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The field of optical microscopy has benefited from recent developments to reach resolutions of the order of ten nanometers. These techniques, called Photo-activated localization microscopy (PALM) or Stochastic Optical Reconstruction Microscopy (STORM), are based on the generation of isolated fluorescence events that make it possible to precisely locate isolated areas that fluoresce successively. The accumulation of positions then provides a super-resolved image whose contrast represents the concentration of fluorophore molecules. We propose to apply these principles to the field of photoacoustic imaging (PA).

In this technique, a very short light pulse is sent into a tissue. While light diffuses into the tissue, which makes high-resolution optical imaging impossible at depth, it is absorbed by specific tissue structures. The light absorption generates a temperature rise which is at the origin of a thermal expansion phenomenon generating ultrasound. Unlike light, ultrasound is only weakly scattered in biological tissue and can be captured on the tissue surface without loss of information. Ultimately, PA imaging provides a deep optical contrast image in tissue. The resolution of the PA image (typically 100 μm) is limited by acoustical diffraction.
To break the diffraction limit, our group has recently used the notion of fluctuation, in terms of illumination [1] or in terms of absorbing medium [2] to image blood flow. These flows have also been imaged by the localization of single absorbers [3], flowing in vessels. The localization method gives a better resolution but nevertheless requires a very low concentration of absorbers. The detectability of single absorbers is then conditioned by the nature of the absorbers and by a sufficient light intensity. We propose here to overcome these limits by invoking a phase transition from liquid to gas. 

It is possible to generate microscopic gas bubbles around nanoscale optical absorbers using the combination of light and ultrasound. The signal emitted by the bubble is specific to the presence of contrast agents and its amplitude is typically 100 times higher than a PA signal. During this internship, the student will design gel-based model media and identify the appropriate exposure parameters (light intensity, sound pressure) for the stochastic observation of cavitation events allowing their localization, the desired condition being that there should be only one bubble generated by acoustic focal spot.

The student will become familiar with lasers, optical instrumentation, programmable ultrasound and nanoparticles. A taste for programming and signal processing (MATLAB) is preferable. The internship can be pursued by a PhD thesis, funded by the ERC COHERENCE project.

References :

[1] Chaigne, T., Gateau, J., Allain, M., Katz, O., Gigan, S., Sentenac, A & Bossy, “Super -resolution photoacoustic fluctuation imaging with multiple speckle illumination,” Optica, vol. 3, no. 1, p. 54, Jan. 2016.

[2] T. Chaigne*, B. Arnal*, S. Vilov, E. Bossy, and O. Katz, “Super-resolution photoacoustic imaging via flow induced absorption fluctuations,” Optica, 2017, in press,

[3] S. Vilov, B. Arnal, and E. Bossy, “Overcoming the acoustic diffraction limit in photoacoustic imaging by localization of flowing absorbers,” Optics Letters, in press, 2017,

Contact :

Emmanuel Bossy :
Bastien Arnal :
Laboratoire Interdisciplinaire de Physique, Université Grenoble Alpes

Stochastic Cavitation