open access publication

Preprint, 2024

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

bioRxiv, Page 2024.04.02.587715, 10.1101/2024.04.02.587715

Contributors

Zhang, Cuiling [1] Sui, Kunyang [1] [2] Meneghetti, Marcello 0000-0002-9621-442X [1] [2] Antonio-Lopez, Jose Enrique [3] Dasa, Manoj Kumar 0000-0001-7601-0617 [4] Berg, Rune Willestofte 0000-0001-6376-9368 [2] Amezcua-Correa, Rodrigo [3] Wang, Yazhou [1] Markos, Christos 0000-0002-9989-5275 (Corresponding author) [1] [5]

Affiliations

  1. [1] Technical University of Denmark
  2. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  3. [2] University of Copenhagen
  4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  5. [3] University of Central Florida
  6. [NORA names: United States; America, North; OECD];
  7. [4] NKT Holding (Denmark)
  8. [NORA names: NKT Holding; Private Research; Denmark; Europe, EU; Nordic; OECD];
  9. [5] NORBLIS ApS, Virumgade 35D, 2830 Virum, Denmark
  10. [NORA names: Denmark; Europe, EU; Nordic; OECD]

Abstract

Abstract Significance Extending the photoacoustic microscopy (PAM) into the mid-infrared (MIR) molecular fingerprint region constitutes a promising route towards label-free imaging of biological molecular structures. Realizing this objective requires a high-energy nano-second MIR laser source. However, existing MIR laser technologies are limited to either low pulse energy or free-space structure which is sensitive to environmental conditions. Fiber lasers are promising technologies for PAM for their potential of offering both high pulse energy and robust performance against environmental conditions. However, MIR high energy fiber laser has 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 ∼2.75 μJ high-pulse-energy nano-second laser at 3.4 μm, 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-orders gas-induced vibrational stimulated Raman scattering (SRS) for nonlinear wavelength conversion, starting from a 1060 nm pump laser to 1409 nm through the 1 st order Stokes generation in the nitrogen-filled 1 st stage ARHCF, then, from 1409 nm to 3.4 μm through the 2 nd stage hydrogen-filled ARHCF. Results The developed Raman laser was used for the first time for transmission-mode MIR-PAM of mouse brain regions containing rich myelin structures. Conclusions This work pioneers the potential use of high-energy and nano-second 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. The proposed ARHCF laser technology is also expected to generate high-energy pulses at the ultraviolet (UV) region, which can significantly improve the lateral resolution of the PAM.

Keywords

Abstract, Mid-infrared laser technology, Raman laser, Raman scattering, SRS, Stokes, Stokes generation, absorption, absorption bands, anti-resonant hollow-core fiber, axons, band, biological molecular structures, brain, brain imaging, brain regions, central nervous system, chemical components, components, conditions, conversion, energy, environmental conditions, fiber laser, fiber laser source, fibers, fingerprint region, free-space, free-space structuring, gas-filled anti-resonant hollow-core fiber, generation, high energy, high pulse energy, high-energy fiber lasers, high-energy pulses, hollow-core fiber, images, label-free imaging, laser, laser mechanism, laser source, laser technology, lateral resolution, low pulse energy, mechanism, mice, microscopy, mid-infrared, molecular fingerprint region, molecular structure, mouse brain, mouse brain regions, myelin, myelin sheath, myelin structure, myelin-rich regions, myelinated regions, nano-second laser, nervous system, nonlinear wavelength conversion, performance, photoacoustic brain imaging, photoacoustic microscopy, potential, potential use, primary chemical components, pulse, pulse energy, region, research stage, resolution, robust performance, scattering, sensitive to environmental conditions, sheath, significance, source, stage, structure, system, technology, ultraviolet, ultraviolet (UV) region, use, wavelength conversion

Funders

  • Lundbeck (Denmark)
  • The Velux Foundations
  • United States Army Research Office

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