The latest advances in photoacoustic imaging - going to the clinic

Clinical application of photoacoustic imaging

Professor Wang Lihong

Photoacoustic imaging is beginning to be applied to clinical patients, and this technology will revolutionize clinical imaging, from early tumor detection to neurological and marker-free histology.

At the 2012 International Society of Optics and Photonics (SPIE) European Photonics Conference held earlier this summer, Wang Lihong, a pioneer in photoacoustic imaging from the University of Washington (St. Louis), delivered the above exciting message in the keynote speech. In a hot forum, Wang Lihong described the latest developments in photoacoustic imaging to a wide range of audiences, including the application of photoacoustic imaging in breast cancer and melanoma.

Photoacoustic imaging technology is believed to replace traditional scanning methods such as magnetic resonance (MRI) and X-ray based tomography in the future. The advantages of photoacoustic tomography (PAT) include the fact that it is a non-ionized technology that does not require biomarkers, and has extremely high resolution, real-time scanning, etc., so it can display some of the fine structures missing from conventional scanning equipment. One of the major limitations of photoacoustic imaging is its imaging depth, but this limitation is being gradually overcome, and now its imaging penetration depth can reach 7 cm.

One of the great advantages of photoacoustic imaging is its malleability. Photoacoustic imaging can be performed from a single cell, to the entire organ, to the entire body of a small animal. Since microscopic imaging and macroscopic imaging are unlikely to use the same contrast agent, it is impossible to observe the ductility of the imaging. But because photoacoustic imaging uses the same contrast agent at all levels, it can be used at all levels.

Light producing sound

In fact, the earliest description of the principle of photoacoustics was the telephone inventor Bell. According to the simple principle of optical sound, he built the earliest "optical phone". Current photoacoustic imaging systems typically use nanosecond laser pulses to illuminate the detection site, which is heated and expands. Thermal expansion produces an acoustic signal whereby it can be received in the form of ultrasound, and the image produced after reconstruction can show the distribution of optical absorption within the target site.
Professor Wang used three examples from different locations to hear the example of thunder. The thunder was originally generated at a point where triangulation could be used to locate the point produced by the thunder. In photoacoustic imaging, a structural image of a target portion of a human tissue can be produced by detecting ultrasonic signals generated by laser light at hundreds of position points and in multiple directions.

Since the scattering of sound waves by biological tissue is much lower than the scattering of photons in the visible region (usually three orders of magnitude lower), these reconstructed images can exhibit higher resolution.

In addition, the wavelength of the laser can be used to detect a specific molecule, and since the intensity of the ultrasonic signal is directly related to the level of light absorption, the non-absorbed molecules thus do not generate a signal, thereby removing the background noise signal of the image, thereby obtaining higher Sharpness of the image.

The University of Washington Optical Imaging Laboratory has been at the forefront of photonics development, and now they have a 512-channel ultrasound array system that can reconstruct perfect quality images. The inter-plane resolution of the mouse photoacoustic whole body scan reached 100 μm.

Clinical progress

Optical techniques such as microscopy are used to image fine structures, non-optical techniques such as X-rays and conventional ultrasound are used to image larger structures such as the entire organ, and photoacoustic imaging "compensates between the two due to its ductility. The gap." Photoacoustic imaging has become a rapidly developing research field. Nowadays, photoacoustic technology is gradually moving from the micro-laboratory stage to the macro-practical practice stage.

The initial clinical application is expected to be used for neonatal brain imaging and blood oxygen saturation testing of prostate cancer. Numerous examples support these visions, including handheld photoacoustic probes developed in collaboration with Philips Research and the Nexus 128 Small Animal Photoacoustic Imaging System developed by Endra, USA.

Breast cancer is another area of ​​application for early clinical testing. Using a 650nm laser at 10 mJ/cm ² (half the energy specified by the American National Standards Institute (ANSI) standard), photoacoustic imaging has been shown to perform in vivo imaging of breast cancer, which will be hundreds of global The screening of 10,000 cases has a fundamental impact.

The biggest problem with breast cancer screening today is the number of surgical cases that can lead to massive tumor removal. Not only is 90% of the surgery unnecessary, but the surgery itself will cause 5% of the complications. The use of photoacoustic imaging-specific screening will significantly reduce the rate of surgery and complications.

Other research and development efforts include confocal photoacoustic microscopy, which has been used to image human melanoma skin cancer using gold nanoparticles and gold nanocage to find specific hormone receptors to show early signs of the disease.

The most impressive feature of photoacoustic technology is the extensive application field that Professor Wang predicts. Photoacoustic imaging and its variants not only provide anatomical information, but also provide functional information, metabolic information, molecular and genetic information. Recent examples include measuring oxygen saturation, unlabeled metabolic rate (a known early indicator of tumor development), and label-free in vivo histological testing (Endra Nexus 128).

In an unpublished research work, photoacoustic microscopy can directly show the release of oxygen from a single red blood cell. This development allows us to explore the details inside the microcirculation, which is also considered a key in early tumor formation. Sex factor.

Clinical imaging innovation

In a recent issue of the American Science Weekly, Professor Wang emphasized how this new technology can break through the limitations of current health screening methods. He wrote: "Expanding small animal metabolic photoacoustic technology to humans will be a metabolic disease. Screening, diagnosis, and treatment have revolutionized, especially in cancer and cerebrospinal diseases."

Reducing metabolic photoacoustic technology to the cellular level will bring more opportunities, because excessive metabolism is the most typical feature of tumors, and metabolic photoacoustic analysis can make early screening of tumors possible, and do not use exogenous contrast agents. .

Photoacoustic technology still faces some challenges. Problems caused by bones, especially those caused by large, dense bones such as the human skull, can cause distortion of the acoustic signal. Also of need to address is the depth of imaging, the scattering problem caused by gas in the body.

How the development of photonics can further advance photoacoustic imaging technology to clinical applications. For deep penetration photoacoustic imaging like conventional CT scans, high energy lasers requiring video-rate pulse repetition are needed. For fast microscopy or endoscopic applications, a high-repetition-rate laser with fast wavelength tuning is required. These are all considered from the perspective of long-term development. But with the commercialization of the first clinical photoacoustic imaging system, it is imperative to ensure that the clinical system is able to pass the approval process that must be passed for each new system.

If these approval procedures are adopted, photoacoustic imaging technology and its various derivative technologies will bring about an innovation in imaging technology, both in basic life science research imaging and clinical case care imaging.

About the Endra Nexus 128 Small Animal Photoacoustic Imaging System

Endra was founded by Enlight Biosciences, a group of seven pharmaceutical companies including Pfizer, Merck, Johnson & Johnson, Abbott, Lilly, Novartis and Astra. The history of Endra's development of photoacoustics dates back to 2001 and has been 11 years old. Endra has been conducting applied research in cancer biology and probe development for more than three years.

The inventor of the Endra Nexus 128 Small Animal Photoacoustic Imaging System is Professor Wang Lihong, who is also a member of the Endra Scientific Advisory team. It is a new, non-invasive, in vivo imaging model with high contrast properties for optical imaging and high penetration depth for ultrasound imaging, providing high resolution and high contrast tissue imaging. The Nexus 128 imaging system enables both endogenous structural imaging and higher contrast images with the aid of contrast enhancers. It can be applied to various research fields such as cardiovascular, drug metabolism, early diagnosis of diseases, gene expression research, stem cells and immunity, tumor biology, brain neurobiology, etc., to provide more reliable and comprehensive experimental data for scientific research.

on Professor Wang Lihong

Wang Lihong, Professor of Huazhong University of Science and Technology, President of International Biomedical Optics Association, Distinguished Professor of Gene K. Beare, University of Washington, St. Louis, Professor of Water Education, Professor of Biomedical Engineering, Texas A&M University, International Society of Optical Engineering (SPIE) ), the American Optical Society (OSA), the American Society of Medical and Biological Engineering (AIMBE), the American Institute of Electronics and Electrical Engineering ( IEEE ) and other members of the Society.