Preclinical laboratories at academic facilities and contract research organizations (CROs) have traditionally relied on five main imaging modalities: optical, acoustic, x-ray, MRI, and nuclear. Now, photoacoustic imaging, which combines optical and acoustic modalities, is enabling some of the most promising medical research, including providing images of biological structures for increased visibility during surgery and facilitating the analysis of plaque composition to better diagnose and treat coronary artery disease (CAD).

The Phocus Mobile from OPOTEK is an ideal light source for photoacoustic imaging applications that require high pulse energies and NIR wavelengths for deep penetration of biological tissue. (Credit: OPOTEK)

With photoacoustic medical imaging, nanosecond lasers deliver light pulses to specific biological tissues. The laser’s energy is absorbed and converted into heat, which generates an ultrasonic (sound) wave that can be detected by a transducer and processed to form an image. Due to the varied response of components in biological tissue based on user-defined laser parameters, images can include information about the function of examined tissues as well.

However, despite its promise, preclinical researchers were limited to utilizing large, fixed benchtop systems mounted to immovable laser tables. Now, compact, mobile photoacoustic platforms are available and ready for use in preclinical and clinical environments, including commercial hospital settings.

Like an ultrasound machine, mobile photoacoustic systems could be transported to patient bedsides or to surgical suites to render extremely detailed diagnostic imaging tests for cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes.

Photoacoustic Systems for Biomedical Imaging

Although photoacoustic imaging equipment has been available for a few decades, the primary limiter to its use has been the largest component in the system, the nanosecond laser used to transmit a pulse of laser light to the area of interest. These lasers, which are available in a wide range of wavelengths, pulse energies, and repetition rates, generate high peak powers and short pulse widths, making them ideal for many photoacoustic applications.

However, fixed nanosecond wavelength lasers like the Nd:YAG often operate outside the ideal wavelengths required to reach a usable depth in biological tissue. These wavelengths are usually within the water absorption transparency window of 650 to 900 nm, given that animals and humans are mostly made of water.

For this reason, pulsed mode Nd:YAGs that emit light at a fixed wavelength of 1064 nm require optical parametric oscillators (OPO) to convert the Nd:YAG fundamental wavelength to the optimal frequency for photoacoustic diagnostic analysis. These OPO lasers are generally referred to as tunable lasers.

To enable required laser tunability, manufacturers like Carlsbad, CA-based OPOTEK have developed fast-tuning technology that ensures that many wavelengths can easily be produced to image a variety of biological materials. Fast tuning also helps to mitigate variations in the field of view due to motion between consecutive images, which allows for more detailed imaging of moving biological processes like blood flow.

OPOTEK, LLC, a global manufacturer of tunable lasers for research and diagnostics, offers solutions for specialized applications including photoacoustic, spectroscopy, diagnostics, hyperspectral imaging, and medical research.

The company’s photoacoustic technology is now being utilized in a wide range of medical research projects.

“We have two OPOTEK lasers — one located in my lab on the primary engineering campus of Johns Hopkins University, and one located in my lab space at the Johns Hopkins Hospital,” says Dr. Muyinatu Bell, an assistant professor and director of the Photoacoustic and Ultrasonic Systems Engineering (PULSE) Lab at Johns Hopkins University.

The PULSE lab is developing the next generation of photoacoustic imaging systems using a combination of optics, acoustics, and robotics.

“In the PULSE Lab, we aim to understand fundamental design requirements for photoacoustic imaging systems that can be used to guide surgeries, as well as augment the vision capabilities of robotic surgical systems,” says Dr. Bell.

The structures of interest in her research include major blood vessels that are hidden by tissue and need to be avoided during surgery, as well as the metal tips of surgical tools. Major blood vessels and tool tips both generate strong photoacoustic signals in comparison to surrounding tissue and can be used to provide surgeons with the information needed to avoid accidental injury, which can lead to excessive bleeding and potentially patient death.

Although still in the research phase, Dr. Bell required a mobile unit to transport the imaging equipment from her lab to operating rooms in the hospital.

“Although we do not make laser transportation trips between campuses, we specifically have the Phocus Mobile for the express purpose of transporting the laser and photoacoustic imaging setup from my lab in the hospital to any operating room in the hospital, where we commonly perform our in vivo experiments,” says Dr. Bell.

The Phocus Mobile from OPOTEK is an ideal light source for photoacoustic imaging applications that require high pulse energies and NIR wavelengths for deep penetration of biological tissue. As early as 2008, the company began to transition from immovable, benchtop OPOs to a mobile form factor.

Over the past decade, OPOTEK has introduced additional innovations to its mobile platform, including fiber bundle delivery, complete automation of all system functions, and fast tuning over the entire wavelength range. The hands-free tunable laser system provides a light-sealed, transportable cart designed for deployment into preclinical environments.

“This laser is built for mobility without sacrificing the high energies that we need to explore the limits of this novel application of photoacoustic imaging for surgical guidance,” adds Dr. Bell.

Fighting Coronary Artery Disease

One area where mobile photoacoustic imaging has the potential to have great impact is in diagnosing and treating coronary artery disease (CAD), a leading cause of death worldwide. CAD is often caused by atherosclerosis — a progressive inflammatory condition in which deposits of plaque buildup in the arteries of the heart, often resulting in heart attack. Early detection of these plaques is difficult due to their motion, size, and the obscuring electrical signals of the heart. Identifying problem lesions that are likely to rupture would improve medical outcomes.

Dr. Raiyan Zaman, an assistant professor in the department of radiology at Harvard Medical School and an assistant investigator at the Gordon Center for Medical Imaging at Massachusetts General Hospital, has been developing a novel method to image CAD plaques using tunable laser light since she was a postdoctoral fellow at the Stanford University School of Medicine.

Circumferential intravascular radioluminescence photoacoustic imaging (CIRPI) combines radioluminescence imaging and photoacoustic tomography with a new optical probe to achieve up to 63 times more signal to noise. Photoacoustic imaging plays a key role in allowing the analysis of plaque composition and its morphology.

“We are trying to minimize the multiple intravascular imaging procedures necessary for a patient who requires intervention for coronary artery disease. These imaging procedures are needed for the detection of stenosis and the evaluation of coronary arterial wall before intervention. Our CIRPI system will combine all these necessary procedures into one imaging session,” says Dr. Zaman.

Dr. Zaman and her team are currently in the process of testing their system in an atherosclerotic animal model followed by clinical translation studies.

“The OPOTEK laser is a key component of our CIRPI system for photoacoustic imaging. This small but powerful tunable laser is perfect for our portable imaging system, enabling us to wheel it to a patient’s bedside,” says Dr. Zaman.

With mobile photoacoustic medical imaging now readily available for preclinical and clinical use, researchers at labs as well as clinicians and patients in hospital settings can benefit from fast, extremely detailed imaging capabilities wherever needed. The technological innovation will spur further advancements in medical research as well as help to improve diagnosis and patient care in clinical environments.

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