Super-resolution photoacoustic imaging could allow scientists to watch blood vessels with improved resolution

November 09, 2017

WASHINGTON - Researchers have reported an approach to photoacoustic imaging that offers vastly improved resolution, setting the stage for detailed in vivo imaging of deep tissue. The technique is based on computational improvements, so it can be performed with existing imaging hardware, and thus could provide a practical and low-cost option for improving biomedical imaging for research and diagnostics.

After further refinements, the approach could offer the opportunity to observe the minute details of processes occurring in living tissue, such as the growth of tiny blood vessels, and therefore provide insights on normal development or disease processes such as cancer.

"Our main goal is to develop a microscope that can see the microvasculature and capillary vessels," said Ori Katz, a researcher with the Hebrew University of Jerusalem, Israel, and senior author of the study. "It's important to be able to watch these grow with nearby tumors, for example."

In Optica, The Optical Society's (OSA) journal for high impact research, the researchers describe overcoming the acoustic diffraction limit, a barrier that previously limited the resolution obtainable with photoacoustic imaging, by exploiting signal fluctuations stemming from the natural motion of red blood cells. Such fluctuations might otherwise be considered noise or viewed as detrimental to the measurements.

"With photoacoustic imaging you can see much deeper in tissue than you can with an optical microscope, but the resolution is limited by the acoustic wavelength," Katz said. "What we have discovered is a way to obtain photoacoustic images with considerably better resolution, without any change in the hardware."

Overcoming the acoustic diffraction limit

Photoacoustic imaging combines optical illumination (which uses light waves) and ultrasound (which uses sound waves) to image biological samples in ways that would not be possible with either modality alone. Optical methods can provide excellent resolution but often only near the surface as light is highly scattered in tissue. Ultrasound can go much deeper but does not offer the same contrast as optical imaging. By integrating the two modalities, researchers have been able to overcome the drawbacks of each to advance a host of applications.

However, the imaging technique does have certain limitations. Photoacoustic imaging relies on acoustic detection, so the image resolution is determined by the acoustic wavelength. While optical microscopy, for example, can see objects on the scale of less than a micron, photoacoustic imaging is limited to tens of microns. This means that photoacoustic imaging cannot resolve small objects like microvessels or capillaries.

Katz devised the method for surpassing the acoustic diffraction limit in collaboration with Emmanuel Bossy, now at Université Grenoble Alpes in Grenoble, France. At the heart of their work is an advanced statistical analysis framework that they apply to images of red blood cells flowing through the vessels; the blood cells facilitate imaging by absorbing light at particular wavelengths. By increasing the resolution computationally, they avoided the need for any additional hardware, so the advances described can be attained using existing photoacoustic imaging systems.

Drawing inspiration from a fluorescence-based technique

The tools needed to achieve super-resolution with photoacoustic imaging were described nearly a decade ago in a work in optical microscopy with the technique super-resolution optical fluctuation imaging (SOFI). Katz and colleagues came to this work after grappling with the problem of the acoustic diffraction limit and discovered that the same mathematics used with SOFI could be used for improving photoacoustic imaging.

"Someone just needed to make the connection," Katz said. "It's the same equation--the wave equation. Mathematically, you could say it's the same problem."

In a study published in Optica last year, Katz and his colleagues demonstrated the ability to surpass the acoustic diffraction limit using a SOFI-inspired photoacoustic imaging technique. That work had two main limitations. First, it required the use of a long-coherence laser, not a standard part of photoacoustic imaging systems, in order to form dynamic structured interference patterns called speckle to create the signal fluctuations. Second, due to their small dimensions, the use of speckles as dynamic illumination resulted in the fluctuations having a low amplitude with respect to the mean photoacoustic signal, which in turn made it difficult to resolve the specimen in question.

In the new Opticastudy, the researchers showed that they could overcome these limitations by applying the statistical analysis framework to the inherent signal fluctuations caused by the flow of red blood cells -- so the researchers didn't need to rely on coherent structured illumination -- and furthermore demonstrated experimentally that they could perform super-resolution photoacoustic imaging using a conventional imaging system.

Moving toward in vivo use

The demonstration served as a proof of principle for the new technique. The researchers are now focused on developing it further, to fulfill its potential for in vivo applications.

Katz described two main challenges in reaching this goal. The first is the problem of motion artifacts. In their demonstration, the researchers imaged blood streaming through small tubes. In animal models and in humans, though, blood flow is only one of the motions they would have to consider. The technique would also need to account for the heartbeat, the changing volume of the vessels and even microscale movements of the tissue itself.

The other main challenge relates to signal levels. In recent experiments blood was the only absorber in play, but in real-world scenarios other absorbers would be present. The researchers are now working on ways to better see the signal originating from flow while suppressing any background signals.

In addition to tackling these challenges, the team is working to apply sophisticated reconstruction algorithms that will further increase the resolution and background reduction by taking into account prior information about blood flow, the imaging system response and other factors.
Paper: T. Chaigne, B. Arnal, S. Vilov, E. Bossy, O. Katz, "Super-resolution photoacoustic imaging via flow induced absorption fluctuations," Optica, Volume 4, Issue 11, 1397-1404 (2017). DOI: 10.1364/optica.4.001397.

About Optica

Optica is an open-access, online-only journal dedicated to the rapid dissemination of high-impact peer-reviewed research across the entire spectrum of optics and photonics. Published monthly by The Optical Society (OSA), Optica provides a forum for pioneering research to be swiftly accessed by the international community, whether that research is theoretical or experimental, fundamental or applied. Optica maintains a distinguished editorial board of more than 40 associate editors from around the world and is overseen by Editor-in-Chief Alex Gaeta, Columbia University, USA. For more information, visit Optica.

About The Optical Society

Founded in 1916, The Optical Society (OSA) is the leading professional organization for scientists, engineers, students and business leaders who fuel discoveries, shape real-life applications and accelerate achievements in the science of light. Through world-renowned publications, meetings and membership initiatives, OSA provides quality research, inspired interactions and dedicated resources for its extensive global network of optics and photonics experts. For more information, visit

Media Contacts:

Rebecca B. Andersen
The Optical Society

Joshua Miller
The Optical Society

The Optical Society

Related Blood Flow Articles from Brightsurf:

Brain regions with impaired blood flow have higher tau levels
In Alzheimer's disease, impaired blood flow to brain regions coincides with tau protein buildup.

3D ultrasound enables accurate, noninvasive measurements of blood flow
A 3D ultrasound system provides an effective, noninvasive way to estimate blood flow that retains its accuracy across different equipment, operators and facilities, according to a new study.

Blood flow recovers faster than brain in micro strokes
Work by a Rice neurobiologist shows that increased blood flow to the brain is not an accurate indicator of neuronal recovery after a microscopic stroke.

Exercise improves memory, boosts blood flow to brain
Scientists have collected plenty of evidence linking exercise to brain health, with some research suggesting fitness may even improve memory.

3D VR blood flow to improve cardiovascular care
Biomedical engineers are developing a massive fluid dynamics simulator that can model blood flow through the full human arterial system at subcellular resolution.

MRI shows blood flow differs in men and women
Healthy men and women have different blood flow characteristics in their hearts, according to a new study.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Blood flow monitor could save lives
A tiny fibre-optic sensor has the potential to save lives in open heart surgery, and even during surgery on pre-term babies.

Changes in blood flow tell heart cells to regenerate
Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish.

Blood flow command center discovered in the brain
An international team of researchers has discovered a group of cells in the brain that may function as a 'master-controller' for the cardiovascular system, orchestrating the control of blood flow to different parts of the body.

Read More: Blood Flow News and Blood Flow Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to