Coherent Raman spectro-imaging with laser frequency combs

Optical spectroscopy and imaging of microscopic samples have opened up a wide range of applications throughout the physical, chemical, and biological sciences. High chemical specificity may be achieved by directly interrogating the fundamental or low-lying vibrational energy levels of the compound molecules. Amongst the available prevailing label-free techniques, coherent Raman scattering has the distinguishing features of high spatial resolution down to 200 nm and three-dimensional sectioning. However, combining fast imaging speed and identification of multiple - and possibly unexpected- compounds remains challenging: existing high spectral resolution schemes require long measurement times to achieve broad spectral spans. Here we overcome this difficulty and introduce a novel concept of coherent anti-Stokes Raman scattering (CARS) spectro-imaging with two laser frequency combs. We illustrate the power of our technique with high resolution (4 cm-1) Raman spectra spanning more than 1200 cm-1 recorded within less than 15 microseconds. Furthermore, hyperspectral images combining high spectral (10 cm-1) and spatial (2 micrometers) resolutions are acquired at a rate of 50 pixels per second. Real-time multiplex accessing of hyperspectral images may dramatically expand the range of applications of nonlinear microscopy.Comment: 8 pages, 3 figure

Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features

Cavity-enhanced dual-comb spectroscopy

The sensitivity of molecular fingerprinting is dramatically improved when placing the absorbing sample in a high-finesse optical cavity, thanks to the large increase of the effective path-length. As demonstrated recently, when the equidistant lines from a laser frequency comb are simultaneously injected into the cavity over a large spectral range, multiple trace-gases may be identified within a few milliseconds. Analyzing efficiently the light transmitted through the cavity however still remains challenging. Here, a novel approach, cavity-enhanced frequency comb Fourier transform spectroscopy, fully overcomes this difficulty and measures ultrasensitive, broad-bandwidth, high-resolution spectra within a few tens of µs. It could be implemented from the Terahertz to the ultraviolet regions without any need for detector arrays. We recorded, within 18 µs, spectra of the 1.0 µm overtone bands of ammonia spanning 20 nm with 4.5 GHz resolution and a noise-equivalent-absorption at one-second-averaging per spectral element of 3 10^-12 cm^-1Hz^-1/2, thus opening a route to time-resolved spectroscopy of rapidly-evolving single-events

BROADBAND SPECTROSCOPY WITH DUAL COMBS AND CAVITY ENHANCEMENT

Author Institution: Max-Planck-Institute for Quantum Optics, 81748 Garching, Germany and Menlo Systems GmbH, 82152 Martinsried, Germany; Max-Planck-Institute for Quantum Optics, 81748 Garching, Germany; Laboratoire de Photophysique Moleculaire, CNRS, Batiment 350, Universite Paris-Sud, 91405 Orsay, France; Institute for Solid State Physics, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8581, Japan; Max-Planck-Institute for Quantum Optics, 81748 Garching, Germany and Laboratoire de Photophysique Moleculaire, CNRS, Batiment 350, Universite Paris-Sud, 91405 Orsay, FranceClassical FTIRs handle the task of massively parallel spectroscopic probing by interferometric detection. In contrast a frequency comb Fourier transform spectrometer (FC-FTS) retains the principle of combining two interferometer beams but uses two inputs from two independent sources. Thus we can offset their frequencies to facilitate multifrequency heterodyne signal processing. The advantages of this spectrometer compared with the classical FTIR include ease of operation (no cumbersome moving delay lines), speed of acquisition (18 $\mu$s demonstrated), collimated long-distance propagation, possibly diffraction-limited microscopic probing, and mid infrared as well as THz operation if necessary. In a recent proof of principle experiment we have dramatically improved the sensitivity by the implementation of an enhancement cavity around the probing volume nderline{\textbf{4}} (55), January 2010}. We recorded, within 18 $\mu$s, spectra of the ammonia 1.0 $\mu$m overtone bands comprising 1500 spectral elements and spanning 20 nm with 4.5 GHz resolution and a noise-equivalent-absorption at one-second-averaging of 1 $10^{-10}$cm$^{-1}$Hz$^{-1/2}$, thus opening a route to time-resolved spectroscopy of rapidly-evolving single-events. Since FC-FTS only needs one detector that is easily available in practically all spectral regions, it can be envisioned that cavity-enhanced FC-FTS will assume a position of dominance for the measurements of real-time ultra-sensitive spectra in the molecular fingerprint region

Power scaling of a high-repetition-rate enhancement cavity

A passive optical resonator is used to enhance the power of a pulsed 78MHz repetition rate Yb laser providing 200fs pulses. We find limitations relating to the achievable time-averaged and peak power, which we distinguish by varying the duration of the input pulses. An intracavity average power of 18kW is generated with close to Fourier-limited pulses of 10W average power. Beyond this power level, intensity-related effects lead to resonator instabilities, which can be removed by chirping the seed laser pulses. By extending the pulse duration in this way to 2ps, we could obtain 72kW of intracavity circulating power with 50W of input power