Activation detection in functional near-infrared spectroscopy by wavelet coherence

Functional near-infrared spectroscopy (fNIRS) detects hemodynamic responses in the cerebral cortex by transcranial spectroscopy. However, measurements recorded by fNIRS not only consist of the desired hemodynamic response but also consist of a number of physiological noises. Because of these noises, accurately detecting the regions that have an activated hemodynamic response while performing a task is a challenge when analyzing functional activity by fNIRS. In order to better detect the activation, we designed a multiscale analysis based on wavelet coherence. In this method, the experimental paradigm was expressed as a binary signal obtained while either performing or not performing a task. We convolved the signal with the canonical hemodynamic response function to predict a possible response. The wavelet coherence was used to investigate the relationship between the response and the data obtained by fNIRS at each channel. Subsequently, the coherence within a region of interest in the time-frequency domain was summed to evaluate the activation level at each channel. Experiments on both simulated and experimental data demonstrated that the method was effective for detecting activated channels hidden in fNIRS data

Développement d'un système d'imagerie photoacoustique pour application à l'athérosclérose

RÉSUMÉ La tomographie photoacoustique est une nouvelle modalité d'imagerie préclinique non invasive combinant l'imagerie optique et les ultrasons. Dans le présente forme, elle permet de mesurer la distribution initiale de pression acoustique générée par l'absorption photonique dans les tissus biologiques, et réflète ainsi les propriétés optiques du spécimen examiné. Cette technique s'appuie notamment sur la diffusion optique dans les tissus pour approfondir le champ d'imagerie par rapport aux techniques d'imagerie optique fonctionnant dans les régimes balistique ou quasi-balistique. Par exemple, elle pourrait notamment permettre l'imagerie des structures profondes chez des modèles murins, qui sont fréquemment utilisés en recherche translationnelle. En outre, les principaux absorbants dans les tissus tels que l'oxyhémoglobine, la désoxyhémoglobine et les lipides, ainsi que les agents de contraste exogènes ont un profil d'absorption distinct qui pourrait être mis à profit par les techniques de différenciation multispectrales. L'objectif global de ce projet est d'appliquer la tomographie photoacoustique pour l'imagerie du système vasculaire chez la souris, et plus spécifiquement l'imagerie moléculaire de la plaque d'athérosclérose. L'imagerie moléculaire vise la détection non invasive de sondes ciblées, dans le but d'apporter une information complémentaire aux données anatomiques. Présentement, plusieurs modalités d'imagerie moléculaire peuvent être appliquées à la détection de la plaque d'athérome. Cependant, aucune ne parvient à s'imposer sur tous les critères décisionnels tels que la sensibilité, la résolution spatiale ou temporelle, le niveau d'exposition à des rayonnements ionisants, la profondeur de pénétration ou le coût. L'imagerie photoacoustique est une modalité hybride entre les techniques optiques et l'imagerie ultrasonore, qui profite donc de la sensibilité de l'optique avec la résolution spatiale ultrasonore. L'arche aortique a été choisie comme région d'intérêt ciblée pour ce projet. En effet, il s'agit du lieu de formation précoce de la plaque chez des modèles de souris athérosclérotiques ; elle fournit également des repères anatomiques uniques permettant un repositionnement précis pour des études répétées d'imagerie. À ce jour, très peu d'études ont été consacrées au système cardiovasculaire en photoacoustique. Les résultats de cette thèse constituent donc une contribution originale au domaine. Étant donné que le sang est à l'origine d'un fort contraste photoacoustique endogène, l'observation de ce contraste purement vasculaire est une condition favorable à la faisabilité de l'imagerie moléculaire dans cette région. Aussi, la majeure partie de ce travail est orientée vers l'obtention de ce contraste sanguin in vivo chez la souris..----------ABSTRACT Photoacoustic tomography has emerged as a new preclinical imaging modality combining optical and ultrasound techniques. In the present implementation, photoacoustic imaging is used to recover the initial distribution of pressure generated by optical absorption in biological tissues. Further computation could allow the recovery of optical properties such as the optical absorption map. This technique relies on optical diusion in turbid media in order to get a deeper eld-of-view compared to optical modalities in the ballistic or nearly ballistic regimes. For instance, it could allow imaging of deep structures or organs in murin models, which are commonly found in translational research. Moreover, the main endogenous absorbing components of tissues such as oxy- or deoxyhemoglobin, lipids, or exogenous contrast agents have a specic absorption prole that could feed multispectral unmixing techniques. The main goal of this projet is to apply photoacoustic tomography for vascular imaging in mice. More specically, the technique is to be applied toward molecular imaging of atherosclerotic plaque. Molecular imaging is directed to noninvasive detection of targeted probes, in order to supplement anatomical data with complementary molecular information. Currently, several imaging modalities can be used to detect the atheroma. However, for each application a compromise must be made given that no technique is able to impose itself with respect to all decision criterias such as sensitivity, spatial or temporal resolution, level of exposure to ionizing radiation, depth of penetration or cost. Photoacoustic imaging is an hybrid modality evolving between optical techniques and conventionnal ultrasound imaging, and therefore benets from the high sensitivity of optics as well as ultrasound spatial resolution. For this project, the aortic arch has been dened as the targeted region of interest. Indeed, this area is prone to early plaque formation in atherosclerotic mice models and provides unique landmarks for repositioning in repeated studies. To date, very few studies have investigated the cardiovascular system in photoacoustics. Hence, the results of this thesis are an original contribution to the eld. Photoacoustic measurements are very sensitive to whole blood, and therefore the detection of vascular contrast represents a window of opportunity for molecular imaging. The main accomplishments of this work have been done toward the detection of vascular contrast in vivo in mice. In the rst part of the thesis, we simulated the direct problem in photoacoustics. The purpose of this methodological objective was to estimate the order of magnitude of the depth of penetration of light in turbid or vascular tissues. The simulated pressure signal was rst investigated by varying multiple parameters such as the source dimensions, homogeneity an

Shedding light into the brain: Methodological innovations in optical neuroimaging

Functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT) are non-invasive techniques used to infer stimulus-locked variations in human cortical activity from optical variations of near-infrared light injected and subsequently detected at specified scalp locations. Relative to functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), these optical techniques are more portable, less invasive and less sensitive to motion artifacts, making them ideal to explore brain activity in a variety of cognitive situations, and in a range of populations, including newborns and children. FNIRS and DOT measure stimulus-locked hemodynamic response in the form of changes in oxy- (HbO) and deoxy- (HbR) hemoglobin concentration taking place in specific areas. This signal is however structurally intertwined with physiological noise owing to cardiac pulsations, respiratory oscillations and vasopressure wave. Furthermore, the absolute magnitude of hemodynamic responses is substantially smaller than these non-informative components of the measured optical signal, and has a frequency which largely overlaps with that of the vasopressure wave. Thus, recovering the hemodynamic response is a challenging task. Several methods have been proposed in the literature to try to reduce physiological noise oscillations and recover the hemodynamic response, but none of them has become a common standard in the optical signal processing pipeline. In this thesis, a novel algorithm, devised to overcome a large subset of drawbacks associated with the use of these literature techniques, is presented and validated. Reduced sensitivity to motion artifacts notwithstanding, the optical signal must always be assumed as contaminated by some form of mechanical instability, most prominently during signal acquisitions from pathological (e.g., stroke patients) or difficult (e.g., newborns) populations. Several techniques have been proposed to correct for motion artifacts with the specific aim of preserving contaminated measures as opposed to rejecting them. However, none of them has become the gold standard in the optical signal processing pipeline, and there are currently no objective approaches to choose the most appropriate filtering technique based on objective parameters. In fact, due to the extreme variability in shape, frequency content and amplitude of the motion artifacts, it is likely that the best technique to apply is data-dependent and, in this vein, it is essential to provide users with objective tools able to select the best motion correction technique for the data set under examination. In this thesis, a novel objective approach to perform this selection is proposed and validated on a data-set containing a very challenging type of motion artifacts. While fNIRS allows only spectroscopic measurements of hemoglobin concentration changes, DOT allows to obtain 3D reconstructed images of HbO and HbR concentration changes. To increase the accuracy and interpretability of DOT reconstructed images, valuable anatomical information should be provided. While several adult head models have been proposed and validated in this context, only few single-ages head models have been presented for the neonatal population. However, due to the rapid growth and maturation of the infant's brain, single-age models fail to capture precise information about the correct anatomy of every infant's head under examination. In this thesis, a novel 4D head model, ranging from the preterm to the term age, is proposed, allowing developmental neuroscientists to make finer-grained choices about the age-matched head model and perform image reconstruction with an anatomy as similar as possible to the real one. The outline of the thesis will be as follows. In the first two chapters of this thesis, the state of the art of optical techniques will be reviewed. Particularly, in chapter 1, a brief introduction on the physical principles of optical techniques and a comparison with other more common neuroimaging techniques will be presented. In chapter 2, the components of the measured optical signal will be described and a brief review of state of the art of the algorithms that perform physiological noise removal will be presented. The theory on which optical image reconstruction is based will be reviewed afterwards. In the final part of the chapter, some of the studies and achievements of optical techniques in the adult and infants populations will be reviewed and the open issues and aims of the thesis will be presented. In chapters 3, 4 and 5, new methodologies and tools for signal processing and image reconstruction will be presented. Particularly, in chapter 3, a novel algorithm to reduce physiological noise contamination and recover the hemodynamic response will be introduced. The proposed methodology will be validated against two literature methods and results and consequent discussion will be reported. In chapter 4, instead, a novel objective approach for the selection of the best motion correction technique will be proposed. The main literature algorithms for motion correction will be reviewed and the proposed approach will be validated using these motion correction techniques on real cognitive data. In chapter 5, instead, a novel 4D neonatal optical head model will be presented. All the steps performed for its creation will be explained and discussed and a demonstration of the head model in use will also be exhibited. The last part of the thesis (chapters 6, 7 and 8) will be dedicated to illustrate three distinct examples of application of the proposed methodologies and tools on neural empirical data. In chapter 6, the physiological noise removal algorithm proposed in chapter 3 will be applied to recover subtle temporal differences between hemodynamic responses measured in two different areas of the motor cortex in short- vs. long- duration tapping. In chapter 7, the same algorithm will be applied to reduce physiological noise and recover hemodynamic responses measured during a visual short-term memory paradigm. In both chapters, cognitive results and a brief discussion will be reported. In chapter 8, instead, the neonatal optical head model proposed in chapter 5 will be applied to perform image reconstruction with data acquired on a healthy full term baby. In the same chapter, the importance of motion artifact correction will be highlighted, reconstructing HbO concentration changes images before and after the correction took place