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Tissue perfusion can be assessed by harmonic imaging of microbubbles which are highly nonlinear and produce strong harmonic components as they scatter the incident ultrasound. However, the harmonic magnitude also depends on the pressure of the transmitted ultrasound and the attenuation of the intervening tissues in the ultrasound path. Thus, the harmonic magnitude may not be a reliable indicator of the presence or absence of microbubbles, and hence, tissue perfusion. Here, we propose a parameter called harmonic to squared fundamental ratio (HSFR) that, under ideal conditions, completely compensates for the effects of tissue attenuation and transmit pressure for superior microbubble detection. In experiments, the target tested is 0.01% microbubble solution or water (as a control). The echoes from these targets obtained with different transmit pressures and attenuation pads are used to compute the HSFR. HSFR is able to separate the microbubble solutions from the control with a single threshold for all combinations of attenuation and transmit intensity tested.