Temporal characterization of the functional density of the vasa vasorum by contrast-enhanced ultrasonography maximum intensity projection imaging.

Objectives: We sought to determine whether contrast-enhanced ultrasound (CEU) microangiography with maximum intensity projection (MIP) processing could temporally evaluate proliferation of the vasa vasorum (VV) in a model of mural hemorrhage.

Background: Expansion of the VV and plaque neovascularization contributes to plaque growth and instability and may be triggered by a variety of stimuli, including vascular hemorrhage. However, quantitative in vivo methods for temporal assessment of VV remodeling are lacking.

Methods: In 24 rabbits fed a high-fat diet, either autologous whole blood or saline was percutaneously injected into the media-adventitia of the femoral artery using ultrahigh-frequency ultrasound guidance. Functional VV density at the injection site and contralateral control artery was assessed 1, 2, and 6 weeks after injection with CEU imaging with MIP processing. In vitro studies with renathane microtubes were also performed to validate linear density measurement with CEU and MIP processing.

Results: In vitro studies demonstrated that MIP processing of CEU data reflected the relative linear density of vessels in a manner that was relatively independent of contrast concentration or microtube flow rate. On CEU with MIP, there was a 3-fold increase in femoral artery VV microvascular density at 1 and 2 weeks after blood injection (p < 0.01 vs. contralateral control), whereas VV density increased minimally after saline injection. At 6 weeks, VV vascular density decreased in blood-treated vessels and was not different from saline-injected or contralateral control vessels.

Conclusions: CEU with MIP processing can provide quantitative data on temporal changes in the functional density of the VV. This method may be useful for evaluating high-risk features of plaque neovascularization or response to therapies aimed at plaque neovessels.