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Blood aggregate detection in micro vascularization by photo-acoustic imaging with optical detection

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Blood is a complex fluid whose composition and physical characteristics tell us about a patient’s health. The rheology of blood can be modified by the phenomenon of aggregation of red blood cells which is at the origin of the coagulation when the blood is at rest, but which can also occur in the blood circulation during certain pathologies. Too large and too numerous aggregates can cause circulatory complications causing a defect in perfusion of certain tissues, which may lead to their necrosis. Monitoring them is therefore an important health issue for patients.

Goal : We propose to develop an instrument to detect in vivo aggregates of red blood cells in micro-blood vessels located a few hundred micrometers under the skin. For this purpose we propose to use the photo-acoustic imaging technique [1,2] which makes it possible to produce images of optical contrast with a detection signal having the propagation and diffusion properties of acoustic waves. Its principle is based on the generation of an acoustic wave by thermo-elastic effect following a thermal variation generated by optical absorption of the object to be imaged. This acoustic wave is then usually detected using piezoelectric transducers, which however have a number of technical limitations [3]. To overcome these limitations, we propose to replace the piezoelectric transducer by an optical detection system developed in the laboratory and using an optical re-injection laser [4]. Optical detection of acoustic waves can be done either longitudinally (displacement measurements) or transversally (overpressure measurements).
With our setup, for single red blood cells to be distinguished from aggregates, it will be necessary to have an optical resolution (micrometric) and thus to optically focus the excitation wave in the biological medium. In addition, continuous blood flow monitoring requires the use of a power-modulated laser rather than a pulse laser to generate photo-acoustic signals [5]. This technique is little used in photoacoustic imaging but has the advantage of requiring compact lasers and above all of generating a signal at a single frequency whose amplitude and phase can be detected easily with a lock-in amplifier.
Our main goal is therefore to produce a transportable device of photo-acoustic imaging working in the frequency domain to perform flow cytometry in vivo [6].

Environment : The OPTIMA team (OPTics and IMAging) of the LIPhy in which this thesis will take place has acquired expertise in laser imaging for a decade and more recently in the light / acoustic wave interaction. This thesis will be carried out in close collaboration with researchers from the Langevin Institute (ESPCI Paris Tech) and INSERM. The research project related to this thesis has already obtained two CNRS funding of up to 40k to finance the project’s equipment.

Contact :

Eric Lacot, eric.lacot@univ-grenoble-alpes.fr

References :

[1] Wang et al, Photoacoustic Tomography : In Vivo Imaging from Organelles to Organs,, Science 335, 1458 (2012).
[2] Beard et al, Biomedical photoacoustic imaging, Interface Focus 1, 602 (2011)
[3] B. Dong et al, Optical detection of ultrasound in Photocaoustic Imging,IEEE Trans. Biomed. Engineering. 64, 4 (2017)
[4]O.Jacquin et al, Experimental comparison of autodyne and heterodyne laser interferometry using an Nd:YVO4 microchip laser,J. Opt. Soc. Am. A 28,1741 (2011)
[5] S. Temenkov et al,Signal to noise analysis of biomedical photoacoustic measurement in time and frequency domains, Rev. Sci. Instrum. 81 124901 (2010)
[6] I. E. I. Galenzha et al, Photo-acoustic flow cytometry, Methods 57, 280 (2012)