The aim of our study was to circumvent the limitations of standard organ chamber experiments using in vivo Doppler Fourier Domain optical coherence tomography (FD OCT) to analyze the vascular function of small arteries of different mouse strains. We showed in a feasibility study that Doppler FD OCT with a spectrum read out rate of 12 kHz allows the determination of blood flow in murine arteries and veins. The high temporal resolution of the system can also be used to quantify the pulse from real-time cross-sectional images by analyzing the intensity alternation inside the vessel lumen.

We have imaged the blood flow velocity of the murine saphenous artery in vivo and its adjacent vein with oppositely directed blood flow in anesthetized C57BL/6 mice at a heart rate of 420 bpm. Tail cuff measurements confirmed the heart rate of 41712 bpm at a systolic blood pressure of 12915 mm Hg. For visualizing the flowing blood in the saphenous artery or vein, the flow velocities were colour coded and overlaid on the structural images. The saphenous artery displayed a diameter of 229.6 mm and exhibited a maximum of systolic blood flow velocity of 136 mm/s. This velocity decreases to 45 mm/s during the diastolic phase of the cardiac cycle. The saphenous vein with a diameter of 265.4 mm showed a blood flow velocity of 14.5 mm/s during the whole cardiac cycle.

Time course of the blood vessel lumen dynamics were analyzed in time series of cross-sectional FD OCT images using image processing software. Vascular function of murine saphenous arteries of male C57BL/6 and LDLR knockout mice was first analyzed at 6 weeks of age. The second measurements were performed at 20 weeks of age after a 14 week feeding period of control or high-fat diet containing 21.2% butter fat and 2.1 mg/kg cholesterol. Vasoconstriction was analyzed in response to 80 mM K⁺, vasodilatation in response to 1 mM SNP. In all 6 groups we determined the inner diameter [mm] during resting condition, after vasoconstriction and after vasodilatation. Other analyzed parameters were the maximum velocity [mm/s] and the time to half maximal diameter change [s] of vasoconstriction and vasodilatation.

In conclusion, using Doppler FD OCT technique we were able to image the blood flow direction and velocity and to analyse the vascular function of small arteries of different mouse strains in response to high-fat diet in vivo. This novel imaging technique offers the ability to quantify differences in early stages of the pathogenesis of atherosclerosis.