Impact of Multiple Responses to a Singles Sonication when Determing Nanobubble Contrast Agent Characteristics

Abstract

Multiple scatter responses were observed in a phantom channel containing nanobubble contrast agent following a single sonication, with agent replacement between trials changing the responses’ relative positioning and intensities. Experimentally, the combined spectrum of several responses can show split peaks instead of a single peak at the sonication’s carrier frequency. This is the result of the real and imaginary components of the complex-valued frequency spectra of individual scatter responses combining in a constructive or destructive manner. In some trials, changes were observed in agent longevity with a time constant of 2.5 milliseconds during multiple sonications. This paper applies two measures to determine whether this longevity variability is real or an algorithmic artefact due to minor position shifts of several responses modifying the way their real and imaginary spectral components interfere. The first power measure determines the spectrum from all phantom data undistorted by reflections from the channel boundaries. The second measure determines the short-term Fourier transform of the hydrophone signal with an analysis window the length of the sonication moved across the full agent response, potentially capturing changes in individual scatter responses. Combining the results from the two metrics confirms that the decrease in agent longevity during multiple sonications is real and not the result of an algorithmic artefact associated with shape changes in the multi-peak spectra during one trial. However, given that the positioning of the multiple responses is uneven across the phantom channel and changes with agent replacement, we conclude that the measure using all available data will be more consistent when used to compare agent-tissue contrast from different imaging schemes.