# Flexible dual-duration multi-wavelength fiber sources for nonlinear and multimodal imaging

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2024 · $485,602

## Abstract

The goal of this research program is to develop robust and flexible dual-duration, multi-
wavelength fiber sources of light for nonlinear and multimodal imaging with orders of magnitude
signal enhancement over the state of the art. Nonlinear imaging enables label-free, deep, and
diffraction-limited imaging in living tissue through a variety of nonlinear interactions that are each
sensitive to specific molecules, symmetries, and structures, including two-photon excitation
fluorescence (2PEF), second- and third-harmonic generation (SHG and THG), and Raman-
sensitive techniques such as coherent anti-Raman scattering (CARS). Moreover, combining
these largely orthogonal modalities yields a rich combination of molecular, structural, and
functional information which has been demonstrated for diagnosing atherosclerosis, neurological
diseases, and cancer, including revealing new biomarkers and clinically relevant signatures
absent even from histologically processed tissue. However, each imaging modality requires
specific and incompatible pulse parameters that cannot be achieved with current ultrashort pulse
technology without sacrificing orders of magnitude in imaging signal strength. This proposal will
establish a new suite of technologies for ultra-short pulse generation that no longer rely on
traditional mode-locked laser-based systems. Building from recent proof-of-concept
demonstrations from the PIs, this research targets flexible and efficient fiber sources of inherently
synchronized multi-wavelength picosecond and femtosecond pulses specific for each nonlinear
imaging modality, with the ability to generate them simultaneously for multimodal imaging. The
research program is based on three Aims: (1) Developing diode-laser driven fiber time-lens
picosecond sources that are efficiently wavelength shifted with fiber parametric amplification for
flexible, multiwavelength picosecond sources; (2) Developing Kerr resonators for femtosecond
pulse generation with high efficiencies and the energy and wavelength flexibility ideal for nonlinear
imaging; and (3) Establishing dual-duration multi-wavelength sources adapted for background
suppressed CARS imaging and 2PEF, SHG, and THG, and demonstrating these sources for
multimodal imaging with unprecedented speeds and contrast using existing multiphoton
microscopes and a commercial microscope system to demonstrate the potential for widespread
adaptation. Our aim is to enable a significant advance for nonlinear and multimodal imaging
contrast and depth at real-time frame rates with a novel source that is low-cost and more
accessible than previous technologies. Successful completion of this program will have major
impact for biomedical research as well as clinical applications of ultrashort-pulse imaging.

## Key facts

- **NIH application ID:** 10944134
- **Project number:** 1R01GM155397-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** William Renninger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $485,602
- **Award type:** 1
- **Project period:** 2024-09-20 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944134

## Citation

> US National Institutes of Health, RePORTER application 10944134, Flexible dual-duration multi-wavelength fiber sources for nonlinear and multimodal imaging (1R01GM155397-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10944134. Licensed CC0.

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