In vivo super-resolution photoacoustic computed tomography by localization of single dyed droplets

In vivo super-resolution photoacoustic computed tomography by localization of single dyed droplets
Super-resolved vascular imaging in vivo. Credit: Pengfei Zhang, Lei Li, and Lihong V. Wang

Photoacoustic computed tomography (PACT) is a non-invasive hybrid imaging technique that excites biological tissues with light and detects the subsequently generated ultrasound to form images. PACT combines the advantages of both optical imaging—high optical contrast, and ultrasonic imaging—high resolution and deep penetration in biological tissues. PACT has been widely used for vascular network mapping, functional brain imaging, and tumor detection in deep tissues.

However, by detecting , PACT cannot escape the doom that is faced by all wave-based imaging techniques: the diffraction of waves presents a fundamental limit on its spatial resolution. Due to ultrasonic diffraction, an absorbing point source is spread out as a disk (point spread function) in its image, which has a size comparable with the ultrasound wavelength. Therefore, structures in tissues are smeared out by this disk and blurred, and any features that are separated by a distance smaller than the ultrasound wavelength cannot be resolved. Although finer resolution can be achieved by detecting ultrasound with shorter wavelengths, the attenuation of ultrasound in tissues becomes stronger accordingly, limiting penetration.

Recently, researchers at the Caltech Optical Imaging Laboratory, directed by Lihong Wang, developed a technique for in vivo super-resolution PACT. It breaks the acoustic diffraction limit by localizing the centers of single dyed flowing in . This technique resolves brain blood vessels at a six-fold finer resolution. The research has been published in Light: Science and Applications.

The researchers fabricated 'photoacoustically bright' oil-in- using a solution of a hydrophobic dye, namely, IR-780 iodide in oil. The sizes of the droplets range from 4 to 30 microns, which are much smaller than the wavelengths of the detected ultrasound, making them excellent photoacoustic point sources. Taking advantage of their small sizes, liquid compliance, and high photoacoustic 'brightness', once injected into the bloodstream, the droplets flow smoothly in blood capillaries and provide excellent tracers for localization-based super-resolution imaging.

By injecting the droplets into brain vessels of live mice, the researchers achieved super-resolution PACT in three steps. The first step is to image single dyed droplets with single laser shots. The data acquisition time of PACT (~50 μs) is so short that the flowing droplets are almost frozen in each frame. The number of the injected droplets was controlled so that droplets are separated by more than half an acoustic wavelength, which guaranteed the image of each one (the disk) does not overlap with those of its neighbors.

The second step is to determine the exact position of each droplet by finding the center of its point spread function. Because the droplets are well-separated, their centers can be localized with precisions that are much smaller than the wavelength. Taking advantage of droplet flow, droplets in closely separated vessels can be spatially resolved as long as they do not show up in the same image frame.

The final step is to repeat the imaging and localizing processes until a sufficient density of source points has been obtained. The researchers continuously acquired 36,000 image frames and localized a total of 220,000 droplets. By marking the positions of all of these point sources in one image, a super-resolved image can be built up, which represents a finer-resolved vascular network since the droplets are confined within the vessels. The of this image exceeds the diffraction limit, because it is determined by the accuracy with which the position of each droplet can be estimated. In addition to the resolution enhancement, tracking the flowing droplets also allowed the researchers to characterize the blood flow speed in the deep brain of live mice.

Super-resolution PACT of microvasculature has an exciting prospect. The technique has the potential to substantially advance the study of normal blood-vessel function, as well as disease, such as angiogenesis in tumors in deep tissue.


Explore further

In vivo skin imaging technology developed

More information: Pengfei Zhang et al, In vivo superresolution photoacoustic computed tomography by localization of single dyed droplets, Light: Science & Applications (2019). DOI: 10.1038/s41377-019-0147-9
Journal information: Light: Science & Applications

Citation: In vivo super-resolution photoacoustic computed tomography by localization of single dyed droplets (2019, April 18) retrieved 21 September 2019 from https://phys.org/news/2019-04-vivo-super-resolution-photoacoustic-tomography-localization.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
16 shares

Feedback to editors

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more