Internship proposal: Calibrated photoacoustic imaging combined with high frequency elastography

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Internship type

M2 internship / last year of engineering school

Duration

6 months, from February 2025

Context

Photoacoustic imaging (PAI, introductory video: https://youtu.be/2f3V0DQNLYg ) is an emerging biomedical imaging modality that enables to map optical absorption at centimeter depth and in sub-millimeter in biological tissue. With acquisitions at multiple optical wavelengths, PAI can reveal the biodistribution of hemoglobin (oxygenated or deoxygenated) and nanometric contrast agents. Photoacoustic imaging is based on the transformation of absorbed optical energy (pulsed excitation) into heat and subsequently into pressure and ultrasound waves. The PAI group of Laboratoire d’Imagerie Biomedicale has recently shown that a calibration of the PAI acquisitions enables to obtain quantitative spectral characterization of photoacoustic and photothermal nanoagents in vitro [1], [2]. We could quantify the light-to-heat conversion efficiency of photothermal nanoagents [2]. When excited with continuous illumination, photothermal nanoagents induce hyperthermia in tissue and can lead to a softening of the tumor [3] with direct implication in immune cell trafficking and access to tumor cell through disrupted tumor stroma [4], [5]. Studies on tumor softening were performed at the Université Paris Cité’s living imaging platform (PIV), but PAI was not available for an evaluation of the nanoagents distribution and the elasticity map was obtained with a clinical machine poorly adapted to pre-clinical imaging on rodent models.

FUJIFILM Visualsonics is one of the pioneering companies marketing photoacoustic imaging scanners. Recently, they have released a shear wave elastography module. In the frame of a collaboration, the device Vevo F2 LAZR-X will be available at PIV and we are aiming at:

  • Implementing the in vitro characterization method developed at the LIB on the device. This part will be in the continuity of promising preliminary results obtained on the previous version of the device in 2023.
  • Characterizing photothermal agents
  • Designing and programming imaging sequences to achieve 3D elastography and photoacoustic imaging of tumors in mice models of cancer.
  • Programming analysis software to merge photoacoustic and elastography maps

Bibliography

  1. T. Lucas et al., « Calibrated Photoacoustic Spectrometer Based on a Conventional Imaging System for In Vitro Characterization of Contrast Agents », Sensors, vol. 22, no 17, p. 6543, août 2022, doi: 10.3390/s22176543.
  2. T. Lucas et al., « Quantitative, precise and multi-wavelength evaluation of the light-to-heat conversion efficiency for nanoparticular photothermal agents with calibrated photoacoustic spectroscopy », Nanoscale, vol. 15, no 42, p. 17085‑17096, 2023, doi: 10.1039/D3NR03727D.
  3. I. Marangon et al., « Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy. », Theranostics, vol. 7, no 2, p. 329‑343, 2017, doi: 10.7150/thno.17574.
  4. A. Nicolas-Boluda et al., « Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment », eLife, vol. 10, p. e58688, juin 2021, doi: 10.7554/eLife.58688.
  5. A. Nicolás-Boluda et al., « Photothermal Depletion of Cancer-Associated Fibroblasts Normalizes Tumor Stiffness in Desmoplastic Cholangiocarcinoma. », ACS Nano, vol. 14, no 5, p. 5738‑5753, mai 2020, doi: 10.1021/acsnano.0c00417.

Objective

The objective of this internship is to perform signal and image processing on the data that will be output by the Vevo F2 LAZR-X in order to: 1) transfer the quantitative spectral evaluation to the new device, 2) perform a correlation between the photothermal nanoparticle distribution and tumor softening. The intern will participate in the experimental work for the in vitro experiments, and will prepare the in vivo experiments with an imaging phantom. However, the in vivo experiments will be performed by authorized personnel at PIV.

Missions

The intern will be in charge of:

  • the implementation of the experimental set-up and the acquisition sequence, together with research engineers at the LIB
  • the acquisition of data on nanoparticle suspensions
  • signal processing to analyze the collected data based on algorithms available at LIB
  • image analyses to correlate photoacoustic and elastography data

Skills

The proposed internship will require good skills in programming (Matlab, Python), and knowledge in signal and image processing. Taste for experimentation and instrumentation will be an asset.

Remuneration

Internship gratification

Contact

Jérôme GATEAU, jerome.gateau[at]sorbonne-universite.fr tel: 01.44.27.22.65
Gilles RENAULT gilles.renault[at]inserm.fr tel: 01 44 41 22 73

Locations of the internship

Laboratoire d’Imagerie Biomédiale, 15 rue de l’école de médecine, 75006 Paris
and
Plateforme d’imagerie du petit animal, 24 rue du Faubourg Saint Jacques, 75014 Paris