Estimating vascular density by using quantitative ultrasound in microbubble enhanced vessel networks

This study investigates the use of quantitative ultrasound techniques for characterizing tumor-related angiogenesis. Neo-vessel density serves as an established biomarker of breast cancer malignancy, making it crucial to develop methods for its quantification. Our approach involves analyzing scattering from ultrasound contrast agents within vascular networks. We assess whether parameters derived from plane wave imaging and full synthetic aperture data acquisition effectively estimate vessel density. Healthy rat kidneys were used as a model for vascular networks. Following anesthesia, microbubbles were injected through the tail vein at an infusion rate of 1.5e8 bubbles/min. Ultrasound data acquisition was performed using a Verasonics L-11-5v linear array transducer connected to a Verasonics 256 Vantage NXT scanner. A full synthetic aperture approach was applied, utilizing all 128 transducer elements to transmit two-cycle Gaussian pulses at a central frequency of 7.6 MHz. Backscattered signals were recorded across all elements, producing a 3-D Inter-Element Response Matrix (IRM). The Diffusion constant and multiple scattering-related parameters were calculated by separating coherent and incoherent backscattered intensities and analyzing the temporal growth of the diffusive halo. Acoustic angiography images were used for comparison, and light sheet imaging served as the ground truth for validating vascular density measurements.