be feasible in a single animal and thus offers the possibility of combining several distinct biological imaging agents in future studies. This innovative imaging strategy using in vivo local delivery of low concentrations of labeled molecular tracers followed by IVUS-NIRF catheter-based imaging holds potential for detection of vulnerable human coronary artery plaques.
Subject(s)
Atherosclerosis/diagnostic imaging , Fluorescent Dyes/chemistry , Molecular Probes/chemistry , Optical Imaging/methods , Spectroscopy, Near-Infrared/methods , Animals , Aorta/metabolism , Aorta/pathology , Atherosclerosis/diagnosis , Atherosclerosis/metabolism , Collagen Type I/metabolism , Feasibility Studies , Fluorescent Dyes/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Male , Plaque, Atherosclerotic/diagnosis , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/metabolism , Rabbits , Reproducibility of Results , Ultrasonography, Interventional/methodsABSTRACT
Given known correlations between vascular health and cognitive impairment, the development of tools to image microvasculature in the whole brain could help investigate these correlations. We explore the feasibility of using an automated serial two-photon microscope to image fluorescent gelatin-filled whole rodent brains in three-dimensions (3-D) with the goal of carrying group studies. Vascular density (VD) was computed using automatic segmentation combined with coregistration techniques to build a group-level vascular metric in the whole brain. Focusing on the medial prefrontal cortex, cerebral cortex, the olfactory bulb, and the hippocampal formation, we compared the VD of three age groups (2-, 4.5-, and 8-months-old), for both wild type mice and a transgenic model (APP/PS1) with pathology resembling Alzheimer's disease (AD). We report a general loss of VD caused by the aging process with a small VD increase in the diseased animals in the somatomotor and somatosensory cortical regions and the olfactory bulb, partly supported by MRI perfusion data. This study supports previous observations that AD transgenic mice show a higher VD in specific regions compared with WT mice during the early and late stages of the disease (4.5 to 8 months), extending results to whole brain mapping.
Subject(s)
Alzheimer Disease/diagnostic imaging , Brain/blood supply , Brain/diagnostic imaging , Histological Techniques/methods , Microscopy, Fluorescence, Multiphoton/methods , Algorithms , Animals , Disease Models, Animal , Equipment Design , Image Processing, Computer-Assisted , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
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.
