Characterization of tumor angiogenesis using quantitative ultrasound and microbubble-enhanced scattering

This work explores quantitative ultrasound for assessing tumor-related angiogenesis. Since neovascular density reflects tumor aggressiveness, its accurate measurement is clinically valuable. We analyze ultrasound backscattered signals from contrast agents distributed throughout the vasculature and investigate whether parameters extracted from these signals can differentiate between vessel density of healthy and tumor-bearing rats. Fibrosarcoma tumors were implanted in the right flanks of three rats, with the left flanks used as internal controls. After anesthesia, microbubbles were injected at an infusion rate of 1.0 × 108 bubbles/min. Ultrasound data were collected using a Verasonics L-11-5v linear array transducer along with a Verasonics 256 Vantage NXT scanner. A full synthetic aperture approach was implemented, transmitting two-cycle Gaussian pulses at 7.6 MHz using all 128 elements. Backscattered signals were recorded across array, producing a 3-D Inter-Element Response Matrix (IRM). Scattering mean free path (SMFP) was computed by separating coherent and incoherent intensities and analyzing temporal growth of the diffusive halo. Significant differences were found between SMFP values of healthy and tumor-bearing tissue data (p = 1.39 × 10−12) with SMFPs of 3.77 ± 1.78 mm for tumor and 9.17 ± 3.94 mm for control. However, single scattering intensity decay rate showed no sensitivity. Acoustic angiography images were also used in this study for comparison.