Project

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Deep optoacoustic imaging with nanoparticle enhanced contrast

Applicant Frenz Martin
Number 127274
Funding scheme Project funding (Div. I-III)
Research institution Institut für angewandte Physik Universität Bern
Institution of higher education University of Berne - BE
Main discipline Other disciplines of Physics
Start/End 01.10.2009 - 31.12.2012
Approved amount 347'162.00
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All Disciplines (2)

Discipline
Other disciplines of Physics
Biophysics

Keywords (13)

Optoacoustic imaging; tumor diagnosis; functionalized gold nanoparticles; optoacoustic microscopy; ultrasound; antibody; plasmon resonance; optroacoustic imaging; contrast enhancement; gold nanoparticles; image reconstruction; displacement-reconstruction-algorithm; molecular imaging

Lay Summary (English)

Lead
Lay summary
In the last three decades, light has been recognized to offer promise for medical diagnosis because of its contrast to tissue properties and its non-ionizing character. Living tissue has two strong main interactions with light, which are scattering and absorption. A great drawback of the use of light for imaging-based medical diagnosis, however, is that the scattering interaction is so pronounced that it limits the resolution for imaging objects deeper than a few hundred micrometers under the tissue surface. On the other hand, ultrasound radiation has a large penetration depth in tissue, but the contrast is limited. The virtues of light and ultrasound can be combined to perform tissue imaging in a manner that beats the disadvantages of purely optical imaging: in optoacoustics the imaging depth-to-resolution ration is governed by ultrasound, while the contrast is provided by light. The most appealing feature of optoacoustic imaging is the possibility to employ exogenous, specifically targeted contrast agents. Particularly interesting exogenous markers are functionalized gold nano-particles, which by virtue of their strong characteristic plasmon absorption, offer a multitude of high contrast molecular imaging opportunities. The project has two goals: (1) Development of a multimodal deep imaging system based on a combined optoacoustic and echo ultrasound scanner which provides morphological as well as molecular and functional information. In parallel we will establish the theoretical background for reducing the background caused by reconstruction artifacts, bulk tissue absorption and secondary echos of OA transients caused by acoustic inhomogeneities. We will further develop and optimize a fast and reliable reconstruction algorithm which implements the displacement-compensation-technique and allows in parallel to extract elastic tissue properties from echo ultrasound signals. (2) To realize a prototype of an "optoacoustic microscope", designed to elucidate the interaction process of nanosecond laser radiation with gold nanoparticles in a cell and tissue environment. This microscope will allow us to determine optimum laser irradiation parameters for future in-vivo applications and provide the data on the distribution of the absorbers that are needed to optimize the reconstruction algorithms.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Vessel orientation-dependent sensitivity of optoacoustic imaging using a linear array transducer
Preisser Stefan, Bush Nigel L., Gertsch-Grover Andreas G., Peeters Sara, Bailey Arthur E., Bamber Jeffrey C., Frenz Martin, Jaeger Michael (2013), Vessel orientation-dependent sensitivity of optoacoustic imaging using a linear array transducer, in JBO, 18(2), 0206011.
Determining the optical properties of a gelatin-TiO2 phantom at 780nm
Akarçay H. Günhan, Preisser Stefan, Frenz Martin, Ricka Jaro (2012), Determining the optical properties of a gelatin-TiO2 phantom at 780nm, in Biomedical Optics Express, 3(3), 418-434.
Mechanics of nanoparticle-mediated photomechanical cell damage
Peeters Sara, Kitz Michael, Preisser Stefan, Wetterwald Antoinette, Rothen-Rutishauser Barbara, Thalmann George N., Brandenberger Christina, Bailey Arthur, Frenz Martin (2012), Mechanics of nanoparticle-mediated photomechanical cell damage, in Biomedical Optics Express, 3(3), 435-446.
Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies
Jaeger Michael, Preisser Stefan, Kitz Michael, Ferrara Domenico, Senegas Sebastien, Schweizer Dieter, Frenz Martin (2011), Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies, in Physics in Medicine and Biology, 56, 5889-5901.
Vapor bubble generation around gold nanoparticles and its application to damaging of cells
Kitz Michael, Preisser Stefan, Wetterwald Antoinette, Jaeger Michael, Thalmann George N., Frenz Martin (2011), Vapor bubble generation around gold nanoparticles and its application to damaging of cells, in Biomedical Optics Express, 2(2), 291-304.
Combined ultrasound and photoacoustic system for real-time high contrast imaging using a linear array transducer
Jaeger Michael, Frenz Martin (2011), Combined ultrasound and photoacoustic system for real-time high contrast imaging using a linear array transducer, in Lihong Wang (ed.), CRC Press, Taylor & Francis Group, Boca Raton, London, New York, 289-298.
Improved contrast optoacoustic imaging of deep breast tumors using displacement-compensated averaging: Phantom studies
Jaeger Michael, Preisser Stefan, Kitz Michael, Frenz Martin (2010), Improved contrast optoacoustic imaging of deep breast tumors using displacement-compensated averaging: Phantom studies, in Photons plus ultrasound: Imaging and Sensing 2010, Bellingham 7564, SPIE-The International Society for Optical Engineering, Bellingham 7564.
Reduction of background in optoacoustic image sequences obtained under tissue deformation
Jaeger Michael, Siegenthaler Lea, Kitz Michael, Frenz Martin (2009), Reduction of background in optoacoustic image sequences obtained under tissue deformation, in Journal of Biomedical Optics, 14(5), 054011-1-054011-10.

Collaboration

Group / person Country
Types of collaboration
DKF-Universität Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Hans-Sigrist Symposium - Laser applications in medical diagnostics 30.11.2012 Bern
PAI workshop – Innovative techniques in hybrid and photoacoustic imaging 16.10.2012 Vienna
International Symposium on Biomedicine and Drug-Development – Nanotechnology: from Bench to Enduser 25.09.2012 Basel
Annual meeting of the Swiss Physical Society 22.06.2012 Zürich
Real time biomedical optoacoustic imaging 15.09.2011 Zürich
Gold-nanoparticles for optoacoustic imaging and therapy 25.05.2011 Seattle
Optoacoustic 3D measurement of blood vessels using a commercial linear ultrasound scanner: Simulations and phantom experiments 14.05.2011 Island of Ven
Optoacoustics for molecular imaging and cancer therapy 20.10.2010 Sydney
Optoacoustic 3D measurement of blood vessels using a commercial linear ultrasound scanner: phantom and mouse experiments 26.08.2010 San Francisco
Combined ultrasonic and optoacoustic imaging system for cancer detection 02.02.2010 Konstanz
Improved contrast imaging of breast tumors using displacement-compensated averaging: Phantom studies 24.01.2010 San Francisco


Associated projects

Number Title Start Funding scheme
116343 Selective cell diagnosis and killing by nanoparticle absorption of pulsed laser radiation 01.04.2007 Project funding (Div. I-III)
142585 Novel Computerised Ultrasound Tomography in Echo Mode - CUTE: Multimodal Ultrasound Imaging for Accurate Diagnosis and Treatment Control 01.09.2012 Ambizione
116343 Selective cell diagnosis and killing by nanoparticle absorption of pulsed laser radiation 01.04.2007 Project funding (Div. I-III)
139238 Quantitative near-infrared spectrophotometry and imaging: A proposal for a frequency domain near infrared spectrophotometer and imager, an ISS Imagent™ 01.12.2011 R'EQUIP
144443 Combined deep optoacoustics and ultrasound for quantitative multimodal imaging of the human body 01.01.2013 Project funding (Div. I-III)
113284 Particle tracking in three-dimensions using multiphoton luminescence in gold nanoparticles 01.10.2006 Project funding (Div. I-III)

Abstract

In the last three decades, light has been recognized to offer promise for medical diagnosis because of its contrast to tissue properties and its non-ionizing character. Living tissue has two strong main interactions with light, which are scattering and absorption. A great drawback of the use of light for imaging-based medical diagnosis, however, is that the scattering interaction is so pronounced that it limits the resolution for imaging objects deeper than a few hundred micrometers under the tissue surface. On the other hand, ultrasound radiation has a large penetration depth in tissue, but the contrast is limited. The virtues of light and ultrasound can be combined to perform tissue imaging in a manner that beats the disadvantages of purely optical imaging: in optoacoustics the imaging depth-to-resolution ration is governed by ultrasound, while the contrast is provided by light.In optoacoustic imaging (OA), a short pulse of light is absorbed by a tissue chromophore, which generates a small but rapid temperature rise leading to the emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves are then detected by an ultrasound array at the tissue surface and recorded to reconstruct a three-dimensional map of the local amount of absorbed energy. The spatial resolution is limited only by the laser pulse duration and the bandwidth of the ultrasound detector. The optical contrast due endogenous absorbers can be used to quantify the concentration of total hemoglobin, the blood oxygen saturation, or the melanin concentration with the spatial resolution of ultrasound. However, the most appealing feature of optoacoustic imaging is the possibility to employ exogenous, specifically targeted contrast agents. Particularly interesting exogenous markers are functionalized gold nano-particles, which by virtue of their strong characteristic plasmon absorption, offer a multitude of high contrast molecular imaging opportunities. Optoacoustics has the potential to image aspects of the internal structure and composition of tissue using harmless non-ionizing radiation, based on moderate to low cost technology. However, optoacoustic imaging still lacks the technological sophistication to be used clinically in humans and has as yet not be able to yield quantitative information on the local properties of tissue. In the present project we would like to contribute to the development of the technique in two complementary areas:In project part A we address one of the most important shortcomings of optoacoustics using a linear array transducer, which is its limited image depth caused by strong background signals identified in the framework of our running NF project 205320-116343. Thereby, the specific aims are to:1. Develop a multimodal deep imaging system based on a combined optoacoustic and echo ultrasound scanner. An important part of the development will be the optimization of a flexible laser illumination system since the illumination geometry essentially determines the light distribution inside the tissue sample. The system is intended to provide morphological as well as molecular and functional information. 2. Establish the theoretical background for reducing the background caused by reconstruction artifacts, bulk tissue absorption and secondary echos of OA transients caused by acoustic inhomogeneities. We will further develop and optimize a fast and reliable reconstruction algorithm which implements the displacement-compensation-technique and allows in parallel to extract elastic tissue properties from echo ultrasound signals. This algorithm will make use of the simultaneously recorded ultrasound and optoacoustic signals obtained by the multimodal imaging system. In addition, we will elaborate the possibilities of the displacement-reconstruction-algorithm to reduce in parallel the speckles in the echo ultrasound.In project part B we seek to understand the basics of the interaction processes taking place when irradiating gold nanoparticles of different size with laser light. A detailed understanding will be the key to quantitative molecular optoacoustic imaging and a prerequisite to optimize optoacoustic therapy. The goal of project part B is3. Realize a prototype of an “optoacoustic microscope”, designed to elucidate the interaction process of nanosecond laser radiation with gold nanoparticles in a cell and tissue environment. The goal is a spatial resolution approaching the size of a single cell. This device will allow us to determine optimum laser irradiation parameters for future in-vivo applications and provide the data on the distribution of the absorbers that are needed to optimize the reconstruction algorithms. Although the project is devoted to the basic investigation of optoacoustic imaging, it is expected to have a strong impact on medical imaging, not only on optoacoustics but also on classical echo ultrasound since the techniques to be developed for background reduction in optoacoustics can also be applied for speckle reduction. This multimodal imaging system will have great potential in assessment of breast cancer tumors since it can provide complementary information of local structural and functional changes in the tissue and microvasculature.
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