Developpement d'un systeme d'imagerie photoacoustique pour application a l'atherosclerose

Photoacoustic tomography has emerged as a new preclinical imaging modality combining optical and ultrasound techniques. In the present implementation, photoacoustic imaging is used to recover the initial distribution of pressure generated by optical absorption in biological tissues. Further computation could allow the recovery of optical properties such as the optical absorption map. This technique relies on optical diffusion in turbid media in order to get a deeper-field-of-view compared to optical modalities in the ballistic or nearly ballistic regimes. For instance, it could allow imaging of deep structures or organs in murin models, which are commonly found in translational research. Moreover, the main endogenous absorbing components of tissues such as oxy- or deoxyhemoglobin, lipids, or exogenous contrast agents have a specific absorption profile that could feed multispectral unmixing techniques.;The main goal of this projet is to apply photoacoustic tomography for vascular imaging in mice. More specifically, the technique is to be applied toward molecular imaging of atherosclerotic plaque. Molecular imaging is directed to noninvasive detection of targeted probes, in order to supplement anatomical data with complementary molecular information. Currently, several imaging modalities can be used to detect the atheroma. However, for each application a compromise must be made given that no technique is able to impose itself with respect to all decision criterias such as sensitivity, spatial or temporal resolution, level of exposure to ionizing radiation, depth of penetration or cost. Photoacoustic imaging is an hybrid modality evolving between optical techniques and conventionnal ultrasound imaging, and therefore benefits from the high sensitivity of optics as well as ultrasound spatial resolution.;For this project, the aortic arch has been defined as the targeted region of interest. Indeed, this area is prone to early plaque formation in atherosclerotic mice models and provides unique landmarks for repositioning in repeated studies. To date, very few studies have investigated the cardiovascular system in photoacoustics. Hence, the results of this thesis are an original contribution to the field. Photoacoustic measurements are very sensitive to whole blood, and therefore the detection of vascular contrast represents a window of opportunity for molecular imaging. The main accomplishments of this work have been done toward the detection of vascular contrast in vivo in mice.;In the first part of the thesis, we simulated the direct problem in photoacoustics. The purpose of this methodological objective was to estimate the order of magnitude of the depth of penetration of light in turbid or vascular tissues. The simulated pressure signal was first investigated by varying multiple parameters such as the source dimensions, homogeneity and intensity in addition to the ultrasound attenuation of the simulated propagating medium. The filtering effect due to the transducers limited bandwidth was also modeled and applied to simulated signals. Monte Carlo simulations were also performed in order to estimate the possible depth of imaging for different values of the optical absorption coefficient. A numerical phantom comprising an artery was used to estimate the effect of spectral dependence of the diffusive medium on the far-reaching absorption.;A photoacoustic imaging apparatus was then designed and developed for imaging the aortic arch in mice. The apparatus comprised an ultrasound static B-mode echocardiographic system to allow anatomical validation of photoacoustic contrast. The electronic components of the acquisition circuit were assembled on a custom printed circuit board. The control state machine was programmed on an FPGA, while the data transfer channel was provided by a USB link. A nearly real-time reconstruction software was designed and implemented for the purpose of fast repositionning. The apparus was characterized and validated by using imaging phantoms.;An experimental setup for small animal imaging was designed and built. Acquisitions were done in vivo using the custom photoacoustic imaging apparatus as well as a commercial photoacoustic system. The echocardiogram allowed formal identification of the ascending aorta and aortic arch. The injection of a molecular probe based on gold nanoshells targeting VCAM-1 was followed by an increase in photoacoustic signal in the aortic region. A vascular contrast was also obtained using a standardized echocardiographic view. These results suggest that photoacoustic imaging could potentially be used for molecular imaging of macroscopic vessels in atherosclerotic murin models.