Chris Xu

Raman scattering underlies a broad range of spectroscopic and light-generation techniques, yet its conventional description, based on the Raman gain spectrum, accurately describes only long-pulse, steady-state dynamics. We employ a time-domain theoretical approach to account for spectrotemporal aspects of continuous frequency-shifting, which are not addressed by prior theories. In particular, molecules with strong Raman responses do not produce an efficient soliton self-frequency shift in gas-filled hollow-core fibers. The time-domain analysis exposes temporal and spectral distortions from the Raman response that impact frequency-shifting detrimentally, and identifies how these distortions can be suppressed by reducing the Raman interaction to a perturbation on the electronic response. Experiments that employ gas mixtures with tunable Raman fractions of the nonlinear response demonstrate up to a four-fold increase in quantum efficiency (from 20% to 80%) compared to the pure molecular gas, and unity-efficiency Raman shifting will be possible. The time-domain framework uncovers phenomena that are inaccessible through the frequency-domain treatment of Raman scattering, and it applies to Raman interactions in solids, liquids, and gases across Raman temporal regimes.

Multimodal microscopy combining various imaging approaches can provide complementary information about tissue in a single imaging session. Here, we demonstrate a multimodal approach combining three-photon microscopy (3PM) and spectral-domain optical coherence microscopy (SD-OCM). We show that an optical parametric amplifier (OPA) laser source, which is the standard source for three-photon (3P) fluorescence excitation and third harmonic generation (THG), can be used for simultaneous optical coherence microscopy (OCM), 3P fluorescence and THG imaging. We demonstrate the system performance in deep mouse brains in vivo with an OPA source operating at 1620 nm center wavelength. We visualized small structures such as myelinated axons, neurons, and large fiber tracts in white matter with high spatial resolution noninvasively using linear and nonlinear contrast mechanisms at depth exceeding 1 mm in the intact adult mouse brain. Our results show that simultaneous OCM and 3PM at the long wavelength window can be conveniently combined for deep tissue imaging in vivo.

High-resolution noninvasive imaging of neuronal activity at single-cell resolution deep within brain tissue is essential for understanding brain function and disease. Here we show that an improved 1300-nm three-photon microscope for maximal excitation and collection efficiency enables imaging up to the three-photon depth limit in the intact mouse brain. Our platform achieves structural imaging of brain vasculature at depths up to 2.5 mm and functional imaging of neural activities at depths up to 2 mm, reaching deep brain regions previously inaccessible by multiphoton imaging. These advances extend the frontier of deep-tissue functional imaging and open new possibilities for longitudinal and mechanistic studies in neuroscience and beyond.

The long-term recording of neural activity could be used to understand complex behaviours and disorders. However, the development of technology capable of such measurements faces a variety of technical challenges, including the relative motion between recording electrodes and tissue and the excessive displaced volume from implanted electronics. Here we report a subnanolitre-volume tetherless optoelectronic microsystem for neural recording. The system relies on light for photovoltaic power and data transfer, through a light-emitting diode, eliminating the need for wires or other tethers. It uses a single AlGaAs diode as both photovoltaic and light-emitting diode. Complementary metal–oxide–semiconductor circuits provide low-noise amplification, pulse-position-modulated encoding and electro-optical transduction. Two-dimensional materials processing techniques, vacuum annealing and atomic layer deposition, in conjunction with a standard complementary metal–oxide–semiconductor fabrication process, provide compact encapsulation against the corrosive conditions of biological media. We show that the subnanolitre neural implant is capable of chronic (365 days) in vivo recordings in awake mice.

We demonstrate efficient frequency down-conversion of femtosecond pulses based on the interplay of Raman-enhanced self-phase modulation and impulsive redshifting in N₂-filled anti-resonant hollow-core fiber. With 20 µJ and 140 fs pulses at 1030 nm launched into a short length of fiber, pulses with durations below 100 fs are generated between 1100 and 1300 nm, with over 26% efficiency and above 5 µJ energy, for peak powers between 50 and 100 MW. The modest experimental requirements and highly efficient conversion make this a practical source for wavelength-specific applications.

This errata corrects the funding information for this paper [ Biomed. Opt. Express 16 , 415 ( 2025 ) 10.1364/BOE.546888 ].

Understanding the brain requires understanding neurons’ functional responses to the circuit architecture shaping them. Here we introduce the MICrONS functional connectomics dataset with dense calcium imaging of around 75,000 neurons in primary visual cortex (VISp) and higher visual areas (VISrl, VISal and VISlm) in an awake mouse that is viewing natural and synthetic stimuli. These data are co-registered with an electron microscopy reconstruction containing more than 200,000 cells and 0.5 billion synapses. Proofreading of a subset of neurons yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections that map up to thousands of cell-to-cell connections per neuron. Released as an open-access resource, this dataset includes the tools for data retrieval and analysis^1,2. Accompanying studies describe its use for comprehensive characterization of cell types^3–6, a synaptic level connectivity diagram of a cortical column⁴, and uncovering cell-type-specific inhibitory connectivity that can be linked to gene expression data^4,7. Functionally, we identify new computational principles of how information is integrated across visual space⁸, characterize novel types of neuronal invariances⁹ and bring structure and function together to uncover a general principle for connectivity between excitatory neurons within and across areas^10,11.

Soliton formation and soliton self-frequency shift are investigated in a hollow-core fiber filled with N₂ gas. With 10-µJ and 80-fs input pulses at 1030 nm, solitons with greater than 500-nJ energy and duration less than 100 fs can be generated between 1090 and 1310 nm. With peak powers above 5 MW, we expect that these pulses will be useful for applications such as nonlinear microscopy.

Three-photon fluorescence microscopy (3PM) has driven rapid progress in deep-tissue imaging beyond the depth limit of two-photon microscopy, with impacts in neuroscience, immunology, and cancer biology. Three-photon excitation places a premium on ultrashort pulses with high peak power in the 1300- and 1700-nm wavelength bands, which allow deepest imaging. The inefficiency and cost of current sources of these pulses present major barriers to the use of 3PM in biomedical research labs. Fiber sources of such pulses could potentially alleviate these problems, but the peak-power limitations of optical fibers have limited their use in 3PM. Here, we describe a fiber-based source of femtosecond pulses with multi-megawatt peak power. Femtosecond pulses at 1030 nm are launched into an antiresonant hollow-core fiber filled with argon. By varying only the gas pressure, pulses with hundreds of nanojoules of energy and sub-100 fs duration are obtained at wavelengths between 850 and 1700 nm. This approach is a new route to an efficient and potentially low-cost source for deep-tissue imaging. In particular, 960-nJ and 50-fs pulses are generated at 1300 nm with a conversion efficiency of 10%. The nearly 20-MW peak power is an order of magnitude higher than the previous best from a femtosecond solid-core fiber source at 1300 nm. As an example of the capabilities of the source, these pulses are used to image structure and neuronal activity in a mouse brain as deep as 1.1 mm below the dura.

Optical imaging of neuronal voltage dynamics is invaluable to studying brain functions. However, high-speed imaging at significant depth is challenging due to the limitations of the short pixel dwell time and the maximum permissible excitation power in tissues. We report high-speed, deep voltage imaging by applying adaptive excitation, which illuminates the regions of interest only. We imaged neuronal voltage activities across two planes down to 500-630 μm depth in the awake mouse brain. Our techniques can be straightforwardly applied to typical two-photon microscopes.