Nonlinear sound-sheet microscopy: Imaging opaque organs at the capillary and cellular scale

• 成果类型: Article
• 署名作者: Heiles, Baptiste; Nelissen, Flora; Waasdorp, Rick; Terwiel, Dion; Park, Byung Min; Ibarra, Eleonora Munoz; Matalliotakis, Agisilaos; Ara, Tarannum; Barturen-Larrea, Pierina; Duan, Mengtong; Shapiro, Mikhail G.; Gazzola, Valeria; Maresca, David
• 署名单位: Delft University of Technology; Royal Netherlands Academy of Arts & Sciences; Netherlands Institute for Neuroscience (NIN-KNAW); California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; University of Amsterdam
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13972
• DOI: 10.1126/science.ads1325
• 发表日期: 2025-04-04
• 关键词: biomolecular ultrasound; contrast agents; brain; FLOW; nanostructures; doppler; deep

摘要

Light-sheet fluorescence microscopy has revolutionized biology by visualizing dynamic cellular processes in three dimensions. However, light scattering in thick tissue and photobleaching of fluorescent reporters limit this method to studying thin or translucent specimens. In this study, we applied nondiffractive ultrasound beams in conjunction with a cross-amplitude modulation sequence and nonlinear acoustic reporters to enable fast and volumetric imaging of targeted biological functions. We reported volumetric imaging of tumor gene expression at the cubic centimeter scale using genetically encoded gas vesicles and localization microscopy of cerebral capillary networks using intravascular microbubble contrast agents. Nonlinear sound-sheet microscopy provides a similar to 64x acceleration in imaging speed, similar to 35x increase in imaged volume, and similar to 4x increase in classical imaging resolution compared with the state of the art in biomolecular ultrasound.