Ultrasound multiple scattering with microbubbles can differentiate between tumor and healthy tissue in vivo

Abstract

Most solid tumors are characterized by highly dense, isotropic vessel networks. Characterization of such features has shown promise for early cancer diagnosis. Ultrasound diffusion has been used to characterize the micro-architecture of complex media, such as bone and the lungs. In this work, we examine a non-invasive diffusion-based ultrasound technique to assess neo-vascularization. Because the diffusion constant reflects the density of scatterers in heterogeneous media, we hypothesize that by injecting microbubbles into the vasculature, ultrasound diffusivity can reflect vascular density (VD), thus differentiating the microvascular patterns between tumors and healthy tissue. The diffusion constant and its anisotropy are shown to be significantly different between fibrosarcoma tumors (n = 16) and control tissue (n = 18) in a rat animal model in vivo. The diffusion constant values for control and tumor were found to be 1.38 ± 0.51 mm 2 μs −1 and 0.65 ± 0.27 mm 2 μs −1 , respectively. These results are corroborated with VD from acoustic angiography (AA) data, confirming increased vessel density in tumors compared to controls. The diffusion constant offers a promising way to quantitatively assess vascular networks when combined with contrast agents, which may allow early tumor detection and characterization.

Imaging methods to evaluate tumor microenvironment factors affecting nanoparticle drug delivery and antitumor response

“…Acoustic angiography has been used to map micro-vascular networks in the TME [218,[220][221][222] , differentiate tumor tissue from healthy tissue [217,221] and various tumor types [223] , as well as monitor response to therapy [37,224] . The dense and tortuous vessel network in solid tumors allow the use of acoustic angiography in the assessment of neo-vascularization for early diagnosis [217] [ Figure 3]. One limitation of acoustic angiography for vascular imaging is the imaging depth (up to several centimeters [218] ).…”

“…Lindsey et al [232] have assessed the combined microvascular and molecular imaging in a technique termed molecular acoustic angiography, suggesting that increased distance from VEGFR2-and selectin-targeting sites showed decreased vessel tortuosity. Lakshman et al [233] performed screening studies of the tumor vasculature in the TME of an orthotopic mouse model of human Figure reproduced with permission from [217] .…”

“…These microbubble contrast agents are confined to the blood stream when injected intravenously. Acoustic angiography has been used to map micro-vascular networks in the TME [ 218 , 220 – 222 ] , differentiate tumor tissue from healthy tissue [ 217 , 221 ] and various tumor types [ 223 ] , as well as monitor response to therapy [ 37 , 224 ] . The dense and tortuous vessel network in solid tumors allow the use of acoustic angiography in the assessment of neo-vascularization for early diagnosis [ 217 ] [ Figure 3 ].…”

Spherical oscillations of encapsulated microbubbles: Effect of shell compressibility and anisotropy

“…Such a super-resolved technique can also be implemented through a photoacoustic device, where the UCAs are excited by light rather than by sound (Vilov et al, 2017). The scattered ultrasound signal of UCAs has also been recently used to discriminate between two networks topologies, with application to cancerous tumor detection (Mohanty et al, 2019).…”

Critical remarks to ‘Pediatric lung ultrasound — pros and potentials’

“…Multiple scattering is becoming a widely studied phenomenon and has proven utility in characterizing disordered media. Exploiting US multiple scattering should be possible to characterize the microarchitectural properties of the lung parenchyma [5].…”