Systems for applying functional near infra-red spectroscopy (FNIRS) to a head of a subject

Abstract

A system for applying functional near infra-red spectroscopy (fNIRS) measurements to the head of a subject, is presented. The system comprising one or more of: a plurality of mirror optrodes, comprising at least one optode capable of connecting to the subject's scalp through a reflector arrangement, wherein the reflector arrangement is attachable to the subject's scalp through a light scattering couplant to be applied to the scalp; sticker optrodes comprising an adhesive fdm with at least one optode embedded into the film, and at least one flexible patch with a flexible support structure which comprises one or more expanded emitter optodes at the upper part of the flexible support structure, and wherein optrodes embedded into the lower part of the flexible support structure are non-expanded emitter and detector optodes. The sticker optrodes and flexible patch are configured to be attached to a hairless area on the subject's head.

Description

[0001] SYSTEMS FOR APPLYING FUNCTIONAL NEAR INFRA-RED SPECTROSCOPY

[0002] (fNIRS) TO A HEAD OF A SUBJECT

[0003] TECHNICAL FIELD

[0004] The present disclosure, in some embodiments thereof, relates to functional near infrared spectroscopy (fNIRS) systems. More particularly, but not exclusively, to systems for applying fNIRS to a head of a subject.

[0005] BACKGROUND fNIRS assesses brain activity by measuring changes in the properties of light as it passes through the skull and is refracted back to a specialized detector. fNIRS estimates changes in the concentration of hemoglobin from changes in absorption and scattering of near infrared light. As light propagates through the head, it is scattered and absorbed by the tissue through which it travels. Because hemoglobin is a significant absorber of near-infrared light, changes in absorbed light can be used to reliably measure changes in hemoglobin concentration, primarily in oxygenated and deoxygenated hemoglobin. Different fNIRS techniques can also analyze properties of the light that propagates through tissue to estimate blood volume and oxygenation. The technique is safe, non-invasive, and can be used with other imaging modalities.

[0006] Alongside EEG, fNIRS is one of the most common non-invasive neuroimaging techniques which can be used in portable contexts. The signal is often compared with the BOLD signal measured by fMRI and is capable of measuring changes both in oxy- and deoxyhemoglobin concentration. The near infrared signal is mostly collected from regions near the cortical surface. fNIRS may also be referred to as Optical Topography (OT) and is sometimes referred to simply as NIRS.

[0007] Home monitoring with portable devices of fNIRS is a growing market. However, when applying fNIRS to a head of a subject, two main challenges arise. The first challenge is a hair problem which relates to two aspects. The first aspect is the difficulty to establish an efficient coupling with the scalp of the subject in areas covered with hair. The second aspect relates to the chromophores in the hair cells absorbing the light, such that a significant amount of light projected to the scalp is absorbed by the hair.

[0008] The second challenge is a motion artefacts problem, due to movement of the optical elements relative to the skin / scalp of the subject. Thus, there is a need for a system for applying fNIRS to a head of a subject, overcoming the hair problem and the motion artifacts problem, yet keeping the system efficient, cost effective and simple to use.

[0009] SUMMARY

[0010] According to some embodiments, provided herein are systems and methods for applying functional near infra-red spectroscopy (fNIRS) to a head of a subject. In a first aspect, a system is presented, which includes a plurality of mirror optrodes, each mirror optrode includes at least one optode capable of connecting to to the subject’s scalp through a reflector arrangement which is attachable to the subject’s scalp through a light scattering couplant to be applied to the scalp. In a first mirror optrode the at least one optode is an emitter optode and in a second mirror optrode the at least one optode is a detector optode.

[0011] Advantageously, according to some embodiments, the reflector arrangement (e.g., mirror) reflects light back to the couplant, so that a higher proportion of the light reaches the target (skin or detecting optode). The light is still absorbed by hair. However, due to the large contact surface between the couplant mass and the skin, it is possible to increase the emitted light energy, thereby overcoming the light absorption by hair and increasing the light energy entering the brain consequently increasing signal to noise ratio (SNR).

[0012] Advantageously, according to some embodiments, motion artifact in the fNIRS signal is also reduced due to relatively large contact surface between the couplant and skin and due to a mechanically stable contact between the optode and couplant.

[0013] Thus, the mirror-optrode represents the complex electro-optic system for coupling between recording devices and skin.

[0014] According to some embodiments, a second system presented herein includes a plurality of sticker optrodes, where each sticker optrode includes an adhesive film with at least one optode embedded into the film, wherein the film is attachable to a hairless area on the subject’s head, and wherein in a first sticker optrode the at least one optode is an emitter optode, and in a second sticker optrode the at least one optode is a detector optode, or the adhesive film comprises at least one emitter optode and at least one detector optode embedded into the film. According to some embodiments, a third system includes one or more of: at least one mirror optrode, at least one sticker optrode and at least one flexible patch.. The at least one mirror optrode includes at least one optode capable of being connected to the subject’s scalp through a reflector arrangement wherein the reflector arrangement is attachable to the subject’s scalp through a light scattering couplant that that may be applied to the scalp. The at least one sticker optrode includes an adhesive fdm with at least one optode embedded into the fdm, wherein the film is configured to be attached to a hairless area on the subject’s head; wherein the at least one optode of the mirror optrode or of the sticker optrode is an emitter optode and the at least one optode of the sticker optrode or of the mirror optrode respectively is a detector optode. The at least one flexible patch includes a flexible support structure configured to be attached to a hairless area on the subject’s head, which comprises which comprises one or more emitter optodes with expanded apertures diameter of about 5-30 mm, located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure which includes emitter and detector optodes with small aperture diameter of about 1-2 mm. The distance between the emitter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emitter- detectors separation.

[0015] According to some embodiments, each of the first, second or third systems may be combined with EEG electrodes, to be an EEG-fNIRS system.

[0016] Advantageously, according to some embodiments, the optodes in sticker-optrodes are arranged in a way that supports both long and short-distance fNIRS channels between sticker- optrodes and between sticker-optrode and mirror-optrode.

[0017] Advantageously, according to some embodiments, the systems presented herein are cost effective, easy to use and may be worn by the patient and / or caregiver at any time (no need for technician visit). In addition, the systems presented herein enable long term recording at home, or sporadic / during night only recording. Advantageously, according to some embodiments, the integration of fNIRS with an EEG system provides better prognostication of seizure onset zone which improves the outcome for future surgery and reduces costs.

[0018] According to some embodiments, a first system for applying functional near infra-red spectroscopy (fNIRS) measurements to a subject head is presented. The system comprises: a plurality of mirror optrodes, each mirror optrode comprising at least one optode capable of being connected to the subject’s scalp through a reflector arrangement, wherein the reflector arrangement is attachable to the subject’s scalp through a light scattering couplant applied to the scalp; and wherein in a first mirror optrode the at least one optode is an emitter optode, and in a second mirror optrode the at least one optode is a detector optode, such that light emitted from a light source by the emitter optode to the subject’s head is scattered by the light scattering couplant, and the reflector arrangement reflects the scattered light back into the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by the reflector arrangement and scattered into the detector optode.

[0019] According to some embodiments, the system further comprises: a plurality of sticker optrodes, each sticker optrode comprises an adhesive film with at least one optode embedded into the film, wherein the film is attachable to a hairless area in the subject’s head, and wherein in a first sticker optrode the at least one optode is an emitter optode, and in a second sticker optrode the at least one optode is a detector optode.

[0020] According to some embodiments, the light scattering couplant is non-conductive or conductive.

[0021] According to some embodiments, the system further comprises:

[0022] EEG electrodes embedded in the mirror optrodes, each EEG electrode being connectable to the subject’s scalp along with at least one optode through or adjacent to the reflector arrangement, wherein the reflector arrangement and the electrode are configured to be attached to the subject’s scalp through a light scattering conductive couplant that may be applied to the scalp; wherein the EEG electrode embedded into the mirror optrodes enables receiving EEG signals from the subject’s brain and / or sensing electric impedance.

[0023] According to some embodiments, the system further comprises:

[0024] EEG electrodes embedded in the sticker optrodes, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and is configured to be connected to the subject’s head through the adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and sensing electric impedance.

[0025] According to some embodiments, the reflector arrangement comprises one or more mirrors and / or reflectors and wherein the reflector arrangement is curved or flat.

[0026] According to some embodiments, the reflector arrangement is a curved reflector or mirror.

[0027] According to some embodiments, the mirror optrodes are configured to be connected to the subject’s head in an area which is covered with hair, such that light emitted from the light source by the emitter optode to the subject’s head is scattered by the couplant around the hair and the reflector arrangement reflects the scattered light back onto the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by the reflector arrangement and scattered around the hair into the detector optode.

[0028] According to some embodiments, the mirror optrode and / or sticker optrode comprise at least one pair of emitter optode and detector optode.

[0029] According to some embodiments, the at least one emitter optode is located at an external layer of the scattering couplant, such that light emitted from the at least one optode, travels through the scattering couplant before reaching the subject’s skin; and thereby covering a larger area of the skin before penetrating the subject’s tissue.

[0030] According to some embodiments, the at least one detector optode is located at an external layer of the scattering couplant, such that light scattered from the skin through the couplant reaches the detector optode.

[0031] According to some embodiments, the mirror optrode further comprises: Magnetic Resonance (MR)-compatible thermal sensor; non ferromagnetic holder with a central canal filled by white electrically conductive couplant; wherein: the reflector arrangement comprises a MR-compatible reflecting layer in a wall of the central canal of the optrode; the reflecting layer is in a cylinder shape covering the walls of the inner canal of the optrode; and a reflective cover is located above the central canal; and wherein a reflective electrode contact is located in the upper part of the mirror optrode, while the MR-compatible thermal sensor is located in the lower part of the mirror optrode, and the optode is located in one of between the EEG-electrode and thermal sensor, or it is inserted into the central canal from the upper part of the optrode.

[0032] According to some embodiments, the wall of the central canal is covered by an MR- compatible reflecting layer.

[0033] According to some embodiments, the reflecting layer is a mirror.

[0034] According to some embodiments, the optode is an optical fiber.

[0035] According to some embodiments, the distance between the emitter optrode and the detector optode in one sticker optrode is about 2 cm.

[0036] According to some embodiments, the distance between the detector optode of a first sticker optrode and the emitter optode of a second sticker optrode located next to each other is about 1 cm.

[0037] According to some embodiments, the distance between the emitter or detector optodes of the first sticker optrode and the emitter or detector optodes respectively of the second sticker optrode located next to each other, is about 3 cm.

[0038] According to some embodiments, the distance between the emitter optode of a first sticker optrode and a detector optode of a second sticker optrode located next to each other is about 3 cm. According to some embodiments, the system further comprises depth electrodes comprising emitter and / or detector elements which are configured to be inserted into the subject’s skull, wherein a plurality of emitters of mirror optrodes or sticker optrodes may be positioned over the subject’s skull, and wherein the plurality of emitters of mirror optrodes or sticker optrodes and the depth electrodes are operated simultaneously, such that optical signals travelling through deep brain structures between l-5cm from the skull inner surface, are detected.

[0039] According to some embodiments, the system enables the detection of hemodynamic changes within deep brain regions.

[0040] According to some embodiments, the system further comprises a sticker optrode set comprising a support structure attached to an additional adhesive film, wherein two or more sticker optrodes are embedded into a lower part of the support structure which is connected to the additional adhesive film and which is configured to be in contact with the subject’s skin.

[0041] According to some embodiments, the system further comprises a plurality of holders for capsules of couplant, wherein a first capsule type comprises electrically conductive light scattering couplant used for EEG and fNIRS and a second capsule type comprises electrically non-conductive light scattering couplant used for fNIRS and not for EEG.

[0042] According to some embodiments, the support structure does not absorb light in the near infrared range, and it scatters light, with a scattering coefficient similar or larger than the scattering coefficient of light in skin at near infrared range of about 600-900nm.

[0043] According to some embodiments, the support structure thickness is about 1-15 mm , such that the light emitted from the emitter optode is scattered over a distance that is more than 10 times the mean free path of the emitted light in the support structure substantially before reaching the additional adhesive film or the subject’s skin.

[0044] According to some embodiments, the support structure comprises a dielectric material.

[0045] According to some embodiments, the emitter optode is a light source embedded into the support structure.

[0046] According to some embodiments, the detector optode is a photodetector embedded into the support structure. According to some embodiments, the support structure further comprises one or more additional optodes and / or electrodes located between the sticker optrodes, such additional optodes and / or electrodes being in different distances from the emitter optodes and / or detector optodes, resulting in long and short-distance separation optical channels between optodes.

[0047] According to some embodiments, the system further comprises at least one emitter optode located at the external layer of the support structure, such that light emitted from the at least one emitter optode, travels through the support structure before reaching the subject’s skin, and thereby covering a larger area of the skin before penetrating the subject’s tissue.

[0048] According to some embodiments, the system further comprising at least one detector optode located at the external layer of the support structure, such that light scattered from the skin through the support structure reaches the detector optode.

[0049] According to some embodiments, an external layer of the support structure is covered with a reflective layer, preventing light from escaping the support structure.

[0050] According to some embodiments, the reflective layer is a reflective mirror.

[0051] According to some embodiments, the emitter optode is an optical fiber connected to a light source; or wherein the light source is mounted into the mirror optrode or sticker optrode.

[0052] According to some embodiments, the detector optode is an optical fiber connected to a photodetector; or wherein the photodetector is mounted into the mirror optrode or sticker optrode.

[0053] According to some embodiments, the photodetector is one of the following: photodiode, avalanche photodiode or photomultiplier.

[0054] According to some embodiments, the light source is a laser, laser diode or a Light Emitting Diode (LED).

[0055] According to some embodiments, the light source is a coherent light source.

[0056] According to some embodiments, the system further comprising one or more ultrasonic transducers for enabling light modulation created by an acousto-optic effect. According to some embodiments, the light source is a non-coherent light source.

[0057] According to some embodiments, the adhesive fdm is transparent and / or scattering in the near infrared range of the light spectrum of 650-1 lOOnm.

[0058] According to some embodiments, the system further comprises a temperature sensor wherein the temperature sensor is embedded into the mirror optrode and / or sticker optrode; or located between two sticker optrodes.

[0059] According to some embodiments, the temperature sensor is fiber-based, or is a thermistor.

[0060] According to some embodiments, the distance between two mirror optrodes is sufficient to allow light to reach the cerebral vasculature.

[0061] According to some embodiments, the distance between two mirror optrodes is about 2- 5 cm.

[0062] According to some embodiments, the system further comprises a flexible patch with a flexible support structure configured to be attached to a hairless area on the subject’s head, which comprises which comprises one or more emitter optodes with expanded apertures diameter of about 5-30 mm , located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure which comprises emitter and detector optodes with small aperture diameter of about 1-2 mm; wherein the distance between the emitter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emitter- detectors separation.

[0063] According to some embodiments, in the one or more emitter optodes with expanded apertures located at the upper part of the flexible support structure, the light source is placed at a distance of up to 15mm from the optodes embedded into the lower part of the flexible support structure, and wherein the scattering couplant is diffusive to expand the angle of the light beam and increase spot size of the illuminating beam over the subject’s skin. According to some embodiments, several optical fibers or small emitters are placed over the outer surface of the flexible support structure, such that the overall power reaching the subject’s skin is a superposition of the different sources.

[0064] According to some embodiments, lasers are coupled to the several optical fibers, or an array of LEDs is positioned above the emitter optode with expanded apertures located at the upper part of the flexible support structure.

[0065] According to some embodiments, the one or more emitter optodes with expanded apertures located at the upper part of the flexible support structure comprise a beam expander with two or more diffractive optical elements (DDEs), wherein a light beam is inputted through a first DOE, and outputted through a second DOE, such that the outputted beam is larger than the inputted beam.

[0066] According to some embodiments, the beam expander is one-dimensional and it is in a planar optics configuration.

[0067] According to some embodiments, at least one linear grating is directly recorded onto a planar optics substrate in the one -dimensional planar optics configuration beam expander.

[0068] According to some embodiments, two input wavelengths in the range of 690-880nm are used.

[0069] According to some embodiments, two gratings are recorded for each of the linear grating, where each linear grating has a high diffraction efficiency for one of the two input wavelengths and not for the other input wavelength.

[0070] According to some embodiments, emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure, and emitter and detector optodes with small apertures diameter located at the lower part of the flexible support structure are positioned within the flexible structure, such that channels of 30-70mm are formed between optodes inside and outside the flexible support structure.

[0071] According to some embodiments, the system further comprising: EEG electrodes embedded in the flexible support stricture, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and is configured to be connected to the subject’s head through adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and sensing electric impedance.

[0072] According to some embodiments, different emitter and detector optodes are operated interchangeably in a way that enables capturing photons that travel through different layers.

[0073] According to some embodiments, emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure are operated on each hemisphere of the brain separately, and light is detected by detectors on the contralateral hemisphere wherein the detectors are either located at the upper or lower part of the flexible support structure.

[0074] According to some embodiments, the emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure, when the small emitters close to the skin are operated on each hemisphere in a scanning manner, such that no cross talk is detected by the emitters.

[0075] According to some embodiments, the emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure may be operated one by one, or in groups or simultaneously to allow selective control of the illumination intensity.

[0076] According to some embodiments, emitter optodes with small apertures diameter located at the lower part of the flexible support structure are operated on each hemisphere in a scanning manner, such that no cross talk is detected by the emitters.

[0077] According to some embodiments, a second system for applying functional near infrared spectroscopy (fNIRS) measurements to a head of a subject is presented. The system comprises one or more of: at least one mirror optrode comprising at least one optode capable of being connected to the subject’s scalp through a reflector arrangement, wherein the reflector arrangement is configured to be attached to the subject’s scalp through a light scattering couplant that may be applied to the scalp; at least one sticker optrode comprising an adhesive film with at least one optode embedded into the film, wherein the film is configured to be attached to a hairless area on the subject’s head; wherein the at least one optode of the mirror optrode or of the sticker optrode is an emitter optode and the at least one optode of the sticker optrode or of the mirror optrode respectively is a detector optode; and at least one flexible patch with a flexible support structure configured to be attached to a hairless area on the subject’s head, which comprises which comprises one or more emitter optodes with expanded apertures diameter of about 5-30 mm, located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure which comprises emitter and detector optodes with small aperture diameter of about 1-2 mm; wherein the distance between the emitter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emitter- detectors separation.

[0078] According to some embodiments, a third system for applying functional near infra-red spectroscopy (fNIRS) measurements to a subject’s head is presented. The system comprises: a plurality of sticker optrodes, each sticker optrode comprising an adhesive film with at least one emitter optode and one detector optode embedded into the film, wherein the film is configured to be attached to a hairless area on the subject’s head.

[0079] According to some embodiments, the system further comprises:

[0080] EEG electrodes embedded in the sticker optrodes, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and it is configured to be connected to the subject’s head through the adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and / or sensing electric impedance.

[0081] According to some embodiments, a system for assessing brain activity through fNIRS measurements is presented herein. The system comprises applying the systems mentioned above, and thereby assessing brain activity. The following embodiments and aspects thereof are described and illustrated in conjunction with systems, tools and methods which are meant to be exemplary and illustrative, not limiting in scope. In various embodiments, one or more of the above-described problems have been reduced or eliminated, while other embodiments are directed to other advantages or improvements.

[0082] Certa embodiments of the present disclosure may include some, all, or none of the above advantages. One or more oilier technical advantages may be readily apparent to those skilled in the art from the figures, descriptions, and claims included herein. Moreover, while specific advantages have been enumerated above, various embodiments may include all, some, or none of the enumerated advantages.

[0083] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In case of conflict, the patent specification, including definitions, governs. As used herein, the indefinite articles “a” and “an” mean “at least one” or “one or more” unless the context clearly dictates otherwise.

[0084] BRIEF DESCRIPTION OF THE DRAWINGS

[0085] Some embodiments of the disclosure are described herein with reference to the accompanying figures. The description, together with the figures, makes apparent to a person having ordinary skill in the art how some embodiments may be practiced. The figures are for the purpose of illustrative description and no attempt is made to show structural details of an embodiment in more detail than is necessary for a fundamental understanding of the disclosure. For the sake of clarity, some objects depicted in the figures are not drawn to scale. Moreover, two different objects in the same figure may be drawn to different scales. In particular, the scale of some objects may be greatly exaggerated as compared to other objects in the same figure.

[0086] In the figures:

[0087] FIGs. 1A-1C schematically show diagrams of mirror optrodes included in a system 100, for applying fNIRS measurements to a head of a subject, according to some embodiments;

[0088] FIG. ID schematically shows an example of two mirror optodes with ultrasound in between, according to some embodiments; FIG. 2 schematically shows a MR compatible mirror optrode, according to some embodiments;

[0089] FIG. 3A schematically shows a diagram of a system 300 including a plurality of sticker optrodes, for applying fNIRS measurements to a head of a subject in hairless areas, according to some embodiments;

[0090] FIG. 3B schematically shows a diagram of a sticker optrode, according to some embodiments;

[0091] FIG. 3C schematically shows an example of two adjacent sticker optrodes, according to some embodiments;

[0092] FIG. 4A schematically shows a sticker optrodes set with two or more sticker optrodes, according to some embodiments;

[0093] FIG. 4B schematically shows a sticker optrode set with a reflective layer covering the upper part / extemal part of the support structure / sticker optrode set, according to some embodiments;

[0094] FIG. 4C schematically shows an example of a side view of a sticker optrode set, used as a sensor 450 sensing of hemodynamic changes in the grey and white matter vasculature at variable depths, according to some embodiments;

[0095] FIG. 4D schematically shows an example of a diffuser configuration, with optical fibers placed over an outer surface of a diffusing support structure according to some embodiments;

[0096] FIG. 4E schematically shows an example of a one-dimensional beam expander in a planar optics configuration using diffractive optical elements (DOEs), according to some embodiments;

[0097] FIG. 5A schematically shows a detailed drawing of sensor 500 over the forehead, according to some embodiments;

[0098] FIG. 5B schematically shows a transverse cut of the sensor 500 along line 510 of FIG. 5A, according to some embodiments;

[0099] FIGs. 6A-6B schematically show a diagram of a system 600 from the inside in a front view and a side view, according to some embodiments; FIG. 7 schematically shows an example of a system 700, applied to a head of a subject, where mirror optrodes 701 are integrated into a wearable cap 703 to ease the use of the system, according to some embodiments;

[0100] FIG. 8 schematically shows a plurality of emitters, positioned over a skull (800) of a subject from mirror or sticker optrodes that are operated simultaneously, according to some embodiments;

[0101] FIGs. 9A-9B schematically shows two configurations of an EEG-fNIRS system with holders of two types of couplant capsules, according to some embodiments;

[0102] FIGs. 10A-10B schematically shows an example of an equipment of an experiment made without a curved mirror above the couplant and with a curved mirror above the couplant from a top view, according to some embodiments; and

[0103] FIGs. 10C-10D schematically shows a side view of an example of an experiment made without a curved mirror above the couplant and with a curved mirror above the couplant, according to some embodiments.

[0104] DETAILED DESCRIPTION

[0105] In the following description, various aspects of the disclosure will be described. For the purpose of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the different aspects of the disclosure. However, it will also be apparent to one skilled in the art that the disclosure may be practiced without specific details being presented herein. Furthermore, well-known features may be omitted or simplified in order not to obscure the disclosure.

[0106] According to some embodiments, provided herein are advantageous systems and methods for applying functional near infra-red spectroscopy (fNIRS) to the head of a subject.

[0107] According to some embodiments, a first system includes a plurality of mirror optrodes, where each mirror optrode includes at least one optode capable of connecting to the subject’s scalp through a reflector arrangement wherein the reflector arrangement is attachable to the subject’s scalp through a light scattering couplant to be applied to the scalp. In a first mirror optrode the at least one optode is an emitter optode which projects light to the subject’s scalp and in a second mirror optrode the at least one optode is a detector optode, such that light emited from a light source by the emiter optode towards the subject’s head is scatered by the light scatering couplant and the reflector arrangement reflects the scatered light back onto the subject’s scalp or the light scatered from the scalp and underlying tissue is reflected by the reflector arrangement and scatered into the detector optode.

[0108] According to some embodiments, a second system includes a plurality of sticker optrodes, where each sticker optrode includes an adhesive fdm with at least one emiter optode and one detector optode embedded into the fdm and the fdm is attachable to a hairless area on the subject’s head.

[0109] According to some embodiments, a third system includes at least one mirror optrode and at least one sticker optrode. The at least one mirror optrode includes at least one optode capable of being connected to the subject’s scalp through a reflector arrangement wherein the reflector arrangement is configured to be attached to the subject’s scalp through a light scatering couplant that may be applied to the scalp. The at least one sticker optrode includes an adhesive fdm with at least one optode embedded into the fdm, wherein the fdm is configured to be atached to a hairless area on the subject’s head, wherein the at least one optode of the mirror optrode or of the sticker optrode is an emiter optode and the at least one optode of the sticker optrode or of the mirror optrode respectively is a detector optode.

[0110] According to some embodiments, each of the first, second or third systems may be combined with EEG electrodes, to be an EEG-fNIRS system.

[0111] Advantageously, the EEG-fNIRS system enables to resolve the hair problem, reduce the motion artifacts problem, combine long-distance- and short-distance-channels for separation between scalp and brain fNIRS signals, and increase the light energy entering brain (increased SNR).

[0112] According to some embodiments, an optode is an optical component such as an optical emiter configured to deliver light such as near infrared light, or a detector configured to measure light e.g. diffusely reflected near infrared light.

[0113] According to some embodiments optodes may include optical fibers, optical detectors such as photodiodes or optical emiters such as LED or lasers.

[0114] According to some embodiments, optrodes are optodes, i.e., optical components combined with electrodes. According to some embodiments, and as used herein, the term light scattering couplant or scattering couplant refers to any medium that enables a change in light propagation by scattering or diffusion or reflection or diffraction.

[0115] According to some embodiments, and as used herein, the term depth electrode refers to electrodes which are configured to record and / or stimulate electrical activity within brain tissue.

[0116] According to some embodiments, the systems presented herein are portable systems, suitable for home recording that may be started or maintained by patients themselves, or possibly with help of one minimally trained caregiver.

[0117] Reference is now made to FIG. 1A, which schematically show a diagram of a system 100, for applying fNIRS measurements to a head of a subject, according to some embodiments. System 100 includes a plurality of mirror optrodes lOla-lOld, according to some embodiments, which are attached to the head of the subject, typically on the scalp or skin of the subject.

[0118] According to some embodiments, system 100 includes at least two mirror optrodes 101a and 101b wherein in mirror optrode 101a the at least one optode 102a is an emitter optode and in mirror optrode 101b the at least one optode 102b is a detector optode, such that light emitted by emitter optode 102b to the subject’s head is scattered by the light scattering couplant 104 and the reflector arrangement 103 reflects the scattered light back into the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by reflector arrangement 103 and scattered into detector optode 102b.

[0119] FIG. IB schematically shows a diagram of one mirror optrode 101c, according to some embodiments. According to some embodiments mirror optrode 101c includes at least one optode 102c which is connected to the subject’s scalp through a reflector arrangement 103. According to some embodiments, reflector arrangement 103 is attached to the subject’s scalp through a light scattering couplant 104 that is applied to the scalp.

[0120] According to some embodiments, the scattering couplant may be a paste, a gel or liquid. According to some embodiments, the scattering couplant is a white paste or nearly white.

[0121] According to some embodiments, the reflector arrangement includes one or more reflectors, for example one or more mirrors. According to some embodiments the one or more reflectors may be flat or curved or concaved or in any other shape. According to some embodiments the reflector arrangement as a whole may be flat or curved or concaved or in any other shape.

[0122] According to some embodiments, optode 102c is an optical fiber coupled to a light source. According to some embodiments, optode 102c may also be a light source such as a LED, a laser or laser diode.

[0123] Advantageously, according to some embodiments, mirror optrodes lOla-lOld may be connected to the subject’s scalp in areas covered with hair, such that light projected from the light source by the emitter optode to the subject’s head is scattered by the couplant around the hair and the reflector arrangement reflects the scattered light back into the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by the reflector arrangement and scattered around the hair into the detector optode, thereby overcoming the hair problem and providing a solution to light absorption by the hair. According to some other embodiments mirror optrodes lOla-lOld may be connected to hairless areas on the subject’s head as well such as on the forehead, around the ears and the like.

[0124] According to some embodiments, the distance between two mirror optrodes is sufficient to allow light to reach the cerebral vasculature.

[0125] According to some embodiments, the distance between two mirror optrodes is about 2- 5 cm.

[0126] According to some embodiments, system 100 may be an EEG-fNIRS system and mirror optrodes lOla-lOld may include at least one EEG electrode 105, which is connected to the subject’s scalp along with at least one optode 102, through or adjacent to reflector arrangement 103, wherein reflector arrangement 103 and electrode 105 are attached to the subject’s scalp through a conductive light scattering couplant, that is applied to the scalp.

[0127] EEG electrode 105 embedded into the mirror optrode such as optrodes lOla-lOld enables receiving EEG signals from the subject’s brain and / or sensing electric impedance.

[0128] FIG. 1C schematically shows an additional configuration of a mirror optrode lOld, according to some embodiments. In this case optode 102d and EEG electrode 105d are connected to reflector arrangement 103d from the side. According to some embodiments, mirror optrode such as mirror optrode 101a may include a pair of optodes (not shown), in this case one optode is an emitter optode and the second optode is a detector optode. According to some embodiments, in the case of a mirror optrode which includes a pair of optodes, system 100 may include at least one mirror optrode.

[0129] According to some embodiments, the light source may be a non-coherent light source, or a coherent light source. According to some embodiments, the light source is a laser, laser diode or a Light Emitting Diode (LED).

[0130] According to some embodiments, system 100 includes a control unit (not shown) which controls the operation of the system. According to some embodiments, the mirror optrodes and EEG electrodes are connected to the control unit through wires or wireless. The control unit controls the light pulses, the timing of light pulses, receives signal from the EEG electrodes and monitors the brain according to the received signals from the EEG-fNIRS system.

[0131] The duration of light pulses may range from very short (fseconds) up to relatively long (seconds).

[0132] According to some embodiments, the system may further include one or more ultrasonic transducers for enabling light modulation created by an acousto-optic effect.

[0133] According to some embodiments, the coupling of light to the skin is achieved using a large-surface-area scattering (white) couplant. This configuration reduces the spatial resolution of the measured volume, i.e., a larger volume tissue is illuminated by a pair of optodes compared to coupling without a large-area white couplant. Therefore, in some embodiments, system 100 may further include an ultrasound emitter (transducer). This transducer may be a single element, or alternatively an array of elements that may direct the ultrasonic beam in different directions.

[0134] FIG. ID schematically shows a mirror-optrode system that includes two optrodes and an ultrasound transducer, according to some embodiments. For simplicity, the electrodes for EEG sensing are not shown, but may be added as necessary according to some embodiments.

[0135] Two mirror-optrodes lOlf and 101g that include a white couplant (conductive or non- conductive) and a curved reflector such as a mirror are presented. Optodes 102f and 102g are connected to each mirror optrode respectively. Optodes 102f and 102g may include light emitters or detectors, either directly embedded within the optrodes or using optical fibers coupled to optrodes lOlf and 101g. According to some embodiment, the light sources are coherent light sources (i.e., laser light sources with a coherent length that is longer than the pathlength of photons inside the tissue, typically larger than 10cm). The two mirror optrodes lOlf and 101g may “overlap” through the white couplant or may be isolated.

[0136] An ultrasound transducer or array of transducers 120 is positioned in contact with the skin, in a way that ultrasonic waves propagate through the skull and insonate the tissue illuminated by either one of the optrodes lOlf or 101g (or both). Wire 121 couples the transducer 120 to a control unit (not shown) that controls the operation of the system. When coherent light is used, ultrasound-tagging of the photons that propagate through the insonated volume is achieved via the Acousto-optic effect. Using methods known in the art, it is possible to measure the optical properties or the concentrations of oxygenated and deoxygenated hemoglobin, or the blood flow, within a region of interest inside the brain, by measuring the tagged photons that propagate within this region.

[0137] According to some embodiments, the use of the ultrasonic transducer enables to improve the spatial resolution of the optical measurement compared to measurements without ultrasonic tagging. The white couplant may transmit the ultrasonic waves efficiently through the hair in addition to scattering light, since it reduces the acoustic impedance mismatch between the hair cells and air. According to some embodiments, when transducer 120 includes an array of transducers, the region of interest may be selected during the operation of the system by selecting the direction and focus of insonation, and therefore the volume of tagging by the ultrasound waves.

[0138] According to some embodiments, the mirror optrode may be a Magnetic Resonance (MR) compatible mirror optrode.

[0139] The simultaneous EEG-fMRI recording combines the high temporal resolution of EEG with the high spatial resolution of fMRI. This enables the detection of hemodynamic correlates of signals recorded by EEG. The disadvantage of MRI is the low temporal resolution. This can be partially compensated by simultaneous recording with fNIRS, which has a high temporal resolution: EEG-fMRI-fNIRS.

[0140] One of the safety issues of EEG-fMRI is the potential heating of EEG electrodes due to MR-scanner-generated radio-frequency oscillations of the magnetic field. According to some embodiments, adding an MR-compatible thermal sensor to EEG-electrode simplifies this problem. FIG. 2 schematically shows a Magnetic Resonance (MR) compatible mirror optrode, according to some embodiments. In this case a mirror optrode further include a Magnetic Resonance (MR) -compatible thermal sensor 203 and a non-ferromagnetic holder 204 with a central canal filled by white electrically conductive couplant 221 and covered by top reflector 222. In this case, according to some embodiments, polymer holder 204 as a part of MR- compatible EEG-electrode is relatively tall, compared to an EEG electrode. This design serves to increase the distance between the electrode contact and the skin. According to some embodiments, polymer holder 204 is a polymer cylinder (or nearly cylinder) with a central canal fdled with a conductive couplant 221 (typically gel or paste). According to some embodiments, the electrode contact 201 is located in the holder's upper part, contacting with the conductive couplant.

[0141] According to some embodiments, in this case, the reflector arrangement includes MR- compatible reflecting layer 205 in a wall of the central canal of the optrode. According to some embodiments, the reflecting layer is in a cylinder shape covering the walls of inner canal of the optrode. In addition, according to some embodiments, a (preferably reflective) EEG electrode contact 201 is located in the upper part of the mirror optrode, while the MR-compatible thermal sensor 203 is located in the lower part of the mirror optrode, and an NIRS optode 202 is located in one of: between EEG-electrode 201 and thermal sensor 203 or alternatively, it is inserted into the central canal from the upper part of the optrode.

[0142] According to some embodiments, the wall of the central canal is covered by an MR- compatible reflecting layer to prevent light absorption by the polymer holder. According to some embodiments, the reflecting layer is a mirror.

[0143] Reference is now made to FIG. 3A which schematically shows system 300, which includes a plurality of sticker optrodes 301a-301e for applying fNIRS measurements to a head of a subject. According to some embodiments, sticker optrodes 301a-301e are attached to a hairless area in the subject’s head. FIG. 3B schematically shows sticker optrodes 301a, according to some embodiments. Each sticker optrode, such as sticker optrode 301a includes an adhesive fdm 304 with at least one optode 302a embedded into film 304, wherein film 304 is attached to a hairless area in the subject’s head. According to some embodiments, optode 302a is an optical fiber. According to some embodiments, in sticker optrode 301a the at least one optode 302a is an emitter optode and in sticker optrode 301b the at least one optode is a detector optode (FIG. 3C). According to some embodiments, sticker optrode such as sticker optrode 301a may include a pair of optodes 302a and 302b, in this case optode 302a is an emitter optode and optode 302b is a detector optode. According to some embodiments in case of a sticker optrode which includes a pair of optodes, system 300 may include at least one sticker optrode.

[0144] According to some embodiments, emitter optode 302a includes the light source mounted into sticker optrode 301a. According to some embodiments, detector optode 302b is an optical fiber connected to a photodetector, or alternatively detector optode 302b includes the photodetector.

[0145] According to some embodiments, the photodetector may be, for example a photodiode, an avalanche photodiode or a photomultiplier.

[0146] According to some embodiments, the adhesive film is transparent and / or scattering in the near infrared range of the light spectrum of 650-1 lOOnm.

[0147] According to some embodiments, sticker optrode 301a may include at least one EEG electrode 305 embedded in sticker optrodes 301a, wherein each EEG electrode is located in the vicinity of emitter optode 302a and detector optode 302b and is connected to the subject’s head through adhesive film 304. Advantageously, the EEG electric wires of EEG electrode 305 embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and sensing electric impedance.

[0148] According to some embodiments, the emitter optode 302a is an optical fiber connected to a light source. According to some embodiments, the emitter optode 302a is a light source.

[0149] According to some embodiments, system 300 includes a control unit (not shown) which controls the operation of the system 300. According to some embodiments, the sticker optrodes and EEG electrodes are connected to the control unit with wires. The control unit controls the light pulses, the timing of light pulses, receives signal from the EEG electrodes and monitors the brain according to the received signals from the EEG-fNIRS system.

[0150] According to some embodiments, system 300 may further include a sticker optrodes set which includes a support structure attached to an additional adhesive film. In the sticker optrodes set, two or more sticker optrodes are embedded into a lower part of the support structure which is connected to the additional adhesive film and which is in contact with the subject’s skin FIG. 3C schematically shows an example of two adjacent sticker optrodes, according to some embodiments. According to some embodiments, the distance between the emitter optode and the detector optode in a sticker optrode is about 2 cm. According to some embodiments, sticker optrode 301c includes two emitter optodes 302c and 302c’, with a distance of about 2cm between them, and sticker optrode 301e includes two detector optrodes 302e and 302e’, with a distance of about 2cm between them. According to some embodiment, the distance between emitter optode 302c (or 302c’) of sticker optrode 301c and the detector optode 302e (or 302e’) of sticker optrode 301e located next to each other is about 1 cm, such that the distance between emitter optode 302c and detector optode 302e is about 3cm.

[0151] According to some embodiments, the distance between the emitter optode or detector optode of the first sticker optrode and the emitter optode or detector optode respectively of the second sticker optrode, located next to each other, is about 3 cm.

[0152] According to some embodiments, sticker-optrodes such as sticker optrode 301a (Fig 3B) comprise at least one emitter optode and at least one detector optode positioned at distances of between l-3cm from each other. Such sticker-optrodes are positioned relative to each other, such that the distances between emitter optodes and detector optodes of different sticker- optrodes are within the range of 0.5-4cm.

[0153] FIG. 4A schematically shows an example of a sticker optrodes set, according to some embodiments. Sticker optrodes set 400, includes an adhesive film 420 and a support structure 410. According to some embodiments, adhesive film 420 is configured to attach sticker optrodes set 400 to the skin or scalp of the subjects, in hairless areas. According to some embodiments, support structure 410, does not absorb light in the near infrared range, but does scatter light, with a scattering coefficient similar or larger than the scattering coefficient of light in skin at near infrared range of about 600-900nm.

[0154] According to some embodiments, in support structure 410 several sticker optrodes are embedded such as sticker optrodes 402. Each sticker optrode includes one or several of: emitter-optodes 402A, , detector-optodes 402B, and EEG or impedance electrodes 402C. According to some embodiments, the sticker optrodes are positioned on the skin-side of sticker optrodes set 400, in close proximity to the skin.

[0155] According to some embodiments, the thickness of support structure 410 is about 1- 10mm, such that the light emitted from the emitter optode is scattered over a distance that is more than 10 times the mean free path of the emitted light in the support structure substantially before reaching the additional adhesive fdm or the subject’s skin.

[0156] According to some embodiments, support structure 410 comprises a dielectric material, to avoid conduction of electrical fields.

[0157] According to some embodiments, emitter optodes 402A, are a light source embedded into support structure 410.

[0158] According to some embodiments, detector optodes 402B, are photodetectors embedded into support structure 410.

[0159] According to some embodiments, a reflective layer covers an external layer of the support structure, to prevent light from escaping from the support structure. FIG. 4b schematically shows an example of a sticker optrodes set with a reflective layer (e.g., mirror) 430. Reflective layer 430 covers the external layer of support structure 410, thereby preventing light from escaping the support structure 410.

[0160] According to some embodiments, support structure 410 further includes one or more additional optodes, and / or electrodes such as elements 409, 411, 412 and 413, located between the sticker optrodes (402) such additional optodes and / or electrodes being in different distances from the emitter optodes 402A, and / or detector optodes 402B, resulting in long and shortdistance separation optical channels between optodes.

[0161] According to some embodiments, sticker optrodes set 400 may further include at least one emitter optode 401A or detector optode 401B located at the external layer of support structure 410, such that light emitted from the one or more pair of optodes 401A, travels through the support structure before reaching the subject’s skin, thereby, covering an area of the skin larger than the area covered by light emitted from emitter optodes 402A, positioned in closer proximity to the skin, before penetrating the subject’s tissue. Thereby, allowing to apply a higher power of light, compared to the light emitted from the one or more emitter optodes 402Apositioned in closer proximity to the skin. Additionally, or alternatively, light scattered from the skin through support structure 410 reaches detector optode 401B.

[0162] According to some embodiments, the distances between sticker optrodes, emitter optodes and detector optodes embedded in the support structure may be as follows: the distance between an emitter optode (such as 302e) and a detector optode (such as 302c) in a sticker optrode embedded into the sticker optrodes set is about 2 cm. According to some embodiment, a sticker optrode such as sticker optrodes 301e and / or sticker optrode 301c may be embedded in a sticker optrodes set and may include two emitter optodes such as 302e and 302e’, with a distance of 2cm between them, and sticker optrode such as 301c includes two detector optrodes such as 302c and 302c’, with a distance of 2cm between them. According to some embodiment, the distance between emitter optode such as 302e (or 302e’) of sticker optrode (such as 301e) and the detector optode (such as 302c (or 302c’)) of sticker optrode (such as 301c) located next to each other is about 1 cm, such that the distance between emitter optode (such as 302e) and detector optode (such as 302c) is about 3cm.

[0163] According to some embodiment, in the sticker optrodes set, the distance between the emitter optode or detector optode of the first sticker optrode and the emitter optode or detector optode respectively of the second sticker optrode located next to each other, is about 3 cm.

[0164] According to some embodiments, the mirror optrode system such as system 100 and the sticker optrode system such as system 300 may further include a temperature sensor. The temperature sensor is embedded into the mirror optrode and / or sticker optrode or located between two sticker optrodes. According to some embodiments, the temperature sensor is fiber-based or is a thermistor.

[0165] According to some embodiments, a brain activity sensor that enables sensing of hemodynamic changes in the grey and white matter vasculature at variable depths, for sensing deeper layers of the brain than current fNIRS solutions, is presented. The brain activity sensor includes at least one flexible patch with a flexible support structure including emitters having apertures (over the skin) with variable areas, and detectors at variable distances from these emitters.

[0166] The brain activity sensor is based on flexile support structures which integrate optodes (light emitters and detectors) for fNIRS and electrodes for EEG (such as support structure 410),. According to some embodiments, the brain activity sensor may include forehead flexible patches or around the ears flexible patches, or any other flexible patches that can be positioned over hairless regions

[0167] FIG. 4C schematically shows an example of a side view of a sticker optrode set, used as a brain activity sensor 450 sensing of hemodynamic changes in the grey and white matter vasculature at variable depths, according to some embodiments. Sensor 450 includes a forehead flexible support structure 460 which may be several millimeters thick (2-5mm), and which incorporating two types of optodes: Skin and Top (expanded) optodes. Trapezoids 461 represent the light emitted or detected through sensor 450. According to some embodiments, a reflective layer 480 (for example a mirror) covers the outer surface of the sensor, to prevent light from escaping the sensor prior to detection

[0168] According to some embodiments, skin optodes 452A-452C, 457, 459 have a small aperture of about l-2mm in diameter, and are positioned in close contact with the skin. The distances between emitters and detectors range between 5mm and 35mm. According to some embodiments, skin optodes may include expanded emitters such as emitter optodes 458. According to some embodiments, top emitter optodes 451 (expanded emitters) are positioned at the upper part of flexible support structure 460, such that emitted light is expanded before reaching the skin resulting in a comparatively larger aperture of about 5-30mm in diameter. According to some embodiments, the allowed exposure of the skin depends on the power per unit area, therefore increasing the diameter of the input aperture enables to increase the light intensity by the square of the radius (area), without exceeding the skin safety limits.

[0169] According to the Beer-Lambert equation the detected light is:

[0170] Idet = I0e-^ffd, where Io is the intensity of the incident light, p is the effective optical attenuation in tissue, and d is the distance travelled by the light between the source and the detector. As the minimal detected light intensity Idet, min is limited by the Noise Equivalent Power of the detector, increasing Io enables light to travel larger distances d. This is enabled by using larger emitter-detector separations. In order to capture photons that may escape through the flexible support structure, it is covered by a reflective layer. According to some embodiments, the skin detectors (for example 452A) are protected by dark masks (not shown), to prevent detection of light that propagates directly through the flexible support structure.

[0171] Consequently, more light can reach deeper layers, with a similar detection sensitivity. According to some embodiments, an adhesive patch 470 is used to couple brain activity sensor 450, which is a reusable sensor, to the skin. Adhesive patch 470 is.disposable, transparent and electrically conductive. According to some embodiments, advantageously, flexible brain activity sensor 450 which integrates the above fNIRS optodes and EEG electrodes in multi levels and multi -distance configurations enables depth selectivity at small (l-3cm) and large (5-7cm) source (emitter)-detector separations. According to some embodiments, two configurations are presented for increasing the aperture of the top emitter in a thin (~5-15mm) and flexible sensor patch: a diffuser configuration and a beam expander configuration. The different configurations deal with how the illuminating light is expanded before reaching the skin interface by the scattering couplant. These configurations provide an increased light intensity without compromising skin safety, which in turn results in a higher SNR, as explained above. Skin safety for near infrared light is about 300mW / cm2, and is taken as a constraint in the configuration, to allow human experiments. Both configurations include a reflective layer, as shown in Fig. 4C.

[0172] According to some embodiments, a first configuration is a diffuser configuration (e.g. the scattering couplant is a diffusing element). A diffuser configuration is used for expanding a beam. In the diffuser configuration, the light source is placed at distance of up to 15mm from the skin-interface and the coupling medium is diffusive (high scattering and low absorption) to expand the angle of the light beam and increase the spot size of the illuminating beam over the skin. The advantage of the diffuser configuration is its relative simplicity and the fewer parameters to adjust and optimize. However, in the diffuser configuration the expansion ratio dictated by the thickness of the flexible brain activity sensor is limited, for reasonable scattering coefficients. This may be overcome by placing several optical fibers or small emitters, over the outer surface of the diffusing support structure. FIG. 4D schematically shows an example of a diffuser configuration, with optical fibers placed over an outer surface of a diffusing flexible support structure according to some embodiments. As can be seen in FIG. 4D, optical fibers 491a, 491b, 491c, 491d, 491e and 491f deliver light to a sensor such as sensor 450, light is scattered by scattering support layer 460. The overall area illuminating the skin depends on the number of fibers and the distance between them, such that the overall power reaching the skin is a superposition of the different sources. As such, a diffuser configuration requires the use of lasers coupled to the optical fibers, or an array of LEDs positioned above the diffuser.

[0173] According to some embodiments, a second configuration is a beam expander configuration (e.g. the scattering couplant is a diffractive or reflective element). FIG. 4E schematically shows a one-dimensional beam expander in a planar optics configuration using diffractive optical elements (DDEs), according to some embodiments. The input planar beam is introduced using a 1stDOE 481 and escapes the expander at the 2ndDOE 482.

[0174] The advantage of the beam expander configuration is the capability to create an expanded spot size while maintaining a thin structure that can be flexible and integrated within a flexible support structure of a sensor such as sensor 450, on curved surfaces. The typical width of these thin structures is around l-2mm.

[0175] Creating the diffractive optical elements (DOEs) involves a specialized fabrication process. It is first needed to optimize the configuration parameters, including the desired expansion ratio, wavelength range, and input beam characteristics, along with integration into the overall sensor and adaptability to curved surfaces. These parameters guide the selection of appropriate materials for the planar optics substrate and the grating recording medium, with suitable optical and mechanical properties.

[0176] At least one linear grating is directly recorded onto the planar optics substrate using advanced techniques such as laser interference lithography, direct laser writing, or holographic exposure, depending on the grating material chosen. These methods enable precise control over the grating parameters, including groove density, modulation depth, and orientation. According to some embodiments, during the recording process, the planar optics substrate is carefully positioned and stabilized to ensure uniform exposure across the entire surface. The recording parameters, such as power, exposure time, and spatial coherence, need to be optimized to achieve the desired grating characteristics and performance.

[0177] After grating recording, additional optical elements, such as lenses or mirrors, may be integrated into the planar optics configuration to further refine the expanded beam's characteristics.

[0178] Linear gratings are wavelength sensitive and usually optimized for specific narrow bandwidths of light at specific angles. Since the hemodynamic measurements require the use of two wavelengths in the range of 690-880nm, this requirement is incorporated into the configuration, and according to some embodiments, two input wavelengths in the range of 750- 850nm are used.

[0179] In order to address this challenge, two possible paths are considered in the design stage of the beam expander configuration, The first, is recording a relatively wide bandwidth response grating. This can be done under specific conditions that include how far separated are the illuminating wavelength, the recording material and its available modulation depth and the geometrical considerations of the configuration. The second path is using a multiplexed approach, meaning recording two gratings for each of the linear grating, where each has a high diffraction efficiency for one of the two input wavelengths and not the other. This method has been used in various configurations, especially in communication systems. The applicability in this approach in the beam expander configuration depends on the desired performance parameters, such as the expansion ratio, the input beam characteristics and adaptation to the curved interface.

[0180] The disadvantage of this approach is the relatively complex initial design and fabrication. However, once optimized, the fabrication process is cheap and relatively simple, using conventional 3D printing or holographic recording technologies.

[0181] The major advantage compared to using diffusers is the higher and controllable expansion ratio that can be achieved, which allows for higher intensity of light to illuminate the brain. Other advantages include: a simpler design of the illuminating beam, a lower light loss within the flexible support structure and the use of cheaper light sources, such as LEDs.

[0182] The challenges of this design are first, folding the optical setup to achieve a compact, and especially low profile, sensor, while maintaining a high input intensity for the optimized signal. And second, designing and fabricating a sensor that can be worn for long periods of times, where the interface to the skin may be curved hard surfaces and / or surfaces with limited access, e.g., the forehead or behind the ear. This requires the design to be flexible, including all optical parts.

[0183] The expanded illumination spot is integrated into a flexible structure which is applied over hairless regions using a single use adhesive. In addition, smaller aperture optodes are also embedded within the flexible support structure. In this configuration selective depth measurements are achieved, similar to conventional spatially-resolved CW-fNIRS, albeit at deeper depths. FIG. 5A schematically shows a detailed drawing of brain activity sensor 500 over the forehead, according to some embodiments. Two (or more) separate flexible patches 551 and 552 are located over hairless regions (for example the forehead). The flexible patches may be attached to the skin using adhesives. The beam expander or diffuser described above are integrated into the flexible support structure, which is diffusive in the case of the diffuser design. Arrows such as arrow 521 indicate conventional 3cm channels between skin emitter

[0184] 504 and detector 502 and ellipses such as ellipse 522 indicate short 1-1.5 cm channels (skin optodes). Expanded emitter 501 is shown as a blurred circle. EEG electrodes such as electrode

[0185] 505 are embedded inside the sensor. The flexible support structure is covered with a reflective coating to prevent light from escaping it (not shown).

[0186] FIG. 5B schematically shows a transverse cut of the sensor 500 along line 510 of Fig. 5A, according to some embodiments. Emission is alternated between expanded emitter 501 and skin emiter 504. Additional expanded (top) detectors 503 (not shown in Fig. 5A) are integrated as part of reflective layer 530 and can be operated to capture light from emiters positioned either within or outside this sensor.

[0187] The two types of optodes, Top (expanded) (501, 503) or skin (small)) (504, 502) are positioned within flexible support structure 560, such that channels of 30-70mm (short and variable distance channels) are formed between optodes inside and outside structure 560. Large area detectors can also be integrated in a way that does not block the emited light, by incorporating the detectors within the reflective layer 530 of the support structure 560. The different types of emiters and detectors are operated interchangeably in a way that enables capturing photons that travel through different tissue layers.

[0188] The scan rate, the sampled depth and the depth selectivity may be optimized, according to a specific task or hypothesis about the depth of the EZ or the cortical area involved in higher- level cognitive tasks. For example, according to some embodiments, two operating modes (for each wavelength of light) may be applied:

[0189] 1. Expanded emission - according to some embodiments, in this mode the expanded emiters are operated on each side separately, and light is detected by the detectors on the contralateral hemisphere (either skin or top detectors). According to some embodiments, the expanded emiters may be operated one by one, or simultaneously to allow selective control of the illumination intensity.

[0190] 2. Skin emission - according to some embodiments, in this mode the small emiters close to the skin are operated on each hemisphere in a scanning manner, such that no cross talk is detected by the emiters.

[0191] According to some embodiments, when the brain activity sensor is integrated with other emiters on other flexible support structures, mirror-optrodes or sticker-optrodes or over-the- head caps, the operation of the sensor is synchronized with that of the other emiters.

[0192] According to some embodiments, a third system is presented herein, which is a combined system and includes one or more of, mirror optrodes, sticker optrodes and / or flexible patch creating the brain activity sensor. According to some embodiments, the combined system includes at least one mirror optrode and at least one sticker optrode. The at least one mirror optrode includes at least one optode connected to the subject’s scalp through a reflector arrangement wherein the reflector arrangement is atached to the subject’s scalp through a light scatering couplant that is applied to the scalp. According to some embodiments, at least one sticker optrode includes an adhesive film with at least one optode embedded into the film, wherein the film is configured to be atached to a hairless area in the subject’s head. According to some embodiments, the at least one optode of the mirror optrode or of the sticker optrode is an emiter optode and the at least one optode of the sticker optrode or of the mirror optrode respectively is a detector optode. According to some embodiments, the flexible patch includes a flexible support structure configured to be attached to a hairless area in the subject’s head, which includes one or more emiter optodes with expanded apertures diameter of about 5-30 mm, located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure including emiter and detector optodes with small aperture diameter of about 1-2 mm. According to some embodiments, the distance between the emiter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emiter- detectors separation.

[0193] FIGs. 6A-6B schematically shows an example of a system 600, which is a combined system that includes mirror optrodes and sticker optrodes atached to a head of a subject, according to some embodiments. FIG. 6A schematically shows a front view of system 600 atached to the subject’s head. As can be seen mirror optrodes 601 are atached to the scalp of the subject which may be covered with hair. According to some embodiments mirror electrodes 601may also be atached to hairless areas on the head of the subject. According to some embodiments, sticker optrodes 602 are atached to hairless areas on the subject’s head, for example the forehead as can be seen in FIG. 6A.

[0194] FIG. 6B schematically shows a side view of system 600 attached to the subject’s head. According to some embodiments, as can be seen in FIG. 6B sticker optrodes 602 are atached around the ears, which is a hairless area on the subject’s head.

[0195] FIG. 7 schematically shows an example of a system 700 of a combined system, applied to a head of a subject, where mirror optrodes 701 are integrated into a wearable cap 703 to ease the use of the system. The sticker optrodes such as sticker optrodes 702 are atached to hairless areas in the subject’s head.

[0196] According to some embodiments, system 700 includes a control unit 707 which controls the operation of system 700. According to some embodiments, the mirror optrodes, sticker optrodes and EEG electrodes are connected to control unit 707 through wires. The control unit controls the light pulses, the timing of light pulses, receives signal from the EEG electrodes and monitors the brain according to the received signals from the EEG-fNIRS system. The connection between the mirror optrodes, sticker optrodes and EEG electrodes, to control unit 707 may also be wireless. According to some embodiments, system 600 in FIGs. 6A-6B includes a control unit (not shown) similar to control unit 707 described above, which controls the operation of system 600.

[0197] According to some embodiments the mirror optrodes and sticker optrodes in systems 600 and 700 are essentially the same as the mirror optrodes described in system 100 and as the sticker optrodes described in system 300.

[0198] According to some embodiments, the at least one emitter optode in the mirror optrode is located at an external layer of scattering couplant 104, such that light emitted from the at least one pair of optodes, travels through the scattering couplant before reaching the subject’s skin, thereby, covering a larger area of the skin before penetrating the subject’s tissue, allowing to apply a higher power of light, compared to the light emitted from the emitter optode applied directly onto the skin.

[0199] According to some embodiments, the at least one detector optode in the mirror optrode is located at an external layer of scattering couplant 104, such that light scattered from the skin through couplant 104 reaches the detector optode.

[0200] According to some embodiments, using a plurality of sticker optrodes, flexible patches and mirror optrodes (either type can be applied exclusively), the whole head can be illuminated simultaneously or periodically by one or preferably by several light sources.

[0201] According to some embodiments, in some users, depth electrodes are configured to be inserted into the parenchyma. Conventional depth electrodes include electrical contact.

[0202] According to some embodiments, depth electrodes with intracerebral optical components embedded within the depth electrode may be used. Such optical elements can be detector components (preferably optical fibers coupled to external detectors) or emitter components, as shown in the FIG. 8.

[0203] FIG. 8 schematically shows a plurality of emitters, positioned over a skull (800) of a subject (from mirror or sticker optrodes) that are operated simultaneously, according to some embodiments. Light (dashed lines such as 804) is diffused within the brain 810 and light from several emiters 801, can reach detector components 803 positioned within several depth electrodes 802.

[0204] It should be noted that the light intensity per area that is emited from each emiter is limited by the safety limit of the skin. Therefore, the intensity of light from a single emiter that reaches a detector component positioned within the depth electrode may be lower than the detection limit of the detector.

[0205] According to some embodiments, when depth electrodes with optical components are operated simultaneously (or at least several emiters are operated simultaneously) with the current embodiment of multiple illumination elements via the scalp, the intensity of light reaching each detector is higher. Consequently, optical signals travelling through deeper brain structures, compared to single emiter operation, or compared to non-invasive sensing, can be detected. Therefore, hemodynamic changes within regions that are not covered with the non- invasive sensors can be reached.

[0206] In addition, all detector elements (such as detector elements 803) are operated simultaneously (by aligning the time-gating for collection of signals, or by simply collecting the photo-detected signal continuously). Therefore, the relative changes in the intensity of light reaching all detectors can be used to calculate changes in the light intensity traveling through the different paths reaching each detector. Consequently, tomographic mapping (within the brain) can be applied to the signals reaching each detector, improving the resolution of intracerebral imaging compared to non-invasive sensing.

[0207] According to some embodiments, the EEG-fNIRS system, such as systems 600 or 700 or 800, may include holders for capsules of couplant. According to some embodiments, there are two types of capsules. A first type of capsule contains electrically conductive and light scatering (white) couplant used for EEG and fNIRS (see element 910 marked as doted circles in Figs. 9A and 9B) . A second capsule type contains electrically non-conductive lightscatering couplant used for fNIRS but cannot be used for EEG coupling (see element 911 marked as lined circles in Figs. 9A and 9B) . The two types of capsules are inserted into holders in the EEG-fNIRS system in a predetermined arrangement. According to some embodiments, the non-conductive light scatering couplant prevents the electrical bridging of the conductive light scatering couplant between capsules. The user can, at different recording sessions, insert the capsules so that the holders of capsules of the first type in the first session are arranged according to the example shown in Fig 9A. Alternatively, the user may use in different sessions different configurations of the EEG-fNIRS system, with prepared and / or inserted capsules in alternative arrangement, for example, as in the arrangement shown in Fig. 9B. Other arrangements can be used.

[0208] According to some embodiments, the EEG-fNIRS system may be integrated into a wearable cap, to ease the attachment of the system to the head of the subject.

[0209] FIGs. 9A-9B schematically shows two exemplary configurations of an EEG-fNIRS system with different arrangements of holders of two types of couplant capsules 910 and 911, according to some embodiments. The location of each capsule 910 and 911 may be changed according to various considerations.

[0210] Example 1 - Phantom study:

[0211] In order to validate the disclosed systems a phantom study was conducted, coupling NIR light into a tissue- mimicking phantom that included optical fibers coupled to the phantom with a white paste (for example Ten20©) as a couplant.

[0212] FIGs. 10A-10B schematically shows an example of an equipment of an experiment made without a curved mirror above the couplant and with a curved mirror above the couplant from a top view, according to some embodiments.

[0213] FIGs. 10C-10D schematically shows a side view of the example of the experiment made without a curved mirror above the couplant and with a curved mirror above the couplant, according to some embodiments.

[0214] The optical attenuation of near infrared light by the paste were measured and determined to be similar to that of brain tissue (about half of the values reported for the brain).

[0215] A tissue mimicking phantom composed of PDMS with 1% (by weight) TiO2 simulating brain tissue was used, with a “skull” 1001 mimicking white PLA layer (8mm thickness) optically coupled to the phantom using a transparent gel.

[0216] A laser emitting light at 830nm was coupled to the “skull” 1001 using multi-mode optical fibers, and a lump of paste 1005 (see Fig. 10A).

[0217] An avalanche photodiode (APD) was coupled to the “skull” 1001 using a similar lump of paste 1005 and an optical fiber bundle with a diameter of 1mm. The direct light between the 2 lumps of paster was blocked using a small cardboard. An additional optical fiber (bundle of 3 fibers with a 200mm diameter) was positioned about 2.8cm below emitter fiber 1003 and coupled to another APD.

[0218] Mirrors were placed over the lumps of paste coupled to the emitter fiber 1003 and detector fiber 1004. Curved mirror 1006 was placed over the paste coupled to emitter fiber 1003, and flat mirror 1002 was placed over the paste coupled to detector fiber 1004.

[0219] The distance between the emitting fiber 1003 and the detector fiber 1004 was about 5cm.

[0220] The light intensity was measured for the APD coupled to detector fiber in table 1 with and without a mirror above the lump of paste coupled to the emitter fiber 1003.

[0221] Table 1

[0222] From Table 1, it can be seen that the addition of the mirror improved the SNR of the non-invasive sensing (above “skull”) by 50% in this experiment and up to 100% in other experiments.

[0223] Unless specifically stated otherwise, as apparent from the following discussions, it is appreciated that throughout the specification discussions utilizing terms such as "processing", "computing", "calculating", "determining", or the like, refer to the action and / or processes of a computer or computing system, or similar electronic computing device, that manipulate and / or transform data represented as physical, such as electronic, quantities within the computing system's registers and / or memories into other data similarly represented as physical quantities within the computing system's memories, registers or other such information storage, transmission or display devices.

[0224] Embodiments of the present invention may include apparatuses for performing the operations herein. This apparatus may be specially constructed for the desired purposes, or it may comprise a general -purpose computer selectively activated or reconfigured by a computer program stored in the computer. Such a computer program may be stored in a computer readable storage medium, such as, but is not limited to, any type of disk including floppy disks, optical disks, CD-ROMs, magnetic-optical disks, read-only memories (ROMs), random access memories (RAMs) electrically programmable read-only memories (EPROMs), electrically erasable and programmable read only memories (EEPROMs), magnetic or optical cards, or any other type of non-transitory memory media suitable for storing electronic instructions, and capable of being coupled to a computer system bus.

[0225] The processes and displays presented herein are not inherently related to any particular computer or other apparatus. Various general-purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct a more specialized apparatus to perform the desired method. The desired structure for a variety of these systems will appear from the description below. In addition, embodiments of the present invention are not described with reference to any particular programming language. It will be appreciated that a variety of programming languages may be used to implement the teachings of the inventions as described herein.

[0226] The principles, uses, and implementations of the teachings herein may be better understood with reference to the accompanying description and figures. Upon perusal of the description and figures present herein, one skilled in the art will be able to implement the teachings herein without undue effort or experimentation. In the figures, same reference numerals refer to same parts throughout.

[0227] In the description and claims of the application, the words “include” and “have”, and forms thereof, are not limited to members in a list with which the words may be associated.

[0228] As used herein, the term “about” may be used to specify a value of a quantity or parameter (e.g. the length of an element) to within a continuous range of values in the neighborhood of (and including) a given (stated) value. According to some embodiments, “about” may specify the value of a parameter to be between 80 % and 120 % of the given value. According to some embodiments, “about” may specify the value of a parameter to be between 90 % and 110 % of the given value. According to some embodiments, “about” may specify the value of a parameter to be between 95 % and 105 % of the given value. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, or components, but do not preclude or rule out the presence or addition of one or more other features, integers, steps, operations, elements, components, or groups thereof.

[0229] While a number of exemplary aspects and embodiments have been discussed above, those of skill in the art will recognize certain modifications, additions and sub-combinations thereof. It is therefore intended that the following appended claims and claims hereafter introduced be interpreted to include all such modifications, additions and sub-combinations as are within their true spirit and scope.

Claims

CLAIMS1. A system for applying functional near infra-red spectroscopy (fNIRS) measurements to the head of a subject, the system comprising: a plurality of mirror optrodes, each mirror optrode comprising at least one optode capable of connecting to the subject’s scalp through a reflector arrangement, wherein the reflector arrangement is attachable to the subject’s scalp through a light scattering couplant to be applied to the scalp; and wherein in a first mirror optrode the at least one optode is an emitter optode, and in a second mirror optrode the at least one optode is a detector optode, such that light emitted from a light source by the emitter optode towards the subject’s head is scattered by the light scattering couplant, and the reflector arrangement reflects the scattered light back onto the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by the reflector arrangement and scattered into the detector optode.

2. The system of claim 1, further comprising: a plurality of sticker optrodes, each sticker optrode comprising an adhesive film with at least one optode embedded into the film, wherein the film is attachable to a hairless area on the subject’s head, and wherein in a first sticker optrode the at least one optode is an emitter optode, and in a second sticker optrode the at least one optode is a detector optode.

3. The system of claim 1, wherein the light scattering couplant is non-conductive or conductive.

4. The system of claim 1, further comprising:EEG electrodes embedded in the mirror optrodes, each EEG electrode being connectable to the subject’s scalp along with at least one optode through or adjacent to the reflector arrangement, wherein the reflector arrangement and the electrode are configured to be attached to the subject’s scalp through a light scattering conductive couplant that may be applied to the scalp; wherein the EEG electrode embedded into the mirror optrodes enables receiving EEG signals from the subject’s brain and / or sensing electric impedance.

5. The system of any one of claims 2 and 4, further comprising:EEG electrodes embedded in the sticker optrodes, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and is configured to be connected to the subject’s head through the adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and sensing electric impedance.

6. The system of claim 1, wherein the reflector arrangement comprises one or more mirrors and / or reflectors and wherein the reflector arrangement is curved or flat.

7. The system of claim 1, wherein the reflector arrangement is a curved reflector or mirror.

8. The system of claim 1 wherein the mirror optrodes are configured to be connected to the subject’s head in an area which is covered with hair, such that light emitted from the light source by the emitter optode to the subject’s head is scattered by the couplant around the hair and the reflector arrangement reflects the scattered light back onto the subject’s scalp or the light scattered from the scalp and underlying tissue is reflected by the reflector arrangement and scattered around the hair into the detector optode.

9. The system of any one of claims 1 or 2, wherein the mirror optrode and / or sticker optrode comprise at least one pair of emitter optode and detector optode.

10. The system of any one of claims 1 or 2, wherein the at least one emitter optode is located at an external layer of the scattering couplant, such that light emitted from the at least one optode, travels through the scattering couplant before reaching the subject’s skin; and thereby covering a larger area of the skin before penetrating the subject’s tissue.

11. The system of any one of claims 1 or 2, wherein the at least one detector optode is located at an external layer of the scattering couplant, such that light scattered from the skin through the couplant reaches the detector optode.

12. The system of claim 4, wherein the mirror optrode further comprises:Magnetic Resonance (MR)-compatible thermal sensor;non ferromagnetic holder with a central canal filled by white electrically conductive couplant; wherein: the reflector arrangement comprises a MR-compatible reflecting layer in a wall of the central canal of the optrode; the reflecting layer is in a cylinder shape covering the walls of the inner canal of the optrode; and a reflective cover is located above the central canal; and wherein a reflective electrode contact is located in the upper part of the mirror optrode, while the MR-compatible thermal sensor is located in the lower part of the mirror optrode, and the optode is located in one of between the EEG-electrode and thermal sensor, or it is inserted into the central canal from the upper part of the optrode.

13. The system of claim 12, wherein the wall of the central canal is covered by an MR- compatible reflecting layer.

14. The system of any one of claims 12 or 13, wherein the reflecting layer is a mirror.

15. The system of claims 1 and 2, wherein the optode is an optical fiber.

16. The system of claim 2, wherein the distance between the emitter optrode and the detector optode in one sticker optrode is about 2 cm.

17. The system of claim 2, wherein the distance between the detector optode of a first sticker optrode and the emitter optode of a second sticker optrode located next to each other is about 1 cm.

18. The system of claims 16 and 17, wherein the distance between the emitter or detector optodes of the first sticker optrode and the emitter or detector optodes respectively of the second sticker optrode located next to each other, is about 3 cm.

19. The system of claim 2 wherein the distance between the emitter optode of a first sticker optrode and a detector optode of a second sticker optrode located next to each other is about 3 cm.

20. The system of claim 2, further comprising depth electrodes comprising emitter and / or detector elements which are configured to be inserted into the subject’s skull, wherein a plurality of emitters of mirror optrodes or sticker optrodes may be positioned over thesubject’s skull, and wherein the plurality of emitters of mirror optrodes or sticker optrodes and the depth electrodes are operated simultaneously, such that optical signals travelling through deep brain structures between l-5cm from the skull inner surface, are detected.

21. The system of claim 20, wherein said system enables the detection of hemodynamic changes within deep brain regions.

22. The system of claims 2 or 5 further comprising a sticker optrode set comprising a support structure attached to an additional adhesive fdm, wherein two or more sticker optrodes are embedded into a lower part of the support structure which is connected to the additional adhesive fdm and which is configured to be in contact with the subject’s skin.

23. The system of any one of claims 4, 5 and 22, further comprising a plurality of holders for capsules of couplant, wherein a first capsule type comprises electrically conductive light scattering couplant used for EEG and fNIRS and a second capsule type comprises electrically non-conductive light scattering couplant used for fNIRS and not for EEG.

24. The system of claim 22, wherein the support structure does not absorb light in the near infrared range, and it scatters light, with a scattering coefficient similar or larger than the scattering coefficient of light in skin at near infrared range of about 600-900nm.

25. The system of claim 22, wherein the support structure thickness is about 1-15 mm , such that the light emitted from the emitter optode is scattered over a distance that is more than 10 times the mean free path of the emitted light in the support structure substantially before reaching the additional adhesive film or the subject’s skin.

26. The system of claim 22, wherein the support structure comprises a dielectric material.

27. The system of claim 22, wherein the emitter optode is a light source embedded into the support structure.

28. The system of claim 22, wherein the detector optode is a photodetector embedded into the support structure.

29. The system of claim 22, wherein the support structure further comprises one or more additional optodes and / or electrodes located between the sticker optrodes, such additional optodes and / or electrodes being in different distances from the emitter optodes and / or detector optodes, resulting in long and short-distance separation optical channels between optodes.

30. The system of claim 22, further comprising at least one emitter optode located at the external layer of the support structure, such that light emitted from the at least one emitter optode, travels through the support structure before reaching the subject’s skin, and thereby covering a larger area of the skin before penetrating the subject’s tissue.

31. The system of claim 22, further comprising at least one detector optode located at the external layer of the support structure, such that light scattered from the skin through the support structure reaches the detector optode.

32. The system of claim 22 wherein an external layer of the support structure is covered with a reflective layer, preventing light from escaping the support structure.

33. The system of claim 32, wherein the reflective layer is a reflective mirror.

34. The system of any one of claims 1-33, wherein the emitter optode is an optical fiber connected to a light source; or wherein the light source is mounted into the mirror optrode or sticker optrode.

35. The system of any one of claims 1-33, wherein the detector optode is an optical fiber connected to a photodetector; or wherein the photodetector is mounted into the mirror optrode or sticker optrode.

36. The system of claim 35, wherein the photodetector is one of the following: photodiode, avalanche photodiode or photomultiplier.

37. The system of claim 34, wherein the light source is a laser, laser diode or a Light Emitting Diode (LED).

38. The system of claim 34, wherein the light source is a coherent light source.

39. The system of claim 38, further comprising one or more ultrasonic transducers for enabling light modulation created by an acousto-optic effect.

40. The system of claim 38, wherein the light source is a non-coherent light source.

41. The system of claim 2, wherein the adhesive fdm is transparent and / or scattering in the near infrared range of the light spectrum of 650-1 lOOnm.

42. The system of any one of claims 1-2, 4-5, further comprising a temperature sensor wherein the temperature sensor is embedded into the mirror optrode and / or sticker optrode; or located between two sticker optrodes.

43. The system of claim 42, wherein the temperature sensor is fiber-based, or is a thermistor.

44. The system of claim 1, wherein the distance between two mirror optrodes is sufficient to allow light to reach the cerebral vasculature.

45. The system of claim 44, wherein the distance between two mirror optrodes is about 2- 5 cm.

46. The system of claim 1, further comprising a flexible patch with a flexible support structure configured to be attached to a hairless area on the subject’s head, which comprises which comprises one or more emitter optodes with expanded apertures diameter of about 5-30 mm , located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure which comprises emitter and detector optodes with small aperture diameter of about 1-2 mm; wherein the distance between the emitter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emitter- detectors separation.

47. The system of claim 46, wherein in the one or more emitter optodes with expanded apertures located at the upper part of the flexible support structure, the light source is placed at a distance of up to 15mm from the optodes embedded into the lower part of the flexible support structure, and wherein the scattering couplant is diffusive to expandthe angle of the light beam and increase spot size of the illuminating beam over the subject’s skin.

48. The system of claim 46, wherein several optical fibers or small emitters are placed over the outer surface of the flexible support structure, such that the overall power reaching the subject’s skin is a superposition of the different sources.

49. The system of claim 48, wherein lasers are coupled to the several optical fibers, or an array of LEDs is positioned above the emitter optode with expanded apertures located at the upper part of the flexible support structure.

50. The system of claim 46, wherein the one or more emitter optodes with expanded apertures located at the upper part of the flexible support structure comprise a beam expander with two or more diffractive optical elements (DDEs), wherein a light beam is inputted through a first DOE, and outputted through a second DOE, such that the outputted beam is larger than the inputted beam.

51. The system of claim 46 wherein the beam expander is one-dimensional and it is in a planar optics configuration.

52. The system of claim 51, wherein at least one linear grating is directly recorded onto a planar optics substrate in the one-dimensional planar optics configuration beam expander.

53. The system of claim 52, wherein two input wavelengths in the range of 690-880nm are used.

54. The system of claim 53, wherein two gratings are recorded for each of the linear grating, where each linear grating has a high diffraction efficiency for one of the two input wavelengths and not for the other input wavelength.

55. The system of claim 46, wherein emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure, and emitter and detector optodes with small apertures diameter located at the lower part of the flexible support structure are positioned within the flexible structure, such that channels of 30-70mm are formed between optodes inside and outside the flexible support structure.

56. The system of claim 46, further comprising:EEG electrodes embedded in the flexible support stricture, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and is configured to be connected to the subject’s head through adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and sensing electric impedance.

57. The system of claim 46, wherein different emitter and detector optodes are operated interchangeably in a way that enables capturing photons that travel through different layers.

58. The system of claim 57, wherein emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure are operated on each hemisphere of the brain separately, and light is detected by detectors on the contralateral hemisphere wherein the detectors are either located at the upper or lower part of the flexible support structure.

59. The system of claim 58, wherein the emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure, when the small emitters close to the skin are operated on each hemisphere in a scanning manner, such that no cross talk is detected by the emitters.

60. The system of claim 59, wherein the emitter optodes with expanded apertures diameter located at the upper part of the flexible support structure may be operated one by one, or in groups or simultaneously to allow selective control of the illumination intensity.

61. The system of claim 57, wherein emitter optodes with small apertures diameter located at the lower part of the flexible support structure are operated on each hemisphere in a scanning manner, such that no cross talk is detected by the emitters.

62. A system for applying functional near infra-red spectroscopy (fNIRS) measurements to a head of a subject, comprising one or more of: at least one mirror optrode comprising at least one optode capable of being connected to the subject’s scalp through a reflector arrangement, wherein the reflectorarrangement is configured to be attached to the subject’s scalp through a light scattering couplant that may be applied to the scalp; at least one sticker optrode comprising an adhesive film with at least one optode embedded into the fdm, wherein the fdm is configured to be attached to a hairless area on the subject’s head; wherein the at least one optode of the mirror optrode or of the sticker optrode is an emitter optode and the at least one optode of the sticker optrode or of the mirror optrode respectively is a detector optode; and at least one flexible patch with a flexible support structure configured to be attached to a hairless area on the subject’s head, which comprises which comprises one or more emitter optodes with expanded apertures diameter of about 5-30 mm, located at the upper part of the flexible support structure, and optrodes embedded into the lower part of the flexible support structure which comprises emitter and detector optodes with small aperture diameter of about 1-2 mm; wherein the distance between the emitter and detector optodes at the lower part of the flexible support structure ranging between 5mm to 35mm, such that the flexible patch creates a brain activity sensor that enables depth selectivity of layers of a subject’s brain, at small ranges of l-3cm and large ranges of 5-7cm, emitter- detectors separation.

63. A system for applying functional near infra-red spectroscopy (fNIRS) measurements to a subject’s head, comprising: a plurality of sticker optrodes, each sticker optrode comprising an adhesive film with at least one emitter optode and one detector optode embedded into the film, wherein the film is configured to be attached to a hairless area on the subject’s head.

64. The system of claim 63, further comprising:EEG electrodes embedded in the sticker optrodes, wherein each EEG electrode is located in the vicinity of the emitter optode and the detector optode and it is configured to be connected to the subject’s head through the adhesive film; wherein the EEG electrodes embedded into the sticker optrodes enable receiving EEG signals from the subject’s brain and / or sensing electric impedance.

5. A system for assessing brain activity through fNIRS measurements, the system comprising applying the systems of any one of claims 1-64, and thereby assessing brain activity.

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