Active phase-nulling of the self-mixing phase in a terahertz frequency quantum cascade laser

We demonstrate an active phase-nulling scheme for terahertz (THz) frequency quantum cascade lasers (QCLs) under optical feedback, by active electronic feedback control of the emission frequency. Using this scheme the frequency tuning rate of a THz QCL is characterised, with significantly reduced experimental complexity compared to alternative approaches. Furthermore, we demonstrate real-time displacement sensing of targets, overcoming the resolution limits imposed by quantisation in previously-implemented fringe counting methods. Our approach is readily applicable to high-frequency vibrometry and surface profiling of targets, as well as frequency-stabilisation schemes for THz QCLs

A model for a pulsed terahertz quantum cascade laser under optical feedback

Optical feedback effects in lasers may be useful or problematic, depending on the type of application. When semiconductor lasers are operated using pulsed-mode excitation, their behavior under optical feedback depends on the electronic and thermal characteristics of the laser, as well as the nature of the external cavity. Predicting the behavior of a laser under both optical feedback and pulsed operation therefore requires a detailed model that includes laser-specific thermal and electronic characteristics. In this paper we introduce such a model for an exemplar bound-to-continuum terahertz frequency quantum cascade laser (QCL), illustrating its use in a selection of pulsed operation scenarios. Our results demonstrate significant interplay between electro-optical, thermal, and feedback phenomena, and that this interplay is key to understanding QCL behavior in pulsed applications. Further, our results suggest that for many types of QCL in interferometric applications, thermal modulation via low duty cycle pulsed operation would be an alternative to commonly used adiabatic modulation

Terahertz Radar Cross Section Characterization using Laser Feedback Interferometry with a Quantum Cascade Laser

Radar cross section (RCS) measurements of complex, large objects are usually performed on scale models so that the measurement is carried out in a well-controlled environment. This letter explores the feasibility of RCS measurement using a terahertz quantum cascade laser via laser feedback interferometry. Numerical simulations show that the RCS information embedded in the non-linear interferometric signals obtained from simple targets can be retrieved through numerical fitting of the well-known excess phase equation. The method is validated experimentally using a terahertz quantum cascade laser and the results are well matched with those obtained from numerical simulations

Multi-spectral terahertz sensing: proposal for a coupled-cavity quantum cascade laser based optical feedback interferometer

We propose a laser feedback interferometer operating at multiple terahertz (THz) frequency bands by using a pulsed coupled-cavity THz quantum cascade laser (QCL) under optical feedback. A theoretical model that contains multi-mode reduced rate equations and thermal equations is presented, which captures the interplay between electro-optical, thermal, and feedback effects. By using the self-heating effect in both active and passive cavities, self-mixing signal responses at three different THz frequency bands are predicted. A multi-spectral laser feedback interferometry system based on such a coupled-cavity THz QCL will permit ultra-high-speed sensing and spectroscopic applications including material identification

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

Coherent imaging using laser feedback interferometry with pulsed-mode terahertz quantum cascade lasers

We report a coherent terahertz (THz) imaging system that utilises a quantum cascade laser (QCL) operating in pulsed-mode as both the source and detector. The realisation of a short-pulsed THz QCL feedback interferometer permits both high peak powers and improved thermal efficiency, which enables the cryogen-free operation of the system. In this work, we demonstrated pulsed-mode swept-frequency laser feedback interferometry experimentally. Our interferometric detection scheme not only permits the simultaneous creation of both amplitude and phase images, but inherently suppresses unwanted background radiation. We demonstrate that the proposed system utilising microsecond pulses has the potential to achieve 0.25 mega-pixel per second acquisition rates, paving the pathway to video frame rate THz imaging

Quantum cascade laser based hybrid dual comb spectrometer

Four-wave-mixing-based quantum cascade laser frequency combs (QCL-FC) are a powerful photonic tool, driving a recent revolution in major molecular fingerprint regions, i.e. mid- and far-infrared domains. Their compact and frequency-agile design, together with their high optical power and spectral purity, promise to deliver an all-in-one source for the most challenging spectroscopic applications. Here, we demonstrate a metrological-grade hybrid dual comb spectrometer, combining the advantages of a THz QCL-FC with the accuracy and absolute frequency referencing provided by a free-standing, optically-rectified THz frequency comb. A proof-of-principle application to methanol molecular transitions is presented. The multi-heterodyne molecular spectra retrieved provide state-of-the-art results in line-center determination, achieving the same precision as currently available molecular databases. The devised setup provides a solid platform for a new generation of THz spectrometers, paving the way to more refined and sophisticated systems exploiting full phase control of QCL-FCs, or Doppler-free spectroscopic schemes