Mid-infrared photoacoustic brain imaging enabled by cascaded gas-filled hollow-core fiber lasers.

Abstract

Significance: Extending the photoacoustic microscopy (PAM) into the mid-infrared (MIR) molecular fingerprint region constitutes a promising route toward label-free imaging of biological molecular structures. Realizing this objective requires a high-energy nanosecond MIR laser source. However, existing MIR laser technologies are limited to either low pulse energy or free-space structure that is sensitive to environmental conditions. Fiber lasers are promising technologies for PAM for their potential to offer both high pulse energy and robust performance, which however have not yet been used for PAM because it is still at the infant research stage.

Aim: We aim to employ the emerging gas-filled anti-resonant hollow-core fiber (ARHCF) laser technology for MIR-PAM for the purpose of imaging myelin-rich regions in a mouse brain.

Approach: This laser source is developed with a high-pulse-energy nanosecond laser at $3.4\mu m$ , targeting the main absorption band of myelin sheaths, the primary chemical component of axons in the central nervous system. The laser mechanism relies on two-order gas-induced vibrational stimulated Raman scattering for non-linear wavelength conversion, starting from a 1060-nm pump laser to $3.4\mu m$ through the two-stage gas-filled ARHCFs.

Results: The developed fiber Raman laser was used for the first time for MIR-PAM of mouse brain regions containing structures rich in myelin. The high peak power of $\sim 1.38\mathrm{kW}$ and robust performance of the generated MIR Raman pulse addressed the challenge faced by the commonly used MIR lasers.

Conclusions: We pioneered the potential use of high-energy and nanosecond gas-filled ARHCF laser source to MIR-PAM, with a first attempt to report this kind of fiber laser source for PAM of lipid-rich myelin regions in a mouse brain. We also open up possibilities for expanding into a versatile multiwavelength laser source covering multiple biomarkers and being employed to image other materials such as plastics.