Evaluation of hyperspectral imaging measurements of changes in hemoglobin oxygenation and oxidation of cytochrome-c-oxidase using a liquid blood phantom

Optical imaging is a non-invasive technique that is able to monitor hemodynamic and metabolic responses during neurosurgery. However, a robust quantification is complicated to perform. To overcome this issue, phantoms that mimic biological tissues are required for the development of imaging systems in order to reach a true standardization. In this work, we explore the possibility to use a combined liquid blood phantom with cytochrome contained yeast to evaluate the reliability of hyperspectral imaging to measure oxygenation and metabolic changes. This phantom can be used to verify the reliability of intraoperative optical setups before moving on to clinical application

A digital instrument simulator to optimize the development of a hyperspectral imaging system for neurosurgery

In recent years, hyperspectral imaging (HSI) has demonstrated its capacity to non-invasively differentiate tumors from healthy tissues and identify cancerous regions during neurosurgery. Indeed, the spectral information contained in the HS images allows to identify more chromophores, refining the information provided by the imaging system, and allowing to identify the unique signature of each tissue types more accurately. Our HyperProbe project aims at developing a novel HSI system optimized for neurosurgery. As part of this project, we are developing a digital instrument simulator (DIS), based on Monte-Carlo (MC) simulations of the light propagation in tissues, in order to optimize both the hardware and data processing pipeline of our novel instrument. This framework allows us (1) to test the effect on the accuracy of the measurement of several hardware parameters, like the numerical aperture or sensitivity of the detector; (2) to be used as numerical phantoms to test various data processing algorithms; and (3) to generate generic data to develop and train machine learning (ML) algorithms. To do so, our framework is based on a 2-step method. Firstly, MC simulations are run to produce an ideal dataset of the photon transport in tissue. Then, the raw output parameters of the simulations, such as the exit positions and directions of the photons, are processed to take into account the physical parameters of an instrument in order to produce realistic images and test various scenarios. We present here the initial development of this DIS

HyperProbe consortium: innovate tumour neurosurgery with innovative photonic solutions

Recent advancements in imaging technologies (MRI, PET, CT, among others) have significantly improved clinical localisation of lesions of the central nervous system (CNS) before surgery, making possible for neurosurgeons to plan and navigate away from functional brain locations when removing tumours, such as gliomas. However, neuronavigation in the surgical management of brain tumours remains a significant challenge, due to the inability to maintain accurate spatial information of pathological and healthy locations intraoperatively. To answer this challenge, the HyperProbe consortium have been put together, consisting of a team of engineers, physicists, data scientists and neurosurgeons, to develop an innovative, all-optical, intraoperative imaging system based on (i) hyperspectral imaging (HSI) for rapid, multiwavelength spectral acquisition, and (ii) artificial intelligence (AI) for image reconstruction, morpho-chemical characterisation and molecular fingerprint recognition. Our HyperProbe system will (1) map, monitor and quantify biomolecules of interest in cerebral physiology; (2) be handheld, cost-effective and user-friendly; (3) apply AI-based methods for the reconstruction of the hyperspectral images, the analysis of the spatio-spectral data and the development and quantification of novel biomarkers for identification of glioma and differentiation from functional brain tissue. HyperProbe will be validated and optimised with studies in optical phantoms, in vivo against gold standard modalities in neuronavigational imaging, and finally we will provide proof of principle of its performances during routine brain tumour surgery on patients. HyperProbe aims at providing functional and structural information on biomarkers of interest that is currently missing during neuro-oncological interventions

A Reliable and Rapid Language Tool for the Diagnosis, Classification, and Follow-Up of Primary Progressive Aphasia Variants

International audienceBackground: Primary progressive aphasias (PPA) have been investigated by clinical, therapeutic, and fundamental research but examiner-consistent language tests for reliable reproducible diagnosis and follow-up are lacking. Methods: We developed and evaluated a rapid language test for PPA ("PARIS") assessing its inter-examiner consistency, its power to detect and classify PPA, and its capacity to identify language decline after a follow-up of 9 months. To explore the reliability and specificity/sensitivity of the test it was applied to PPA patients (N = 36), typical amnesic Alzheimer's disease (AD) patients (N = 24) and healthy controls (N = 35), while comparing it to two rapid examiner-consistent language tests used in stroke-induced aphasia ("LAST", "ART"). Results: The application duration of the "PARIS" was ∼10 min and its inter-rater consistency was of 88%. The three tests distinguished healthy controls from AD and PPA patients but only the "PARIS" reliably separated PPA from AD and allowed for classifying the two most frequent PPA variants: semantic and logopenic PPA. Compared to the "LAST" and "ART," the "PARIS" also had the highest sensitivity for detecting language decline. Conclusions: The "PARIS" is an efficient, rapid, and highly examiner-consistent language test for the diagnosis, classification, and follow-up of frequent PPA variants. It might also be a valuable tool for providing end-points in future therapeutic trials on PPA and other neurodegenerative diseases affecting language processing

Tomographie optique diffuse résolue en temps : Applications fonctionnelles en neurosciences.

Diffuse optical tomography is a new modality of functional medical imaging. Its application to the study of brain activity is very promising. In this context, this work deals with understanding light propagation through the head thanks to simulations based on the diffusion equation which is solved by the finite element method on models obtained by the segmentation of MRI. These simulations show the weak penetration of light in the brain because of the particular optical properties of the head which implies a strong influence of superficial layer in the signal detected at the surface. We built a time-resolved photon counting system suited for clinical environment based on picosecond laser diodes at four different wavelengths. Its performances have been optimized considering the clinical environment. We obtained an apparatus with a shot noise limited signal to noise ratio and with and impulse response function around 100-300 ps at half maximum. This system allowed the detection of the variation of cerebral activity. The cerebral origin of the absorption variations detected at the head surface has been proved thanks to the comparison of experiments and simulations of brain activation. Simulations results allowed to propose original methods to spatially localize cerebral activity based on the "microscopic Beer-Lambert law" which is a function of photons time of flight. These methods allow to obtain depth-related information on the variations of oxy- and deoxy-hemoglobin concentration due to the cerebral hemodynamic response thanks to the time-resolved concentration difference maps.La tomographie optique diffuse est une nouvelle modalité d'imagerie médicale fonctionnelle. Elle présente de nombreux atouts pour le suivi de l'activité cérébrale. Dans ce contexte, ces travaux s'articulent autour de la compréhension de la propagation lumineuse au travers de la tête par l'intermédiaire de simulations fondées sur la résolution de l'équation de diffusion par la méthode des éléments finis sur des modèles anatomiques issus de la segmentation d'IRM. Nous avons mis en évidence la faible pénétration cérébrale de la lumière en raison des propriétés optiques particulières de la tête, et donc la forte influence des structures anatomiques superficielles dans le signal détecté en surface. Nous avons réalisé un système fondé sur le comptage de photons résolu en temps adapté à l'environnement clinique et qui repose sur l'utilisation de diodes laser picoseconde à quatre longueurs d'onde différentes. Les performances de l'ensemble ont été optimisées en tenant compte des nombreux impératifs cliniques ce qui a permis de réaliser et d'optimiser un appareil dont le rapport signal à bruit est uniquement limité par le bruit de photons et ayant une réponse impulsionnelle de l'ordre de 100-300 ps à mi-hauteur. Ce système a permis la détection de la variation de l'activité cérébrale. L'origine cérébrale des variations d'absorption détectées à la surface a été avérée grâce à la comparaison de l'expérience avec les simulations d'activation cérébrale. Les résultats des simulations ont permis de proposer des méthodes originales de localisation spatiale de l'activité cérébrale fondées sur la "loi de Beer-Lambert microscopique" qui est une fonction du temps de vol des photons. Elles permettent d'obtenir une information sur la profondeur des variations de concentration d'oxy-hémoglobine et de déoxy-hémoglobine, liées à la réponse hémodynamique cérébrale, grâce aux cartes de variations de concentration résolues en temps

Time-resolved diffuse optical tomography,Functional applications in neurosciences

La tomographie optique diffuse est une nouvelle modalité d'imagerie médicale fonctionnelle. Elle présente de nombreux atouts pour le suivi de l'activité cérébrale. Dans ce contexte, ces travaux s'articulent autour de la compréhension de la propagation lumineuse au travers de la tête par l'intermédiaire de simulations fondées sur la résolution de l'équation de diffusion par la méthode des éléments finis sur des modèles anatomiques issus de la segmentation d'IRM. Nous avons mis en évidence la faible pénétration cérébrale de la lumière en raison des propriétés optiques particulières de la tête, et donc la forte influence des structures anatomiques superficielles dans le signal détecté en surface. Nous avons réalisé un système fondé sur le comptage de photons résolu en temps adapté à l'environnement clinique et qui repose sur l'utilisation de diodes laser picoseconde à quatre longueurs d'onde différentes. Les performances de l'ensemble ont été optimisées en tenant compte des nombreux impératifs cliniques ce qui a permis de réaliser et d'optimiser un appareil dont le rapport signal à bruit est uniquement limité par le bruit de photons et ayant une réponse impulsionnelle de l'ordre de 100-300 ps à mi-hauteur. Ce système a permis la détection de la variation de l'activité cérébrale. L'origine cérébrale des variations d'absorption détectées à la surface a été avérée grâce à la comparaison de l'expérience avec les simulations d'activation cérébrale (B.Montcel et al. Applied Optics, 44, 1942-1947, 2005). Les résultats des simulations ont permis de proposer des méthodes originales de localisation spatiale de l'activité cérébrale fondées sur la "loi de Beer-Lambert microscopique" qui est une fonction du temps de vol des photons. Elles permettent d'obtenir une information sur la profondeur des variations de concentration d'oxy-hémoglobine et de déoxy-hémoglobine, liées à la réponse hémodynamique cérébrale, grâce aux cartes de variations de concentration résolues en temps.Diffuse optical tomography is a new modality of functional medical imaging. Its application to the study of brain activity is very promising. In this context, this work deals with understanding light propagation through the head thanks to simulations based on the diffusion equation which is solved by the finite element method on models obtained by the segmentation of MRI. These simulations show the weak penetration of light in the brain because of the particular optical properties of the head which implies a strong influence of superficial layer in the signal detected at the surface. We built a time-resolved photon counting system suited for clinical environment based on picosecond laser diodes at four different wavelengths. Its performances have been optimized considering the clinical environment. We obtained an apparatus with a shot noise limited signal to noise ratio and with and impulse response function around 100-300 ps at half maximum. This system allowed the detection of the variation of cerebral activity. The cerebral origin of the absorption variations detected at the head surface has been proved thanks to the comparison of experiments and simulations of brain activation (B.Montcel et al. Applied Optics, 44, 1942-1947, 2005). Simulations results allowed to propose original methods to spatially localize cerebral activity based on the "microscopic Beer-Lambert law" which is a function of photons time of flight. These methods allow to obtain depth-related information on the variations of oxy- and deoxy-hemoglobin concentration due to the cerebral hemodynamic response thanks to the time-resolved concentration difference maps

Tomographie optique diffuse résolue en temps (Applications fonctionnelles en neurosciences)

La tomographie optique diffuse est une nouvelle modalité d'imagerie médicale fonctionnelle. Elle présente de nombreux atouts pour le suivi de l'activité cérébrale. Dans ce contexte, ces travaux s'articulent autour de la compréhension de la propagation lumineuse au travers de la tête par l'intermédiaire de simulations fondées sur la résolution de l'équation de diffusion par la méthode des éléments finis sur des modèles anatomiques issus de la segmentation d'IRM. Nous avons mis en évidence la faible pénétration cérébrale de la lumière en raison des propriétés optiques particulières de la tête, et donc la forte influence des structures anatomiques superficielles dans le signal détecté en surface. Nous avons réalisé un système fondé sur le comptage de photons résolu en temps adapté à l'environnement clinique et qui repose sur l'utilisation de diodes laser picoseconde à quatre longueurs d'onde différentes. Les performances de l'ensemble ont été optimisées en tenant compte des nombreux impératifs cliniques ce qui a permis de réaliser et d'optimiser un appareil dont le rapport signal à bruit est uniquement limité par le bruit de photons et ayant une réponse impulsionnelle de l'ordre de 100-300 ps à mi-hauteur. Ce système a permis la détection de la variation de l'activité cérébrale. L'origine cérébrale des variations d'absorption détectées à la surface a été avérée grâce à la comparaison de l'expérience avec les simulations d'activation cérébrale (B.Montcel et al. Applied Optics, 44, 1942-1947, 2005). Les résultats des simulations ont permis de proposer des méthodes originales de localisation spatiale de l'activité cérébrale fondées sur la "loi de Beer-Lambert microscopique" qui est une fonction du temps de vol des photons. Elles permettent d'obtenir une information sur la profondeur des variations de concentration d'oxy-hémoglobine et de déoxy-hémoglobine, liées à la réponse hémodynamique cérébrale, grâce aux cartes de variations de concentration résolues en temps.Diffuse optical tomography is a new modality of functional medical imaging. Its application to the study of brain activity is very promising. In this context, this work deals with understanding light propagation through the head thanks to simulations based on the diffusion equation which is solved by the finite element method on models obtained by the segmentation of MRI. These simulations show the weak penetration of light in the brain because of the particular optical properties of the head which implies a strong influence of superficial layer in the signal detected at the surface. We built a time-resolved photon counting system suited for clinical environment based on picosecond laser diodes at four different wavelengths. Its performances have been optimized considering the clinical environment. We obtained an apparatus with a shot noise limited signal to noise ratio and with and impulse response function around 100-300 ps at half maximum. This system allowed the detection of the variation of cerebral activity. The cerebral origin of the absorption variations detected at the head surface has been proved thanks to the comparison of experiments and simulations of brain activation (B.Montcel et al. Applied Optics, 44, 1942-1947, 2005). Simulations results allowed to propose original methods to spatially localize cerebral activity based on the "microscopic Beer-Lambert law" which is a function of photons time of flight. These methods allow to obtain depth-related information on the variations of oxy- and deoxy-hemoglobin concentration due to the cerebral hemodynamic response thanks to the time-resolved concentration difference maps.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Time-resolved and spectral-resolved optical imaging to study brain hemodynamics in songbirds,.

International audienceContrary to the intense debate about brain oxygen dynamics and its uncoupling in mammals, very little is known in birds. In zebra finches, picosecond optical tomography (POT) with a white laser and a streak camera can measure in vivo oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentration changes following physiological stimulation (familiar calls and songs). POT demonstrated sufficient sub-micromolar sensitivity to resolve the fast changes in hippocampus and auditory forebrain areas with 250 µm resolution. The time-course is composed of (i) an early 2s-long event with a significant decrease in Hb and HbO2, respectively -0.7 µMoles/L and -0.9 µMoles/L (ii) a subsequent increase in blood oxygen availability with a plateau of HbO2 (+0.3µMoles/L) and (iii) pronounced vasodilatation events immediately following the end of the stimulus. One of the findings of our work is the direct link between the blood oxygen level-dependent (BOLD) signals previously published in birds and our results. Furthermore, the early vasoconstriction event and post-stimulus ringing seem to be more pronounced in birds than in mammals. These results in bird, a tachymetabolic vertebrate with a long lifespan, can potentially yield new insights for example in brain agin