High frequency ultrasound nonlinear scattering from porphyrin nanobubbles

Pellow C, Tan J, Chérin E, Demore CME, Zheng G, Goertz DE

Ultrasonics, 2020

DOI: 10.1016/j.ultras.2020.106245

Emerging contrast imaging studies have highlighted the potential of nanobubbles for both intravascular and extravascular applications. Reports to date on nanobubbles have generally utilized low frequencies (<12 MHz), high concentrations (>10⁹ mL⁻¹), and B-mode or contrast-mode on preclinical and clinical systems. However, none of these studies directly examined nanobubble acoustic signatures systematically to implement nonlinear imaging schemes in a methodical manner based on nanobubble behaviour. Here, nanobubble nonlinear behaviour is investigated at high frequencies (12.5, 25, 30 MHz) and low concentration (10⁶ mL⁻¹) in a channel phantom, with different pulse types in single- and multi-pulse sequences to examine behaviour under conditions relevant to high frequency imaging. Porphyrin nanobubbles are demonstrated to initiate nonlinear scattering at high frequencies in a pressure-threshold dependent manner, as previously observed at low frequencies. This threshold behaviour was then utilized to demonstrate enhanced nanobubble imaging with pulse inversion, amplitude modulation, and a combination of the two, progressing towards the improved sensitivity and expanded utility of these ultrasound contrast agents.