Non-invasive intracranial pressure sensing system and method

Abstract

Aspects of the present disclosure provide a non-invasive intracranial pressure sensing device comprising an interference near infrared spectroscopy iNIRS system, the iNIRS system comprising: a light emitting arrangement comprising: a light source for emitting light; a sample delivery channel coupled to the light source and arranged to be coupled to the scalp of the subject to direct light from the light source towards brain tissue of the subject; and a reference channel coupled to the light source for receiving light from the light source; a light detection arrangement for coupling to the scalp of the subject and the light emitting arrangement, the light detection arrangement comprising an interference optical detector for receiving: (i) reference light from the reference channel, and (ii) sample light from the brain of the subject, the sample light comprising light emitted from the light source; wherein the optical detector is arranged to combine the sample light with the reference light to provide a combined light signal comprising one or more components of a beat frequency between the sample light and the reference light; and wherein the sensing device comprises a controller for processing data indicative of the combined light signal to determine an intracranial blood pressure indication of the subject based on at least one characteristic of a pulsating waveform of the one or more identified pulses of blood flow through a brain of the subject.

Description

Technical Field

[0001] The present disclosure relates to the field of imaging and analysis. In particular, the present disclosure relates to interferometric near infrared spectroscopy (iNIRS) systems and methods for neural imaging and analysis. Background Art

[0002] Near infrared spectroscopy (NIRS) is a spectroscopic method that uses the near infrared region of the electromagnetic spectrum (e.g., between 780 and 2500 nm). NIRS systems can be used to provide non-invasive monitoring of the scattering and absorption properties of a medium. Radiation at NIRS wavelengths is less easily absorbed by human skin (and bone) than visible light, so NIRS radiation can penetrate the skin and skull and penetrate into brain tissue. NIRS can be used as a technique for non-invasive imaging of human brain tissue by monitoring the scattering and absorption properties of NIRS radiation within the brain tissue.

[0003] While NIRS methods can be extended to monitor oxygenation, blood flow monitoring is necessary to infer metabolic-related information when multiple wavelengths are used. Diffusion correlation spectroscopy (DCS) can non-invasively monitor blood flow in the brain by measuring the temporal fluctuations of light emitted from a sample. DCS can also extract other brain indicators, including intracranial pressure (ICP). However, to extract ICP, existing DCS methods require additional equipment and extensive averaging, resulting in a cumbersome and slow method. In addition, to quantify blood flow, DCS requires optical properties, which are usually assumed or implemented by individual NIRS instruments. Finally, since DCS and NIRS rely only on light intensity, they ignore half of the information related to scattered light, which is encoded in the optical phase. Therefore, the measurement results are affected by the additional assumptions brought about by ignoring phase information.

[0004] Therefore, there is a great need for technologies that provide improved neural monitoring and analysis that combine NIRS and DC into a single modality and rapidly provide both optical and dynamic properties of biological tissues. Summary of the invention

[0005] Various aspects of the disclosure are listed in the independent claims, and optional features are listed in the dependent claims. Various aspects of the disclosure may be provided in combination with each other, and features of one aspect may be applied to other aspects.

[0006] In one aspect, a non-invasive intracranial pressure sensing device is provided, comprising an interferometric near infrared spectroscopy (iNIRS) system. The iNIRS system comprises: a light emitting arrangement, comprising: a light source for providing (e.g., wavelength-scanned) light emission (e.g., a light source for emitting light having a scanned wavelength); a sample delivery channel coupled to the light source and arranged to be coupled to a subject's scalp to direct light from the light source toward the subject's brain tissue; and a reference channel coupled to the light source for receiving light from the light source; a light detection arrangement for coupling to the subject's scalp and the light emitting arrangement, the light detection arrangement comprising an interferometric optical detector for receiving: (i) reference light from the reference channel, and (ii) sample light from the subject's brain tissue, the sample light comprising light emitted from the light source (e.g., some of the sample light may have propagated from the light source through the subject's scalp and skull and passed through a portion of the subject's brain tissue before being scattered toward the detector). The optical detector is arranged to combine the sample light with the reference light to provide a combined light signal, the combined light signal comprising one or more components of a beat frequency between the sample light and the reference light. The sensing device includes a controller for processing data indicative of the combined optical signal to determine an indication of intracranial blood pressure of the subject based on at least one characteristic of a pulsation waveform of one or more identified pulses of blood flow through brain tissue of the subject.

[0007] Various embodiments may enable non-invasive acquisition of intracranial blood pressure (ICP). This approach may be advantageous because alternative methods for determining ICP may be so invasive that their use is limited to situations where ICP measurement is most necessary (and therefore worth the high risks associated with invasive ICP measurement).

[0008] Processing the data indicative of the combined light signal may include obtaining blood flow data indicative of one or more pulses of blood flow through the brain of the subject. For example, this may include data containing a cerebral blood flow index value. The cerebral blood flow index value may provide an indication of the speed of blood movement in a given volume of the subject's brain. The controller may be used to obtain extra-cerebral blood flow data indicative of one or more pulses of blood flow through an extra-cerebral region of the subject's body. The extra-cerebral blood flow data may include blood pressure values ​​for the one or more pulses of extra-cerebral blood flow. The extra-cerebral blood flow data may include blood flow index values ​​for the one or more pulses of extra-cerebral blood flow (and the controller may be used to determine corresponding extra-cerebral blood pressure values ​​therefrom).

[0009] The controller may be configured to determine an indication of intracranial blood pressure of the subject based on the cerebral blood flow data and the extracerebral blood flow data. The controller may determine an indication of ICP based on a comparison between the cerebral blood flow data and the extracerebral blood flow data. The comparison may include aligning the cerebral blood flow data with the extracerebral blood flow data so that pulses of blood flowing through the subject's brain tissue are aligned with corresponding pulses of blood flow flowing through an extracerebral region of the subject's body. The alignment may include associating each cerebral blood flow pulse with a corresponding extracerebral blood flow pulse (e.g., so that the two pulses correspond to the same heartbeat cycle—even if they are slightly out of phase because the two pulses are measured in different regions of the subject's body). Comparing the two pulses may include comparing: (i) one or more characteristics of a pulsation waveform of a blood flow pulse flowing through the subject's brain tissue, and (ii) one or more characteristics of a pulsation waveform of a blood flow pulse flowing through an extracerebral region of the subject's body.

[0010] The extracerebral blood flow data may include an indication of blood pressure values ​​of blood flow pulses flowing through an extracerebral region of the subject's body. For example, extracerebral blood flow may refer to a superficial (e.g., not too deep) region of the subject's body, such as their scalp (above their skull). For example, the extracerebral blood flow data may include a series of values ​​(e.g., a time-ordered sequence) of blood pressure in an extracerebral region of the subject's body. The extracerebral blood flow data may provide blood pressure values ​​of the pulsation waveform of each blood flow pulse (e.g., blood pressure values ​​at multiple points during each pulse of blood flow flowing through the extracerebral region of the subject's body). The controller may be used to determine an indication of the subject's intracranial blood pressure based on: (i) the pulsation waveform of one or more identified pulses of blood flow flowing through the subject's brain tissue, and (ii) the corresponding pulsation waveform of the blood pressure of one or more pulses of blood flow flowing through the extracerebral region of the subject's body.

[0011] For example, the controller may be used to determine the ICP based on the extracerebral blood pressure value at a given point during the extracerebral blood pressure pulsation waveform (e.g., where the given point during the pulsation waveform corresponds to a selected point during the pulsation waveform of the cerebral blood flow, such as a minimum value of the cerebral blood flow value). The controller may be used to determine the intracranial blood pressure indication of the subject based on the identified critical closure pressure of the blood vessels in the brain tissue of the subject. The critical closure pressure may include the pressure value when the blood vessel in the brain tissue of the subject is closed. For example, the controller may be used to detect blood vessel closure based on changes in cerebral blood flow data (e.g., a decrease in cerebral blood flow value, such as to zero or a known minimum value). The controller may be used to identify the point during the cerebral pulsation waveform at which the blood vessel is closed. The controller may be used to identify the corresponding point during the pulsation waveform of the extracerebral pressure. The controller may be used to determine the ICP based on the corresponding pressure associated with the blood vessel (and the blood vessel is closed due to the surrounding ICP).

[0012] The controller can be used to process data indicative of the combined light signal to obtain cerebral blood flow index data of blood flow flowing through the brain tissue of the object. The pulsation waveform of one or more identified pulses of blood flow flowing through the brain tissue of the object includes the pulsation waveform of the cerebral blood flow index. For example, the cerebral blood flow data may include a series of values ​​of the cerebral blood flow index (CBFi), such as a time-ordered series of cerebral blood flow index values. The controller can be used to determine the ICP based on one or more characteristics associated with these CBFi values. For example, the characteristic may relate to the shape of the pulsation waveform, such as a characteristic indicating the shape of each pulse. The characteristic may include an indication of at least one of the following: a maximum value and / or a minimum value, a difference between a maximum value and a minimum value, an average value and / or a variance of a value, a rate of change of a value, and the like.

[0013] The sensing device can be used to obtain extracerebral blood flow data using an iNIRS system. The iNIRS system can be used to obtain extracerebral blood flow data and cerebral blood flow data using the same source-detector channel. The iNIRS system can be used to obtain extracerebral blood flow index data. The controller can be used to process the extracerebral blood flow index data to obtain a value of extracerebral blood pressure. The optical detection arrangement can be used to couple to the scalp of the subject so that the detector obtains a combined optical signal, the combined optical signal comprising: (i) a component of a beat frequency associated with a sample light propagated from the brain tissue of the subject, and (ii) a component of a beat frequency associated with a sample light propagated from an extracerebral region of the subject's body. The controller can be used to separate data associated with the extracerebral region of the subject's body and data associated with the brain tissue of the subject (e.g., separating data from the same combined optical signal into two separate data groups: one for brain data and one for extracerebral data). The controller can be used to separate the data based on the time of flight of the sample light. The controller can be used to determine cerebral blood flow data and extracerebral blood flow data based on the separated data.

[0014] The iNIRS system may include multiple optical detectors. Each optical detector may be used to obtain cerebral blood flow data of the brain tissue of the subject. The controller may be used to determine an intracranial blood pressure indication based on the characteristics of the pulsation waveform of the pulses of blood flow flowing through the brain tissue of the subject detected by the multiple detectors. The device may be used to obtain extracerebral blood flow data of different extracerebral regions of the body of the subject based on combined optical signals associated with different detectors. The detectors may be arranged to be spatially distributed around the scalp of the subject so that at least some of the blood flow pulses detected by different detectors come from different parts of the brain tissue of the subject. The iNIRS system may include two source-detector channels: (i) a brain source-detector channel for obtaining cerebral blood flow data, and (ii) an extracerebral source-detector channel for obtaining extracerebral blood flow data. The sensing device may include an extracerebral blood flow sensor for obtaining extracerebral blood flow data. The extracerebral blood flow sensor may be used to obtain pressure values ​​of the extracerebral blood flow pulses.

[0015] The controller may be used to determine an intracranial blood pressure indication based on a difference between a diastolic value and a systolic value of one or more pulses of blood flow through the brain tissue of the subject. The controller may be used to determine an intracranial blood pressure indication based on a pulsatility index of a blood flow pulse flowing through the brain tissue of the subject. The controller may be used to determine an intracranial blood pressure indication of the subject based on a shape difference between: (i) one or more blood flow pulses flowing through the brain tissue of the subject, and (ii) one or more blood flow pulses flowing through an extracerebral region of the subject's body. The controller may be used to determine an intracranial blood pressure indication of the subject based on the diastolic value of the blood flow pulses. The iNIRS system may include two or more light sources, wherein a first light source in the light sources is used to provide (e.g., wavelength-scanned) emission of light at multiple wavelengths above an absorption wavelength such as oximetry, and wherein a second light source in the light sources is used to provide (e.g., wavelength-scanned) emission of light at multiple wavelengths below an absorption wavelength such as oximetry. The controller may be used to determine an intracranial blood pressure indication based on sample light received from each of the two light sources.

[0016] The controller may be configured to obtain time-of-flight data based on the combined light signal, wherein the time-of-flight data comprises a data surface comprising a time-ordered series of flight time distributions of photons of sample light arriving at the optical detector from the light source. The controller may be configured to determine cerebral blood flow data based on changes in the data surface. The controller may be configured to determine the cerebral blood flow data based on an attenuation rate associated with the data surface. The controller may be configured to obtain an indication of one or more optical properties of a brain tissue of the subject based on the time-of-flight data. The one or more optical properties of the brain tissue of the subject may include a scattering coefficient and / or an absorption coefficient. The controller may be configured to determine cerebral blood flow data of the brain tissue of the subject based on: (i) one or more optical properties of the brain tissue of the subject, and (ii) changes in the intensity of the sample light received at the optical detector.

[0017] In one aspect, a method of non-invasive intracranial pressure sensing is provided, the method comprising: operating a light source to provide (e.g., wavelength scanned) emission of light; delivering light from the light source through: (i) a sample channel and toward a subject's brain tissue, and (ii) a reference channel; receiving at an interferometric optical detector: (i) reference light from the reference channel, and (ii) sample light from the subject's brain tissue, the sample light comprising light emitted from the light source; combining the sample light and the reference light at the optical detector to provide a combined light signal, the combined light signal comprising one or more components of a beat frequency between the sample light and the reference light; processing data indicative of the combined light signal to determine an indication of the subject's intracranial blood pressure based on at least one characteristic of a pulsation waveform of one or more identified pulses of blood flow through the subject's brain tissue.

[0018] In one aspect, a non-invasive intracranial pressure sensing device is provided, comprising an interferometric near-infrared spectroscopy (iNIRS) system, the iNIRS system comprising: a light emitting arrangement comprising: a light source for providing (e.g., wavelength-scanned) emission of coherent light; a sample delivery channel coupled to the light source and arranged to be coupled to a subject's scalp to direct light from the light source toward the subject's brain tissue; and a reference channel coupled to the light source for receiving light from the light source; a light detection arrangement for coupling to the subject's scalp and the light emitting arrangement, the light detection arrangement comprising an interferometric optical detector for receiving: (i) reference light from the reference channel, and (ii) sample light from the subject's brain tissue, the sample light comprising light emitted from the light source, wherein the optical detector is arranged to combine the sample light with the reference light to provide a combined light signal, the combined light signal comprising the sample light and the reference light. one or more components of the beat frequency between the sample light; and a signal processing and conversion circuit coupled to the detector and used to generate combined light signal data from the combined light signal; wherein the sensing device includes a controller, the controller being used to: process the combined light signal data to obtain time-of-flight data, the time-of-flight data including multiple flight time distributions of photons of sample light reaching the optical detector from the light source; process the time-of-flight data to obtain an indication of one or more optical properties of the subject's brain tissue; determine cerebral blood flow data of the subject's brain tissue based on: (i) one or more optical properties of the subject's brain tissue, and (ii) changes in the intensity of the sample light received at the optical detector, wherein the cerebral blood flow data includes an indication of one or more pulses of blood flow flowing through the subject's brain tissue; and determine an indication of the subject's intracranial blood pressure based on the shape of the one or more pulses of blood flow flowing through the subject's brain tissue.

[0019] Aspects of the present disclosure include one or more computer program products comprising computer program instructions for programming a processor to control the operation of an interferometric near-infrared spectroscopy system, such as controlling the operation of a light emitting arrangement and a light detecting arrangement, to perform any of the methods disclosed herein.

[0020] Embodiments may provide iNIRS systems and methods for neuroimaging and analysis of brain tissue of a subject. Compared to the above-mentioned fNIRS technology, the iNIRS system and method of the present disclosure involve a completely different method for performing neuroimaging and analysis. Embodiments may provide improved methods for performing iNIRS neuroimaging and analysis. As disclosed herein, the iNIRS system of the present disclosure includes two light sources and one or more light detectors. The iNIRS system of the present disclosure may also include a controller arranged to receive output signals from one or more light detectors.

[0021] Each light source may include a light generating element arranged to generate light (e.g., near infrared light). For example, each light generating element may include a laser. Each light source may include an optical arrangement coupled to the light generating element. The optical arrangement of each light source may be used to deliver the generated light from the light generating element to each of one or more different locations. The optical arrangement of each light source may be arranged to direct some of the light from the light generating element toward the area to be sampled. The optical arrangement of each light source may be arranged to direct some of the light to each light detector. The optical arrangement of each light source may include a plurality of light delivery channels. The plurality of light delivery channels may include one or more sample delivery channels and / or one or more reference delivery channels. Each light delivery channel may include an optical channel, such as an optical fiber. Each light delivery channel may be used to transmit light along the length of the channel (e.g., from the light generating element to the scalp of the subject or the light detector). The optical arrangement of each light source may include an optical splitter for splitting light to each of the different delivery light channels.

[0022] The iNIRS system can be arranged so that when mounted on the head of a subject (e.g., for providing neuroimaging and analysis of the subject's brain tissue), the optical arrangement of each light source is used to direct some light toward the subject's scalp. For example, the optical arrangement of each light source may include a sample delivery channel (e.g., operable to direct sample light toward the subject's scalp). The iNIRS system can be arranged so that when in use, the optical arrangement of each light source can direct some light directly to a light detector (e.g., for combination with sample light from the subject's brain tissue). For example, the optical arrangement of each light source may include a reference delivery channel (e.g., operable to direct reference light to one or more of the light detectors). The optical arrangement of each light source can be used to deliver light from a light generating element to each light channel. The optical arrangement of each light source can be used to deliver: (i) light to a sample light delivery channel (sample light), and (ii) light to a reference delivery channel (reference light). For example, the optical arrangement of each light source may include an optical splitter for splitting light received from a light generating element into each of the different channels.

[0023] The iNIRS system can be arranged so that in use, when mounted on the brain tissue of the subject, the sample light can be directed toward the scalp and brain tissue of the subject (e.g., through the sample delivery channel), and the reference light can be directed toward each light detector (e.g., through the reference delivery channel). Each light source can be arranged to provide wavelength-scanned light emission (e.g., each light source can be arranged to output light of each of a plurality of different wavelengths over a selected time period). For example, each light source can include an adjustment element for controlling the operation of the light generating element to output light of each of a plurality of different wavelengths. Each light source can be arranged to scan the wavelength of the light output by the light source (e.g., increase or decrease the wavelength). Each light source can be arranged to provide chirped light emission, wherein each chirp (or pulse) comprises a wavelength scan. Each light source can be arranged to output continuous chirps having the same wavelength scan, for example, such that the wavelength of the light output from the light source varies according to a repeating pattern.

[0024] Each photodetector may provide an interferometric optical detector. Each photodetector may include an optical arrangement. The optical arrangement of the photodetector is used to guide the light to be detected (e.g., from the scalp of the subject) into the photodetector. The optical arrangement of the photodetector may include a plurality of light receiving channels. The plurality of light receiving channels may include one or more sample light receiving channels and / or one or more reference light receiving channels. Each light receiving channel may include an optical channel, such as an optical fiber.

[0025] The iNIRS system can be arranged such that when mounted on the head of a subject (e.g., for providing neuroimaging and analysis of brain tissue of the subject), the optical arrangement of the light detectors is used to receive light emitted from the light sources (e.g., that has passed from the light sources through the brain tissue of the subject). For example, the optical arrangement of the light detectors can include a sample receiving channel (e.g., operable to receive sample light from each light source that has passed through the brain tissue of the subject). The iNIRS system can be arranged such that, in use, the optical arrangement of the light detectors can receive some of the light from each light source that has propagated directly from the light source (e.g., has propagated along the light channel). For example, the optical arrangement of the light detectors can include a reference receiving channel (e.g., operable to receive reference light from one or more light sources). Each light detector can be coupled to each light source such that a reference delivery channel of the light source is coupled to a reference receiving channel of the light detector (e.g., such that reference light can propagate from the light generating element to the light detector via the reference delivery channel and the reference receiving channel).

[0026] The optical arrangement of the light detector can be used to deliver to the light detector: (i) light from a sample light receiving channel (sample light), and (ii) light from a reference receiving channel (reference light). For example, in use, the detector is arranged to receive: (i) sample light from each light source that has passed through the brain tissue of the subject, and (ii) reference light from each light source that has propagated along one or more reference channels to the light detector.

[0027] The photodetector may be arranged to combine the reference light with the sample light to provide a combined light signal. For example, the photodetector may include an optical combiner (e.g., for combining light on a reference receiving channel with light on a sample receiving channel). The combined light signal may include multiple components of a beat frequency (e.g., a frequency corresponding to the wavelength difference between the sample light and the reference light). Each photodetector is used to convert the received combined light signal into one or more electrical signals indicating the combined light signal. For example, the detector may include one or more photodiodes. Each photodiode may output an electrical signal (e.g., a current) indicating the combined light signal. The detector may include a balanced photodetector (e.g., including two photodiodes, the two photodiodes may be 180° out of phase, and the output of the balanced photodetector may be a combination of the current outputs of the two photodiodes). The detector may optionally include a current to voltage conversion circuit and / or one or more amplifiers for amplifying the electrical signal.

[0028] The iNIRS system may include at least one analog to digital converter arranged to convert an electrical signal representing the sample light (e.g., a combined light signal) into one or more digital signals. The controller is arranged to process the digital signals to determine one or more characteristics of the brain tissue of the subject. The controller may be used to determine optical characteristics (e.g., absorption and / or scattering) of the brain tissue of the subject. The controller may be used to determine one or more dynamic characteristics of the brain tissue of the subject (e.g., characteristics of the brain tissue of the subject that change over time). For example, the controller may be used to detect the presence of motion within the brain tissue of the subject (e.g., due to movement of blood within the brain tissue, such as flow).

[0029] The controller can be used to process the digital signals to obtain time-of-flight information for the photons of sample light that propagate from each light source through the brain tissue of the subject to the light detector. The controller can be used to identify the penetration depths associated with the different flight times of the sample light photons (and optionally, the expected trajectories of the photons through the brain tissue). The controller can be used to obtain a time-ordered sequence of the flight time distributions of the sample light photons that arrive at each light detector. The controller can be used to process the time-ordered sequence to identify changes in the flight time distributions over time, such as identifying attenuation and / or decay rates between successful flight time distributions. The controller can be used, for example, to provide depth-resolved processing by filtering the flight time data to focus only on photons within a selected flight time range (e.g., to identify changes in the optical properties of the brain tissue at (one or more) penetration depths associated with the flight time range). The controller can be used to process the data received from the light detector to provide depth-resolved autocorrelated time-of-flight information of the brain tissue of the subject.

[0030] The controller can be used to process received data indicating sample light received at the light detector, and output a control signal based on the received data. The control signal can provide an indication of a time-of-flight distribution (e.g., the controller can be used to output a time-of-flight distribution). The control signal can provide an indication of one or more characteristics determined based on the time-of-flight distribution, such as an indication of the optical properties of brain tissue (e.g., scattering coefficient and / or absorption coefficient, and / or how these optical properties have changed / are changing). The control signal can provide an indication of blood flow within the brain tissue of the subject. The control signal can provide a depth-resolved indication of one or more characteristics of the brain tissue of the subject (e.g., related to a specific area within the brain tissue of the subject, such as within a selected penetration depth range). The control signal can include one or more characteristics of the brain tissue of the subject, such as an indication of intracranial pressure, blood flow index, arterial elasticity, brain oxygen metabolic rate. Medical characteristics can be associated with a specific area / depth within the brain tissue of the subject. The control signal can include an actuation command for a brain-computer interface, for example, to control the operation of the device based on the actuation command. The control signal can include an image for display, wherein the image represents a portion of the brain tissue of the subject (determined based on the received sample light). BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Some examples of the present disclosure will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0032] Figure 1 A schematic diagram of the iNIRS system is shown.

[0033] Figure 2 A schematic diagram showing cerebral blood flow index data is shown.

[0034] Figure 3a to Figure 3c A schematic diagram illustrating a method of processing data acquired using an iNIRS system is shown.

[0035] Figure 4a A schematic diagram of the iNIRS system is shown.

[0036] Figure 4b A schematic diagram illustrating a method of processing data acquired using an iNIRS system is shown.

[0037] In the drawings, the same reference numerals are used to denote the same elements. DETAILED DESCRIPTION

[0038] The present disclosure relates to non-invasive monitoring of intracranial pressure (ICP). An interferometric near infrared spectroscopy (iNIRS) system is used to obtain time-of-flight data of photons of light propagating from a light source to a light detector (wherein at least some of the above photons will have passed through the brain tissue of the subject). Based on the temporal evolution of the time-of-flight data, one or more characteristics associated with blood flow within the brain tissue of the subject can be identified. Specifically, a pulsation waveform of a pulse of blood flow flowing through the brain tissue of the subject can be identified. An indication of the ICP of the brain of the subject can be determined based on one or more characteristics of the pulsation waveform. In order to further improve the accuracy of ICP, one or more characteristics of extracerebral blood flow can also be obtained and these characteristics can be compared with cerebral blood flow characteristics. The iNIRS system can be used to obtain cerebral blood flow data and extracerebral blood flow data. An indication of ICP can be determined based on a difference between the pulsation waveforms of cerebral blood flow and extracerebral blood flow. This difference may indicate a restraining force exerted on the pulsation of cerebral blood flow, which does not exist for extracerebral blood flow (for example, because the volume of the skull is fixed).

[0039] Interferometric Near-Infrared Spectroscopy (iNIRS)

[0040] Figure 1 A schematic diagram of an interferometric near infrared spectroscopy (iNIRS) system 10 is shown. The iNIRS system 10 includes a light source 20, a plurality of light detectors 30, and a controller 40. Figure 1 Inset A of FIG. 4 shows a more detailed view of one of the light detectors 30 .

[0041] The iNIRS system 10 includes a light source modulator 22 and an optical splitter 24. The iNIRS system 10 includes a sample delivery channel 25 and a reference delivery channel 26. The iNIRS system 10 is shown coupled to a subject's head 2. The iNIRS system 10 includes a sample delivery probe 25a and a plurality of sample receiving probes 35a. Each light detector 30 has an associated sample receiving probe 35a, a sample receiving channel 35, a reference delivery channel connection 28, and a reference receiving channel 36.

[0042] The light source regulator 22 may include a source for providing a variable electrical control signal (eg, a variable current or voltage provider). The light source regulator 22 is coupled to the light source 20. The light source regulator 22 may be electrically connected to the light source 20 to provide a variable current / voltage to the light source 20.

[0043] The light source 20 may include a laser. For example, the laser may be a distributed feedback laser (DFB) or a MEMS vertical cavity surface emitting laser (MEMS-VCSEL). The light source 20 is coupled to an optical splitter 24. The optical splitter 24 has an input end for receiving light from the light source 20. The optical splitter 24 has two output ends for transmitting the light from the light source 20 to two independent channels. A sample delivery channel 25 is coupled to the optical splitter 24 (to receive light from the optical splitter 24), and a reference delivery channel 26 is coupled to the optical splitter 24 (to receive light from the optical splitter 24). The sample delivery channel 25 couples the optical splitter 24 to a sample delivery probe 25a. The sample delivery probe 25a is to be placed at a position on the scalp of the subject.

[0044] Other types of suitable lasers include distributed Bragg reflector lasers (DBR), Fourier domain mode locking lasers (FDML), vertical cavity surface-emitting lasers (VCSEL). Additionally or alternatively, a pulsed supercontinuum laser can be used in combination with a pulse stretching mechanism (e.g., a grating or GRISM pulse stretcher or a length of dispersive fiber). For example, such an arrangement can be used to temporally separate the wavelengths in the pulses so that frequency chirped pulses are produced (e.g., for ultimately providing an interference pattern when comparing a sample pulse to a reference pulse).

[0045] The reference delivery channel 26 couples the optical splitter 24 to each of the photodetectors 30. For each detector, a reference delivery connection 28 couples the reference delivery channel 26 to a reference receiving channel 36 of that detector. Each reference receiving channel 36 is coupled to a photodetector 30 of that reference receiving channel. Each photodetector 30 is connected to the light source 20 to directly receive reference light from the light source 20 (via one or more reference channels). Each sample receiving probe 35a is placed on the scalp of the subject. Each sample receiving probe 35a is coupled to a sample receiving channel 35. Each sample receiving channel 35 is coupled to a photodetector 30 of that sample receiving channel. Each photodetector 30 is connected to receive sample light from the light source 20 (via a sample delivery channel and a sample receiving channel, and via brain tissue of the subject between the sample delivery channel and the sample receiving channel).

[0046] There are a plurality of different photodetectors 30. Each detector may include an interferometer, such as a Mach-Zehnder interferometer. Each of the different photodetectors 30 is coupled to the same light source 20 (via one or more reference channels). The photodetectors 30 may be spatially separated from the light source 20. The photodetectors 30 may also be spatially separated from each other, or they may be co-located on sufficiently similar tissue regions so that the received signals may be averaged together. In order for reference light to reach the photodetectors 30 from the light source 20, the reference light will propagate directly along one or more reference channels. In order for sample light to reach the photodetectors 30 from the light source 20, the sample light will propagate indirectly via the subject's brain tissue. The sample light is delivered to the subject's scalp via one or more delivery channels. The sample light may then pass through the subject's brain tissue, be received via one or more sample receiving channels 35, and be transmitted to the photodetectors 30. Thus, illumination of the subject's brain tissue may use a different light channel than detection of light from the subject's brain tissue.

[0047] The controller 40 may include any suitable component having data receiving and processing functions. For example, the controller 40 may include at least one application specific integrated circuit (ASIC). Other examples of the controller 40 may include a field programmable gate array (FPGA) and / or a data acquisition module (DAQ). The controller 40 is coupled to each detector. The controller 40 may be connected to each detector via a wired connection (for receiving an electrical signal indicating detection from the detector), and / or the connection may be wireless (for receiving transmission data indicating detection from the detector). The controller 40 is coupled to the light source regulator 22. The connection may be wired or wireless.

[0048] The iNIRS system 10 can be at least partially mounted in a garment on the subject's head 2. For example, the iNIRS system 10 can be disposed in a hat / cap worn by the subject on his head 2. The head garment can be arranged to hold the light source 20 and the detector in a fixed arrangement relative to the subject's scalp. Some or all of the above components can be provided with the head garment. For example, the head garment can include a plurality of housing portions for housing the light source 20 and the light detector 30. The channels connecting the light source and the light detector 30 can be provided as part of the head garment (e.g., they can be wired through corresponding channel housing portions of the head garment). The controller 40 can be separate from the head garment (e.g., wirelessly connected), or the controller 40 can also be provided as part of the head garment (e.g., provided by an ASIC in the head garment, which can be wired to the detector and / or light source modulator 22). For example, the garment can be used to house the source channel and the detection channel and the probe, while the other components of the system are located elsewhere.

[0049] Some or all of the channels of the iNIRS system 10 may be provided by optical fibers. The optical splitter of the present disclosure may include a fiber-optic splitter. The iNIRS system 10 may include lenses, reflection and / or refraction devices for beam steering, as appropriate. For example, the sample delivery probe 25a may include one or more lenses for spreading sample light from the sample delivery channel 25 onto the brain tissue space of the subject. As another example, one or more of the sample receiving probes 35a may include a lens for focusing the received light into the sample receiving channel 35 connected to the sample receiving probe 35a. As another example, the probe may be a bare fiber that has been cut and / or polished.

[0050] The iNIRS system 10 is arranged to provide a plurality of source-detector pairs for each light source 20. In other words, the iNIRS system 10 is arranged so that each light detector 30 can receive two forms of light: (i) reference light, and (ii) sample light. Each detector is arranged to receive reference light directly from the light source 20 (the reference light will, for example, propagate along one or more pathways from the light source 20 to the light detector 30 without passing through the subject's brain tissue). Each detector is also arranged to receive sample light indirectly from the light source 20 (the sample light will have been directed toward the subject's scalp tissue, and a portion of the sample light may have passed through the subject's brain tissue on the way to the detector, for example, the sample light will not have only passed through the optical pathway between the light source 20 and the light detector 30).

[0051] The detectors 30 are arranged to be placed on the scalp of the subject to provide imaging of a selected region of the subject's brain. At least some of the detectors 30 are arranged to be spatially separated from the light source 20. One or more (e.g., each) of the light detectors 30 can be arranged to be sufficiently spaced apart from the light source 20 so that at least some of the photons of the sample light from the light source 20 received at the light detector 30 will have penetrated into the brain tissue of the subject. For example, the source-detector spacing can be selected so that the light detector 30 is arranged to receive sample light photons that have undergone multiple scattering events (e.g., have been scattered multiple times between the source and the detector as they pass through the subject's head 2). In other words, the source-detector spacing can be selected so that the light detector 30 receives deep penetrating photons from the subject's brain tissue. Such photons can have a longer flight time from the source to the detector than photons that penetrate more shallowly and experience fewer scattering events.

[0052] Detectors 30 may be arranged to be spatially close to each other on the subject's scalp. The arrangement of detectors 30 may be selected so that the detectors image similar areas of the subject's brain. For example, detectors 30 may be located within a threshold distance of each other on the subject's scalp so that the data they acquire may be averaged (e.g., to provide an average value for the same volume of the subject's brain). That is, detectors 30 may be arranged to spatially probe the same volume of tissue within the subject's brain. For example, the detectors may be arranged to be within an attenuation length of each other's tissue (e.g., within the sum of the absorption coefficient and the scattering coefficient).

[0053] The light source 20 is arranged to generate light and direct the light (via a reference channel) toward the subject's scalp and the light detector 30. The optical splitter 24 is arranged to receive the light generated by the light source 20 and split the light into two channels: (i) toward the subject's scalp using a sample delivery channel 25 and a sample delivery probe 25a, and (ii) to the light detector 30 using a reference delivery channel 26 and a reference receiving channel 36. The splitter is used so that most of the light is directed toward the subject's scalp. For example, the splitter can be a 90:10 splitter or a 99:1 splitter. The sample delivery channel 25 is arranged to receive sample light from the splitter and deliver the sample light (via a sample delivery probe 25a) to the subject's scalp. The reference delivery channel 26 is arranged to receive reference light from the splitter and deliver the sample light (via a reference receiving channel 36) to the detector.

[0054] Each reference delivery connection 28 is arranged to deliver some reference light propagating along the reference delivery channel 26 to one of the reference receiving channels 36. Each reference receiving channel 36 is arranged to deliver reference light to a light detector 30 for the reference light. The sample receiving probe 35a is arranged to receive sample light from the brain tissue of the subject. The sample receiving probe 35a can focus the received sample light onto the sample receiving channel 35. The sample receiving channel 35 is arranged to deliver the received sample light to the light detector 30 for the sample light. The sample receiving probes 35a can be arranged on the scalp of the subject close to each other.

[0055] Each detector is arranged to receive two inputs: (i) reference light directly from the light source 20, and (ii) sample light indirectly from the light source 20 (e.g., having passed through the subject's brain tissue and through the subject's scalp skin and skull). For example, each detector may include two or more input ports. A first input port of the detector may be coupled to a reference delivery channel 26 of the detector. A second input port of the detector may be coupled to a sample delivery channel 25 of the detector. The detector (as an interferometer) is arranged to combine the reference light with the sample light. The detector and controller 40 are arranged to determine one or more characteristics of the subject's brain tissue based on the combination of the reference light and the sample light (described in more detail below).

[0056] The light source 20 is used to provide wavelength scanning light emission. To this end, the light source 20 can be used to generate a series of light pulses for emission. During each pulse, the wavelength of the light can be "scanned" within a certain wavelength range. For example, the scan can be in the form of a chirped pulse. The light will be emitted at multiple different wavelengths during one pulse. For example, the wavelength can increase or decrease continuously during one pulse (the rate of change of the wavelength can be constant or variable). A series of chirped pulses can be continuous (for example, the time interval between pulses is zero). The light source 20 can be used to continuously emit a series of pulses, each of which has a wavelength scan. However, it should be understood that the light source 20 does not need to provide continuous scanning. For example, the light source can be tuned in steps rather than continuously, so that the light source 20 emits light of different wavelengths at different time intervals (for example, each of the multiple wavelengths is emitted at discrete time intervals). The light source 20 can scan unidirectionally (for example, only increase or decrease the wavelength during a wavelength scan), or bidirectionally (for example, increase and decrease the wavelength during a wavelength scan). Unidirectional scanning can be beneficial because it increases the number of photons detected in each scan.

[0057] The controller 40 may be used to selectively control the wavelength scanning of the light source 20. The light source modifier 22 is arranged to control the wavelength emission of light from the light source 20. For example, the light source modifier 22 may be arranged to apply a selected current (or voltage) to the light source 20 to select the wavelength emission from the light source 20. The wavelength scanning of the light source 20 may be controlled by using the light source modifier 22 to apply a corresponding electrical signal to the light source 20. The controller 40 may be arranged to control the application of current / voltage to the light source 20 using the light source modifier 22 to provide a selected pattern for the wavelength of light emitted by the light source 20.

[0058] The light source 20 can be controlled to perform wavelength scanning according to a selected mode of scanning. For example, the light source 20 can scan a selected range of light wavelengths and / or the light source 20 can scan the light wavelength according to a selected sweep profile (e.g., linear increasing, sinusoid, triangular, etc.). For example, the light source 20 can scan according to a selected sweep rate or a selected total sweep time. The light source 20 is used to perform wavelength scanning of light, so that during one wavelength scan, the light will be directed to the brain tissue of the subject through the sample delivery channel (and directed to the detector via the reference channel) at each of a plurality of different wavelengths. The wavelength of the light emitted by the light source 20 will vary with time. In this way, an indication of the time when light was emitted from the light source 20 can be determined based on the wavelength of the light.

[0059] The light source 20 can be used to scan through a selected wavelength range. For example, the light source 20 can be used to scan with an optical frequency within the range of 50 GHz. For example, this can enable the light source 20 to emit modulated light of multiple different wavelengths, such as between 829.94 nm and 830.06 nm when centered at 830 nm, or between 1309.857 nm and 1310.143 nm when centered at 1310 nm. The light source 20 can be used to scan a wavelength range (e.g., approximately around the wavelength of its center) of at least 0.025 nm (e.g., at least 0.05 nm, such as at least 0.075 nm, such as at least 0.1 nm, such as at least 0.11 nm). The light source 20 can have high output power, long coherence time, and wide range mode-hop-free wavelength tuning. The light source 20 can have a relatively narrow linewidth and a long coherence length, for example, because the light source 20 does not scan a particularly large bandwidth.

[0060] The light sources disclosed herein can be used to provide highly coherent light, for example, sufficiently coherent light, for emission. It should be understood that a light source cannot both emit fully coherent light and provide wavelength-scanned light emission, for example, because light of different wavelengths will change phase at different rates. The light sources disclosed herein can be controlled to scan a relatively narrow wavelength range compared to the absolute wavelength of the light source. In other words, the difference between the maximum wavelength and the minimum wavelength of a wavelength scan will be relatively small compared to the absolute wavelength. Each light source can be used to emit light (i.e., an electric field) whose phase does not vary much over time.

[0061] The iNIRS system of the present disclosure will receive sample light and reference light originating from the same light source. The light source of the present disclosure is used to provide wavelength-scanned sufficiently coherent light emission so that the sample light and reference light received at the optical detector will have relatively similar phases. Therefore, the combination of the sample light and the reference light will produce sufficient constructive interference between the two waves (e.g., the two light wave streams will have sufficiently similar phases so that the resulting combined light signal will contain a constructive combination of the two light waves). In other words, the coherence length of the light source can be such that multiple scattering in the tissue does not reduce the coherence or fringe contrast below the noise floor of the measurement.

[0062] For example, each light source of the present disclosure may include a laser. The laser may be selected based on the coherence length of the laser, for example, to enable the above-mentioned constructive interference to occur between the sample light and the reference light. In other words, the iNIRS system may be arranged so that the maximum expected flight delay time of the sample photons (received at the optical detector having passed through the brain tissue of the subject) relative to the reference light photons (received at the optical detector having propagated along one or more reference channels) is within the coherence time period of the laser (e.g., the optical path length difference between the sample light and the reference light is within the coherence length of the laser). During this coherence time period, the phase of the light emitted by the laser is approximately stable (although the wavelength of the emitted light changes). Therefore, the combined light signal at the optical detector may have no amplitude loss (e.g., the interference occurring at the detector may be fully constructive).

[0063] For example, an iNIRS system can be configured to have a coherence length or range of approximately 50 m in air, e.g., a light source having a coherence length between 50 m and 100 m (coherence time period between 166 ns and 333 ns) can be selected. It should be understood that this particular range is not intended to be limiting, but rather to illustrate an approximate range of light sources. A light source can be selected such that the coherence length of the light source is two or more times greater than the maximum expected optical path length difference, e.g., the coherence length can be three or four times or more. A light source having a coherence length much greater than the optical path length can improve the accuracy of measuring sample photons that have undergone a large number of scattering interactions within the subject's brain tissue.

[0064] The iNIRS system 10 is arranged so that the source-detector path lengths of the reference light and the sample light are different. In other words, the iNIRS system 10 is arranged so that the average or expected optical path length of light propagating from the light source 20 via the subject's brain tissue to each detector will be different from the optical path length of light propagating from the light source 20 via the reference channel to the above detectors.

[0065] As will be understood in the context of the present disclosure, photons of sample light directed toward the subject's brain tissue may propagate from the light source 20 to the light detector 30 via a virtually infinite number of different paths. The photons of sample light may experience a large number of scattering events, and therefore the path between the sample delivery probe 25a and the sample receiving probe 35a is very tortuous. The iNIRS system 10 is arranged to provide neuroimaging and analysis based at least in part on activity in the subject's brain tissue. The flight time of the sample photons from the light source 20 to the light detector 30 will increase as the path length increases. Therefore, photons that have a longer propagation path and penetrate deeper into the subject's brain tissue will take even longer to reach the light detector 30. The longer the flight time of the sample light photons, the deeper the photons may penetrate the subject's brain tissue.

[0066] The iNIRS system 10 is arranged so that the shortest flight time of a photon of light traveling from the light source 20 to the light detector 30 will be the time for a photon of reference light to travel along the reference channel. The sample light photons will have a longer flight time than the reference light. The sample light photons that penetrate the deepest into the subject's brain tissue are likely to be those photons with the longest flight time to the light detector 30.

[0067] The iNIRS system 10 is arranged to determine the distribution for time of flight (DTOF) of sample light photons. To this end, a temporal point spread function (TPSF) can be determined, which is similar to the DTOF, but the TPSF includes an instrument response function (IRF), which can then be filtered out (e.g., deconvolved and / or subtracted) using post-processing. Each determined DTOF can provide a distribution of the flight time of all sample light photons incident on the light detector 30 at a given time point. The DTOF can contain a collective average representing a large number of incident photons (in each TOF bin in a plurality of different TOF bins). The intensity of each TOF bin will provide an indication of the number of incident photons at the TOF. The phase of the TOF bin (e.g., obtained using Fourier analysis) can represent the average phase of all photons arriving at the TOF bin. As described in more detail below, multiple characteristics of the brain tissue of the object can be determined based on the DTOF data obtained for the brain tissue of the object. To obtain such data, the iNIRS system 10 is used to obtain an interference pattern of the combination of reference light and sample light as received at a given light source 20 .

[0068] The iNIRS system 10 is arranged so that each light detector 30 receives sample light and reference light, and combines the sample light and the reference light using a light combiner. For example, each detector may provide an interferometer component (combined with a sample light channel and a reference light channel) for combining the reference light and the sample light to obtain an interference pattern (interference pattern).

[0069] The light source 20 is used to emit sufficiently coherent light. The resulting interference pattern of the light from the light source 20 (as obtained at each detector) may include a combined signal having a beat frequency (or intermediate frequency / difference frequency) component corresponding to the wavelength difference between: (i) the wavelength of the sample light photon received by the light detector 30 at a given time point, and (ii) the wavelength of the reference light photon received by the light detector 30 at that time point. Due to the limitations of the inherent line width of the laser and the optical frequency scanning rate, the reference light within a single sampling interval should be of substantially narrow and uniform wavelength, because the received reference light photons will be transmitted from the light source 20 to the light detector 30 (through the reference channel) at the same distance. The sample light will include photons of different wavelengths, where the wavelength of each sample light will correspond to the flight time of the photon and its unique path in the tissue (due to the wavelength scanning of the light source 20). Therefore, the resulting interference pattern will contain multiple different beat frequencies (due to different differences in wavelength). In the case where the sample path is longer than the reference path, a higher beat frequency may correspond to a photon with a higher flight time (a photon that penetrates deeper).

[0070] Each photodetector 30 includes an optical combiner for combining light and providing the combined light (which may include one or more components corresponding to the beat frequency) to a signal processing circuit. Each detector may include a square-law detector. For example, each detector may be used to create an interference pattern based on the optical frequency difference between the incident sample and reference optical fields, for example, the detected intensity or power is proportional to the square of the incident electric field, and the incident electric field is the sum of the sample and reference optical fields. Therefore, the detected intensity or power (in the form of photocurrent) is equal to the square of the sum of the incident sample and reference optical fields. These detectors may include photodiodes, avalanche photodiodes and / or fast line scan cameras, streak cameras, and fast CCD or CMOS sensors. The detector may be a high-bandwidth detector. For example, the detector may be used to resolve interference fringes at frequencies of 100 MHz or higher, such as up to 1 GHz. The detector may include a single spot detector. For example, the optical fiber used in the detector may be single-mode. If a multimode detector is used, the detector may include a square-law detector array, such as a photodiode array, a focal plane array, a fast line scan camera, or a fast CCD array. The detector may also include a balanced detector array. For example, a balanced detector array can be used to combine and (e.g., evenly) split the reference and scattered light to a pair of out-of-phase detectors, such as using a 4-port (2-in, 2-out, 50:50 ratio) fiber coupler or beam splitter cube. Balanced detectors can enhance the signal-to-noise ratio of the detected signal by rejecting incoherent portions of the signal. Balanced photodetectors can also make full use of all the light transmitted through the interferometer and suppress common noise, such as laser intensity noise.

[0071] In other words, each light detector 30 may include a light combiner for combining sample light and reference light to provide a combined light signal. The iNIRS system 10 is arranged to process the combined light signal to obtain an indication of the intensity of light incident on the light detector 30 at a given point in time (e.g., by using optical off-frequency mixing and / or balanced detection). The iNIRS system 10 is arranged to obtain a plurality of such indications, for example, the light detector 30 may be arranged to repeatedly obtain an indication of the intensity of light incident on the light detector 30. In other words, the iNIRS system 10 is arranged to measure the phase or frequency shift between the photons of light in the two inputs (reference and sample) of the detector, and attribute this difference to the characteristics of the intervening brain tissue with respect to the sample light.

[0072] Each obtained interference pattern can be Fourier analyzed (e.g., using FFT or IFT) to obtain an indication of the DTOF of the sample light photons incident on the light detector 30. When a square-law detector is used, the intensity on the detector can be proportional to the square of the total electric field intensity. The rate of change of the optical frequency multiplied by the time delay can cause the frequency of the interference fringes present in each interference pattern. In other words, a Fourier transform interference pattern containing multiple beat frequencies can be used to indicate the photon flight time associated with those beat frequencies present in the interference pattern.

[0073] In order to obtain DTOF data of sample light photons, the light detector 30 is arranged to combine the two light inputs (sample light and reference light) into a combined light beam. The light detector 30 is arranged to convert the combined light beam into an electrical signal representing the combined light signal. The iNIRS system 10 includes at least one digitizer, which is arranged to receive electrical signals indicating the combined light signal and convert these electrical signals into digital data representing the combined light signal. These digital data can be processed to obtain one or more different characteristics of the subject's brain tissue for neural imaging and analysis.

[0074] An example of an arrangement for converting a received optical signal into digital data is as follows Figure 1 As shown in the illustration A of FIG. Illustration A shows an arrangement of components that can be used as the light detector 30 of the present disclosure. Figure 1 As shown in the iNIRS system 10 , the detector 30 receives two inputs: (i) reference light that has propagated along the reference delivery channel 26 and the reference receiving channel 36 , and (ii) sample light that has been received by the sample receiving probe 35 a and delivered to the detector via the sample receiving channel 35 .

[0075] As shown, the detector may include an optical combiner and splitter 301, a first optical channel 302a and a second optical channel 302b, a balanced photodetector 303, a transimpedance amplifier 304, an amplifier 305, and an analog to digital converter (ADC) 306. The ADC 306 is arranged to provide a digital signal output 307.

[0076] The optical combiner and splitter 301 is coupled to the reference receiving channel 36 and the sample receiving channel 35. The optical combiner and splitter 301 is arranged to receive the sample light and the reference light, and combine the sample light and the reference light to provide a combined optical signal. The optical combiner and splitter 301 is arranged to split the combined optical signal into two independent channels: a first optical channel 302a and a second optical channel 302b. For example, this can be a 50:50 split (or approximately so). The first optical channel 302a and the second optical channel 302b are coupled to a balanced photodetector 303. Each optical channel guides light to an associated photodiode. The balanced detector is arranged to provide an output based on the difference between the outputs from the two photodetectors. Two photodetectors will typically be provided so that the beat signals on each photodiode are 180° out of phase with each other, and therefore the coherent AC terms will be forward combined with each other. The balanced photodetector 303 is arranged to output a current corresponding to the difference between the output currents of the two photodetectors. Balanced photodetector 303 may remove any unwanted DC terms from the signal, such as slow fluctuations from light source 20 or other common mode effects, such as noise.

[0077] The photodetector 30 is used to convert the current output by the balanced photodetector 303 into a corresponding voltage using a current-to-voltage converter. Figure 1As shown in the illustration A of , the converter may include a transimpedance amplifier 304. The voltage output by the transimpedance amplifier 304 is then amplified using an amplifier 305. The amplifier may be used to scale the output signal to the full range of the ADC and limit the electronic frequency of the circuit to further maximize the SNR. The amplified voltage is then provided to the ADC 306 for digitization. The ADC 306 includes a digitizer with sufficient bandwidth so that the full signal bandwidth containing the time-of-flight information can be digitized without attenuation. For example, the bandwidth of the digitizer may be at least the same as the bandwidth of the combined optical signal. For example, the sampling rate of the digitizer may be selected to be high enough to meet the Nyquist criterion for processing the signal bandwidth. The digitizer may be provided as part of each optical detector 30, or the digitizer may be part of the controller 40, and the controller 40 may be coupled to each optical detector 30 to receive the electrical signal to be digitized from the optical detector. For each combined optical signal, a digital signal output 307 is provided, which gives a digital representation of the combined optical signal (and therefore also a digital representation of the sample light incident on the optical detector 30 when generating and measuring the combined optical signal).

[0078] The iNIRS system 10 is used to obtain a plurality of digital signal outputs 307 indicating sample light incident on the light detectors 30. Specifically, each light detector 30 is used to repeatedly combine light signals (sample light and reference light) to provide a digital signal output 307 representing each combined light signal. For example, for each light detector 30, a time series of digital signal outputs 307 can be obtained, wherein each subsequent digital signal output 307 corresponds to a subsequent time point at which the combined light signal is obtained and measured (and the digital signal output 307 represents the obtained and measured combined light signal). As described above, each of these signals can indicate the sample light DTOF at that time point of that detector.

[0079] In other words, the iNIRS system 10 is used to obtain multiple time-sequenced DTOFs for each of the multiple different photodetectors 30. The digitizer can provide digital outputs indicative of the different measurements, and these digital outputs can optionally be processed in a variety of ways to provide DTOF data. Examples of these steps will now be described.

[0080] The controller 40 can be used to receive raw digital interferogram data (e.g., data representing an interferogram obtained by converting a combined optical signal into digital data). The raw interferogram can be divided into individual scans of a wavelength scan emission from the light source 20. For example, the scan rate of the light source 20 and the time when the first scan begins can be used to determine the scan period. The data can then be divided into groups, each of which represents a single scan. An optional Hilbert transform can be performed on the data at this stage. The data can be windowed (e.g., using a Hanning window or a Blackman-Harris window) to reduce side lobes in the data. Fourier analysis can be performed on the data, which can be inverse or forward. For example, an inverse Fourier transform can be performed. Fourier analysis can be performed for each wavelength scan of the light source 20. The resulting data can be in the form of a series of time point spread functions (TPSFs), each TPSF corresponding to an associated wavelength scan. The TPSF data can be processed to remove the instrument response function (IRF) therefrom to provide DTOF data.

[0081] In other words, the iNIRS system 10 can be used to determine a time-ordered sequence of the distribution of flight time (DTOF) of sample light photons incident on each of a plurality of different detectors. These DTOF data can be processed to provide information related to a plurality of different physical properties of the subject's brain tissue. The DTOF data can be used to determine the optical properties of the medium through which the sample light has passed. Each TOF bin in the DTOF can represent a selected volume within the subject's brain, and each DTOF represents the total volume of tissue detected by the photons (e.g., each DTOF can represent a weighted average of the properties of brain tissue and other tissues (such as scalp, skull, etc.) through which the photons have passed). Optical properties include scattering and absorption properties of the subject's brain tissue. The DTOF data can be used to determine the dynamic properties of the subject's brain tissue, such as changes in specific properties over time. This includes how the optical properties evolve over time, and properties indicating motion (e.g., caused by blood flow) within the subject's brain tissue. The iNIRS system 10 can be used to Fourier transform (e.g., FFT) the obtained TOF distribution to obtain gamma data, wherein the dynamic signal can be obtained from the temporal changes of the gamma signal.

[0082] The time-ordered sequence of DTOF can be considered as corresponding to the data surface in the 3D volume.The surface can represent the DTOF of each subsequent DTOF (ordered in time), and therefore the surface shows the evolution of each independent DTOF and DTOF over time.The surface can provide a large amount of data, according to which the characteristics of the brain tissue of the object can be determined.The time fluctuation analysis of the DTOF value over time (for example, decay) can provide the indication of one or more dynamic characteristics of the brain tissue of the object.That is, decay analysis can be used to identify that one or more characteristics in the brain tissue of the object are changing, and optionally identify the rate (for example, using decay rate) that these characteristics are changing.The order of the decay of DTOF (for example, decaying with t, t2, etc.) can be used to determine one or more characteristics of the type of motion (for example, diffusion or flow).

[0083] The controller 40 may store data associating the time of flight of the sample light photon with an indication of the average path trajectory of the photon. This may include an indication of the depth of penetration of the photon into the brain tissue of the object, and / or an indication of the region through which the photon passes from the light source 20 to the brain tissue of the object. The controller 40 may be used to process the data by dividing the DTOF data into selected time of flight bins. Within each TOF bin, the data may provide depth-resolved evolution data of the brain tissue of the object. That is, since TOF may be associated with a specific penetration depth or region, each TOF bin may contain data showing characteristics associated with a specific penetration depth or region. Therefore, the evolution of the data within each TOF bin may provide an indication of how one or more characteristics of the brain tissue of the object evolve. For example, when the evolution indicates a change in motion (e.g., blood flow), the motion and the region in which the motion occurs may be identified. To this end, the TOF-resolved attenuation slope may be used to identify a curve of a specific TOF (e.g., a specific penetration depth / region) decaying over time.

[0084] In other words, the iNIRS system 10 is used to perform autocorrelation, where the DTOF of consecutive wavelength scans are combined to evaluate the light field fluctuations over time at the light detector 30. Because of the correlated fluctuations of the DTOF over time, the fluctuations can be quantified. The fluctuations can also be depth resolved by identifying the correlated TOF (and therefore the correlated penetration depth / region) where the fluctuations occur.

[0085] The controller 40 can be used to process the data received from the photodetector 30 to provide time-of-flight information that is depth-resolved and autocorrelated with the subject's brain tissue. The controller 40 can be used to use this information to obtain a plurality of different characteristics of the subject's brain tissue, such as an indication of intracranial pressure (ICP), blood flow index, arterial elasticity, etc. These characteristics of the subject's brain tissue can be used for a variety of different forms of neural imaging and analysis, such as in brain-computer interfaces, for imaging brain regions to identify potential localized damage or stroke, and / or for monitoring neural responses to substances (e.g., drugs).

[0086] Intracranial pressure (ICP)

[0087] As described above, the iNIRS system 10 includes an optical interferometer arranged to combine the sample light with the reference light to provide a combined light signal. The system 10 can detect the frequency of the light received by the detector. The received light (i.e., the combined light signal) will include light of multiple beat frequencies between the sample light and the reference light. The iNIRS system 10 also includes a signal processing and conversion circuit coupled to the detector 30 and used to generate combined light signal data from the combined light signal (i.e., generate data indicating the received combined light signal).

[0088] The controller 40 of the iNIRS system 10 is used to process the combined light signal data to obtain time-of-flight data, which includes multiple time-of-flight distributions of photons of sample light arriving at the optical detector 30 from the light source 20. The controller 40 can be used to process the combined light signal data to obtain a data surface containing multiple time-of-flight distributions (e.g., a time-ordered sequence of DTOF) that are continuous in time. The controller 40 can be used to process the data surface to obtain an indication of autocorrelation decay. Each autocorrelation can provide an indication of the degree of similarity between a first DTOF distribution and a previous DTOF distribution (or even a portion of a first DTOF distribution and a corresponding portion of a subsequent DTOF distribution, for example, where the portion represents a certain time-of-flight (TOF) bin). Autocorrelation decay can provide an indication of how the autocorrelation changes over time, for example, an indication of how the autocorrelation is changing. In other words, the controller 40 can be used to obtain an indication of any time fluctuation in the DTOF distribution obtained for the object over time. The DTOF distribution can contain data for each bin in a plurality of TOF bins. Some of these TOF bins (usually those with longer times) can represent the volume of tissue in the brain of the object. Controller 40 may be used to identify temporal fluctuations associated with the volume of one or more tissues within the subject's brain.

[0089] The controller 40 is also used to obtain an indication of the scattering coefficient and the absorption coefficient of the brain tissue of the subject. The controller 40 can determine the coefficients using the time-of-flight data (e.g., based on one or more of the obtained DTOFs). For example, the controller 40 can determine the coefficients based on one or more statistical moments (e.g., mean / variance) of the DTOF (or TPSF) distribution (or multiple such distributions) and / or based on the shape of the DTOF (or TPSF) distribution (or multiple such distributions).

[0090] The controller 40 is used to determine the cerebral blood flow index of the subject based on the obtained scattering coefficient and absorption coefficient and the autocorrelation attenuation. To this end, the controller 40 can be used to attribute the temporal fluctuation of the volume of the subject's brain to the blood movement in the area. The cerebral blood flow index can provide a relative measure of the movement occurring within the tissue in the subject's brain.

[0091] The controller 40 is used to obtain cerebral blood flow data of the subject's brain tissue (i.e., tissue within the subject's brain). The cerebral blood flow data can be determined based on detected changes occurring within the subject's brain tissue. The controller 40 can be used to detect changes associated with blood within the subject's brain tissue. These changes may be associated with the flow of blood through the subject's brain tissue. In other words, the controller 40 can be used to detect an indication that blood is moving in a given area of ​​the subject's brain by determining that a subsequent DTOF distribution is undergoing decorrelation.

[0092] As described above, the controller 40 can be used to determine a cerebral blood flow index (CBFi) of the subject's brain tissue. CBFi can provide an indication of motion occurring within the subject's brain. For example, CBFi can provide a relative measurement describing motion occurring within the subject's brain. The motion can be attributed to the movement (e.g., flow) of blood through the subject's brain. CBFi provides a relative measure. CBFi can include an indication of average velocity in bulk tissue. For example, CBFi for a given volume within the subject's brain can provide an indication of the average velocity of motion occurring within the volume. The motion can be attributed to the movement of blood, and therefore CBFi can provide an indication of average blood flow velocity. For example, an increase in the value of CBFi can indicate an increase in velocity within the brain volume.

[0093] The iNIRS system can be sensitive to all forms of motion of blood flowing through the subject's brain. For example, the blood flow monitored by the iNIRS system 10 can be directed to blood vessels within the brain tissue, such as to blood perfused in the microvasculature of the subject's brain tissue, and / or can be directed to Brownian motion type motion through the subject's brain tissue (rather than blood flow through larger tubular structures (e.g., veins or arteries)). It should be understood that the specific form of blood motion detected by the iNIRS system will depend on the volume of tissue examined by the iNIRS system.

[0094] The iNIRS system 10 may be used to measure an indication of the perfusion pressure of blood flow within brain tissue. CBFi may provide an indication of the behavior of blood as it flows through such regions of the subject's brain tissue.

[0095] The iNIRS system 10 can be used to obtain data of the subject's brain tissue at a sufficiently high rate to identify changes in blood flow through the subject's brain tissue. Specifically, the iNIRS system 10 can be used to obtain data at a sufficiently high rate to identify changes in the subject's blood flow due to the subject's heart pulsation (e.g., to identify systolic and diastolic characteristics of blood flow). For example, the iNIRS system 10 can be used to obtain data at a rate of at least 10 Hz (such as greater than 20 Hz, for example, between 10 Hz and 100 Hz).

[0096] Controller 40 is used to obtain cerebral blood flow data (i.e., data containing indications of blood flow within a subject's brain tissue), the data containing indications of one or more pulses of blood flow through the subject's brain tissue. Controller 40 may determine a CBFi of the subject's brain tissue, wherein the pulses of blood flow through the subject's brain tissue are evident in the determined CBFi of the subject's brain tissue. Examples of such determined CBFi are described in Figure 2 Shown in.

[0097] Figure 2 An example of the evolution of the determined CBFi of a subject's brain tissue over time is shown. Figure 2, two pulses are shown. The pulses occur in a cyclic and repetitive manner (although each individual pulse may vary in size and shape, and the frequency with which the pulses occur may also vary). In general, each pulse will have a diastolic CBFi value (e.g., a lower CBFi value) and a systolic value (e.g., a higher CBFi value). During a pulse, the CBFi may start at its diastolic value (its lowest value) and then quickly increase to its systolic value (its highest value). The CBFi will then drop back from the systolic value to the diastolic value, but the CBFi may temporarily increase (or at least begin to decrease at a slower rate) at least once as the CBFi drops from the systolic value to the diastolic value. Once back to the diastolic value, the process will repeat again (due to the pulsation of the subject's heart).

[0098] The iNIRS system 10 is used to obtain a measurement signal using optical interferometry, from which the controller 40 of the iNIRS system 10 can obtain cerebral blood flow data indicating the behavior of blood flowing through the subject's brain tissue (e.g., the controller 40 can obtain data such as Figure 2 Time evolution of the CBFi values ​​shown).

[0099] As will be described in more detail below, controller 40 is used to process cerebral blood flow data to determine an indication of ICP of the subject's brain tissue. Controller 40 may be used to determine ICP based on one or more characteristics of the pulsation waveform of the blood flow. To this end, controller 40 may use any of a number of suitable characteristics. In an example, the characteristic may describe the shape of the pulsation waveform or other relative measurements related to the pulsation waveform.

[0100] The volume of a subject's brain tissue will be limited by its skull. The skull is typically very rigid, so the subject's brain tissue is within a fixed internal volume of the skull. This internal volume does not change, so as the pressure within the skull increases, the material in this internal volume will be compressed (and vice versa). This will also apply to pulses of blood flowing through the subject's brain tissue. In order for blood to flow through the subject's brain tissue, some of the brain tissue must be compressed to make room for the blood to pass through. The extent to which the subject's brain tissue can be compressed to accommodate the blood flow will depend on the subject's ICP. For a given pulse of blood flow through the subject's brain tissue, the extent to which the brain tissue is compressed to accommodate the blood flow will decrease as the ICP increases (because the brain tissue is already more compressed as the ICP increases). Accordingly, some blood flow may slow (e.g., due to increased resistance to its movement), and / or the amount of blood flowing per unit time may decrease.

[0101] The controller 40 is configured to use the cerebral blood flow data to determine an indication of the effect of ICP on the pulsation waveform of blood flow through the subject's brain tissue. The controller 40 may be configured to identify changes in the pulsation waveform, such as changes in the shape of the pulsation waveform and / or changes in the maximum / minimum values ​​of the pulsation waveform, and to use this information to determine an indication of the subject's ICP. For example, the controller 40 may be configured to determine an indication of ICP based on the maximum and / or minimum CBFi values ​​of the pulses of blood flow through the subject's brain tissue and / or based on any differences between these values.

[0102] refer to Figure 2 , an example method of determining ICP will now be described. As described above, Figure 2 CBFi values ​​of a pulsating waveform of a pulse of blood flow through a subject's brain tissue determined using the iNIRS system 10 of the present disclosure are shown. The controller 40 is used to determine for each pulse an indication of its systolic (e.g., highest) CBFi value and diastolic (e.g., lowest) CBFi value. Both values ​​are in Figure 2 In addition, the controller 40 is used to determine the average CBFi value of each pulse (also shown in Figure 2 ). The controller 40 is used to determine a cerebral blood flow pulsatility index value based on the diastolic, systolic, and average CBFi values ​​of the pulse. For example, for each pulse, the CBFi pulsatility index can be determined as the difference between the systolic value and the CBFi diastolic value divided by the average CBFi value. The controller 40 can be used to determine an indication of ICP based on the determined CBFi pulsatility index. For example, the controller 40 can utilize stored data (e.g., in a lookup table) that links the CBFi pulsatility index value to the ICP value (e.g., this can use a known regression relationship between the CBFi pulsatility index and ICP).

[0103] Now refer to Figure 3a to Figure 3c Another example method of determining ICP is described. For this method, an additional data stream is used in combination with the CBFi data obtained by the iNIRS system 10. The additional data stream contains data indicating one or more pulses of blood flow in a region of the subject's body that is different from its brain tissue, referred to as extracerebral blood flow data. The extracerebral blood flow data will be from a region of the subject's body that is not subject to the same fixed volume constraints imposed by the subject's skull. The method includes comparing one or more characteristics of the pulsation waveform of the cerebral blood flow with corresponding characteristics of the pulsation waveform of the extracerebral blood flow. The ICP indication of the subject's brain tissue can then be determined based on the differences between the subject's cerebral blood flow pulses and the extracerebral blood flow pulses (e.g., based on differences in the shape and / or value of the pulsation waveforms).

[0104] Figure 3a and Figure 2 resemblance, Figure 3aCBFi values ​​of the pulsation waveform of the pulse of blood flow flowing through the brain tissue of the subject determined using the iNIRS system 10 of the present disclosure are shown. Figure 3b Shown with Figure 3a Similar graphics, however, Figure 3b Shown are pulses of extracerebral blood flow. Extracerebral blood flow is directed to portions of a subject's body that are not constrained by a fixed volume (such as is the case within the subject's skull). In such extracerebral regions, each pulse of blood flow will have a pulsating waveform that exhibits less influence of pressure applied to the vessel from surrounding tissue. In other words, for a vessel in an extracerebral region, the tissue surrounding the vessel may be relatively less affected by local pressure fluctuations (i.e., increases in pressure cannot be accommodated by corresponding increases in volume) than may occur within the subject's skull. For example, extracerebral blood flow may refer to the flow of blood through a subject's veins or arteries (such as those in their scalp).

[0105] exist Figure 3b In the example of FIG. 1 , the figure shows a graph of arterial blood pressure (ABP) over time (rather than Figure 3a ABP pulsation waveform ( Figure 3b ) may be related to CBFi( Figure 3a ) appear relatively similar. Controller 40 may be used to align in time the respective pulsatile waveforms of the cerebral blood pulse and the extracerebral blood pulse. For example, it will be appreciated that the pulse timings of different regions of the body may be offset, and thus controller 40 may be used to align a pulse from one region with a corresponding pulse in another region (so that a comparison of the two waveforms is associated with the same pulse, even though the pulses were measured at slightly different time periods).

[0106] In one example, controller 40 may be configured to compare different values ​​of the two pulses (e.g., diastolic, systolic, and / or average) in the manner outlined above. In this case, controller 40 may use the value of extracerebral blood flow to provide an indication of a baseline pulsatility index of the pulsatility of the subject's blood flow, wherein any difference between the baseline pulsatility index and the CBFi pulsatility index is attributed to the effect of ICP on the pulsatility of blood flow through the subject's brain tissue (e.g., using a regression analysis-like method to convert the difference in pulsatility index between cerebral blood flow and extracerebral blood flow into an indication of ICP).

[0107] Figure 3c Another example of determining ICP based on cerebral blood flow data and extracerebral blood flow data is shown in FIG. Figure 3cIn FIG. 1 , cerebral blood flow data is plotted against extracerebral blood flow data, with the cerebral blood flow data shown on the y-axis as CBFi and the extracerebral blood flow data shown on the x-axis as ABP. The two data graphs (i.e., data for cerebral blood flow and extracerebral blood flow) are aligned on the graph, for example, so that their linear regions substantially overlap (or at least approach each other if the data graphs do not completely overlap). Figure 3c As shown, there is a linear region starting from where the line intersects the x-axis (labeled "CrCP") until the region where the data diverges (labeled "dicrotic notch"), and there is an annular region. Figure 3c As shown in , the curve intersects the x-axis (ie, the CBFi value is 0) where the ABP value is positive. The controller 40 of the iNIRS system 10 can be used to process the brain data and the extracerebral data to identify the value of this point (CrCP).

[0108] CrCP represents the critical closure pressure of blood vessels in the subject's brain tissue. As described above, CBFi provides information related to the movement of blood through blood vessels in the subject's brain tissue. As the CBFi value decreases, this indicates that there is less blood movement within the subject's brain tissue (e.g., a CBFi measurement of zero can indicate the absence of any blood flow). Figure 3c The intersection of the x-axis in the graph of CBFi represents the value of arterial blood pressure when CBFi is zero (i.e., no blood is flowing through the blood vessels in the subject's brain tissue). This is called the critical closing pressure because it is the pressure at which the small blood vessels in the brain "close". In other words, the value of CrCP represents the condition at which the pressure in the blood vessels is low enough that the blood vessels are forced to close (due to the external pressure applied to them).

[0109] Controller 40 is used to determine a value of CrCP for one or more blood vessels in the subject's brain tissue. Controller 40 is used to determine an indication of ICP based on the value of the CrCP. Comparison between arterial blood pressure and CBFi (at the same / corresponding points during the pulsatile waveform) can provide an indication of blood pressure in the subject's artery when the blood vessel in the subject's brain tissue is closed. An indication of ICP can be determined based on this information (i.e., based on the pressure when the blood vessel is "closed"). For example, ICP can be determined as the external pressure that needs to be applied to the blood vessel to cause the blood vessel to close. This can include a vascular compliance term, which represents the force applied to the blood from the blood vessel wall (e.g., to account for the presence of some blood pressure in the blood vessel, such as the subject's arterial blood pressure).

[0110] Although in Figure 3c, but it should be understood that controller 40 need not generate the corresponding graphs (which are used to illustrate the method). Controller 40 can be used to compare extracerebral blood flow data (e.g., blood pressure data of one or more veins / arteries outside the subject's brain tissue) and cerebral blood flow data (e.g., CBFi values ​​of one or more blood vessels within the subject's brain tissue). Based on the comparison, controller 40 can be used to identify a corresponding pressure (e.g., in the subject's veins / arteries) for blood vessel closure in the subject's brain tissue. Controller 40 can be used to determine an indication of ICP based on the CrCP value (e.g., by determining a required pressure in the subject's brain that will cause cerebral blood vessel closure).

[0111] In the method of obtaining extracerebral blood flow data, it should be understood that any suitable device can be used to obtain the data. For example, the iNIRS system 10 can be provided in combination with a separate sensing element for obtaining such data. A separate sensing element can be used to measure the blood pressure of a separate area of ​​the subject's body (e.g., one of its limbs (e.g., an arm or its hand / finger)). The sensing element can be used to obtain data (e.g., including diastolic values ​​and / or systolic values, and / or average values) containing an indication of one or more characteristics of the pulsating waveform in the area of ​​the subject's body. For example, the sensing element can be used to obtain an indication of how the blood pressure changes over time during the pulsating waveform of blood flowing through the vein / artery of the subject.

[0112] Additionally or alternatively, the iNIRS system 10 of the present disclosure may be used to obtain cerebral blood flow data and extracerebral blood flow data. For example, the iNIRS system 10 may include a single source-detector channel that may be arranged to generate a combined optical signal from which data representing cerebral blood flow and extracerebral blood flow may be obtained (e.g., both data are initially contained in one spectrogram / interferogram).

[0113] Figure 4a An example iNIRS system 10 is shown that is arranged to provide such functionality.

[0114] Figure 4a The iNIRS system 10 described above Figure 1 The iNIRS system 10 is similar to the iNIRS system 10 of the present invention, so repeated components will not be described again. As described above, the iNIRS system 10 is arranged to split light from a light source 20 (not shown) (via an optical splitter 24) into a sample delivery channel 25 and a reference delivery channel 26. The optical detector 30 then receives the reference light (from the reference delivery channel 26) and the sample light (from the sample receiving channel 35). A sample delivery probe 25a and a reference delivery probe 35a are also shown.

[0115] Figure 4aAlso shown are the different layers of a subject's head. The topmost layer is the scalp skin surface 101. The second layer below the scalp skin surface is the scalp tissue 102. The scalp tissue will include a number of arteries and veins. Below the scalp tissue is the subject's skull 103, and located within their skull is brain tissue 104. The veins and arteries within the subject's scalp tissue are relatively unconstrained by their skull. That is, in this area of ​​the subject's body, the volume expansion of the veins / arteries is not hindered by their skull (as the blood vessels within the subject's brain tissue are hindered). Therefore, an increase in blood pressure in the veins / arteries can cause a corresponding increase in volume in these areas.

[0116] In order for photons to reach the subject's brain tissue from the light source 20 (and through the sample delivery channel 25 and the sample delivery probe 25a), the photons must penetrate the subject's scalp skin surface, the scalp tissue, and the skull. In order for the photons to reach the veins / arteries in the subject's scalp tissue, the photons only need to penetrate the subject's scalp skin surface (and relevant portions of the scalp tissue). Two example photon paths for sample light to reach the detector 30 from the light source 20 are shown: a shallow photon path 202 and a deep photon path 204. The deep photon path between the light source 20 and the light detector 30 is much longer than the shallow photon path (because the deep photon path goes deeper into the subject's brain tissue). For both photon paths, there are multiple scattering events that occur within the subject's head. In this example, photons propagating along the shallow photon path will interact with at least one blood-carrying region of the subject's scalp tissue (e.g., a vein or artery), and photons propagating along the deep photon path will interact with at least one blood vessel within the subject's brain tissue.

[0117] The light source 20 will emit a greater number of photons, and the paths that these photons take from the light source 20 through the subject's head to the detector 30 will be different. The sample delivery probe 25a and the sample receiving probe 35a are spatially arranged on the subject's scalp so that at least some of the sample light photons that reach the detector 30 from the light source 20 will propagate along shallow photon paths and some will propagate along deep photon paths. For example, the probes will be sufficiently separated in space to allow some deep photon paths to occur.

[0118] Figure 4b The distribution of the flight time of sample light photons received at the detector 30 is shown. As shown, the peak of the number of sample light photons occurs at a relatively short flight time, and then the number of arriving photons decreases at a longer flight time. As described above, the flight time of the sample light photons approximately corresponds to their penetration depth. That is, photons that penetrate deeper will have a longer flight time than photons that penetrate shallower.

[0119] Figure 4bThe flight time distribution shown in contains sample light photons along the shallow path (and can provide information related to extracerebral blood flow) and sample light photons along the deep path (and can provide information related to cerebral blood flow). Figure 4b As shown, shallow photon path photons have shorter flight times than deep photon path photons. Within this single interferogram, the controller 40 can be used to obtain information on cerebral blood flow and extracerebral blood flow.

[0120] To this end, the controller 40 is used to separate cerebral blood flow from extracerebral blood flow. This can include the controller 40 separating cerebral blood flow data from extracerebral blood flow data based on time-of-flight data. For example, when the time-of-flight of the received sample light photons is lower than a first threshold, the controller 40 can be used to attribute the received sample light photons to the scalp tissue of the subject. When the time-of-flight of the received sample light photons is lower than a second threshold, the controller 40 can be used to attribute the received sample light photons to the brain tissue of the subject. For example, the first threshold and the second threshold can be different (for example, so that the time-of-flight of photons that may have been scattered from the skull of the subject is between the first threshold and the second threshold). In other words, the controller 40 can be used to obtain depth resolution information of the received sample light photons. The depth resolution information can include an indication of whether the photons penetrated the skull of the subject. The controller 40 can select photons that have not penetrated the skull to obtain extracerebral data from them, and select photons that have penetrated the skull to obtain intracerebral data from them.

[0121] The controller 40 may be configured to process the cerebral blood flow data and the extracerebral blood flow data separately. For example, the controller 40 may be configured to obtain time-of-flight data (e.g., including a measured distribution of time-of-flight) and to separate the time-of-flight data into different data streams: (i) an extracerebral data stream (for shorter time-of-flight photons that may be associated with scalp tissue), and (ii) a cerebral data stream (for longer time-of-flight photons that may be associated with brain tissue). Each data stream may be processed independently in the manner described above to obtain blood flow index data that includes an indication of one or more pulses of blood flowing through a relevant region of the subject's body (e.g., through veins / arteries in their scalp or blood vessels in their brain tissue).

[0122] The controller 40 may be used to process the extracerebral blood flow data to obtain an indication of one or more characteristics of the pulsation waveform of the extracerebral blood flow (e.g., to obtain blood flow index data of pulses of blood flow flowing through veins / arteries in the subject's scalp tissue). The controller 40 may be used to determine pressure data of pulses of blood flow flowing through veins / arteries of the subject (which may be apparent from the blood flow index data obtained using the iNIRS system 10). For example, the controller 40 may store known conversion data that converts blood flow index values ​​into corresponding pressure values ​​(e.g., using a method similar to the CBFi pulsation index method described above). The controller 40 may be used to obtain extracerebral blood flow pressure data, e.g., data containing pressure values ​​of blood flow pulses at different time periods during each pulsation waveform of a pulse of blood flow flowing through the subject's scalp tissue. The controller 40 may use the extracerebral pressure data and the cerebral blood flow index data (e.g., as described above) to obtain pressure data of the pulses of blood flow flowing through the subject's scalp tissue. Figure 3a to Figure 3c An indication of intracranial pressure is determined in a manner described, such as by identifying a CrCP value of the subject's brain tissue.

[0123] Thus, the iNIRS system 10 can be used to obtain brain data and extracerebral data through iNIRS measurements. The brain data can include cerebral blood flow index data of one or more pulses of blood flowing through blood vessels in the subject's brain tissue. The extracerebral data can include blood pressure data of one or more pulses of blood flowing through the subject's scalp vascular system. The controller 40 can be used to process these two data streams obtained using the iNIRS system 10, and determine the subject's ICP based on the two data streams. For example, the controller 40 can be used to align the obtained scalp tissue blood pressure data with the obtained cerebral blood flow index data, and thereby determine an indication of an extracerebral blood pressure value at which one or more blood vessels in the subject's brain tissue are closed. Based on the critical closure pressure, the controller 40 can determine an indication of the ICP.

[0124] In the above about Figure 2In the example described in FIG. 4 , the iNIRS system 10 uses one light source and one detector (i.e., only one source-detector channel). However, this should not be considered limiting. The iNIRS system 10 may include multiple light sources and / or multiple light detectors. Each light source may be coupled to multiple other detectors (e.g., via multiple reference channels). Multiple light detectors may be juxtaposed (e.g., they may be disposed in the same area on the subject's scalp / or close to each other on the subject's scalp). Then, different light detectors may each be arranged to detect photons of sample light from the same light source that have passed through similar areas of the subject's brain tissue. The controller 40 may be used to combine data from different light detectors (e.g., averaging them to provide a single combined readout of the subject's brain tissue). For example, the controller 40 may be used to determine cerebral blood flow index data (and optionally, extracerebral data) of the subject's brain tissue based on data obtained using multiple optical detectors. This arrangement may improve the signal-to-noise ratio of measurements obtained using the iNIRS system 10.

[0125] The iNIRS system 10 may include multiple source-detector channels associated with different regions of the subject's brain tissue. For example, there may be multiple optical detectors located at different locations on the subject's scalp (these optical detectors may be coupled to the same light source or different light sources). The controller 40 may be used to obtain multiple ICP measurements using the multiple detectors of the iNIRS system 10 (as described above, but for each of the multiple detectors). The controller 40 may then determine the ICP value of the subject based on the multiple ICP measurements from the different detectors. For example, because the ICP may be relatively constant for different regions of the subject's brain tissue, this arrangement may improve the reliability of the measurement.

[0126] In the above example, the iNIRS system 10 can use one source-detector channel to obtain cerebral blood flow data and extracerebral blood flow data. However, the iNIRS system 10 may not necessarily obtain extracerebral blood flow data, for example, an additional sensor may be provided for obtaining extracerebral blood flow pressure values. Additionally or alternatively, different iNIRS source-detector channels may be used to obtain extracerebral data, for example, where the source and detector are arranged closer to each other on the subject's scalp (e.g., to increase the selection of short-distance sample photons from the source to the detector). For example, the iNIRS system 10 may include an extracerebral source-detector channel (one source and one detector for measuring extracerebral blood flow, and one or more (e.g., multiple) optical detectors for measuring cerebral blood flow).

[0127] In the above example, extracerebral blood flow data can be obtained using the iNIRS system 10 to measure the characteristics of blood flow in the subject's scalp tissue. However, this should not be considered limiting, as other areas can also be used for extracerebral data. For example, the iNIRS system 10 can be used to measure the characteristics of the subject's neck, ears, forehead, etc., or even to measure the characteristics of areas farther away from their brain tissue (e.g., where more than one source-detector channel is used). The iNIRS system 10 can be used to obtain blood flow data for areas of the subject's body (not within their skull) where the monitored blood flow has no significant external constraints (i.e., where the blood flows through an area that is not substantially compressed). For example, extracerebral blood can flow in veins / arteries under the subject's skin, which is not significantly compressed by surrounding matter.

[0128] The iNIRS system 10 may include multiple light sources. The above light sources may emit light of different wavelength ranges. The iNIRS system 10 may be used to determine ICP based on measurements obtained using light in each of the multiple different wavelength ranges. The iNIRS system 10 may include a first light source and a second light source, the first light source being used to emit light in a wavelength range higher than an absorption wavelength such as blood oximetry, and the second light source being used to emit light in a wavelength range lower than an absorption wavelength such as blood oximetry. The controller 40 may be used to determine ICP based on optical signals received from the first light source and the second light source. Providing such a first light source and a second light source may make the measurement of changes in blood oxygenation values ​​more reliable (for example, because one light source will emit light in a wavelength range that is more suitable for absorption by oxygenated hemoglobin, and the other light source will emit light in a wavelength range that is more suitable for absorption by deoxyhemoglobin).

[0129] It should be understood that in the context of the present disclosure, the examples described herein are not intended to be limiting. Rather, the examples describe certain potential methods of implementing the claimed technology. For example, an iNIRS system is described as having a series of optical cables that provide channels and probes for coupling these channels to the scalp of a subject. However, it should be understood that the probes themselves can be part of the optical channels, or no probes may be provided at all. Similarly, the arrangement of reference channels is intended only to indicate that reference light is delivered from the light source to the light detector via the optical channels (rather than via the subject's brain tissue). For example, each light source may include a reference channel for each light detector, wherein the reference channel connects the light source directly to the light detector. In this case, there may be no reference connection at all in the system. Optionally, and as Figure 1As shown, reference light can be transmitted on a common reference light channel, where some of the reference light is extracted from the common reference light channel to each optical detector. The light source can also be arranged to deliver light to one of a plurality of different locations on the subject's scalp. For example, the light source can be coupled to a plurality of different sample delivery channels, each sample delivery channel extending (e.g., from an optical splitter) toward the subject's scalp.

[0130] It should be understood that the specific arrangement of the signal processing circuits of the detectors shown should not be considered limiting. Each light detection arrangement 130 is used to combine sample light and reference light to provide a combined light signal having a component of one or more beat frequencies, and to process those combined light signals to determine one or more characteristics of the subject's brain tissue. Any suitable signal processing and / or conversion circuitry may be used. For example, a transimpedance amplifier may not be required (e.g., depending on the photodetector / ADC, a current-to-voltage conversion may not be required, or this may be performed in a different manner). Similarly, a balanced photodetector need not be used, but a single photodetector, such as a photodiode, may be used. Similarly, the arrangement shown in the figure with an ADC need not be considered limiting. For example, multiple ADCs may be used (e.g., one for each detector output stream), or all detector output streams may be fed into a common ADC.

[0131] In addition, as will be understood in the context of the present disclosure, the above teachings can be implemented using a time domain diffuse correlation spectroscopy (TD-DCS) system. For example, one aspect of the present disclosure can provide a TD-DCS system for obtaining an indication of such a pulsating waveform of cerebral blood flow, and the controller 40 can be used to process the TD-DCS data to obtain an indication of ICP.

[0132] It will be appreciated from the above discussion that the examples shown in the accompanying drawings are merely exemplary and include features that may be generalized, removed, or replaced as described herein and in the claims. In general, with reference to the accompanying drawings, it will be appreciated that schematic functional block diagrams are used to indicate the functionality of the systems and devices described herein. In addition, processing functions may also be provided by devices supported by electronic devices. However, it should be understood that the functionality does not need to be divided in this manner and should not be construed as meaning any specific hardware structure other than the hardware described and claimed below. The functionality of one or more elements shown in the accompanying drawings may be further subdivided and / or distributed in the device of the present disclosure. In some examples, the functionality of one or more elements shown in the accompanying drawings may be integrated into a single functional unit.

[0133] As readers in the art will appreciate in the context of the present disclosure, each example described herein can be implemented in a variety of different ways. Any feature of any aspect of the present disclosure can be combined with any other aspect of the present disclosure. For example, method aspects can be combined with device aspects, and features described by the operation of specific elements of reference devices can be provided in methods that do not use those specific types of devices. In addition, unless it is explicitly stated that certain other features are necessary for its operation, each feature of each example is intended to be independent of the features described in combination therewith. Each of these independent features can of course be combined with any other feature of the example describing the feature, or combined with any other feature or combination of features of any other example described herein. In addition, without departing from the present invention, equivalents and modifications not described above may also be adopted.

[0134] Certain features of the methods described herein may be implemented in hardware, and one or more functions of the device may be implemented in method steps. It will also be understood that in the context of the present disclosure, the methods described herein do not need to be performed in the order in which the methods are described, nor in the order in which the methods are described in the accompanying drawings. Therefore, the aspects of the present disclosure described with reference to a product or device are also intended to be implemented as a method, and vice versa. The methods described herein may be implemented in a computer program, or hardware, or any combination thereof. Computer programs include software, middleware, firmware, and any combination thereof. Such a program may be provided as a signal or network message, and may be recorded on a computer-readable medium, such as a tangible computer-readable medium that may store a computer program in a non-temporary form. Hardware includes computers, handheld devices, programmable processors, general-purpose processors, application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), and logic gate arrays.

[0135] Any controller of the present disclosure may be implemented with fixed logic or programmable logic such as software and / or computer program instructions executed by a processor such as a logic gate component. The controller may include a central processing unit (CPU) and its associated memory, which may be connected to a graphics processing unit (GPU) and its associated memory. Other types of programmable logic include programmable processors, programmable digital logic (e.g., field programmable gate arrays (FPGAs), tensor processing units (TPUs), erasable programmable read-only memories (EPROMs), electrically erasable programmable read-only memories (EEPROMs), application specific integrated circuits (ASICs), or any other type of digital logic, software, code, electronic instructions, flash memory, optical disks, CD-ROMs, DVD ROMs, magnetic cards or optical cards, other types of machine-readable media suitable for storing electronic instructions, or any suitable combination thereof). Specifically, any controller of the present disclosure may be provided by an ASIC.

[0136] Other examples and variations of the present disclosure will be apparent to skilled artisans in the context of the present disclosure.

Claims

1. A non-invasive intracranial pressure sensing device, comprising an interferometric near infrared spectroscopy (iNIRS) system, wherein the iNIRS system comprises: Lighting arrangement, comprising: A light source for emitting light; a sample delivery channel coupled to the light source and arranged to be coupled to the subject's scalp to direct light from the light source toward brain tissue of the subject; and a reference channel coupled to the light source for receiving light from the light source; a light detection arrangement for coupling to the subject's scalp and the light emitting arrangement, the light detection arrangement comprising an interferometric optical detector for receiving: (i) reference light from the reference channel, and (ii) sample light from the subject's brain, the sample light comprising light emitted from the light source; wherein the optical detector is arranged to combine the sample light with the reference light to provide a combined light signal, the combined light signal comprising one or more components of a beat frequency between the sample light and the reference light; and Wherein the sensing device includes a controller for processing data indicative of the combined light signal to determine an indication of intracranial blood pressure of the subject based on at least one characteristic of a pulsation waveform of one or more identified pulses of blood flow through the brain of the subject.

2. The sensing device according to claim 1, wherein: Processing the data indicative of the combined light signal includes: obtaining cerebral blood flow data indicative of one or more pulses of blood flow through a brain of the subject; and Wherein the controller is used to obtain extracerebral blood flow data indicating one or more pulses of blood flow through an extracerebral region of the subject's body.

3. The sensing device according to claim 2, wherein: The controller is configured to determine the intracranial blood pressure indication of the subject based on the cerebral blood flow data and the extracerebral blood flow data.

4. The sensing device according to claim 3, wherein: The extra-cerebral blood flow data includes a blood pressure indicative of the pulse of blood flow through the extra-cerebral region of the subject's body.

5. The sensing device according to claim 4, wherein: The controller is used to determine the intracranial blood pressure indication of the subject based on: (i) the pulsatile waveform of one or more identified pulses of blood flow through the subject's brain, and (ii) the corresponding pulsatile waveform of the blood pressure of one or more pulses of blood flow through the extra-cerebral region of the subject's body.

6. The sensing device according to claim 5, wherein: The controller is configured to determine the indication of the intracranial blood pressure of the subject based on an identified critical closure pressure of a blood vessel in a brain of the subject.

7. A sensing device according to any one of the preceding claims, wherein: The controller is for processing the data indicative of the combined light signal to obtain cerebral blood flow index data of blood flow through the subject's brain, and Wherein, the pulsation waveform of one or more identified pulses of blood flow through the subject's brain comprises a pulsation waveform of the cerebral blood flow index.

8. A sensing device according to any one of the preceding claims, wherein: The sensing device is used to obtain the extracerebral blood flow data using the iNIRS system, optionally wherein the iNIRS system is used to obtain the extracerebral blood flow data and the cerebral blood flow data using the same source-detector channel.

9. The sensing device according to claim 8, wherein: The iNIRS system is used to obtain extracerebral blood flow index data, and wherein the controller is used to process the extracerebral blood flow index data to obtain a value of extracerebral blood pressure.

10. The sensing device according to claim 8 or 9, wherein: The light detection arrangement is for coupling to the subject's scalp so that the detector obtains a combined light signal comprising: (i) a component of a beat frequency associated with sample light propagating from the subject's brain, and (ii) a component of a beat frequency associated with sample light propagating from an extra-brain region of the subject's body.

11. The sensing device according to claim 10, wherein: The controller is for separating data associated with the extra-cerebral region of the subject's body from data associated with the subject's brain.

12. The sensing device according to claim 11, wherein: The controller is configured to separate the data based on a flight time of the sample light.

13. A sensing device according to any one of the preceding claims, wherein: The iNIRS system includes a plurality of optical detectors, wherein each optical detector is used to obtain cerebral blood flow data of the subject's brain.

14. The sensing device according to claim 13, wherein: The controller is configured to determine the intracranial blood pressure indication based on characteristics of pulsation waveforms of pulses of blood flow through the subject's brain detected by the plurality of detectors.

15. A sensing device according to claim 13 or 14 as dependent on claim 2 or any claim dependent thereon, wherein: The apparatus is for obtaining extra-cerebral blood flow data for different extra-cerebral regions of the subject's body based on combined light signals associated with the different detectors.

16. An iNIRS system according to any one of the preceding claims, wherein: The light source is used to provide wavelength-scanning light emission.

17. A sensing device according to claim 2 or any claim dependent therefrom, wherein: The iNIRS system includes two source-detector channels: (i) a brain source-detector channel for obtaining brain blood flow data, and (ii) an extra-brain source-detector channel for obtaining extra-brain blood flow data.

18. A sensing device according to claim 2 or any claim dependent therefrom, wherein: The sensing device comprises an extracerebral blood flow sensor for obtaining extracerebral blood flow data, and optionally, the extracerebral blood flow sensor is used to obtain a pressure value of a pulse of the extracerebral blood flow.

19. A sensing device according to any one of the preceding claims, wherein: The controller is used to determine the intracranial blood pressure indication based on the difference between diastolic and systolic values ​​of the one or more pulses of blood flow through the subject's brain, optionally wherein the controller is used to determine the indication based on a pulsatility index of the pulses of blood flow through the subject's brain.

20. A sensing device according to any one of the preceding claims, wherein: The iNIRS system comprises two or more light sources, wherein a first one of the light sources is operable to provide wavelength-swept light emission at a plurality of wavelengths above an iso-oximetry absorption wavelength, and wherein a second one of the light sources is operable to provide wavelength-swept light emission at a plurality of wavelengths below an iso-oximetry absorption wavelength; and Wherein, the controller is used to determine the intracranial blood pressure indication based on sample light received from each of the two light sources.

21. A sensing device according to any one of the preceding claims, wherein: The controller is configured to obtain time-of-flight data based on the combined light signal, wherein the time-of-flight data comprises a data surface containing a time-ordered sequence of flight time distributions of photons of sample light reaching the optical detector from the light source.

22. The sensing device according to claim 21, wherein The controller is configured to determine cerebral blood flow data based on changes in the data surface, optionally wherein the controller is configured to determine the cerebral blood flow data based on an attenuation rate associated with the data surface.

23. The sensing device according to claim 22, wherein: The controller is for obtaining an indication of one or more optical properties of the subject's brain based on the time-of-flight data, optionally wherein the one or more optical properties of the subject's brain include a scattering coefficient and / or an absorption coefficient; and Wherein, the controller is used to determine the cerebral blood flow data of the brain of the subject based on the one or more optical properties of the brain of the subject.

24. A method for non-invasive intracranial pressure sensing, the method comprising: Operate the light source to emit light; delivering light from the light source through: (i) a sample channel and toward a brain of the subject, and (ii) a reference channel; receiving at an interferometric optical detector: (i) reference light from the reference channel, and (ii) sample light from the subject's brain, the sample light comprising light emitted from the light source; combining the sample light and the reference light at the optical detector to provide a combined light signal, the combined light signal comprising one or more components of a beat frequency between the sample light and the reference light; Data indicative of the combined light signal is processed to determine an indication of intracranial blood pressure of the subject based on at least one characteristic of a pulsation waveform of one or more identified pulses of blood flow through a brain of the subject.

25. A computer program product comprising computer program instructions to program a controller to control the operation of a light emitting arrangement and a light detecting arrangement to perform the method according to claim 24.

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