Ultrafast laser ablation for targeted atherosclerotic plaque removal

Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

Subsurface ablation of atherosclerotic plaque using ultrafast laser pulses

Donald Benjaman Conkey, Thomas Jean Victor Marie Lanvin, Demetri Psaltis

We perform subsurface ablation of atherosclerotic plaque using ultrafast pulses. Excised mouse aortas containing atherosclerotic plaque were ablated with ultrafast near-infrared (NIR) laser pulses. Optical coherence tomography (OCT) was used to observe the ablation result, while the physical damage was inspected in histological sections. We characterize the effects of incident pulse energy on surface damage, ablation hole size, and filament propagation. We find that it is possible to ablate plaque just below the surface without causing surface damage, which motivates further investigation of ultrafast ablation for subsurface atherosclerotic plaque removal. (C)2015 Optical Society of America

Optical Soc Amer2015

Subsurface ablation of tissue by ultrafast laser

Thomas Jean Victor Marie Lanvin

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 GW.cm-2. 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.

EPFL2017

Endoscopic low coherence interferometry applied to tri-dimensional contouring of upper airways

Yves Delacrétaz

This thesis presents a novel approach for optical tri-dimensional contouring, requiring only one acquisition to extract a contour depth. It is based on an interferometric setup, using a reduced coherence light source, and is fully adaptable to endoscopic procedure commonly in used in ear-nose-throat (ENT) medicine. It has been demonstrated that the method can be successfully applied to imaging of porcine upper airways. Although this method uses interferometry to obtain depth range measurement, the phase signal is not directly evaluated, rather the location of the coherent superposition of two waves is extracted, and thus provides a robust technique even in harsh environment. The key feature is to extract the coherent area on the image by locating intentionally induced fringes created by off-axis superposition of a smooth reference wave and an object wave coming from a rough or diffusing sample through an optical system with limited aperture. A model for the propagation of the light through the optical system has been developed. It takes into account the broadened emission spectrum of the light source, as well as the statistical speckle effect induced by the illumination of a rough surface with partially coherent light. Simulated results have been carefully compared with measurements, both in the spatial domain and in the Fourier domain (spatial frequencies response), which has permitted to better understand the processes involved in the creation of the interference fringes, and improve the design of the device. Different filters have been investigated in order to extract the depth information from acquired interferograms. By using Gabor filterbanks, which do not need any a priori knowledge of the signal, selectivity of the extracted signal has been enhanced by a factor of 1.3 compared to a simple local Fourier spectrum evaluation, and time of the extraction procedure divided by 6, even when compared to fast iterative calculation in the Fourier spectrum. Moreover, by imposing the frequency and/or orientation of the signal to detect, which can be known by a simple calibration procedure, it has been proved that the selectivity can be further enhanced by a factor of 2.5, keeping the calculation time as short or even shorter. A compact prototype has been designed and built, with a specific multiple fibers arrangement for illumination. The system is separated in two parts: the first one is directly attached to the rigid endoscope, and contains imaging as well as recombining object/reference wave optics, and the detector. It fits into a box with overall dimensions of 115 × 83 × 94 mm. The second part contains the laser source, the scanning arm and the injection optics for the fibered system. It is designed to be left on a small cart. This device can potentially be brought to the bedside, and used during routine endoscopic check-up. Associated with the device, a complete framework has been elaborated in order to simplify the acquisition procedure as well as the signal processing. This results in a fully automated environment taking in charge hardware control, data storage and signal processing, up to the tri-dimensional scene rendering.