High-power fiber lasers for contrast-enhanced photoacoustic microscopy at longer near-infrared band

Abstract

In demand of label-free deep-tissue imaging for clinical and diagnostic applications, photoacoustic imaging (PAI) emerges as a promising hybrid tool combining high optical contrast with relatively low acoustic attenuation. Typically, PAI at the longer near-infrared window (1700nm-2000nm) has intrinsic advantages in penetration depth due to the diminished tissue scattering, minimal tissue absorption, and high maximum laser fluence permissible. In addition, plenty of chemical bonds, i.e., C-H and O-H bonds, commonly existing in biological samples, have molecular overtone bands at this region. Based on these molecular overtone transitions, PAI can identify specific chemical bonds in a label-free manner. Therefore, PAI at this band has been developed to many modalities for a wealth of applications in spectroscopy, microscopy, tomography, and endoscopy by tremendous global efforts. However, the inferior pulse stability of the solid-state laser and the strong water absorption at this band in the bio-tissue impactfully injures the image contrast. It motivates the creation of a robust high-power laser with a contrast-enhancing approach.

Tackling these challenges, this thesis aims to develop a high-power fiber laser for contrast-enhanced photoacoustic imaging at the longer near-infrared band. This target is achieved from two aspects: (1) exploring different fiber laser techniques to exploit an optimal excitation source; (2) developing nonlinear illumination models:

(1) Four high-power fiber lasers empowered by gain-switching technique and fiber optical parametric oscillator (FOPO) are constructed to exploit the optimal excitation source. Two are gain-switched fiber lasers, and the rest of the two are FOPO-based ones. The first gain-switched laser is an actively gain-switched thulium-doped fiber laser (TDFL) tunable from 1690nm to 1760nm. Optical-resolution photoacoustic microscopy (OR-PAM) is developed with tens of microns lateral resolution. The obtained microscopic images indicate the source’s advantage of spectroscopic imaging on various lipid-rich samples. However, its broad pulse duration confines efficient photoacoustic signal generation and 3-D imaging. As a result, a passively gain-switched TDFL switchable at 1700/1725/1750 nm realizes tens of micron-joule pulse energy and 16.7ns pulse width. It perfectly meets all of the requirements and demonstrates volumetric imaging of the lipid content in beef tissue. The first FOPO-based laser is a thulium-assisted optical parametric oscillator (TAOPO) tunable from 1700nm to 1750nm with 2-ns pulse width. The superior spectral tunability and temporal stability, together with a high pulse rate, indicate its potential for high-contrast OR-PAM, but the insufficient pulse energy still prevents it from imaging biological tissue. Lastly, with a similar principle, a hybrid fiber optical parametrically-oscillating emitter at 1930nm is built successfully with micro-joule pulse energy to accommodate the OR-PAM system to O-H bond imaging.

(2) Two nonlinear OR-PAM systems are developed in this thesis for contrast-enhanced imaging. Both of them are investigated with the TDFL at 1.7µm. Firstly, Grüneisen-relaxation photoacoustic microscopy (GR-PAM) yields an 8.26-fold contrast enhancement by converting linear pressure function to a quadratic one. Secondly, double-illumination photoacoustic microscopy (DIOR-PAM) successfully achieves a sensitivity enhancement by a factor of 1.89 on adipose tissue, which shows a satisfactory agreement with the theoretical estimated contrast-enhanced factor 1.74 given by the photon transport Monte Carlo simulation.