Ultrafast amplitude modulation for molecular and hemodynamic ultrasound imaging
Ultrasound is playing an emerging role in molecular and cellular imaging thanks to new micro- and nanoscale contrast agents and reporter genes. Acoustic methods for the selective in vivo detection of these imaging agents are needed to maximize their impact in biology and medicine. Existing ultrasound pulse sequences use the nonlinearity in contrast agents' response to acoustic pressure to distinguish them from mostly linear tissue scattering. However, such pulse sequences typically scan the sample using focused transmissions, resulting in a limited frame rate and restricted field of view. Meanwhile, existing wide-field scanning techniques based on plane wave transmissions suffer from limited sensitivity or nonlinear artifacts. To overcome these limitations, we introduce an ultrafast nonlinear imaging modality combining amplitude-modulated pulses, multiplane wave transmissions, and selective coherent compounding. This technique achieves contrast imaging sensitivity comparable to much slower gold-standard amplitude modulation sequences and enables the acquisition of larger and deeper fields of view, while providing a much faster imaging framerate of 3.2 kHz. Additionally, it enables simultaneous nonlinear and linear image formation and allows concurrent monitoring of phenomena accessible only at ultrafast framerates, such as blood volume variations. We demonstrate the performance of this ultrafast amplitude modulation technique by imaging gas vesicles, an emerging class of genetically encodable biomolecular contrast agents, in several in vitro and in vivo contexts. These demonstrations include the rapid discrimination of moving contrast agents and the real-time monitoring of phagolysosomal function in the mouse liver.
© 2021 Published under an exclusive license by AIP Publishing. Submitted: 18 March 2021; Accepted: 20 May 2021; Published Online: 14 June 2021. C.R. and M.G.S. conceived the study. C.R. developed sequence acquisitions and acquired data. C.R. and D.W. developed the processing model. D.M. produced the GVs. Z.J. helped conceiving the dynamic in vitro study. B.L. assisted with the in vivo study. C.R. and M.G.S wrote the first draft of the manuscript. All authors edited and approved the final version of the manuscript. This research is supported by the National Institutes of Health (No. R01-EB018975). C.R. is supported by the Human Frontier Science Program (Grant No. LT000217/2020-C). Related research in the Shapiro laboratory is supported by the Chan Zuckerberg Initiative, the Pew Charitable Trust, the David and Lucile Packard Foundation and the Heritage Medical Research Institute. Data Availability: The data that support the findings of this study as well as the scripts to process the data are openly available in GitHub at https://github.com/ClaireRabut/Rabut_2021_uAM_processing_and_data, Ref. 30.
Submitted - 2021.05.18.444561v1.full.pdf
Published - 5.0050807.pdf
Supplemental Material - apl21-ar-02315_suppmaterial.pdf