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

Baptiste Heiles; Flora Nelissen; Rick Waasdorp; Dion Terwiel; Byung Min Park; Eleonora Munoz Ibarra; Agisilaos Matalliotakis; Tarannum Ara; Pierina Barturen-Larrea; Mengtong Duan; Mikhail G Shapiro; Valeria Gazzola; David Maresca

doi:10.1126/science.ads1325

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

Baptiste Heiles, Flora Nelissen, Rick Waasdorp, Dion Terwiel, Byung Min Park, Eleonora Munoz Ibarra, Agisilaos Matalliotakis, Tarannum Ara, Pierina Barturen-Larrea, Mengtong Duan, Mikhail G Shapiro, Valeria Gazzola, David Maresca

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

Abstract

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 ~64× acceleration in imaging speed, ~35× increase in imaged volume, and ~4× increase in classical imaging resolution compared with the state of the art in biomolecular ultrasound.

Original language	English
Pages (from-to)	eads1325
Journal	Science
Volume	388
Issue number	6742
DOIs	https://doi.org/10.1126/science.ads1325
Publication status	Published - 04 Apr 2025

Keywords

Animals
Capillaries/diagnostic imaging
Mice
Microbubbles
Contrast Media
Microscopy, Fluorescence/methods
Humans
Nonlinear Optical Microscopy/methods
Brain/blood supply
Gene Expression

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title = "Nonlinear sound-sheet microscopy: Imaging opaque organs at the capillary and cellular scale",

abstract = "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 ~64× acceleration in imaging speed, ~35× increase in imaged volume, and ~4× increase in classical imaging resolution compared with the state of the art in biomolecular ultrasound.",

keywords = "Animals, Capillaries/diagnostic imaging, Mice, Microbubbles, Contrast Media, Microscopy, Fluorescence/methods, Humans, Nonlinear Optical Microscopy/methods, Brain/blood supply, Gene Expression",

author = "Baptiste Heiles and Flora Nelissen and Rick Waasdorp and Dion Terwiel and Park, {Byung Min} and Ibarra, {Eleonora Munoz} and Agisilaos Matalliotakis and Tarannum Ara and Pierina Barturen-Larrea and Mengtong Duan and Shapiro, {Mikhail G} and Valeria Gazzola and David Maresca",

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doi = "10.1126/science.ads1325",

language = "English",

volume = "388",

pages = "eads1325",

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T1 - Nonlinear sound-sheet microscopy

T2 - Imaging opaque organs at the capillary and cellular scale

AU - Heiles, Baptiste

AU - Nelissen, Flora

AU - Waasdorp, Rick

AU - Terwiel, Dion

AU - Park, Byung Min

AU - Ibarra, Eleonora Munoz

AU - Matalliotakis, Agisilaos

AU - Ara, Tarannum

AU - Barturen-Larrea, Pierina

AU - Duan, Mengtong

AU - Shapiro, Mikhail G

AU - Gazzola, Valeria

AU - Maresca, David

PY - 2025/4/4

Y1 - 2025/4/4

N2 - 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 ~64× acceleration in imaging speed, ~35× increase in imaged volume, and ~4× increase in classical imaging resolution compared with the state of the art in biomolecular ultrasound.

AB - 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 ~64× acceleration in imaging speed, ~35× increase in imaged volume, and ~4× increase in classical imaging resolution compared with the state of the art in biomolecular ultrasound.

KW - Animals

KW - Capillaries/diagnostic imaging

KW - Mice

KW - Microbubbles

KW - Contrast Media

KW - Microscopy, Fluorescence/methods

KW - Humans

KW - Nonlinear Optical Microscopy/methods

KW - Brain/blood supply

KW - Gene Expression

U2 - 10.1126/science.ads1325

DO - 10.1126/science.ads1325

M3 - Article

C2 - 40179181

SN - 0036-8075

VL - 388

SP - eads1325

JO - Science

JF - Science

IS - 6742

ER -

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

Abstract

Keywords

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