O. I. Ivashkina

Tailoring the soliton output of a photonic crystal fiber for enhanced two-photon excited luminescence response from fluorescent protein biomarkers and neuron activity reporters

Dual-cladding photonic crystal fibers (PCFs) with two zero-dispersion points are used to enhance the two-photon excited luminescence (TPL) response from fluorescent protein biomarkers and neuron activity reporters in dye-cell experiments and in in vivo work on transgenic mice and tadpoles. The soliton transmission of ultrashort pulses through a PCF suppresses dispersion-induced temporal pulse spreading, maintaining a high level of field intensity needed for efficient TPL excitation. The soliton self-frequency shift, stabilized against laser power fluctuations by a specific PCF dispersion design, is employed to accurately match the wavelength of the soliton PCF output with the two-photon absorption spectrum of dye or fluorescent protein biomarker molecules, enhancing their TPL response and allowing the laser damage of biotissues to be avoided.

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli.

Photonic-crystal-fiber platform for multicolor multilabel neurophotonic studies

A supercontinuum source based on a highly nonlinear photonic-crystal fiber (PCF) is combined with a hollow-core photonic-band-gap fiber (PBGF) spectral filter for a multiplex, high-repetition-rate fiber-based interrogation of fluorescent-protein neuron-activity reporters, and fluorophore conjugate antibody labels in the brain of transgenic mice. The hollow PBGF selects those parts of the supercontinuum output of the highly nonlinear PCF that can efficiently excite the fluorescence of the biomarkers but supports no guidance within the bands, where the supercontinuum light scattered by the brain tissues could hinder the detection of the fluorescence response of the biomarkers, thus allowing a high-contrast detection of well-resolved responses from each type of biomarkers.

Ionization penalty in nonlinear Raman neuroimaging.

Light-assisted ionization accompanying coherent anti-Stokes Raman scattering (CARS) of ultrashort laser pulses in brain tissue is shown to manifest itself in a detectable blueshift of the anti-Stokes signal. This blueshift can serve as an indicator of ionization processes in CARS-based neuroimaging.

Air-guided photonic-crystal-fiber pulse-compression delivery of multimegawatt femtosecond laser output for nonlinear-optical imaging and neurosurgery

Large-core hollow photonic-crystal fibers (PCFs) are shown to enable a fiber-format air-guided delivery of ultrashort infrared laser pulses for neurosurgery and nonlinear-optical imaging. With an appropriate dispersion precompensation, an anomalously dispersive 15-lm-core hollow PCF compresses 510-fs, 1070-nm light pulses to a pulse width of about 110 fs, providing a peak power in excess of 5MW. The compressed PCF output is employed to induce a local photodisruption of corpus callosum tissues in mouse brain and is used to generate the third harmonic in brain tissues, which is captured by the PCF and delivered to a detector through the PCF cladding. V C 2012 American Institute of Physics. [doi:10.1063/1.3681777]

Two‐photon imaging of fiber‐coupled neurons

Optical coupling between a single, individually addressable neuron and a properly designed optical fiber is demonstrated. Two-photon imaging is shown to enable a quantitative in situ analysis of such fiber-single-neuron coupling in the live brain of transgenic mice. Fiber-optic interrogation of single pyramidal neurons in mouse brain cortex is performed with the positioning of the fiber probe relative to the neuron accurately mapped by means of two-photon imaging. These results pave the way for fiber-optic interfaces to single neurons for a stimulation and interrogation of individually addressable brain cells in chronic in vivo studies on freely behaving transgenic animal models, as well as the integration of fiber-optic single-neuron stimulation into the optical imaging framework.

Nonlinear-optical brain anatomy by harmonic-generation and coherent Raman microscopy on a compact femtosecond laser platform

An extended-cavity Cr:forsterite laser is integrated with a photonic-crystal fiber soliton frequency shifter and a periodically poled lithium niobate spectrum compressor for simultaneous harmonic-generation and coherent Raman brain imaging. Adapting the laser beam focusing geometry to the tissue morphology is shown to enable complementarity enhancement in tissue imaging by second- and third-harmonic generation, as well as coherent Raman scattering, facilitating quantitative image analysis.

Fiber-optic probes for in vivo depth-resolved neuron-activity mapping

Specialty fiber probes are used for in vivo depth-resolved mapping of neuron activity through the optical detection of fluorescent-protein reporters expressed inside the living brain of anesthetized transgenic mice. Supercontinuum radiation produced by highly nonlinear photonic-crystal fibers is employed to demonstrate a simultaneous multicolor interrogation of several biomarkers in a model aqueous solution system, thus suggesting the way toward a multiplex mapping of various types of neuron dynamics inside the living brain.

Enhancing the locality of optical interrogation with photonic-crystal fibers

Small-core photonic-crystal fibers (PCFs) are shown to enhance the locality of optical interrogation in fiber-probe-based imaging. We demonstrate that, in a typical fluorescence imaging experiment, the longitudinal dimension of the interrogated region closely follows the amtan−1θd scaling with the effective mode radius am and the beam-divergence angle θd. The confinement of optical interrogation provided by small-core, high-index-step PCF probes is high enough to enable interrogation of individual neurons in a typical brain imaging experiment.

Fiber-optic Raman sensing of cell proliferation probes and molecular vibrations: Brain-imaging perspective

Optical fibers are employed to sense fingerprint molecular vibrations in ex vivo experiments on the whole brain and detect cell proliferation probes in a model study on a quantitatively controlled solution. A specifically adapted spectral filtering procedure is shown to allow the Raman signal from molecular vibrations of interest to be discriminated against the background from the fiber, allowing a highly sensitive Raman detection of the recently demonstrated EdU (5-ethynyl-2′-deoxyuridine) labels of DNA synthesis in cells.