Nav: Home

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

April 18, 2019

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 ultrasonic waves, 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 droplets flowing in blood vessels. 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-water droplets 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 ultrasound 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 spatial resolution 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.
-end-


Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences

Related Blood Vessels Articles:

Human textiles to repair blood vessels
As the leading cause of mortality worldwide, cardiovascular diseases claim over 17 million lives each year, according to World Health Organization estimates.
How high levels of blood fat cause inflammation and damage kidneys and blood vessels
Viral and bacterial infections are not the only causes of inflammation of body tissue.
3D printing, bioinks create implantable blood vessels
A biomimetic blood vessel was fabricated using a modified 3D cell printing technique and bioinks.
When blood vessels are overly permeable
In Germany alone there are around 400,000 patients who suffer from chronic inflammatory bowel diseases.
Nicotine-free e-cigarettes can damage blood vessels
A Penn study reveals single instance of vaping immediately leads to reduced vascular function.
Creating blood vessels on demand
Researchers discover new cell population that can help in regenerative processes.
Self-sustaining, bioengineered blood vessels could replace damaged vessels in patients
A research team has bioengineered blood vessels that safely and effectively integrated into the native circulatory systems of 60 patients with end-stage kidney failure over a four-year phase 2 clinical trial.
Found: the missing ingredient to grow blood vessels
Researchers have discovered an ingredient vital for proper blood vessel formation that explains why numerous promising treatments have failed.
How sickled red blood cells stick to blood vessels
An MIT study describes how sickled red blood cells get stuck in tiny blood vessels of patients with sickle-cell disease.
Like a zipper -- how cells form new blood vessels
Blood vessel formation relies on the ability of vascular cells to move while remaining firmly connected to each other.
More Blood Vessels News and Blood Vessels Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.