Non-invasive vascular elastography (NIVE) was recently introduced to characterize mechanical properties of superficial arteries. In this paper, the feasibility of NIVE and its applicability in the context of high-frequency ultrasound imaging is investigated. First, experiments were performed in vitro on vessel-mimicking phantoms. Polyvinyl alcohol cryogel was used to create two double-layer vessels with different mechanical properties. In both cases, the stiffness of the inner layer was made softer. Radial stress was applied within the lumen of the phantoms by applying incremental static pressure steps with a column of a flowing mixture of water-glycerol. The vessel phantoms were insonified at 32 MHz with an ultrasound biomicroscope to provide cross-section sequences of radio-frequency (RF) ultrasound data. The Lagrangian speckle model estimator (LSME) was used to assess the two-dimensional-strain tensors, and the composite Von Mises elastograms were computed. A new implementation of the LSME based on the optical flow equations was introduced. Deformation parameters were estimated using an inversion algorithm. For each in vitro experiment, both layers of approximately 1 mm were distinguished. Second, the use of the method for the purpose of studying small vessels (MicroNIVE) in genetically engineered rodents was introduced. Longitudinal scans of the carotid artery were performed at 40 MHz. The in vivo results give confidence in the feasibility of MicroNIVE as a potential tool to non-invasively study the impact of targeted genes on vascular remodelling in rodents.