Diffuse optics often results in ill-posed inverse problems. Here we investigate a time-of-flight (TOF) informed interferometric diffuse optical approach, which applies a series of TOF filters to multiply scattered light collected via the human head. Rather than 1D data sets which are typical of diffuse optics, we obtain a 2D data set at a single source-collector separation, where the dimensions are TOF filter width and correlation time lag. We investigate recovery of optical properties, layer thicknesses, and blood flow indices by fitting a 3-layer model of the human head. We recover reasonable brain-to-scalp blood flow index ratios.
Diffuse correlation spectroscopy is a widely used optical technique for recovery of blood flow. Its applications have included monitoring of ischemia, blood flow in tumors, and cerebral blood flow. Recently, several variants on this technology have been developed with potential to enhance sensitivity to deep tissues, increase signal-to-noise ratio, and lower costs. Here, we employ diffuse correlation spectroscopy, speckle contrast optical spectroscopy, and interferometric diffusing wave spectroscopy concurrently to measure in vivo and in vitro flow. The results elucidate the advantages and disadvantages of each modality and will aid researchers in selecting a blood flow monitoring method for specific applications.
Interferometric DOS (iDOS) is a new class of approaches that promises to improve the quantitative accuracy and depth specificity of blood flow index (BFI). iDOS techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDOS instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. With a deep TOF filter applied to a high throughput interferometer, we demonstrate brain-specific BFI imaging.
In this work, we demonstrate a fiber-based interferometric Diffuse Optical Spectroscopy (iDOS) approach to obtain quasi-concurrent information at early and late times of flight via a simple fiber optic switch. Time-of-flight (TOF) filtering is enabled by reducing the effective temporal coherence of the laser source, here achieved through rapid wavelength tuning. Early and late TOFs are alternatively interrogated by optical switches that select between reference paths with short and long time delays, respectively. This approach is used on a human forearm to obtain quasi-concurrent deep and superficial blood flow index at baseline and during occlusion.
In-vitro testing of novel photodynamic therapy/radiotherapy procedures relies heavily on the use of different assays to fully probe various parameters such as cytotoxicity or cell-death pathways. These assays utilise sometimes expensive dyes or antibodies, along with cumbersome sample preparation for flow-cytometry. In this work, we propose a novel image-processing algorithm that uses the flow cytometry plots obtained through a Propidium Iodide based live-dead assay on cancerous and non-cancerous cells to deduce the possible cell-death mechanisms in the process of radiotherapy. Propidium Iodide (PI) is a membrane-impermeable dye taken up by those cells with loss of cell membrane integrity, and does not give any information about the integrity of intracellular components or cellular death pathways. In our novel image-processing algorithm, we determine the centroid of the Forward Scatter (FSC) and the Side Scatter (SSC) cytometer plots of such a PI assay, after suitable clustering. This algorithm is initially applied to an unirradiated control cell population where the FSC centroid gives an estimate of the mean cell size, while the SSC centroid gives the baseline granularity of the cell population. Thereafter, the centroids of the FSC and the SSC plots are calculated for the irradiated cell population, and the deviation in these centroids calculated. These differences are correlated to change in average cell size and denaturation/granularity, and serve as a useful substitute for the cell death mechanism. This can potentially pave the way for in-situ qualitative cell-death analysis in large-volume in-vitro studies in a cost-effective manner.
Photodynamic therapy and radiotherapy have traditionally relied on fixed wavelength sources (typically 1064 nm Nd:YAG laser), due to their ready availability. But with advances in development of wide wavelength spanning Raman fiber lasers, a greater flexibility in choice of the light source is provided. In a previous work by our group, we demonstrated the first use of a widely tunable Raman fiber laser (from 1-1.5 um) in achieving varying degrees of cytotoxicity with wavelength at fixed power and exposure for an epithelial breast cancer cell line. However, the reasons for this variation in cytotoxicity was unknown. In this work, we analyse the causes of this variation of cytotoxicity with wavelength for the same epithelial breast cancer cells irradiated in-vitro. Cell-viability is performed through a Propidium-Iodide based assay analysed through a flow cytometer. Thereafter, with the implementation of a novel-image processing algorithm on the same cytometer plots, we obtain a surprising insight into the reasons for cell death for certain wavelengths of irradiation. Specifically, we hypothesise that the effect of these wavelengths is twofold: to desiccate the water content of the cells, leading to reduction in cell size; and to lead to increased granularity or denaturation in the intra-cellular components. We make a surprising observation that cell size reduction is not as correlated with cytotoxicity as increased granularity. This paves the way for a better and insightful deployment of tunable wavelength Raman lasers in photodynamic therapy with the choice of an optimum wavelength to achieve the greatest tumoricidal effect.
The fields of photodynamic therapy (PDT) and radiation therapy customarily rely on lasers operating at a fixed wavelength (typically 1064 nm Nd:YAG laser), primarily because of the traditional availability of such lasers. However, Raman fiber lasers have made concurrent technological progress to emerge as wavelength-agile laser sources, capable of providing high laser powers at any wavelength, primarily from the 1 -2.0 um wavelengths. In this work, we explore for the first time, the use of a high power, wavelength-tunable Raman fiber laser for performing a wavelength-dependent cell-killing effect study on cancerous and healthy cell lines. Specifically, we irradiate at different wavelengths (from 1 um to 1.6 um) breast cancer cells and healthy cells from a cell line, cultured in well plates. Our in-house built Raman laser is power-tunable apart from being wavelength-tunable, the power and duration of irradiation was optimised for achieving the best contrast between viability of cancerous vs. healthy cells. Flow cytometry is used for cell-viability tests. The results give interesting insights on the choice of wavelengths and we show that 1064 nm lasers traditionally used are not the best choice of wavelength to use for this application while 1480nm lasers performed best. We conclusively demonstrate that other wavelengths exist for achieving the best death rate in cancerous cells, leaving healthy cells unharmed. This can pave the way for deployment of Raman fiber lasers as an alternative laser source for this application which can tune the output wavelength to optimize the required laser tissue interaction. For the keywords, select up to 8 key terms for a search on your manuscript's subject.
We have demonstrated a simple technique to make continuous wave (CW), tunable visible lasers. In this experiment, the output from a CW, tunable Raman fiber laser (RFL) is frequency doubled using LBO crystal in a single pass configuration. By tuning the output wavelength of RFL from 1.1-1.3um visible light in green to red wavelengths are generated. The efficiency and output power can be substantially improved by placing the crystal within a resonator cavity and pumping using a polarized RFL with narrower linewidth. Also, by tuning the operating wavelength of Yb laser (1060-1100 nm) broadband visible wavelength tunability can be achieved.
Narrow linewidth fiber lasers find widespread applications in beam combining, frequency conversion and remote detection. Power scaling of these lasers is mainly limited by Stimulated Brillouin scattering (SBS). Currently, SBS is mitigated through linewidth broadening and/or fibers with enhanced mode area. The latter suffers from problems of beam degradation and modal instability making line broadening the primary technique for SBS suppression. Line broadening can be achieved with phase modulation of lasers using white noise, pseudo-random bit streams or arbitrary waveform generators. The simplest implementation is with white noise source with the latter two requiring greater resources. We recently demonstrated a 10GHz linewidth 0.5kW polarization maintaining fiber laser, where it was observed that the SBS threshold did not directly scale with linewidth. This effect was identified as arising from the slow roll-off of the spectrum in white-noise modulated spectra which seeds the SBS process. The seeding is due to the reflections from the fiber end facet at these broadened linewidths where the spectrum has appreciable power at the Stokes wavelength. This is anticipated to be fundamental limiter for power scaling of narrow linewidth fiber lasers. In this work we overcome these drawbacks through a simple phase modulation scheme that incorporates noise waveforms together with sinusoidal modulation. This enables the spectrum to have sharp roll-off with flatter central region resulting in substantial reduction in seeding of SBS from end facet. With this simple architecture, we demonstrate scaling of SBS limited power by more than 1.5 times over pure noise modulation.
High power polarised narrow linewidth sources are of immense importance in coherent beam combining (increased path length accuracy), spectral beam combining (reduced angular spread), non-linear frequency conversion (increased parametric gain) and remote detection. Power scaling of narrow linewidth sources is primarily limited by Stimulated Brillouin Scattering which can be overcome by spectral broadening before amplification to higher powers. Various applications have different requirements of spectral purity and power which can be met if the source line width is tunable. We demonstrate a narrow line width polarisation maintaining (PM) laser with continuous linewidth tuning from ~2.88 GHz to ~9.88 GHz with over 20 W of output power with a polarisation extinction ratio (PER) greater than 20 dB. We achieve continuous linewidth tuning through pure phase modulation of a 1064 nm DBR laser with a white noise source whose bandwidth and power are tuned with a low pass filter bank and variable attenuation of the drive voltage to the modulator. This dual control mechanism enables gapless tuning of the linewidth of the source. A cascade of optimized PM Yb-doped fiber preamplifier and power amplifier is used to scale the output power to over 20W. Combined with the wavelength tuning of the DBR seed, the tunable spectral width makes it versatile for use in a wide range of applications.
We report the surprising observation of yellow to red visible light flashes in the splice point connecting the seed stage to the power amplifier in a high power, narrow-linewidth, polarisation-maintaining Ytterbium doped fiber laser. The multistage laser delivers upto 500W of power with a tuneable linewidth between 2.88 GHz to 9.88 GHz at 1064 nm. For different linewidths, the visible flashes were observed at different power levels of the laser. We observed a strong correlation between these flashes to the appearance of backward pulses with the onset of Stimulated Brillouin Scattering (SBS). We identify the cause for the flashes to be a two part phenomena. Beyond a threshold level, SBS results in the formation of high peak power pulses. These pulses undergo cascaded Raman scattering into higher order stoke wavelengths. These higher order pulses are unaffected by the isolator separating the amplifier stages and moves back into the seed stage with lower effective area, higher NA fibers. We recently demonstrated that 2nd and 3rd harmonic generation can occur in high NA, low effective area fibers assisted by Cherenkov-type phase matching between core light in the NIR and cladding light in the visible. Through processing of the images of the flash acquired with high resolution, we identified the wavelengths to be a mixture of the second harmonic components of the 2nd and 3rd order Raman Stokes of the 1064 nm laser wavelength (1175nm/588nm and 1240nm/620nm). We anticipate the use of these flashes as a potential monitor for the onset of SBS.
Power scaling of narrow-linewidth, continuous-wave, fiber lasers with near-diffraction-limited beam quality is primarily limited by stimulated Brillouin scattering (SBS). Among several SBS mitigation techniques, line broadening by phasemodulation has been widely used. Recently, enhanced SBS seeding (threshold reduction) due to spectral overlap between the backscattered, line-broadened signal and the SBS gain spectrum has been reported. Backscattering of the signal is composed of the Rayleigh component and reflections from the end termination. However, in high power amplifiers with small lengths of optical fiber used, the Rayleigh component of the backscatter is anticipated to be small. Here, we report conclusive experimental evidence that even very small reflections from the output facet are enough to substantially reduce the SBS threshold due to spectral overlap. We demonstrate this in a 500W, white noise phasemodulated, narrow-linewidth, polarization-maintaining power amplifier operating at 1064nm. Two commonly used fiber terminations are utilized. In the first case, the amplifier is terminated by a high-power laser cable with an end-cap and anti-reflection coating and in the second case, by an angle cleaved passive delivery fiber. Back-reflections from the angle cleaved facet (<80) providing ~70dB isolation (ideal case) was enough to enhance SBS. We analyzed the threshold differences between the two cases as a function of linewidth from 4.91GHz to ~10GHz. At smaller linewidths, the difference was negligible while at larger linewidths, there was a substantial difference in thresholds (<20%). This linewidth dependent difference in thresholds was accurately simulated by the backward seeding of SBS by the linebroadened signal, thus conclusively proving this effect.
In this work, we demonstrate an architecture to perform Raman-based power combining and simultaneous wavelength conversion of two independently controlled high-power Ytterbium doped fiber lasers operating at different wavelengths into a single laser line at the 1.5-micron band. Specifically, we have been able to achieve an in-band output power of ∼99W with a conversion of ∼64% of the quantum limited efficiency. This power combining is illustrated for different cases of the input wavelengths of the Ytterbium fiber laser. In each case, we have been able to demonstrate a power combining of >87 W in the final 1.5-micron band, with more than 85% of the fraction of the power residing in the final desired band.
Cascaded Raman lasers enable high powers at various wavelength bands inaccessible with conventional fiber lasers. However, the input and output wavelengths are fixed by the multitude of fiber gratings in the system providing feedback. In this work, we demonstrate a high power, tunable, grating-free cascaded Raman fiber laser with an output power of >30W and a continuous tuning range from 1440nm to 1520nm. This corresponds to the entire in-band pumping region of Erbium doped gain media. Our system is enabled by three novel aspects – A grating free feedback mechanism for Raman lasers, a filter fiber to terminate the Raman cascade at the required wavelength band and a tunable high-power Ytterbium doped fiber laser as input. In this work, the primary system is a novel, cascaded Raman conversion module which is completely color blind to the input pump source and does wavelength band conversion at high efficiency. In addition, the conversion module also provides high spectral purity of greater than 85% at the required wavelength by terminating the cascade using high distributed losses provided by specialty Raman filter fibers. Using a high-power Ytterbium doped fiber laser continuously tuned from 1060nm to 1100nm and Raman filter fiber with distributed loss beyond 1520nm, we achieve a continuously tunable 1440nm to 1520nm laser corresponding to 5th or 6th Raman Stokes shift of the input. To the best of our knowledge, the reported powers at these wavelengths have been the highest for tunable Raman fiber lasers and is currently only limited by the input power.
In this work, we report and analyse the surprising observation of a rainbow of visible colors, spanning 390nm to 620nm, in silica-based, Near Infrared, continuous-wave, cascaded Raman fiber lasers. The cascaded Raman laser is pumped at 1117nm at around 200W and at full power we obtain ∼100 W at 1480nm. With increasing pump power at 1117nm, the fiber constituting the Raman laser glows in various hues along its length. From spectroscopic analysis of the emitted visible light, it was identified to be harmonic and sum-frequency components of various locally propagating wavelength components. In addition to third harmonic components, surprisingly, even 2nd harmonic components were observed. Despite being a continuous-wave laser, we expect the phase-matching occurring between the core-propagating NIR light with the cladding-propagating visible wavelengths and the intensity fluctuations characteristic of Raman lasers to have played a major role in generation of visible light. In addition, this surprising generation of visible light provides us a powerful non-contact method to deduce the spectrum of light propagating in the fiber. Using static images of the fiber captured by a standard visible camera such as a DSLR, we demonstrate novel, image-processing based techniques to deduce the wavelength component propagating in the fiber at any given spatial location. This provides a powerful diagnostic tool for both length and power resolved spectral analysis in Raman fiber lasers. This helps accurate prediction of the optimal length of fiber required for complete and efficient conversion to a given Stokes wavelength.
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