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Conrad William Merkle, Marco Augustin, Danielle J. Harper, Vivek Jay Srinivasan, Gerhard Garhofer, Bernhard Baumann; 4D contrast-enhanced OCT improves in vivo visualization of neovascular structure and hemodynamics in mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3070.
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Neovascularizations (NVs) are an important characteristic of many vision-threatening eye diseases. NVs, which often grow in diving or ascending orientations, can be difficult to study in vivo due to the lack of depth information provided by fluorescence angiography and the low intrinsic scattering signal of vessels oriented parallel to the beam axis when imaged by Optical Coherence Tomography (OCT) and even OCT angiography (OCTA). We hypothesize that by injecting a lipid-based OCT contrast agent, we can better visualize and study the hemodynamics within these critical vessels in a mouse model in vivo.
A Very Low Density Lipoprotein Receptor (VLDLR) knockout (-/-) mouse model (n = 2, age 15-18 months), an established model of sub-retinal NV, and a wild type control (n = 1, age 16 months) were imaged with a custom spectral domain OCT ophthalmoscope under isoflurane anesthesia. The OCT system was centered at 840 nm with a bandwidth of 100 nm for 3.8 µm axial resolution in tissue. A 3 mL/kg body weight bolus of Intralipid 20%, a lipid emulsion used here as an OCT contrast agent, was injected via the tail vein. Repeated 2D scanning was performed during the injection to track the bolus passage. OCT angiogram volumes were acquired once before and repeatedly after injection.
Injection of the lipid-based contrast agent significantly improved signal within the NVs (Fig 1A) both in intensity and angiogram images. Particle tracking methods (Fig 1B,C) were applied to the 2D scans by synthesizing line scans from the XZ plane to quantify velocity within individual NVs and demonstrate flow speed both into (1.1 ± 0.5 mm/s) and out of (1.3 ± 0.3 mm/s) the same lesion simultaneously. Cylindrically averaged angiogram profiles were acquired in 3D along 8 NVs and 14 healthy vessels and tracked precisely across all time points. The contrast-enhanced angiogram signal decayed faster within NVs relative to healthy vessels (Fig 2). The estimated half-life in the NVs was lower than the 95% confidence interval for healthy vessels, whereas the 2 healthy groups showed reasonable agreement.
Contrast-enhanced OCT greatly increases visibility of NVs and enables further investigations into retinal hemodynamics in vivo. Preclinical applications of this technique may help study the extent of physical and hemodynamic disruptions that NVs cause in various disease models in vivo.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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