Quantitative assessment of angiogenic microvasculature using Ultrasound multiple scattering with microbubble contrast agents

In tumors, angiogenesis (formation of new blood vessels) is established as a biomarker of malignancy. A random, isotropic, high-density vessel network is linked to tumor invasiveness. Ultrasound quantification of angiogenic micro-architecture could help increase the specificity of ultrasound for cancer diagnosis. We exploit multiple scattering by microbubbles populating angiogenic networks to characterize an effective medium diffusivity via the diffusion constant (D). The inter-element response matrix is acquired using an L11-4v linear array transducer operating at 7.8 MHz. D is computed from the time evolution of the incoherent contribution to the backscattered intensity in the near field. D is measured in fibrosarcoma tumors subcutaneously implanted in rats (n = 16), and in control, healthy tissue (n = 18). D is measured for two different orientations (Coronal and Transverse) and the anisotropy of the microvasculature is evaluated via the ratio of the D values obtained in the two different orientations. D was found significantly different between control (1.38 ± 0.51 mm2/μs) and tumor (0.65 ± 0.27 mm2/μs) (p