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A new method for detection of ultrasound contrast agent micro-bubbles is presented and analyzed. The method transmits dual frequency pulse complexes (frequency separation ~ 1:10), and the signals from at least two complexes with opposite polarity of the low frequency pulse is combined to suppress the signal scattered from tissue and enhance the signal scattered from micro-bubbles. The method has larger CTR and CNR than current methods using the 2nd harmonic band of the scattered signal, especially for the high frequency above the bubble resonance frequency. The methods have special interest for high frequency imaging of neo-angiogenesis in tumors and the vasa vasorum of arterial plaque.