Photoacoustic microscopy can be used to diagnose diseases such as cancer and cardiovascular disease.
In its conception, photoacoustic microscopy (PAM) is elegance itself, capitalizing on the strengths of light microscopy and ultrasound, two mainstays of modern imaging. It combines the molecular sensitivity of optical waves with the deep penetration of ultrasonic waves to generate high-resolution images of optically absorbing biomolecules—among them hemoglobin, lipids and melanin—that can be used to diagnose diseases such as cancer and cardiovascular disease.
This makes PAM an exciting innovation. Currently, it is difficult to image these molecules without the drawbacks of using contrast agents. Thanks to a recent NSF CAREER Award, Song Hu, an assistant professor of biomedical engineering, has the opportunity to be among the first to translate PAM into an imaging device that will find its place in operating rooms and clinics alongside MRIs and X-rays.
“Over the last five years, we have made significant progress demonstrating the use of PAM to understand disease mechanisms,” Hu says. “In particular, we have developed a technique called multi-parametric PAM, which enables us to look at the circulation system from a number of perspectives at the same time. In the next stage of my career, I would like to see PAM have a more direct clinical impact.”
Absorbing Light. Emitting Acoustic Waves.
PAM is a sophisticated application of a basic principle of physics. When a light wave is tuned to the optical absorption band of a molecule, electrons in the molecule absorb the photon energy and cause a tiny temperature rise. In other words energy goes into the molecule as light and comes out as heat. That’s why, in everyday life, black objects, which consist of molecules that absorb different frequencies of light, become hot when left in the sun. Furthermore, when objects are heated, they expand.
In his PAM system, Hu uses a nanosecond pulsed laser beam that he has tuned to the absorption peaks of the molecules he wants to study. They absorb light and induce expansion and contraction of the surrounding tissue with the pulsing of the laser beam, generating an acoustic wave that the ultrasound detector picks up. Other molecules with low absorption don’t react to the laser, providing contrast that is ideal for creating molecule-specific images.
Read about the CAREER Award for Steven Bowers, assistant professor in UVA's Charles L. Brown Department of Electrical & Computer Engineering.
Multi-parametric photoacoustic microscopy of the mouse brain
As Hu sees it, miniaturization is the key to realizing PAM’s clinical potential. With funding from the CAREER Award, he will tackle a series of projects designed to reduce the bench-top PAM system to a manageable size. Currently, the laser that generates the light beam for photoacoustic excitation is quite bulky. Hu plans to sidestep this difficulty by having it output pulses to a flexible fiber optic cable. “Using fiber optics will allow us to put the laser in a remote position and route the light to where it is needed,” he says.
Fiber optics also sets the stage for developing a wearable PAM device, another goal of Hu’s CAREER Award. Such a wearable device could be used to image blood oxygenation and metabolic activity in the conscious brain, which would potentially be useful in diagnosing extreme cases of epilepsy. He is also working on developing a handheld PAM device that may allow brain surgeons to identify and remove tumor tissue that they might otherwise have missed, lessening the chances that the cancer will recur. This is complicated work, involving optical and mechanical design, numerical simulation, microfabrication, data processing and instrument development.
Gen Z PAM
The interdisciplinary reach of the project and its potential impacts are one reason that Hu is so excited by the educational component of the CAREER Award. The award will enhance his ability to mentor undergraduate students in his laboratory, integrate information about PAM in the biomedical engineering curriculum and extend outreach to local high-school students. “I want to take advantage of the CAREER program to get more young people excited about PAM and its potential,” Hu says. “There are opportunities for them to join us in pioneering this cutting-edge technology.”
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