The selection of the low frequency for radial modulation imaging at 20 MHz

Background: Radial modulation (RM) is a promising dual band approach for high frequency microbubble (MB) imaging. A low frequency (LF) ultrasound pulse is used to manipulate the MB radius while a synchronized high frequency (HF) pulse successively measures MB backscatter in compressed and expanded states. RM signal amplitude has been shown to increase with LF signal amplitude, but is ultimately limited by the infiltration of LF harmonics into the HF bandwidth at higher LF pressure. The ideal LF for maximizing RM signal remains controversial, and frequencies at and below resonance have been reported. This study was designed to investigate the modulation frequency and amplitude that maximize RM signal. Methods: Lipid-encapsulated perfluorocarbon MB (3.54 ± 1.76 µm) were circulated in a 6 mm diameter cellulose tube. A 20 MHz single element transducer was concentrically housed in the center of hollow 1 and 2.25 MHz transducers and the resulting confocal pressure fields were calibrated with a hydrophone. During insonation of the circulating MB, 50 independent HF line pairs were recorded while varying LF pressure from 0.02 to 0.4 mechanical index (MI). The RM signal was defined as the mean HF backscatter power difference between the low and high pressure phases of the modulating LF, normalized by the high pressure HF backscatter power. Radio-frequency signal and spectra were also analyzed for LF harmonics. Results: Simulation and experimental data for this MB suspension both predicted higher RM at resonance frequency for the same MI. However, our experimental data demonstrate that the RM reaches a 60% maximum that is the same for both frequencies and is reached at 0.1 < MI < 0.15. This plateau just precedes the appearance of LF harmonics in the HF bandwidth when MI > 0.15. Also, we show that RM allows high resolution single MB specific imaging with very efficient tissue suppression. Conclusions: Our results suggest that a MI in the 0.1–0.15 range produced the same maximal RM amplitude in the studied MB population for both LF studied. LF harmonics were negligible at these pressure levels. These findings should help with the development of high frequency molecular imaging.