Multiphoton interactions with transparent tissues [electronic resource] : applications to imaging and surgery
Keywords: Applied Physics

Ultrafast lasers offer an advantage of highly localized interactions with transparent materials due to non-linearity of multiphoton processes with laser intensity. Biological and medical applications of these interactions can be nominally divided into two classes: (1) diagnostic imaging and spectroscopy and (2) plasma-mediated surgery. Imaging techniques, such as multiphoton fluorescence, harmonic generation, and stimulated Raman scattering typically employ relatively low power laser sources to avoid damage to the specimens. Surgical applications, on the other hand, rely on formation of plasma at the focus of high peak power laser beam. Current paradigm in applications of multiphoton interactions is based on scanning of a focused beam within the sample in order to image extended areas or produce long cuts point-by-point. We demonstrate several optical systems based on a new paradigm -- distributed multiphoton interactions, where the scanning is reduced or even not required at all. In the area of diagnostic imaging, we have developed and successfully tested a wide-field Coherent Anti-Stokes Raman Scattering (CARS) microscopy technique, which is based on simultaneous imaging of the extended area of the sample. The signal generation relies on the non-phase-matching illumination, and the image acquisition is performed from the entire illuminated area without scanning, using an array detector. We have characterized the spatial and spectral resolution of the method, and demonstrated its chemical selectivity. Optimization of the illumination geometry and proper selection of the wavelengths of the pump and Stokes beams allowed acquisition of the myelin-specific images of nerve tissue with diffraction-limited spatial resolution of 0.5[mu]m. Single-shot imaging capability has been demonstrated on a test sample of polystyrene beads. In surgical applications of ultrafast lasers the extent of the rupture zone in tissue is often determined by dynamics of cavitation bubble resulting from the optical breakdown. Typically tissue cutting is performed point-by-point using a scanning laser. We have studied the possibilities of enhancing the cutting efficiency using two methods. First approach is based on hydrodynamic interactions between two simultaneously created bubbles. A theoretical model of the flow induced by the cavitation bubbles was developed and experimentally verified. Based on experimentally measured rupture threshold strain of a material we derived the shape of the rupture zone for a given distance between the focal spots. We have found that for the threshold strain of 0.7, a continuous cut is 1.35 longer than the one produced by two bubbles applied sequentially. This ratio increases up to 1.7 if a linear series of multiple bubbles is applied simultaneously. Counter-propagating liquid jets forming during collapse of two bubbles in inviscid liquid can increase the rupture zone up to a factor of 2.5. Alternative approach to extending the cutting zone in transparent tissue is based on generation of optical breakdown in a highly elongated zone. By focusing a picosecond laser pulse with a combination of a lens and an axicon we have obtained breakdown zone with aspect ratio of 250:1. The axial intensity distribution was analyzed based on the shape of the resulting cavitation bubble, and was further confirmed by numerical evaluation of a Fresnel diffraction integral. We have optimized the incident laser beam profile to obtain uniform intensity along the breakdown region and to minimize the amount of energy deposited into the sample. We also demonstrate dielectric breakdown and associated cavitation with adjustable length and axial position controlled by modulation of the laser beam profile using an amplitude mask.