Subsurface ablation of tissue by ultrafast laser

Laser-induced optical breakdown (LIOB) is a multiphoton process which can be used for selective removal of material. It revolves around the creation of a plasma in the focal volume of a beam, and requires very high peak intensities in the order of the For this reason, ultrafast lasers sending high energy pulses with very short durations below 1 ps are favorite tools for triggering LIOB. The local creation of the plasma can induce a sharp rise in temperature and pressure over a few micrometers, which produce a cavitation bubble. The combined mechanical effects from the bubble creation and chemical effects from the free electrons in the plasma can induce dramatic changes in and around the focal volume. This is particularly true in sensitive samples such as biological tissues, where cells can be selectively destroyed by LIOB. The axial and lateral confinement of the plasma creation due to the multiphoton nature of LIOB opens interesting perspectives in the field of microsurgery. In this regard, the work presented in this thesis concerns the analysis of the effects of LIOB in soft biological tissues. More specifically, we investigate the case of arterial tissues and the opportunities this technique could offer in the treatment of atherosclerosis. First, we present the current knowledge on the mechanism and impact of LIOB on the surrounding medium, and particularly in biological samples. We discuss their modeling, both via simulation and replication in organic and inorganic phantoms. We consider the theory of the linear and non-linear mechanisms driving the evolution of the plasma density in the focal volume, the minimum requirements for the creation of a cavitation bubble, and optical effects which can modify the shape of a plasma. We then observe the behavior described by this theory in transparent and scattering phantoms mimicking biological tissues, and investigate scanning approaches to remove volumes of material. The following section of this thesis is devoted to investigating the effect of LIOB at the cellular level. We discuss an approach according to which LIOB may be of interest in the treatment of atherosclerosis or other pathologies which could benefit from the control of the population of cells undergoing controlled cell death (apoptosis). We then investigate the effect of LIOB on populations of epithelial cells in 2D and 3D cultures. We monitor the increase in the number of necrotic and apoptotic cells, in different regimes of ablation. We then present the methods and results of subsurface ablation in arterial tissue, both healthy and atherosclerotic. On ex-vivo experiments, we focus on the observation of a bubble produced by LIOB, and the structural damage generated. On in-vivo experiments, we investigate the effect on necrosis and apoptosis of cells around the target area, and compare our findings with the results obtained in cell cultures and phantoms. Finally, delivering the high intensities pulses to the target area in a minimally invasive way is essential in biomedical applications of LIOB, and we investigate this question in the final part of this thesis. We present two different approaches to answer this challenge: first by the use of transmission of pulses via a hollow-core photonic crystal fiber, and secondly by wavefront shaping of a pulse through a multicore fiber. Through both methods, we demonstrate subsurface ablation of biological tissue.

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