Intravital Microscopy of the Beating Murine Heart to Understand Cardiac Leukocyte Dynamics.

Cardiovascular disease is the leading cause of worldwide mortality. Intravital microscopy has provided unprecedented insight into leukocyte biology by enabling the visualization of dynamic responses within living organ systems at the cell-scale. The heart presents a uniquely dynamic microenvironment driven by periodic, synchronous electrical conduction leading to rhythmic contractions of cardiomyocytes, and phasic coronary blood flow. In addition to functions shared throughout the body, immune cells have specific functions in the heart including tissue-resident macrophage-facilitated electrical conduction and rapid monocyte infiltration upon injury. Leukocyte responses to cardiac pathologies, including myocardial infarction and heart failure, have been well-studied using standard techniques, however, certain questions related to spatiotemporal relationships remain unanswered. Intravital imaging techniques could greatly benefit our understanding of the complexities of in vivo leukocyte behavior within cardiac tissue, but these techniques have been challenging to apply. Different approaches have been developed including high frame rate imaging of the beating heart, explantation models, micro-endoscopy, and mechanical stabilization coupled with various acquisition schemes to overcome challenges specific to the heart. The field of cardiac science has only begun to benefit from intravital microscopy techniques. The current focused review presents an overview of leukocyte responses in the heart, recent developments in intravital microscopy for the murine heart, and a discussion of future developments and applications for cardiovascular immunology.

Aberration-diverse optical coherence tomography for suppression of multiple scattering and speckle.

Multiple scattering is a major barrier that limits the optical imaging depth in scattering media. In order to alleviate this effect, we demonstrate aberration-diverse optical coherence tomography (AD-OCT), which exploits the phase correlation between the deterministic signals from single-scattered photons to suppress the random background caused by multiple scattering and speckle. AD-OCT illuminates the sample volume with diverse aberrated point spread functions, and computationally removes these intentionally applied aberrations. After accumulating 12 astigmatism-diverse OCT volumes, we show a 10 dB enhancement in signal-to-background ratio via a coherent average of reconstructed signals from a USAF target located 7.2 scattering mean free paths below a thick scattering layer, and a 3× speckle contrast reduction from an incoherent average of reconstructed signals inside the scattering layer. This AD-OCT method, when implemented using astigmatic illumination, is a promising approach for ultra-deep volumetric optical coherence microscopy.

Gigahertz frequency comb offset stabilization based on supercontinuum generation in silicon nitride waveguides.

Silicon nitride (Si3N4) waveguides represent a novel photonic platform that is ideally suited for energy efficient and ultrabroadband nonlinear interactions from the visible to the mid-infrared. Chip-based supercontinuum generation in Si3N4 offers a path towards a fully-integrated and highly compact comb source for sensing and time-and-frequency metrology applications. We demonstrate the first successful frequency comb offset stabilization that utilizes a Si3N4 waveguide for octave-spanning supercontinuum generation and achieve the lowest integrated residual phase noise of any diode-pumped gigahertz laser comb to date. In addition, we perform a direct comparison to a standard silica photonic crystal fiber (PCF) using the same ultrafast solid-state laser oscillator operating at 1 µm. We identify the minimal role of Raman scattering in Si3N4 as a key benefit that allows to overcome the fundamental limitations of silica fibers set by Raman-induced self-frequency shift.

Broadband mid-infrared frequency comb generation in a Si(3)N(4) microresonator.

We demonstrate broadband frequency comb generation in the mid-infrared (MIR) from 2.3 to 3.5 µm in a Si(3)N(4) microresonator. We engineer the dispersion of the structure in the MIR using a Sellmeier equation we derive from experimental measurements performed on Si(3)N(4) films from the UV to the IR. We use deposition-anneal cycling to decrease absorption losses due to vibrational transitions in the MIR and achieve a Q-factor of 1.0×10(6). To our knowledge, this is the highest Q reported in this wavelength range for any on-chip resonator.

Octave-spanning coherent supercontinuum generation in a silicon nitride waveguide.

We demonstrate the generation of a supercontinuum spanning more than 1.4 octaves in a silicon nitride waveguide using sub-100-fs pulses at 1 µm generated by either a 53-MHz, diode-pumped ytterbium (Yb) fiber laser or a 1-GHz, Yb:CaAlGdO(4) (Yb:CALGO) laser. Our numerical simulations show that the broadband supercontinuum is fully coherent, and a spectral interference measurement is used to verify that the supercontinuum generated with the Yb:CALGO laser possesses a high degree of coherence over the majority of its spectral bandwidth. This coherent spectrum may be utilized for optical coherence tomography, spectroscopy, and frequency metrology.

Effects of multiphoton absorption on parametric comb generation in silicon microresonators.

We investigate theoretically the parametric frequency comb generation in silicon microresonators at telecom and mid-infrared (MIR) wavelengths in the presence of multiphoton absorption and free-carrier effects using a modified Lugiato-Lefever model. We show that parametric oscillation may occur at MIR wavelengths, provided that the free-carrier lifetime is sufficiently short or the optical pump power is sufficiently low, but is inhibited at telecom wavelengths. In addition, we propose an etchless, air-clad silicon microresonator that enables an octave-spanning frequency comb in a completely passive device.

Octave-spanning mid-infrared supercontinuum generation in silicon nanowaveguides.

We report, to the best of our knowledge, the first demonstration of octave-spanning supercontinuum generation (SCG) on a silicon chip, spanning from the telecommunications c-band near 1.5 µm to the mid-infrared region beyond 3.6 µm. The SCG presented here is characterized by soliton fission and dispersive radiation across two zero group-velocity dispersion wavelengths. In addition, we numerically investigate the role of multiphoton absorption and free carriers, confirming that these nonlinear loss mechanisms are not detrimental to SCG in this regime.

Strong polarization mode coupling in microresonators.

We observe strong modal coupling between the TE00 and TM00 modes in Si3N4 ring resonators revealed by avoided crossings of the corresponding resonances. Such couplings result in significant shifts of the resonance frequencies over a wide range around the crossing points. This leads to an effective dispersion that is one order of magnitude larger than the intrinsic dispersion and creates broad windows of anomalous dispersion. We also observe the changes to frequency comb spectra generated in Si3N4 microresonators due to polarization mode and higher-order mode crossings and suggest approaches to avoid these effects. Alternatively, such polarization mode crossings can be used as a tool for dispersion engineering in microresonators.

Bandwidth shaping of microresonator-based frequency combs via dispersion engineering.

We investigate experimentally and theoretically the role of group-velocity dispersion and higher-order dispersion on the bandwidth of microresonator-based parametric frequency combs. We show that the comb bandwidth and the power contained in the comb can be tailored for a particular application. Additionally, our results demonstrate that fourth-order dispersion plays a critical role in determining the spectral bandwidth for comb bandwidths on the order of an octave.

Microresonator-based comb generation without an external laser source.

We demonstrate a fiber-microresonator dual-cavity architecture with which we generate 880 nm of comb bandwidth without the need for a continuous-wave pump laser. Comb generation with this pumping scheme is greatly simplified as compared to pumping with a single frequency laser, and the generated combs are inherently robust due to the intrinsic feedback mechanism. Temporal and radio frequency (RF) characterization show a regime of steady comb formation that operates with reduced RF amplitude noise. The dual-cavity design is capable of being integrated on-chip and offers the potential of a turn-key broadband multiple wavelength source.

Route to stabilized ultrabroadband microresonator-based frequency combs.

We perform the first theoretical modeling of the full spectral-temporal dynamics of octave-spanning parametric microresonator comb generation through use of the Lugiato-Lefever model extended to include higher-order dispersion and self-steepening. We show that three distinct stages are necessary to achieve single-pulse modelocking and discuss the dispersion characteristics required for ultrabroadband, stabilized comb generation. Our simulations agree well with previous experimental demonstrations and predict many of the observed features, including multipulse generation, dispersive wave generation, modelocking, and comb stabilization.

Modelocking and femtosecond pulse generation in chip-based frequency combs.

We investigate simultaneously the temporal and optical and radio-frequency spectral properties of parametric frequency combs generated in silicon-nitride microresonators and observe that the system undergoes a transition to a mode-locked state. We demonstrate the generation of sub-200-fs pulses at a repetition rate of 99 GHz. Our calculations show that pulse generation in this system is consistent with soliton modelocking. Ultimately, such parametric devices offer the potential of producing ultra-short laser pulses from the visible to mid-infrared regime at repetition rates from GHz to THz.

Supercontinuum generation in a high index doped silica glass spiral waveguide.

We demonstrate supercontinuum (SC) generation at both 1550 nm and 1288 nm in a compact (< 5mm(2)) 45 cm spiral waveguide composed of CMOS-compatible doped high-index glass. While both wavelengths have weak dispersion and are near zero dispersion points, they present different symmetries. At 1550 nm, the normal dispersion regime takes place at longer wavelengths, whereas at 1290 nm it is at shorter wavelengths, and we observe features in the SC spectra that clearly reflect this. In particular, the spectrum at 1550 nm is more than 300 nm wide (limited by detection) and is well reproduced by simulations based on the measured dispersion. This work represents a practical on-chip broadband wavelength source with potential use in many important applications.

Dispersion engineered As(2)S(3) planar waveguides for broadband four-wave mixing based wavelength conversion of 40 Gb/s signals.

We demonstrate broadband wavelength conversion of a 40 Gb/s return-to-zero signal using four-wave-mixing (FWM) in a dispersion engineered chalcogenide glass waveguide. The 6 cm long planar rib waveguide 2 mum wide was fabricated in a 0.87 mum thick film etched 350nm deep to correspond to a design where waveguide dispersion offsets the material leading to near-zero dispersion in the C-band and broadband phase matched FWM. The reduced dimensions also enhance the nonlinear coefficient to 9800 W(-1)km(-1) at 1550 nm enabling broadband conversion in a shorter device. In this work, we demonstrate 80 nm wavelength conversions with 1.65 dB of power penalty at a bit-error rate of 10(-9). Spectral measurements and simulations indicate extended broadband operation is possible.

Net-gain from a parametric amplifier on a chalcogenide optical chip.

We report first observation of net-gain from an optical parametric amplifier in a planar waveguide. This was achieved in a low-loss As(2)S(3) planar waveguide, with a strong nonlinearity (gamma approximately 10 /W/m) and tailored anomalous dispersion yielding efficient Raman-assisted four-wave mixing at telecom wavelengths. The experiments were in good agreement with theory, and indicate a peak net-gain greater than +16 dB for the signal and idler (+30 dB neglecting coupling losses) and a broad bandwidth spanning 180 nm.

Low-threshold supercontinuum generation in highly nonlinear chalcogenide nanowires.

We demonstrate low-threshold supercontinuum generated in a highly nonlinear arsenic selenide chalcogenide nanowire with tailored dispersion. The tapered submicrometer chalcogenide fiber exhibits an ultrahigh nonlinearity, n(2) approximately 1.1x10(-17) m(2)/W and an effective mode area of 0.48 mum(2), yielding an effective nonlinearity of gamma approximately 93.4 W/m, which is over 80,000 times larger than standard silica single-mode fiber at a wavelength of approximately 1550 nm. This high nonlinearity, in conjunction with the engineered anomalous dispersion, enables low-threshold soliton fission leading to large spectral broadening at a dramatically reduced peak power of several watts, corresponding to picojoule energy.

Ultrafast all-optical chalcogenide glass photonic circuits.

Focus Serial: Frontiers of Nonlinear Optics

2R optical regenerator in As2Se3 chalcogenide fiber characterized by a frequency-resolved optical gating analysis.

We present a detailed analysis of a 2R optical regenerator based on self-phase modulation in As(2)Se(3) chalcogenide glass fiber using frequency-resolved optical gating (FROG). We obtain good agreement between the FROG measurements and theory, and confirm that the output pulses are near-transform limited. We show that two-photon absorption improves the profile of the power transfer function while not degrading the temporal performance.

All optical wavelength conversion via cross phase modulation in chalcogenide glass rib waveguides.

We demonstrate all-optical wavelength conversion in a 5 cm As(2)S(3) chalcogenide glass rib waveguide with 5.4 ps pulses over a wavelength range of 10 nm near 1550 nm. We present frequency resolved optical gating (FROG) measurements that show good converted pulse integrity in terms of amplitude and phase in the frequency and time domains. The short interaction length ensures that dispersion induced walk-off does not hinder the conversion range of the device.