Photoacoustic Imaging 1 Photoacoustic Imaging and Therapy in Biomedicine Nicholas Tobey and Grace Yook Optical Engineering Dr. Kasra Daneshvar July 16, 2010
Photoacoustic Imaging 2 Abstract When a pulsed beam of light strikes a medium, the medium emits sound waves that vary in intensity with the amount of light absorbed. If these sound waves can be detected, a reconstruction of the medium becomes possible. Since the wavelength of light used can be altered to fit the absorption spectra within the medium, this adaptable technique has many uses, including accurate detection of some cancers, and possible treatment.
Photoacoustic Imaging 3 Background Photoacoustic imaging, also called photoacoustic tomography (PAT), is the use of a laser pulse to generate sound waves. PAT is based on the principles of photoacoustics, stating that when a medium absorbs some of the light that strikes it, the temperature of the medium increases slightly. As the material becomes heated, it expands, increasing the pressure and creating a miniature sound wave. Through this process, light is converted into heat and sound (Harren, F.). Photoacoustic principles were first observed by Alexander Graham Bell and were utilized in his invention of the photophone, a device that could transmit sound signals on beams of light (Spike, 2006, p. 2). Sound waves nears the projecting end of the device would cause a mirror to vibrate, forcing light to focus and disperse. These light signals strike selenium cells in the receiver. Selenium cells are phototransistors, that is, they become less resistive to electric flow when lit. The fluctuating resistance resulting from the modulated beam of light altered the amount of current flowing to speakers on the receiving end, generating and recreating the sound. A modern photoacoustic imaging device, based on the proposals of Theodore Bowen, consists mainly of four components: a laser, a series of ultrasound receivers, a conical lens, and a processor unit (Emelianov, Donnel, 2009, p. 35). The lens diffuses the light from the laser across the medium. The medium absorbs some of the light, generating sound waves that, while inaudible, can be detected by the ultrasound receivers. The processor unit obtains information on the sound waves from the ultrasound receivers and attempts to reconstruct an image of the medium. The image, usually overlaid on an ultrasound image, shows the level of absorption in each part of the medium, allowing the components of the medium to be distinguished and identified. With each pulse, the generated image can be updated in real-time. Photoacoustic tomography is regarded for its adaptability; the laser can generate electromagnetic waves in many frequencies and can be adjusted depending on the needs of the
Photoacoustic Imaging 4 experiment (Emelianov, Donnel, 2009, p. 35). Lower frequencies and higher wavelengths can penetrate the medium to greater depths at the cost of resolution, while higher frequencies and lower wavelengths create images with good resolution but cannot fully penetrate relatively large mediums. Thus, photoacoustic tomography systems require a wavelength to be chosen that provides sufficient contrast within the medium, proper penetration, and resolution accurate enough to identify and locate the different components within the medium. A good example to aid in the visualization of photoacoustic imaging is the interaction between lightning and thunder. When lightning strikes, the air around the bolt of lightning is heated quickly and expands outward, increasing the air pressure and creating sound waves (Emelianov, Donnel, 2009, p. 34). The principles that cause the sound of thunder also guide photoacoustic imaging. When the wavelength of the laser pulse is within the range of visible light, the technique can also be referred to as optoacoustic tomography (OAT). When the laser pulse is at radio frequency, the technique can be called thermoacoustic tomography (TAT) (Xu, Wang, 2006, p. 2). Research Question How can Photoacoustic Imaging be applied in biologic fields of study, particularly it use in biomedicine to detect and treat cancer? Applications PAT systems are most effective when there is sufficiently large contrast between the elements of the medium. For example, at certain wavelengths, the absorption spectra of oxygenated and deoxygenated hemoglobin diverge sharply. Lihong Wang, a professor at Washington University, used PAT to image the brain of a rat when it was at rest and when each of its whiskers was stimulated (Emelianov, Donnel, 2009, p. 35). Since the oxygenated hemoglobin has a higher absorption rate, if
Photoacoustic Imaging 5 the stimulation causes an increase in oxygen consumption within a region of the brain, the image during the stimulation will show a higher amount of absorption when compared to the image of the rat at rest. Lihong was able to map the regions of the rat brain that were used by the rat in response to the stimulation. This process can be used to attempt to understand the composition and function of the brain. The majority of PAT's applications, however, are in the field of medicine. Cancerous cells, as a result of their rapid growth, have distinct distinguishing properties when compared to normal cells. Cancerous cells have a higher concentration of water and many times the concentration of blood; blood flows more rapidly to cancerous cells in order to fuel the rapid growth of the tumors (Xu, Wang, 2006, p. 15). Since water absorbs electromagnetic waves in the radio frequencies and blood absorbs waves in near-ir frequencies, OAT has the potential to reveal locations in tissue of high blood and water concentration and thus areas with high probability of containing tumors. There are three tested methods for detecting tumors. Two of these, specialized radio-frequency imaging, and near-ir laser-based imaging, are used to detect breast cancer (Xu, Wang, 2006, p. 16). These systems have benefits over older conventional cancer detection systems. Both of them use energy with wavelengths in the radio level, and are thus non-ionizing and less damaging to tissues than other methods, like x-rays, and they are less expensive to use and implement than older methods. Dr. Robert Kruger developed a machine that uses an array of ultrasound detectors nested on a hemisphere (Xu, Wang, 2006, p. 16). Used as part of a TAT system that emitted pulsed radio waves, Kruger created an image showing the absorption of the wave within the breast. Their machine did not function with complete accuracy, likely due to using wavelengths that were too weak to give sufficient contrast. The Department of Biomedical Engineering at Texas A&M University made attempts to reproduce and improve Kruger's design (Xu, Wang, 2006, p. 16). The new design used an ultrasound detector rotating around the breast. Still, the department encountered difficulty, as the relatively weak
Photoacoustic Imaging 6 strength of the radio waves was unable to create sufficient contrast to detect the cancer, although it was suggested that using multiple sources of radiation could improve the level of contrast in the resulting image. Tumors can also be detected used pulsed lasers with frequencies close to infrared, since the increased blood supply within the tumor readily absorbs the light produced by the laser. A small sample of optoacoustic devices have been built with the intent of measuring the level of near-ir light that is absorbed as it passes through the breast. For example, the laser optoacoustic imaging system (or LOIS) placed a laser on one side of the breast and an array of ultrasound detectors on the the other end (Xu, Wang, 2006, p. 17). While the resulting imaging could clearly identify a tumor, the resolution of the image was poor in one direction. Another device developed more recently was the photoacoustic mamoscope (or PAM). The PAM would slightly compress the breast between a sheet of glass and an array of ultrasound receivers. The light from the laser would enter the medium through the glass and travel across the breast to the receivers, which would then reconstruct an image of the breast. Unfortunately, the resolution of the image was even poorer than the resolution for LOIS. The third usage of OAT for has the advantage of being able to detect many types of cancer, and is not exclusive to breast cancer. Instead of attempting to identify the absorption properties of tumors, researchers have experimented with injecting tissue with particles that have a known absorption spectrum. Often, gold nanoparticles are used, as the particles have different spectra depending on their shape, making them an adaptable tool for use (Emelianov, Donnel, 2009, p. 37). Since many types of cancer generate excessively large quantities of human epidermal growth factor receptor 2, or HER2, antibodies are attached to the particles, causing them to cluster around the HER2 in the cancerous cells' membranes. PAT can then be used to discover the locations and density of the particles, revealing the areas of the tissue with a high probability of containing cancer cells. PAT with gold nanoparticles can also be used as a possible method to treat cancer. When the
Photoacoustic Imaging 7 tissue absorbs the pulsed light beams, the temperature of the medium increases slightly. If the energy is absorbed primarily by the gold nanoparticles, the particles can be heated, damaging the cancerous tissue around it while minimizing the damage to other healthy tissue (Emelianov, Donnel, 2009, p. 38). This treatment can be preferable to other forms of cancer treatment due to the lack of collateral damage to the body, specifically targeting and damaging tumors. PAT has found uses and applications outside of biomedicine. Ozone depletion due to nitric oxide was a large problem and could not be detected (Spike, p. 4). By using a photoacoustic detector, scientists were able to create their first photoacoustic spectroscopy study. Photoacoustic spectroscopy was a technique to study the concentration of gases through the use of light and sound. By using a photoacoustic detector, scientists were able to conduct an experiment to measure the problems of ozone depletion through the man-made nitric oxide emission. The experiment was conducted by measuring the nitric oxide in the stratosphere through a balloon photo detector at 28 km in the air (Zeninarl, 2007). Scientists pulsed a light that was absorbed by molecules, which, in turn rose in temperature. The temperature increase created pressure waves. These pressure waves could be detected because of the acoustic waves that were emitted and composition, concentration, and other properties were discovered (Spike, p. 4). Photoacoustic imaging has many potential uses for detection, both in biology and ecology. It's multiple uses and adaptability made it a powerful tool with multiple applications. PAT will doubtlessly form the foundation of a new genre of biomedicine with the ability to map the usage of oxygen within organs, such as the brain, and more rapidly detect anomalies within the human body, increasing the effectiveness of treatment. Since the image can be rapidly updated, PAT can be used during operations to create a relevant and accurate image of the patient. With the introduction of nanoparticles into the patient, PAT becomes a viable means of treatment for cancer. With further research, the ability to focus and direct light from PAT systems may enable effective treatment for other disorders and anomalies,
Photoacoustic Imaging 8 replacing treatment that is either too costly, too impractical, or too ineffective. Outside of biomedicine, photoacoustic systems can be used to detect the makeup of mediums such as the atmosphere, leading to a greater understanding of changes in the environment over time. As new methods are discovered to apply the principles of photoacoustics, PAT systems will become more accurate with increased resolution, and PAT will become an effective and widespread tool in biology and biomedicine.
Photoacoustic Imaging 9 References Xu M., Wang L. (2006, Jul 30). Photoacoustic imaging in biomedicine. Scientific Instruments, 77. Emelianov S., Li P., Donnell M. (2009, May). Photoacoustics for molecular imaging and therapy. Physics Today. (p. 34-39) Harren, F. (n.d.). What is Photoacoustics, (http://www.tracegasfac.science.ru.nl/whatis.htm) Spike, B. (2006; April 21). The Photoacoustic Effect (http://uw.physics.wisc.edu/~timbie/p325/spike_photoacoustic_effect.pdf) Zeninarl, V, Joly, L, Parvitte, P, Durry, G, & Courtois, C. (2007). Acoustic detection of nitric oxide with Helmholtz resonant quantum cascade laser sensor. Infrared Physics & Technology, 51(2), Retrieved from http://www.sciencedirect.com/science?