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The feasibility of tissue harmonic imaging with a prototype intravascular ultrasound (IVUS) system using a conventional single-element rotating IVUS catheter was investigated. Hydrophone measurements showed fundamental peak pressures of 1.9 MPa on-axis of such a catheter in water. The second harmonic signal at 40 MHz built up to 0.55 MPa, corresponding to 11 dB below the peak fundamental pressure. Experiments performed in a tissue-mimicking phantom and in a rabbit aorta in vivo showed the feasibility of tissue harmonic imaging with a conventional IVUS catheter. When we applied averaging of four neighboring RF-lines in the in vivo acquisition, the signal-to-noise ratio of the harmonic image increased to 25 dB.