University of Minnesota
Department of Biomedical Engineering
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Professor Shai Ashkenazi

Shai Ashkenazi

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Biomedical Imaging, Optics, Optoacoustic Devices, Photoacoustic Imaging

Optoacoustic devices represent a sensitive ultrasonic transduction technology well matched to endoscopic and minimally invasive imaging probes. The technology is based on optical resonators for detecting ultrasound and thin thermoelastic films for converting optical pulses to ultrasound. Our group develops novel Fabry-Perot, microring and other optical resonators based ultrasound receivers. Thin metal nano-structures, optimized for high frequency ultrasound generation, are combined with these receivers to form an integrated all-optical ultrasound transducer.

Photoacoustics is an imaging modality combining optical illumination with ultrasound detection to create an image of the optical properties of a tissue in-vivo and non-invasively without significant degradation from optical scattering. We are studying the application of nanotechnology to design agents for photoacoustic functional and molecular imaging.

Optical microring resonators for ultrasound detection

Our group pioneered a research on using array of optical microring resonators for ultrasound detection. Each microring has a different resonance wavelength allowing signal multiplexing by wavelength selection, while sharing a common bus waveguide. High ultrasound sensitivity was demonstrated based on elastic deformation of the polymer microring structure. This concept is a highly attractive for minimally invasive ultrasound imaging applications such as intravascular imaging. The research, funded by the NIH (R01), is conducted in collaboration with Prof. J. Guo (University of Michigan). This 4-year project, started at Sep. 2007, is aimed at developing novel optical techniques for high-frequency and high-sensitivity ultrasound detection and broadband ultrasound generation. To develop this imaging technology we intend to investigate in detail the underlying physical principles, and explore a number of candidate device structures in order to set a solid foundation for the future implementation of integrated transducer arrays for intravascular and intra-catheter applications.

This new imaging technology would open up possibilities unimaginable so far in diagnosis and treatment of cardio-vascular diseases. It would allow integrating highly compact imaging arrays of large element count for high quality imaging in minimally invasive procedures such as angioplasty, stenting, and recanalzation of totally occluded arteries.

It can also propel development of other applications such as a needle imager. Compact, high resolution imaging probe mounted at the tip of a biopsy needle would allow precise biopsy guiding. It would also provide very high resolution imaging of deep lying tissue structure, otherwise not accessible by conventional ultrasound imaging.

Thin film optoacoustic transducers

Optoacoustic technology utilizes optical methods to generate and detect ultrasound. During the last decade several research groups have demonstrated its potential in forming dense arrays of ultrasound receivers for high resolution 3D imaging. We have focused in our research on developing high frequency and wide bandwidth (up to 100 MHz) optoacoustic transducers and integration techniques optimized for minimally-invasive catheter based imaging probes. Sensitive ultrasound detectors based on polymer thin film optical resonator (etalon) were developed. The active area for detection is defined by the spot size and location of a laser beam probing the etalon surface. Etalon detectors show better sensitivity than conventional piezoelectric transducers of similar size. We have also developed highly efficient ultrasound transmitters, based on thermoelastic expansion of thin light absorbing films illuminated by a pulsed laser. To integrate a receiver and a transmitter in a single thin film device we have designed a gold nano-structure optimized for high reflectivity at 1550 nm wavelength and high absorption at 800 nm. This layer was utilized for both etalon mirror and thermoelastic generation in an integrated optoacoustic transducer. To facilitate the development of catheter based devices, optic fiber-bundles are investigated for light delivery between a console system and a remote optoacoustic imaging probe.

Photoacoustic lifetime imaging

Fluorescent probes were developed throughout the last three decades as a powerful tool for imaging biological processes; probing intra-cellular ion and molecular concentrations; tagging proteins; and detecting enzymes activity. These techniques are invaluable for in-vitro or small animal studies. However, their use in clinical applications is limited due to strong light scattering that prevents detection or imaging in tissue. This project presents an alternative method for imaging the response of fluorescent sensor dyes by photoacoustic imaging. It, therefore, combines the vast range of applications of fluorescence probes with a non-invasive in-vivo imaging modality. It relies on a technique, recently developed in our lab, for photoacoustic probing of dye’s excited state lifetime. The technique will be applied for tissue oxygen imaging, a crucial parameter in radiation therapy for cancer patients.

Studies performed during the last two decades clearly indicate a strong correlation between tumor aggressiveness, survival rate, therapy efficacy, and tumor hypoxia. Currently, a direct non-invasive tissue oxygenation imaging modality does not exist. Indirect imaging, such as (FMISO) PET, radio-labled EF5 uptake, 18F MRI, and BOLD MRI, were developed; however, these techniques are not widely used in oncology clinics because of high cost and limited availability. Oxygen probing fluorescent dye can provide sensitive detection of oxygen in the physiological range. Oxygen probing fluorescent dyes can provide sensitive detection of oxygen in the physiological range. Fluorescence emission is quenched in the presence of oxygen leading to a non-radiative decay of the excited electronic state. Recently, we have developed a double pulse (pump-probe) photoacoustic method to measure lifetime of oxygen sensitive dye. A first pulse is used to excite the dye. A second pulse (wavelength optimized for high absorption of the excited state) is fired after a controlled delay to probe the excited state.   The photoacoustic signals generated by the second pulse at a range of pump-probe delays are detected and used to quantify the lifetime of the excited state. Preliminary experiments show equivalency of photoacoustic and fluorescence based lifetime measurements.

This project focuses on developing this new imaging technology for non-invasive in-vivo imaging of tissue oxygenation which is a critical physiological parameter for cancer treatment planning. It can be implemented for imaging of breast, bladder and prostate cancer.

Nanoparticles for photoacoustic functional imaging

US. We are developing a non-invasive, prostate cancer specific, imaging modality. The technique is based on photoacoustic imaging of nano-particles designed to bind specifically to prostate cancer cells (or tumor-associated neovasculature endothelial cells). Ultimately, this project will lead to enhanced sensitivity and specificity in prostate cancer detection. Moreover, it will allow for image guided biopsy, image guided treatment and treatment monitoring.

Preliminary experiments in collaboration with Prof. N. Kotov (Chemical Eng., Univ. of Michigan), and Prof. R. Kopelman (Chemistry, Univ. of Michigan) have successfully demonstrated cancer cell targeting and high detection sensitivity in the nM range.

Selected Publications

S. –W. Huang, S. –L. Chen, T. Ling, A. Maxwell, L. J. Guo, and S. Ashkenazi, “Low-noise wideband ultrasound detection using polymer microring resonators”, Accepted for publication in Applied Physics Letters (Apr. 2008)

T. D. Horvath, G. Kim, R. Kopelman, and S. Ashkenazi, “Ratiometric Photoacoustic Sensing of pH using a Sonophore”, accepted for publication in The Analyst (2008)

S. Ashkenazi, S.-W. Huang, T. Horvath, Y. –E. L. Koo, and R. Kopelman, “Photoacoustic probing of fluorophore excited state lifetime with application to oxygen sensing”, J. of Biomedical Optics 13, 034023 (2008).

Y. Hou, S. Ashkenazi, S.-W. Huang, and M. O’Donnell, “All-optical Theta-array for 3D Ultrasound Imaging”, submitted to IEEE Trans. Ultrason. Ferroelect. Freq. Contr. (2008).

Y. Hou, S.-W. Huang, S. Ashkenazi, R. Witte, and M. O’Donnell, “Thin polymer etalon arrays for high-resolution photoacoustic imaging”, submitted to IEEE Trans. Ultrason. Ferroelect. Freq. Contr. (2008).

X. Yang, E. Stein, S. Ashkenazi, and L. V. Wang “Nanoparticle for Photoacoustic Imaging”, to appear in Wiley Interdisciplinary Reviews: Nanomedicine (Invited review article)

A. Maxwell, S.-W. Huang, T. Ling, J.-S. Kim, S. Ashkenazi, and L. J. Guo, “Polymer Microring Resonators for High-Frequency Ultrasound Detection and Imaging”, IEEE Journal of Selected Topics in Quantum Electronics, 14(1), p.191 (2008).

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nano-rod contrast agent for prostate cancer detection by photoacoustic imaging”, J. Appl. Phys. 102, 064701 (2007).

S. Ashkenazi, Y. Hou, S.-W. Huang, T. Buma, and M. O’Donnell, “High frequency optoacoustic transducers for ultrasonic and photoacoustic imaging”, in Photoacoustic imaging ed. L. V. Wang (invited book chapter)

G. Kim, S. W. Huang, M. O’Donnell, R. Agayan, K. Day, M. Day, R. Kopelman and S. Ashkenazi, “Indocyanine Green embedded PEBBLEs as a Contrast Agent for Photoacoustic Imaging”, Journal of Biomedical Optics 12 (4) 044020 July/August (2007).

Y. Hou, J.-S. Kim, S. Ashkenazi, S.-W. Huang, L. J. Guo, and M. O'Donnell, “Broadband all-optical ultrasound transducers”, Appl. Phys. Lett. 91, 073507 (2007).

Y. Hou, J.-S. Kim, S.-W. Huang, S. Ashkenazi, L. J. Guo, and M. O’Donnell, “Characterization of a broadband all-optical ultrasound transducer – from optical and acoustical properties to imaging”, accepted for publication in IEEE Trans. Ultrason, Ferroelect. Freq. Contr. (2007).

C. Y. Chao, S. Ashkenazi, S. W. Huang, M. O’Donnell, and L. J. Guo, “High-frequency ultrasound sensors using polymer microring resonators”, IEEE Trans. Ultrason, Ferroelect. Freq. Contr. 54,(5) pp. 957 – 965 (2007).

Y. Hou, S. Ashkenazi, and M. O’Donnell, “Improvements in Optical Generation of High Frequency Ultrasound”, IEEE Trans. Ultrason. Ferroelect. Freq. Contr. 54, (3) pp. 682-686 (2007)

Y. Hou, J. S. Kim, S. Ashkenazi, M. O’Donnell, and L. J. Guo, “Optical generation of high frequency ultrasound using two-dimensional gold nanostructure”, Appl. Phys. Lett. 89, pp. 093901 (2006)

S. Ashkenazi, Y. Hou, T. Buma and M. O'Donnell, “Optoacoustic imaging using thin polymer etalon”, Appl. Phys. Lett. 86, pp. 134102-1-3 (2005)

S. Ashkenazi, C. Y. Chao, L. J. Guo, and M. O’Donnell, “Ultrasound detection using polymer microring optical resonator”, Appl. Phys. Lett. 85, pp. 5418-20 (2004)

S. Lukaschuk, S. Ashkenazi, V. Lebedev and V. Steinberg, “New light scattering technique based on phase time derivative correlation function”, Europhysics Letters 56, pp. 808 (2001)

S. Ashkenazi and V. Steinberg, “Spectra and statistics of velocity and temperature fluctuations in turbulent convection”, Physical Review Letters 83, pp. 4760 (1999).

S. Ashkenazi and V. Steinberg, “High Rayleigh number turbulent convection in a gas near the gas-liquid critical point”, Physical Review Letters 83, pp. 3641 (1999).

S. Ashkenazi and E. Polturak, “An acoustic laboratory experiment to determine the coefficient of mutual diffusion of gases”, American Journal of Physics 56, pp. 836 (1988).