Job ID: 118754

Project for potential PhD student in photoacoustic imaging

Position: Ph.D. Student

Deadline: 20 May 2024

City: Marseille

Country: France

Institution: INT - Institut des Neurosciences de la Timone CNRS UMR 7289 & Institut Fresnel

Department:

Description:

Motivation

The study of large scale neuronal circuits throughout the brain is currently one of the biggest challenge in neurobiology. However, high resolution non-invasive imaging of neuronal activity is limited to shallow depths due to prominent light scattering beyond one millimeter. Recently, photoacoustic imaging has been developed to overcome this issue. This  fascinating technique relies on ultrasound generation upon the absorption of a light pulse, thus  enabling to probe optical absorption contrast at large depth in biological tissue.

This imaging modality has been used to record the activity of neurons through variations in the optical properties of specific molecules (“proxies”).  Endogenous contrast (such as blood – thus hemoglobin – concentration or its oxygen saturation), or exogenous contrast (with calcium sensitive fluorescent indicators [1]) can therefore be probed several millimeters inside the intact brain.

Importantly, it has recently been shown that genetically encoded fluorescent markers can generate a photoacoustic signal, as these molecules are primarily optical absorbers [2]. Furthermore, recent proofs of concept have demonstrated that, using  fluorescent indicators, it is possible to image changes in their absorption due to neuronal activity [3]. However, these studies were limited by sub-optimal molecular probes and low-frequency piezoelectric ultrasonic sensors, which severely limited spatial resolution.

Using and all-optical photoacoustic imaging approach allows overcoming this limitation. Based on optical interference measurement of the acoustic field using a Fabry-Perot cavity [4], this technology can provide high-resolution images (<50-100 µm). A new imaging system of this kind has been acquired as part of a joint project between INT (where the system is installed and where most of the PhD work will be carried out) and the Fresnel Institute.

The goal of this PhD project is to:

(i) explore, validate and optimize high-resolution photoacoustic imaging of neuronal activity via calcium indicators in brain and/or spinal cord slices in-vitro, using a multimodal device combining the photoacoustic imaging system, a wide-field epifluorescence microscope and an ultrathin multi-electrode array chip for additional electrophysiological recordings [5].

(ii) identify which of the available genetically encoded fluorescent indicators are best suited to this technique, both in-vitro and in-vivo.

(iii) demonstrate the applicability to small animals (rodent and non-human primate) by optoacoustically imaging  calcium activity in anaesthetized and/or awake small animals (rats…).

Why you should apply

By joining our research groups at the Fresnel Institute and the Timone Neuroscience Institute  (INT) in Marseille, you will gain hands-on experience in cutting-edge optical imaging approaches and neurobiology. We are seeking talented and enthusiastic students motivated to participate in groundbreaking research.

This is a unique opportunity to gain experience in a wide range of skills, from optics and electronics to in-vitro and in-vivo imaging in tissue slices and awake small animals, along with image and signal processing.

You will build upon both the existing equipment as well as the combined expertise of the PIs involved in the project, regarding photoacoustic imaging, optical microscopy, signal processing and neurobiology. In addition to technical skills, you will also gain a strong understanding of the biology and neuroscience behind our research.

On top of a thrilling research environment, the city of Marseille offers a high quality of life, with limited living costs and a unique combination of a culture and nature.

Requirements

To be considered for this PhD project, you should have a strong background in physics, optics, electrical engineering, neuroscience (with some experience in optical imaging) or any related field. Basic programming skills are a strong plus (Matlab or Python), as well as a certain taste for tinkering. As you will be evolving in an international environment, you must be fluent in English (at least C1), and exhibit excellent communications capabilities (written and spoken).

Application

Please send a detailed CV, a cover letter describing your interests and past achievements (max. 1 page), a copy of your university transcripts, as well as names, affiliations, and email addresses of two referees to frederic.chavane@univ-amu.fr and thomas.chaigne@fresnel.fr with the subject line “[Application]”.

We look forward to hearing from you!

References

[1]             T.-W. Chen et al., “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature, vol. 499, no. 7458, pp. 295–300, juillet 2013, doi: 10.1038/nature12354. Available: http://www.nature.com/nature/journal/v499/n7458/full/nature12354.html. [Accessed: Jul. 01, 2016] [2]             G. S. Filonov, A. Krumholz, J. Xia, J. Yao, L. V. Wang, and V. V. Verkhusha, “Deep-Tissue Photoacoustic Tomography of a Genetically Encoded Near-Infrared Fluorescent Probe,” Angewandte Chemie International Edition, vol. 51, no. 6, pp. 1448–1451, Feb. 2012, doi: 10.1002/anie.201107026. Available: http://doi.wiley.com/10.1002/anie.201107026. [Accessed: Mar. 10, 2017] [3]             X. L. Deán-Ben et al., “Functional optoacoustic neuro-tomography for scalable whole-brain monitoring of calcium indicators,” Light: Science & Applications, vol. 5, no. 12, p. e16201, Aug. 2016, doi: 10.1038/lsa.2016.201. Available: http://www.nature.com/doifinder/10.1038/lsa.2016.201. [Accessed: Dec. 02, 2016] [4]             E. Zhang, J. Laufer, and P. Beard, “Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues,” Appl. Opt., AO, vol. 47, no. 4, pp. 561–577, Feb. 2008, doi: 10.1364/AO.47.000561. Available: http://www.osapublishing.org/abstract.cfm?uri=ao-47-4-561. [Accessed: Nov. 28, 2016] [5]             M. J. Donahue et al., “Multimodal Characterization of Neural Networks Using Highly Transparent Electrode Arrays,” eNeuro, vol. 5, no. 6, Nov. 2018, doi: 10.1523/ENEURO.0187-18.2018. Available: https://www.eneuro.org/content/5/6/ENEURO.0187-18.2018. [Accessed: Apr. 09, 2024]