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Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain., This project was funded by Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad/FEDER (PHOTODEMENTIA, DPI2015-64358-C2-1-R), Instituto de Salud Carlos III/FEDER (MEDPHOTAGE, DTS16/00087), the “Severo Ochoa” Program for Centers of Excellence in R\&D (SEV-2015-0522), the Obra Social “la Caixa” Foundation (LlumMedBcn), AGAUR-Generalitat (2017 SGR 1380), LASERLAB-EUROPE IV, and “Fundació La Marató TV3.”

We report on a simple chemical etching method that enables nonlinear tapering of Polymer Optical Fiber (POF) tips to manufacture Compound Parabolic Concentrator (CPC) fiber tips. We show that, counter-intuitively, nonlinear tapering can be achieved by first etching the core and not the cladding. The etching mechanism is modelled and etched tips are characterized both geometrically and optically in a fluorescence glucose sensor chemistry. A Zemax model of the CPC tipped sensor predicts an optimal improvement in light capturing efficiency of a factor of 3.96 compared to the conventional sensor with a plane-cut fiber tip. A batch of eight CPC fiber tips has been manufactured by the chemical etching method. The batch average showed an increase of a factor of 3.16, which is only 20% less than the predicted value. The method is reproducible and can be up-scaled for mass production.

International audience; We have developed a broadband time-resolved multi-channel near-infrared spectroscopy system that can monitor the physiological responses of the adult human brain. This system is composed of a supercontinuum laser for the source part and of an intensified charge-coupled device camera coupled with an imaging spectrometer for the detection part. It allows the detection of the spectral, from 600 to 900 nm, and spatial dimensions as well as the arrival time of photon information simultaneously. We describe the setup and its characterization in terms of temporal instrument response function, wavelength sensitivity, and stability. The ability of the system to detect the hemodynamic response is then demonstrated. First, an in vivo experiment on an adult volunteer was performed to monitor the response in the arm during a cuff occlusion. Second, the response in the brain during a cognitive task was monitored on a group of five healthy volunteers. Moreover, looking at the response at different time windows, we could monitor the hemodynamic response in depth, enhancing the detection of the cortical activation. Those first results demonstrate the ability of our system to discriminate between the responses of superficial and deep tissues, addressing an important issue in functional near-infrared spectroscopy.

We report on highly accurate femtosecond (fs) laser micromachining of a compound parabolic concentrator (CPC) fiber tip on a polymer optical fiber (POF). The accuracy is reflected in an unprecedented correspondence between the numerically predicted and experimentally found improvement in fluorescence pickup efficiency of a Förster resonance energy transfer-based POF glucose sensor. A Zemax model of the CPC-tipped sensor predicts an optimal improvement of a factor of 3.96 compared to the sensor with a plane-cut fiber tip. The fs laser micromachined CPC tip showed an increase of a factor of 3.5, which is only 11.6% from the predicted value. Earlier state-of-the-art fabrication of the CPC-shaped tip by fiber tapering was of so poor quality that the actual improvement was 43% lower than the predicted improvement of the ideal CPC shape.

A new compact and flexible picosecond laser system for multi-wavelength time-resolved tissue spectroscopy was developed. Characterization on diffusive phantoms in terms of stability during fast switching, and linearity for absorption and scattering were performed.

In this work we present a medical device for non-invasive oxygen saturation assessment in stroke patients. The system based on time-resolved near infrared spectroscopy was fully characterized and tested on healthy volunteers.

We present simultaneous diffuse correlation spectroscopy (DCS) and time resolved spectroscopy (TR NIRS) measurements on exercising and non-exercising vastus lateralis muscle. We discuss the results at two different exercise levels.

In order to study hemodynamic changes involved in muscular metabolism by means of time domain fNIRS, we need to discriminate in the measured signal contributions coming from different depths. Muscles are, in fact, typically located under other tissues, e.g. skin and fat. In this paper, we study the possibility to exploit a previously proposed method for analyzing time-resolved fNIRS measurements in a two-layer structure with a thin superficial layer. This method is based on the calculation of the time-dependent mean partial pathlengths. We validated it by simulating venous and arterial arm cuff occlusions and then applied it on in vivo measurements. (C) 2016 Optical Society of America

© 2015 Optical Society of America. Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique capable of monitoring tissue perfusion. The normalized temporal intensity autocorrelation function generated by DCS is typically characterized by assuming that the movement of erythrocytes can be modeled as a Brownian diffusion-like process instead of by the expected random flow model. Recently, a hybrid model, referred to as the hydrodynamic diffusion model, was proposed, which combines the random and Brownian flow models. The purpose of this study was to investigate the best model to describe autocorrelation functions acquired directly on the brain in order to avoid confounding effects of extracerebral tissues. Data were acquired from 11 pigs during normocapnia and hypocapnia, and flow changes were verified by computed tomography perfusion (CTP). The hydrodynamic diffusion model was found to provide the best fit to the autocorrelation functions; however, no significant difference for relative flow changes measured by the Brownian and hydrodynamic diffusion models was observed.

We propose a new algorithm, based on a linear regression model, to statistically estimate the hemodynamic activations in fNIRS data sets. The main concern guiding the algorithm development was the minimization of assumptions and approximations made on the data set for the application of statistical tests. Further, we propose a K-means method to cluster fNIRS data (i.e. channels) as activated or not activated. The methods were validated both on simulated and in vivo fNIRS data. A time domain (TD) fNIRS technique was preferred because of its high performances in discriminating cortical activation and superficial physiological changes. However, the proposed method is also applicable to continuous wave or frequency domain fNIRS data sets. (C) 2015 Optical Society of America

Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep tissue, by taking advantage of multi-distance (previously reported in the literature) or multi-exposure (reported here) approach. This method promises to use inexpensive detectors to obtain good signal-to-noise ratio, but it has not yet been implemented in a suitable manner for a mass production. Here we present a new, compact, low power consumption, 32 by 2 single photon avalanche diode (SPAD) array that has no readout noise, low dead time and has high sensitivity in low light conditions, such as in vivo measurements. To demonstrate the capability to measure blood flow in deep tissue, healthy volunteers were measured, showing no significant differences from the diffuse correlation spectroscopy. In the future, this array can be miniaturized to a low-cost, robust, battery operated wireless device paving the way for measuring blood flow in a wide-range of applications from sport injury recovery and training to, on-field concussion detection to wearables. Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad (PHOTODEMEN-TIA (DPI2015-64358-c1 and c2 (MINECO/FEDER)), Instituto de Salud Carlos III/FEDER(MEDPHOTAGE DTS16/00087), the “Severo Ochoa” Programme for Centres of Excellence inR&D (SEV-2015-0522), the Obra social “la Caixa” Foundation (LlumMedBcn), LASERLAB-EUROPE IV. J.L.Hollmann acknowledges the Marie Curie COFUND (FP7-PEOPLE-2013-COFUND) fellowship.

Neural activity is an important biomarker for the presence of neurodegenerative diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a surrogate marker for treatment effects. These pathologies may occur and evolve in a long time-period, thus, noninvasive, transcutaneous techniques are necessary to allow a longitudinal follow-up. In the present work, we have customized noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize changes in cerebral blood flow (CBF) induced by neural activity. We were able to detect changes in CBF in the somatosensory cortex by using a model of electrical forepaw stimulation in rats. The suitability of DCS measurements for longitudinal monitoring was demonstrated by performing multiple sessions with the same animals at different ages (from 6 to 18 months). In addition, functional DCS has been cross-validated by comparison with functional magnetic resonance imaging (fMRI) in the same animals in a subset of the time-points. The overall results obtained with transcutaneous DCS demonstrates that it can be utilized in longitudinal studies safely and reproducibly to locate changes in CBF induced by neural activity in the small animal brain., The project was funded by Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad (PHOTODEMENTIA, DPI2015-64358-C2-1-R and DPI2015-64358-C2-2-R, PHOTOSTROKE), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra social “la Caixa” Foundation (LlumMedBcn), Instituto de Salud Carlos III / FEDER (Medphotage, DTS16/00087), AGAURGeneralitat (2014-SGR725, 2014SGR-1555), LaserLab-Europe IV. We are indebted to the Experimental MRI 7T Unit of the IDIBAPS for the technical help.

A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laserDoppler flowmeter, is also presented. © 2014 Optical Society of America.

We have designed a compact dual wavelength (687 nm, 826 nm) multi-channel (16 sources, 8 detectors) medical device for muscle and brain imaging based on time domain functional near infrared spectroscopy. The system employs the wavelength space multiplexing approach to reduce wavelength cross-talk and increase signal-to-noise ratio. System performances have been tested on homogeneous and heterogeneous tissue phantoms following specifically designed protocols for photon migration instruments. Preliminary in vivo measurements have been performed to validate the instrument capability to monitor hemodynamic parameters changes in the arm muscle during arterial occlusion and in the adult head during a motor task experiment. © 2013 Optical Society of America.

We present a method to determine chromophore concentrations, blood saturation, and epidermal thickness of human skin from diffuse reflectance spectra. Human skin was approximated as a plane-parallel slab of variable thickness supported by a semi-infinite layer corresponding to the epidermis and dermis, respectively. The absorption coefficient was modeled as a function of melanin content for the epidermis and blood content and oxygen saturation for the dermis. The scattering coefficient and refractive index of each layer were found in the literature. Diffuse reflectance spectra between 490 and 620 nm were generated using Monte Carlo simulations for a wide range of melanosome volume fraction, epidermal thickness, blood volume, and oxygen saturation. Then, an inverse method was developed to retrieve these physiologically meaningful parameters from the simulated diffuse reflectance spectra of skin. A previously developed accurate and efficient semiempirical model for diffuse reflectance of two layered media was used instead of time-consuming Monte Carlo simulations. All parameters could be estimated with relative root-mean-squared error of less than 5% for (i) melanosome volume fraction ranging from 1% to 8%, (ii) epidermal thickness from 20 to 150 mum, (iii) oxygen saturation from 25% to 100%, (iv) blood volume from 1.2% to 10%, and (v) tissue scattering coefficient typical of human skin in the visible part of the spectrum. A similar approach could be extended to other two-layer absorbing and scattering systems.