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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.”

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.

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.

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

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.