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The elastic properties of skin are of great interest in dermatology because they are affected by many pathological conditions. In this paper, a technique for in vivo mechanical strain imaging of the skin based on high-frequency ultrasound (HFUS) is presented. Elastic skin properties are assessed applying suction to the skin surface with a stepwise increased vacuum and estimating the resulting displacements in a spatially resolved manner. Acquired radio frequency (R-F) echo signals and their envelope are analyzed for this purpose. A computer-controlled vacuum system with a digital pressure control loop was developed for precise and reproducible deformation. In a first processing step, the skin surface is segmented. Local axial strains inside the skin are estimated from axial displacements, which are estimated from consecutive echo signal frames analyzing the phase of the complex cross correlation function of analytical echo signals. Furthermore, speckle tracking is applied to estimate axial and lateral displacements and to quantify axial and lateral strains. The correlation coefficient of windowed echo signals compensated for displacements are used as a measure to validate the estimated strains, which is essential to accomplish reliable in vivo measurements. Phantom experiments were performed to validate the proposed technique. Results of in vivo measurements are presented, showing the potential for mechanical strain imaging in the skin in vivo.