Professional Engineering 2 MECH4601 Photoacoustic Tomography This report aims to discuss the development, applications and limitations of the latest technology in Optical Imaging, Photoacoustic Tomography. The University of Sydney 2012 Professional Engineering 2 MECH4601 Table of Contents 1. ABSTRACT 3 2. INTRODUCTION 4 3. UNDERLYING PHYSICAL PRINCIPALS 5 4. PAT SYSTEM AND SAFETY 6 5. APPLICATIONS OF PAT 7 6. LIMITATIONS AND RECOMMENDATIONS 8 6.1 LIMITATION 8 6.2 RECOMMENDATIONS 8 7. SUMMARY 9 8. REFERENCES Assignment 4 10 2 Professional Engineering 2 MECH4601 1. Abstract Photoacoustic Tomography (PAT) is the latest optical imaging system, which combines high optical contrast and ultrasonic resolution in a single modality. Such technology has never before been available due to strong optical scattering of photons in tissue which limit investigation at superficial depths[1]. Based on the physical principals of the Photoacoustic effect, PAT is capable of performing anatomical and functional imaging at various system levels Images have gone from a few mm to several cm below the skin, fundamentally changing the way patients are diagnosed. However one limitation of this new technology is phase distortion of sound waves due to bone. Having the possibility of many applications in medicine, ongoing research is highly recommended to alleviate the problem. This report will discuss the technical development of PAT, its application in medicine, and the need for a solution to the limitation. Assignment 4 3 Professional Engineering 2 MECH4601 2. Introduction Since the discovery of X-rays in the early 1900’s, medical imaging has been a sub-speciality in the diagnostic industry. Proven to have extensive use during World War II, it was noted that a greater need for resources and more accurate technologies was needed for the future. This ideology, concurrent with the rapid developments in digital computing led to an explosion in medical imaging techniques, which over the past 25 years, have fundamentally changed the way patients are diagnosed. Today, multiple technologies exist for multiple purposes. X-Rays, Medical Resonance Imaging (MRI) and Computed Tomography (CT) have been the most commonly used methods used for general diagnostics and continue to dominate the industry. However, it is Photoacoustic Tomography (PAT), the latest development in optical imaging, that promises to change the way patients are diagnosed. By addressing the main issues associated with current imaging modalities, physicians have come up with the solution to two of the most commonly asked questions: 1. How can we overcome the optical transport free mean path? 2. How can we improve the quality of our images? Optical imaging methods, such as PAT, are non-invasive techniques that use near-infrared (NIR) light to measure the optical properties of tissue[2]. Commercially available optical imaging techniques such as confocal microscopy and two-photon microscopy cannot however cannot penetrate tissue deeper than the optical transport free mean path of skin, being approximately 1mm[3]. In biological tissue, light transfer is dominated by scattering of photons. As photons transition from a ballistic regime into a diffusive regime on the transport free mean path, the photons are eventually so scattered it isn’t possible to untangle their paths and create an image deeper than 1mm. By employing PAT however, light photons are converted into sound photons, which scatter a thousand times less than light, and allow for an image up to 7cm in depth to be generated. Despite penetration levels increasing, it is with sound benefit that the image resolution is not deteriorated, rather improved. As ultrasonic scattering is much weaker than optical scattering, the wavelength of the detected photoacoustic wave is sufficiently short. As a result, photoacoustic waves provide better resolution than optical waves beyond the depth limitation[3]. Physicians can now move away from low quality images they are used too where they are left to interpret lights and shadows, and instead use high contrast, super depth images for medical diagnosis. However, being such a new technology, physicians and engineers are still looking to address one limitation regarding PAT as a result of its application: 1. Phase distortion due to bone This report will explore the underlying physical principals of PAT and the system associated with producing super depth high resolution images. Subsequently, applications in the medical industry will be discussed and a need for a solution to the above limitation explored. Finally, a summary will highlight the main concepts and ideas mentioned in the report, which aim to see PAT commercialised on a grand scale in the near future. Assignment 4 4 Professional Engineering 2 MECH4601 3. Underlying Physical Principals The fundamental physics beneath photoacoustic imaging is the photoacoustic effect. The photoacoustic effect involves converting optical energy into acoustic energy as a result of optical absorption and thermal expansion[4] The process of generating a photoacoustic image via the photoacoustic effect can be broken down into the following steps as show in the schematic (Figure 1): 1. Optical Irradiation: Biological tissues are light by nanosecond laser pulses which lead to the localized rapid temperature rise (several mill degrees) and the generation of wideband ultrasound pulses due to thermal expansion. 2. Ultrasonic Detection: The light excited ultrasound pulses propagate in the biological tissues and can be detected on a boundary surrounding the biological tissues by typical ultrasonic transducers used in ultrasonography. 3. Image Formation: Detected signals are amplified, digitized and transferred to a computer where the final image is generated. Figure 1: Schematic of Photoacoustic Effect [4] Given thermal diffusion in soft tissue at room temperature is approximately 10 microns[5], it can be ignored for most biomedical applications. Therefore by only considering the thermal expansion mechanism, the photoacoustically generated acoustic field in tissue is described by the following wave equation[4]: Equation 1: Wave equation Where, C Β Cp I(t) Speed of acoustic wave in the tissue Thermal expansion coefficient Specific heat at constant pressure Temporal profile of laser pulse Generated acoustic pressure wave Optical energy absorbed in the tissue (which is the product of tissue absorption coefficient a r and optical fluence ). A great deal of this technique is based heavily on the optical properties of tissue. Theoretically, any chromophore (part of molecule responsible for colour) that has an optical absorption signature can potentially provide PAT contrast as long as appropriate wavelengths are applied and system sensitivity sufficient[6]. Thus depending on what molecule is being investigated, being haemoglobin, water, or lipids, a specific PAT image can be developed provided the conditions are right. Assignment 4 5 Professional Engineering 2 MECH4601 4. PAT System and Safety The acquired and generated ultrasound wave from Equation 1 is recovered by a photoacoustic imaging system that can then be used for further image reconstruction. Figure 2 shows a typical photoacoustic imaging system which generally composes of: Lighting system Signal detecting system Object placement system Computer control system Figure 2: Typical Imaging System [4] For the purpose of this investigation, the figures in Table 1 are to be considered during experimentation as studies[7] have shown them to be within safety limits. Factor Duration of Laser Pulse Repetition Rate Laser Wavelength Light Incident on Tissue Safety Level 10ns 10-50Hz 532 – 1064nm <22mJ/cm2 Table 1: PAT Safety Levels In a PAT system, the acoustic pressure is detected by scanning an ultrasound transducer over a surface that encloses the photoacoustic source. To reconstruct the internal source distribution, the universal back projection algorithm is applied to further derivations[1] of equation 1. This method is suitable for three imaging geometries: Planar Spherical Cylindrical surfaces The differing imaging geometries have been introduced to cater for the varying surfaces and applications being investigated. For example, a spherical transducer can be used for applications in breast imaging, whereas planar transducer for skin imaging. Ensuring the correct geometry is used during imaging maximises the absorption levels of the ultrasounds, and increases the resolution of the developed image. With regards to safety, a PAT system employs no health risks as low-intensity non ionizing waves are used unlike ionizing X-ray radiation. Also, in comparison to an MRI system, there is no bulky, expensive machinery that requires a strong magnetic field. It is therefore completely safe for patients with metal implants, such as pacemakers or prosthetics, to have a PAT scan. Hence a PAT system can be regarded as relatively simple, and guarantee the safety of patients undergoing treatment. Assignment 4 6 5. Applications of PAT Professional Engineering 2 MECH4601 With safety of primary concern during the development of new technologies, PAT has so far proven to provide the safest, most comfortable form of diagnosis. It is for this reason applications of PAT have extended into the primary medical areas such as breast imaging for cancers, and brain imaging of functional processes. Currently 36 women in Australia are diagnosed with breast cancer every day[8]. The gold standard in cancer detection is still biopsy, however the process can be long and costly and only used to confirm the results of a mammogram. A recent study[9] has shown promising results for the use of PAT for diagnosis, with the advantages of being nonionizing and requiring no or mild breast compression, which can make the process a lot more comfortable for patients. Tumours require oxygen and nutrients to fuel their exponential growth. As an optical imaging modality, PAT can detect the presence of a tumour by comparing the presence of oxyhaemoglobin with deoxyhaemoglobin since they each absorb light at a different wavelength, being 1064 nm and 755nm respectively[4]. By imaging the two wavelengths, quantitative information of the oxygenation ratio can be extracted from the images and used to determine the stage of the cancer. Figure 3 shows a comparison between mammography, ultrasonography, and a PAT image in the detection of a cancer, with the PAT image giving the clearest indication of the presence of a tumor. With regards to brain imaging, PAT can clearly identify different soft tissue in the body based on the optical absorption properties. Conditions such as strokes, head injuries, tumours and brain infections can therefore be monitored, and severity of condition determined. PAT can provide rich contrasts for high-resolution structural and functional imaging, as shown in Figure 4 and 5. It is known that near infrared light can penetrate through the skull to the cortex and be used for functional brain imaging at low spatial resolution. For cortical functions, PAT can potentially provide similar penetration but with a higher resolution. Figure 4: (a) Brain lesion of rat imaged by PAT (b) Open skull photograph [1] Figure 3: (a) X-Ray mammograph of a dense breast does not show signs of a Assignment 4 tumour; (b) Doppler ultrasonography shows an increased blood flow (c) PAT clearly shows a tumour[10] Figure 5: PAT image of rat in vivo [1] 7 Professional Engineering 2 MECH4601 6. Limitations and Recommendations 6.1 Limitation Based on the physical principals of PAT, it has become the known solution to two common limitations of current imaging modalities: 1. Surpassing the optical transport free mean path 2. Producing high resolution images However as a recently new technology, one particular limitation has come to surface with regards to its application: phase distortion due to bone. Compared to light, sound does not pass through bone easily. Since sound travels through bone and soft tissue at different speeds, there is a phase distortion when the waves pass from one medium to another[5]. The behaviour of sound waves based on the principals of science therefore pose as a limitation when imaging tissue under bone, primarily the brain. Image quality is known to degrade significantly once the fontanels of the brain close. This is because the skull severely attenuates and distorts ultrasonic waves. The skull basically functions as an irregular lens causing phase distortion and reducing the quality of an image considerably. Tests on small animal skulls and rhesus monkeys have successfully been conducted [7], and the extension of PAT to human imaging is an area of research. With the potential for improvement, phase distortion due to bone appears to be a tractable limitation. Despite no major clinical studies to date, meeting the basic requirements in terms of range, resolution and patient instrument interface for this particular application seems feasible. 6.2 Recommendations Despite no current solution of phase distortion due to bone, it is highly recommended that the physical principals of the Photoacoustic effect be re-examined and modifications to the use of ultrasound waves developed. Collaboration with other research groups, such as the Optical Imaging Laboratory department of The Washington University, St Louis can also be encouraged. Highly informed academics are involved with ongoing research and welcome the input of physicians, engineers or mathematicians to help address the main issue with PAT. Assignment 4 8 Professional Engineering 2 MECH4601 7. Summary Photoacoustic Tomography (PAT) is playing an increasingly important role in the field of biomedicine and clinical applications. Being a recently developed technology, its prospect as a primary imaging modality are promising, despite its limitation due to functionality. The main problems with current imaging methods are the inability to overcome the optical transport free mean path and produce high resolution images. However based on the Photoacoustic effect, PAT can combine strong optical contrast and high ultrasonic resolution in a single modality, breaking through this fundamental depth limitation and achieve super depth high-resolution optical images. More so, PAT proves to be amongst the safest imaging modalities. Unlike ionizing X-rays, PAT employs the use of non-ionizing ultrasound waves which reduce the exposure of radiation to users and operators during their lifetime. Applications in breast imaging have so far shown to produce better results than current methods, such as mammograms. Given breast cancer is the most common type of cancer affecting Australian woman, PAT has the potential to increase the rates of early stage cancer detection thus increasing a suffers chance of survival. Similarly, by employing the use of PAT for brain imaging, conditions such as strokes and lesions can be identified and investigated more clearly. However, it is crucial that investigation remain on going, as limitations of the technology do exist. Of main concern, is phase distortion due to obstruction by bone. Since sound travels at different speeds through bone and tissue, a problem arises once the waves make the transition between the two mediums. Early studies have shown encouraging results, however ongoing research is recommended to alleviate this problem. Thus in light of its capabilities and flexibilities, Photoacoustic Tomography is expected to play an essential role in biomedical studies and clinical practice. With ongoing research and further investigations, engineers and physicians hope to commercialize this technology and see doctors and patients benefit from it on a grand scale. Assignment 4 9 8. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Professional Engineering 2 MECH4601 Biophotonics and Imaging Laboratory (BAIL), Department of Biomedical Engineering. Oregon Health & Science University, 2007. Jeandron, M., Special report: optical breast imaging. Medical Physics, 2007. V, W.L., Prospects of Photoacoustic Tomography. Med Phys, 2008. 35(12): p. 5758-5767. Tam, A.C., Applications of photoacoustic sensing techniques. Reviews of Modern Physics, 1986. 58(2): p. 381431. Sun Y, J.H., Quantitative three-dimensional photoacoustic tomography of the finger joints: an in vivo study. Journal of Biomedical Optics, 2009. 14(6): p. 064002. Wanga, J.Y.a.L.V., Photoacoustic tomography: fundamentals, advances and prospects. Wiley Online Library, 2011. Sun Y, J.H., O’Neill BE, Photoacoustic Imaging: An Emerging Optical Modality in Diagnostic and Theranostic Medicine. J Biosens Bioelectron, 2011. 2(108). Breast Cancer: Statistics. 2010 13/05/2012]; Available from: http://www.breastcancer.org.au/about-breastcancer/statistics.aspx. S. Manohar, A.K., J. C. G. van Hespen, W. Steenbergen, and T. G. van Leeuwen,, Pho- toacoustic mammography laboratory prototype: imaging of breast tissue phantoms. Journal of Biomedical Optics Express, 2004. 9: p. 1172-81. S. a. Ermilov, T.K., A. Conjusteau, M. H. Leonard, R. Lacewell, K. Mehta, T. Miller, and a.A.a. Oraevsky, Laser optoacoustic imaging system for detection of breast cancer. Journal of Biomedical Optics, 2009. 14: p. 24007. Assignment 4 10