Interference near infrared spectroscopy system

Abstract

A method of operating an interferometric near-infrared spectroscopy (iNIRS) system, the system comprising a light emitting device comprising a light source and a light detecting device comprising an interferometric optical detector. The iNIRS system comprises a plurality of optical channels arranged to define a first optical channel path, a second optical channel path and a reference optical channel path. The method comprises: providing a wavelength scanned light emission by the light source; transmitting first sample light from the light source to the subject through the first optical channel path and transmitting first sample light received from the subject to the detector; transmitting second sample light from the light source to the subject through the second optical channel path and transmitting second sample light received from the subject to the detector; transmitting reference light from the light source to the detector along a reference channel through the reference optical channel path.

Description

Technical Field

[0001] This disclosure relates to the field of interferometic near infrared spectroscopy (iNIRS) systems. For example, such iNIRS systems can be provided for neural imaging and analysis. Background Technology

[0002] Near-infrared spectroscopy (NIRS) is a spectroscopic method that uses the near-infrared region of the electromagnetic spectrum (e.g., between 700 nm and 2500 nm). NIRS systems can be used to provide non-invasive monitoring of the scattering and absorption properties of a medium. Compared to visible light, NIRS wavelengths are less easily absorbed by human skin (and bone), allowing NIRS radiation to penetrate the skin and skull and reach brain tissue. By monitoring the scattering and absorption properties of NIRS radiation within brain tissue, NIRS can be used as a non-invasive imaging technique for human brain tissue.

[0003] While NIRS methods can be extended to monitor oxygenation, blood flow monitoring is essential for inferring information about metabolism when using multiple wavelengths. Diffuse correction spectroscopy (DCS) can be used non-invasively to monitor blood flow in the brain by measuring the temporal fluctuations of light re-emitted from a sample. DCS can further extract other brain parameters, including intracranial pressure (ICP). However, existing DCS methods require additional equipment and extensive averaging to extract flow, making the final method complex and time-consuming. Furthermore, DCS requires optical properties to quantify blood flow, which are typically assumed or obtained from a separate NIRS instrument. Finally, because both DCS and NIRS rely solely on light intensity, they discard half of the information about scattered light encoded in optical phase. As a result, measurements are affected by additional assumptions arising from neglecting phase information.

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

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

[0006] In one aspect, an interferometric near-infrared spectroscopy (iNIRS) system is provided, comprising a light-emitting device and a light-detecting device. The light-emitting device includes a light-emitting source for providing wavelength scanning, and the light-detecting device includes an interferometric optical detector. The iNIRS system includes multiple optical channels configured to define a first optical channel path, a second optical channel path, and a reference optical channel path. The first optical channel path is configured to: (i) extend between the light source and an object to transmit first sample light from the light source to the object, and (ii) extend between the object and a detector to transmit first sample light received from the object to the detector. The second optical channel path is configured to: (i) extend between the light source and the object to transmit second sample light from the light source to the object, and (ii) extend between the object and the detector to transmit second sample light received from the object to the detector. The reference optical channel path is configured to extend between the light source and the detector to transmit reference light from the light source to the detector along a reference channel. The detector is configured to: combine a reference light and a first sample light to provide optical signals at multiple first beat frequencies between the first sample light and the reference light; and combine the reference light and the second sample light to provide optical signals at multiple second beat frequencies between the second sample light and the reference light. A first optical channel path has a different length than a second optical channel path to suppress spectral overlap between the first and second beat frequencies.

[0007] The embodiments enable the detector to provide a single interferogram containing two separate beat frequency distributions. These two beat frequency distributions can be separated and used to provide two separate time-of-flight distributions of the sample light photons. Digital processing can be performed on these two distributions to provide imaging of the object. The embodiments can enable the acquisition of more data per measurement cycle. The embodiments can also enable the acquisition of more data without the need for additional signal processing circuitry. For example, more sample light photon time-of-flight distributions can be obtained from each individual digitizer channel of the analog-to-digital converter.

[0008] An iNIRS system is configured such that photons of the sample light can have two or more optical paths through the optical channels of the iNIRS system. That is, the system is configured such that sample light photons emitted from the light source and received by the detector may have traveled through two or more different routes, for example, through two or more different portions of the optical channels (regardless of the path the sample light photons take through the object to be imaged). For example, the iNIRS system may include at least one of: (i) two different sample delivery channels for coupling the light source to the object to be imaged, and (ii) two different sample receiving channels for coupling the object to be imaged to the detector. Optical channel path length differences can be provided by having one of the sample delivery channels have a different length than the other, and / or having one of the sample receiving channels have a different length than the other. For example, the iNIRS system may include two sample delivery channels and two sample receiving channels, one sample delivery channel being longer than the other, and one sample receiving channel being longer than the other. Each different optical channel path may include different combinations of sample delivery channels and sample receiving channels through which light can travel between the light source and the detector.

[0009] One aspect of this disclosure provides an interferometric near-infrared spectroscopy (iNIRS) system comprising a light-emitting device and a light-detecting device. The light-emitting device includes a light source, a sample transfer channel, and a reference channel. The light source is used to provide light emission for wavelength scanning. The sample transfer channel is coupled to the light source and configured to be coupled to an object to be imaged to guide light from the light source to the object. The reference channel is coupled to the light source to receive light from the light source. The light-detecting device includes a first sample receiving channel, a second sample receiving channel, and an interferometric optical detector. The first sample receiving channel is configured to be coupled to the object to receive first sample light from the object. The second sample receiving channel is configured to be coupled to the object to receive second sample light from the object. The first and second sample lights each include light emitted from the light source. The interferometric optical detector is coupled to: (i) the first sample receiving channel for receiving the first sample light, (ii) the second sample receiving channel for receiving the second sample light, and (iii) the reference channel for receiving reference light. The optical detector is configured to: combine a reference light and a first sample light to provide optical signals with multiple first beat frequencies between the first sample light and the reference light; and combine the reference light and the second sample light to provide optical signals with multiple second beat frequencies between the second sample light and the reference light. The first sample receiving channel has a different length than the second sample receiving channel to suppress spectral overlap between the first and second beat frequencies.

[0010] Another aspect of this disclosure provides an interferometric near-infrared spectroscopy (iNIRS) system comprising a light-emitting device and a light-detecting device. The light-emitting device includes a light source, a first sample transport channel, and a second sample transport channel. The light source is used to provide light emission for wavelength scanning. The first sample transport channel is coupled to the light source and configured to be coupled to an object to guide light from the light source to the object. The second sample transport channel is coupled to the light source and configured to be coupled to the object to guide light from the light source to the object. A reference channel is coupled to the light source to receive light from the light source. The light-detecting device includes a sample receiving channel and an interferometric optical detector. The sample receiving channel is configured to be coupled to the object to receive first sample light and second sample light from the object. The first sample light includes light emitted from the light source traveling along the first sample transport channel, and the second sample light includes light emitted from the light source traveling along the second sample transport channel. The interferometric optical detector is coupled to: (i) the sample receiving channel for receiving the first and second sample light, and (ii) the reference channel for receiving reference light. The optical detector is configured to: combine a reference light and a first sample light to provide optical signals with multiple first beat frequencies between the first sample light and the reference light; and combine the reference light and the second sample light to provide optical signals with multiple second beat frequencies between the second sample light and the reference light. The first sample transmission channel has a different length than the second sample transmission channel to suppress spectral overlap between the first and second beat frequencies.

[0011] Such an example could provide an iNIRS system where two (or more) optical channel paths are defined (using two or more sample delivery channels and / or two or more sample receiving channels). The two different optical channel paths will have different lengths to avoid spectral overlap between the first and second beat frequencies.

[0012] For the iNIRS system of this disclosure, a portion of the first optical path may share a common optical path with a portion of the second optical path. The common optical path may: (i) couple a light source to an object, or (ii) couple an object to a detector.

[0013] Multiple optical channels may include a sample delivery channel, a first sample receiving channel, and a second sample receiving channel. The sample delivery channel is coupled to a light source and configured to couple to an object to guide first and second sample light from the light source to the object; the first sample receiving channel is configured to couple to the object to receive first sample light from the object; and the second sample receiving channel is configured to couple to the object to receive second sample light from the object. For example, an iNIRS system may have two separate sample receiving optical channels. A first optical channel path may include a sample delivery channel and a first sample receiving channel (e.g., provided by the sample delivery channel and the first sample receiving channel). A second optical channel path may include a sample delivery channel and a second sample receiving channel (e.g., provided by the sample delivery channel and the second sample receiving channel). The first sample receiving channel may have a different length than the second sample receiving channel, thereby providing a length difference between the first and second optical channel paths. For example, sample receiving channels of different lengths can be used to provide a difference in optical channel path lengths. A reference channel may couple a light source to a detector. For example, the detector may be coupled to each of the following: (i) a first sample receiving channel for receiving a first sample light, (ii) a second sample receiving channel for receiving a second sample light, and (iii) a reference channel for receiving a reference light.

[0014] The iNIRS system may include an analog-to-digital converter (ADC) for acquiring sample data containing indications of a first and a second beat frequency detected by an optical detector. The sample data may include interferogram data. For example, the sample data may include data describing an interferogram obtained by an interferometer of the detector. That is, a first portion of the sample data may represent the portion of the interferogram containing the first beat frequency, and a second portion of the sample data may represent the portion of the interferogram containing the second beat frequency. The iNIRS system may be used to acquire sample data for the first and second beat frequencies using a single ADC channel. In other words, the ADC may be used to acquire a digital signal representing two simultaneously acquired beat frequency distributions (the first and second beat frequencies). This digital signal may be filtered and separated, for example, using a fast Fourier transform (FFT), to provide two separate distributions (both acquired simultaneously using the same detector). The system may include a controller for processing the sample data to obtain: (i) first sample data containing an indication of the first beat frequency detected by the optical detector, and (ii) second sample data containing an indication of the second beat frequency detected by the optical detector. For example, the controller may be able to separate data associated with a first sample light and data associated with a second sample light. Processing the sample data may include separating the first and second sample data based on beat frequency indication.

[0015] The controller can be used to process sample data such that: (i) the first sample data contains detected beat frequencies below a threshold frequency, and (ii) the second sample data contains detected beat frequencies above a threshold frequency. The controller can be used to: (i) obtain first time-of-flight data of a first sample light based on the first sample data, and (ii) obtain second time-of-flight data of a second sample light based on the second sample data. For example, the controller can first obtain (e.g., interferogram) time-of-flight data, and then separate the first and second sample data based on their respective time-of-flight times. The controller can be used to average the first and second time-of-flight data to provide combined time-of-flight data. The controller can be used to align the first and second time-of-flight data based on a time offset associated with the length difference between the first and second optical channel paths (e.g., the length difference between the first and second sample receiving and / or transmitting channels). Aligning the first and second time-of-flight data may include at least one of the following: (i) applying a fixed time offset associated with the difference in the duration of light travel along the first and second optical channel paths (e.g., due to differences in the length of the sample receiving and / or transmitting channels); and (ii) applying the time offset based on one or more features in the first and second time-of-flight data and corresponding features in the second time-of-flight data. For example, features may include peaks (e.g., the time of flight in which the maximum intensity amplitude occurs), minimum / maximum values ​​(e.g., the lowest or highest time of flight in the time-of-flight distribution), and / or averages (e.g., the average of all recorded time-of-flight values, such as an average value).

[0016] The length difference between the first and second optical channel paths (e.g., between the first and second sample receiving and / or transport channels) can be at least as large as the distance corresponding to the expected time width (e.g., spectral width) of the distribution of time of flight (DTOF) associated with the first sample light. The iNIRS system may include multiple optical channels configured to define three or more optical channel paths, which are configured to: (i) extend between the source and the object, and (ii) extend between the object and the detector, wherein each optical channel path has a different length than the others to suppress spectral overlap between beat frequencies associated with the optical channel paths. For example, there may be three different sample receiving and / or transport channels, each with a different length than the others. The number of different optical channel paths (e.g., different combinations of sample transport and sample receiving channels through which light can travel between the source and the detector) can be selected based on the digitization bandwidth of a single ADC channel. For example, different numbers (and arrangements) of optical channel paths can be selected to maximize the use of full digital bandwidth while suppressing spectral overlap between beat frequencies associated with their respective optical channel paths.

[0017] The optical detection device may include a beam combining element for combining light from different sample receiving channels into a single channel. A detector may be coupled to the single channel for receiving sample light from that single channel. The light source may be a first light source, and the light-emitting device may include a second light source. An interferometric optical detector may be configured to receive: a first sample light from the second light source, a second sample light from the second light source, and a second reference light from the second light source.

[0018] The optical detection device can be a first optical detection device, and the iNIRS system can include a second optical detection device, which includes a second detector. Multiple optical channels can be configured to define a third optical channel path, a fourth optical channel path, and a second reference optical channel path. The third optical channel path is configured to: (i) extend between the light source and the object to transmit a third sample light from the light source to the object, and (ii) extend between the object and the second detector to transmit the third sample light received from the object to the second detector; the fourth optical channel path is configured to: (i) extend between the light source and the object to transmit a fourth sample light from the light source to the object, and (ii) extend between the object and the second detector to transmit the fourth sample light received from the object to the second detector; and the second reference optical channel path is configured to extend between the light source and the second detector to transmit reference light from the light source to the second detector along a second reference channel. For example, the second optical detection device can include a third sample receiving channel, a fourth sample receiving channel, and a second interference optical detector. A third sample receiving channel is configured to be coupled to an object to receive a third sample light from the object; a fourth sample receiving channel is configured to be coupled to the object to receive a fourth sample light from the object (the third and fourth sample lights each comprise light emitted from a light source); and a second interferometric optical detector may be coupled to: (i) the third sample receiving channel for receiving the third sample light, (ii) the fourth sample receiving channel for receiving the fourth sample light, and (iii) a reference channel for receiving reference light. The second detector may be configured to: combine the reference light and the third sample light to provide optical signals of multiple third beat frequencies between the third sample light and the reference light; and combine the reference light and the fourth sample light to provide optical signals of multiple fourth beat frequencies between the fourth sample light and the reference light. The third optical channel path has a different length than the fourth optical channel path to suppress spectral overlap between the third and fourth beat frequencies (e.g., the third sample receiving channel may have a different length than the fourth sample receiving channel). The iNIRS system may be used to average data acquired from each of the detected first beat frequencies to the detected fourth beat frequencies (e.g., associated with each of the first to fourth sample lights).

[0019] Multiple optical channels may include a first sample delivery channel, a second sample delivery channel, and a sample receiving channel. The first sample delivery channel is coupled to a light source and configured to be coupled to an object to guide first sample light from the light source to the object; the second sample delivery channel is coupled to the light source and configured to be coupled to the object to guide second sample light from the light source to the object; and the sample receiving channel is configured to be coupled to the object to receive the first and second sample light from the object. A first optical channel path may include the first sample delivery channel and the sample receiving channel. A second optical channel path may include the second sample delivery channel and the sample receiving channel. The first sample delivery channel may have a different length than the second sample delivery channel, thereby providing a length difference between the first and second optical channel paths.

[0020] Multiple optical channels may include a first sample delivery channel, a second sample delivery channel, a first sample receiving channel, and a second sample receiving channel. The first sample delivery channel is coupled to a light source and configured to be coupled to an object to guide light from the first light source to the object; the second sample delivery channel is coupled to a light source and configured to be coupled to the object to guide light from the second light source to the object; the first sample receiving channel is configured to be coupled to the object to receive first sample light from the first sample delivery channel and first sample light from the second sample delivery channel from the object; and the second sample receiving channel is configured to be coupled to the object to receive second sample light from the first sample delivery channel and second sample light from the second sample delivery channel from the object. The first sample delivery channel may have a different length than the second sample delivery channel, and the first sample receiving channel may have a different length than the second sample receiving channel to suppress spectral overlap between: (i) a first beat frequency of the first sample light from the first sample delivery channel, (ii) a first beat frequency of the first sample light from the second sample delivery channel, (iii) a second beat frequency of the second sample light from the first sample delivery channel, and (iv) a second beat frequency of the second sample light from the second sample delivery channel.

[0021] Examples may provide an iNIRS system for neuroimaging and analysis of a subject's brain tissue. For example, the object to be imaged may be the subject's brain. Images of the subject's brain are formed non-invasively by simultaneously measuring numerous locations. These measurements are achieved by combining first and second source channels with first and second receiver channels in a spatial pattern.

[0022] Each light source may include a light-generating element configured to generate light (e.g., near-infrared light) and optics for guiding that light. For example, each light-generating element may include a laser. The optics may be configured to guide a portion of the light from the light-generating element to the area to be sampled. Each light transmission and / or reception channel may include an optical channel, such as an optical fiber. Each optical channel may be used to transmit light along its length (e.g., from the light-generating element to the object to be imaged and / or from the object to a photodetector). The optics of each light source may include a beam splitter for splitting light into each of the different transmission optical channels. The iNIRS system may be configured such that, when mounted on a subject's head (e.g., for neuroimaging and analysis of the subject's brain tissue), the optics of each light source are used to guide a portion of the light to the subject's scalp (e.g., through one or more sample delivery channels). For example, the optics of each light source may include a beam splitter for splitting light received from the light-generating element into each of the different channels (e.g., to a reference channel and one or more sample delivery channels).

[0023] The iNIRS system can be configured such that, in use, when mounted on a subject's scalp and brain tissue, sample light can be directed to the subject's scalp and brain tissue (e.g., via a sample delivery channel), and reference light can be directed to each photodetector (e.g., via a reference delivery channel). Each light source can be configured to provide (e.g., wavelength scanning) light emission (e.g., each light source can be configured to output light of each of a plurality of different wavelengths within a selected time period). For example, each light source may include a modification 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 configured to scan the wavelength of its output light (e.g., increase or decrease the wavelength). Each light source can be configured to provide chirped emission of light, wherein each chirp (or "pulse") includes a wavelength scan. Each light source can be configured to output sequential chirps with the same wavelength scan, e.g., such that the wavelength of the light output from the light source changes according to a repetition pattern.

[0024] Each photodetector may provide an interferometric optical detector. Each photodetector may include optical elements. The optical elements of the photodetector are used to guide light to be detected (e.g., from the subject's scalp) into the photodetector. The optical elements of the photodetector may include one or more light receiving channels. The iNIRS system may be configured such that, when mounted on the subject's head (e.g., for neuroimaging and analysis of the subject's brain tissue), the optical elements of the photodetector are used to receive light emitted from a light source (e.g., light that has traveled from the light source through the subject's brain tissue). The photodetector may include a combiner (e.g., for combining light on a reference receiving channel with light on one or more sample receiving channels). Each photodetector is used to convert the received combined optical signal into one or more electrical signals indicative of the combined optical signal (e.g., to provide interferogram data). For example, the detector may include one or more photodiodes. Each photodiode may output an electrical signal (e.g., current) indicative of the combined optical signal. The detector may include a balanced photodetector (e.g., the balanced photodetector includes two photodiodes that may be 180° out of phase with each other, and the output of the balanced photodetector may be a combination of the current outputs of the two photodiodes). The detector may optionally include current-to-voltage conversion circuitry and / or one or more amplifiers for amplifying the electrical signal. The amplifiers may be used with a specified gain to scale the voltage signal to achieve the optimal dynamic range of the signal received from the brain (i.e., strong photons arriving early and photons arriving later).

[0025] The iNIRS system may include at least one analog-to-digital converter configured to convert an electrical signal representing sample light (e.g., a combined optical signal) into one or more digital signals. A controller is configured to process the digital signals to determine one or more properties of a subject's brain tissue. The controller may be used to determine the optical properties of the subject's brain tissue (e.g., for absorption and / or scattering). The controller may be used to determine one or more dynamic properties of the subject's brain tissue (e.g., properties of the subject's brain tissue that change over time). For example, the controller may be used to detect the presence of motion within the subject's brain tissue (e.g., due to the movement of blood within the brain tissue, such as flow).

[0026] The controller can be used to process digital signals to obtain time-of-flight information of photons from a first and second sample light source traveling through the subject's brain tissue to a photodetector from each light source. The controller can be used to identify the penetration depth (and optionally, the expected trajectory of the photons through the brain tissue) associated with different times of flight of the sample light photons. The controller can be used to obtain a time-ordered sequence of the sample light photons arriving at each photodetector. The controller can be used to process this time-ordered sequence to identify changes in the time-of-flight distribution over time, such as identifying attenuation and / or attenuation rates between successful time-of-flight distributions. The controller can be used to provide depth-resolved processing, for example, by filtering the time-of-flight data to focus only on photons within a selected time-of-flight range (e.g., to identify changes in the optical properties of the brain tissue at the penetration depth associated with that time-of-flight range). The controller can be used to process data received from the photodetector to provide depth-resolved autocorrelation time-of-flight information of the subject's brain tissue.

[0027] The controller can be used to process received data indicating sample light received at a photodetector and to output control signals based on that received data. The control signals can provide an indication of the time-of-flight distribution (e.g., the controller can output a time-of-flight distribution). The control signals can provide an indication of one or more properties determined based on the time-of-flight distribution, such as the optical properties of brain tissue (e.g., scattering and / or absorption coefficients, and / or past / present changes in these properties). The control signals can provide an indication of blood flow within the subject's brain tissue. The control signals can provide a depth-resolved indication of one or more properties of the subject's brain tissue (e.g., associated with specific regions within those subject's brain tissue, such as within a selected range of penetration depths). The control signals can include indications of one or more properties of the subject's brain tissue, such as intracranial pressure, blood flow index, arterial elasticity, and cerebral oxygen consumption rate. Medical properties can be associated with specific regions / depths within the subject's brain tissue. The control signals can include activation instructions for a brain-computer interface, e.g., to control the operation of the device based on those activation instructions. The control signals can include an image for display, wherein the image represents a portion of the subject's brain tissue (e.g., determined based on the received sample light). Attached Figure Description

[0028] Some examples of this disclosure will now be described by way of example only, with reference to the accompanying drawings, in which: Figure 1 A schematic diagram of an example iNIRS system is shown.

[0029] Figure 2 A graph depicting the flight time data of the incident photon is shown.

[0030] Figures 3a to 3eA schematic diagram of an example iNIRS system is shown.

[0031] In the accompanying drawings, the same reference numerals are used to indicate the same elements. Detailed Implementation

[0032] This disclosure relates to an iNIRS system for an object to be imaged. For this purpose, the system is configured to guide light to the object along one or more sample-transmitting optical channels, and to receive a portion of the light from the object and guide it to an optical detector along one or more sample-receiving optical channels. These optical channels are configured such that there are at least two distinct optical paths between the light source and the object and / or at least two distinct optical paths between the object and the detector. The channels are configured such that these optical paths have different lengths from each other. Therefore, as light travels from the light source (via the object to be imaged) to the detector, the light can travel along optical channels of different lengths, depending on which channel the light travels through. This difference in optical channel lengths is large enough that when the received light is combined with a reference light at the detector, there will be very little or no spectral overlap between the resulting beat frequencies associated with a first optical path length and a second optical path length, respectively. Thus, two different time-of-flight distributions can be obtained through a single digitizer channel.

[0033] Now refer to Figure 1 An example describing an interferometric near-infrared spectrophotometry (iNIRS) system.

[0034] 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, at least one detector 30, and a controller 40. Although in Figure 1 Only two detectors 30 are shown in the figure, but the system 10 may include multiple detectors 30. Illustration A shows... Figure 1 A more detailed view of the light detector 30 shown in dashed box A.

[0035] The iNIRS system 10 may include a light source modifier 22 and a beam 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 an object to be imaged; in this example, the object may be the head 2 of a subject (e.g., for providing neuroimaging). The iNIRS system 10 includes a sample delivery probe 25' and a plurality of sample receiving probes. In the example where the object is the head 2 of a subject, the probes may be used to couple the optical channels to the subject's scalp.

[0036] Figure 1 Two photodetectors 30 are shown. Each photodetector 30 has an associated reference receiving channel 36. The reference receiving channel 36 is used to receive reference light from the light source 20 (e.g., from the reference transmission channel 26). Figure 1 One of the photodetectors 30 shown is coupled to the subject's scalp 2 via two optical channels: a first sample receiving channel 351 and a second sample receiving channel 352 (using a first sample receiving probe 351' and a second sample receiving probe 352', respectively). The other photodetector 30 shown is coupled to the subject's scalp 2 via one optical channel: a sample receiving channel 35 (using an associated sample receiving probe 35'). As will be understood, multiple different sample receiving channels can be provided distributed around different areas of the subject's scalp (e.g., for imaging different regions of the subject's brain tissue). Alternatively, or in turn, the sample receiving channels can be located at the same location on the subject's scalp, for example, such that the data obtained from the overlapping areas imaged for each such channel can be averaged. In other examples, it is not necessary to provide a second sample receiving probe 35', sample receiving channel 35, and detector 30; instead, only the first probe / receiving channel / detector is provided.

[0037] The light source modifier 22 may include a source (e.g., a variable current or voltage provider) for providing a variable electrical control signal. The light source modifier 22 is coupled to the light source 20. The light source modifier 22 may be electrically connected to the light source 20 to provide it with a variable current / voltage.

[0038] 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). Light source 20 is coupled to beam splitter 24. Beam splitter 24 has an input for receiving light from light source 20. Beam splitter 24 has two outputs for transmitting light from light source 20 to two separate channels. Sample delivery channel 25 is coupled to beam splitter 24 (to receive light from it), as is reference delivery channel 26. Sample delivery channel 25 couples beam splitter 24 to sample delivery probe 25'. Sample delivery probe 25' will be placed on the subject's scalp.

[0039] Other suitable types of lasers include distributed Bragg reflector lasers (DBRs), Fourier domain mode-locked lasers (FDMLs), and vertical cavity surface-emitting lasers (VCSELs). Alternatively, pulsed supercontinuum lasers can be used in combination with pulse stretching mechanisms, such as gratings or GRISM pulse stretchers or the length of dispersive fiber. For example, such an arrangement can be used to temporally separate wavelengths in a pulse, resulting in frequency-chirped pulses (e.g., to ultimately provide an interferogram when comparing sample and reference pulses). Alternatively, wavelength scanning can be provided by using highly coherent lasers such as external cavity diode lasers (ECDLs), DBR lasers, feedback-stabilized lasers, or line-locked lasers, and passing the output through an electro-optic IQ modulator. This IQ modulator can be driven by an electrical signal, thereby shifting the wavelength of the light without directly modulating the source (e.g., the laser). Compared to directly modulated lasers, this can produce light with higher coherence, thus offering an advantage in signal-to-noise ratio (SNR). This arrangement can also be combined with optical amplifiers to achieve a so-called Master Oscillator Power Amplifier (MOPA) structure.

[0040] Reference transmission channel 26 couples beam splitter 24 to each photodetector 30. For each detector 30, a reference transmission connection 28 can be provided to couple reference transmission channel 26 to a reference receiving channel 36 of that detector 30. Each reference receiving channel 36 is coupled to its photodetector 30. In other words, each photodetector 30 can be connected to light source 20 to receive reference light directly from light source 20 (via one or more reference channels). Each sample receiving probe can be placed on the scalp of the subject. Each sample receiving probe can be coupled to an associated sample receiving channel. Each sample receiving channel is coupled to its photodetector 30. In other words, each photodetector 30 is connected for indirectly receiving sample light from light source 20 (e.g., receiving light that has traveled through the sample transmission channel, through a portion of the subject's head, and into the receiving channel associated with that detector 30).

[0041] Multiple different photodetectors 30 can exist. Each detector 30 may be provided with an interferometer, such as a Mach-Zehnder interferometer (when receiving sample light and reference light from the light source). Each of the different photodetectors 30 can be coupled to the same light source 20 (each via one or more reference channels). The photodetectors 30 can be spatially separated from the light source 20. Multiple photodetectors 30 can also be spatially separated from each other, or can be located in the same location in sufficiently similar regions of the tissue such that the received signals can be averaged together. To allow the reference light to reach the photodetector 30 from the light source 20, the reference light will travel directly along one or more reference channels. To allow the sample light to reach the photodetector 30 from the light source 20, the sample light will travel indirectly through the subject's brain tissue. The sample light is guided to the subject's scalp via one or more sample delivery channels 25'. The sample light can then travel through the subject's brain tissue in parallel into the receiving channel and into the optical detector. Therefore, the irradiation of the subject's brain tissue can be performed using a different optical channel than the one used to detect light from the subject's brain tissue.

[0042] Controller 40 may include any suitable component with data receiving and processing capabilities. For example, controller 40 may include at least one application-specific integrated circuit (ASIC). Other examples of controller 40 may include a field-programmable gate array (FPGA) and / or a data acquisition module (DAQ). Controller 40 is coupled to each detector. Controller 40 may be connected to each detector 30 via a wired connection (for receiving electrical signals indicating detection results from detector 30), and / or the connection may be wireless (for receiving transmitted data indicating detection results from detector 30). Controller 40 is coupled to light source modifier 22. This connection may be wired or wireless.

[0043] The iNIRS system 10 can be at least partially housed within clothing covering the subject's head 2. For example, the iNIRS system 10 can be housed in a hat / cap worn by the subject on the subject's head 2. The head clothing can be configured to maintain a fixed arrangement of the light source 20 and the detector relative to the subject's scalp. Some or all components can be provided with the head clothing. For example, the head clothing can include multiple storage sections for housing the light source 20 and the photodetector 30. Channels connecting the light source and the photodetector 30 can be provided as part of the head clothing (e.g., these channels can be wired through corresponding channel storage sections of the head clothing). The controller 40 can be separate from the head clothing (e.g., and wirelessly connected), or the controller 40 can also be provided as part of the head clothing (e.g., provided by an ASIC within the head clothing, which can be wired to the detector and / or light source modifier 22). For example, the clothing can be used to house the light source channels and detection channels, as well as probes, while other components of the system are located elsewhere.

[0044] Some or all of the optical channels of the iNIRS system 10 may be provided by optical fiber. The beam splitter disclosed herein may include an optical fiber splitter. The iNIRS system 10 may include lenses, reflecting and / or refractive devices for beam steering, as appropriate. For example, the sample delivery probe 25' may include one or more lenses to spatially distribute sample light from the sample delivery channel 25 toward the subject's brain tissue. As another example, one or more sample receiving probes may include lenses for focusing received light into a sample receiving channel associated with that lens (such as one connected to the sample receiving probe). As another example, the probe may be bare fiber that has been cut and / or polished.

[0045] The iNIRS system 10 is configured to provide multiple light source-detector pairs for each light source 20. In other words, the iNIRS system 10 is configured such that each photodetector 30 can receive two forms of light: (i) reference light and (ii) sample light. Each detector 30 is configured to receive reference light directly from the light source 20 (the reference light will travel from the light source 20 to the photodetector 30 along one or more channels, e.g., without traversing the subject's brain tissue). Each detector 30 is also configured to receive sample light indirectly from the light source 20 (the sample light will have already been directed to the subject's scalp tissue, and a portion may have already traversed the subject's brain tissue on its way to the detector 30; e.g., the sample light will not only traverse the optical channel between the light source 20 and the photodetector 30).

[0046] Detector 30 is positioned on the subject's scalp to provide imaging of selected regions of the subject's brain. At least a portion of detector 30 is configured to be spatially separated from light source 20. One or more (e.g., each) photodetectors 30 may be configured to be sufficiently spaced from light source 20 such that at least a portion of the photons of sample light from light source 20 received at photodetector 30 will have penetrated into the subject's brain tissue. For example, the light source-detector interval may be selected such that photodetector 30 is configured to receive sample light photons that have undergone multiple scattering events (e.g., scattered multiple times between the source and detector as they travel across the subject's head 2). In other words, the light source-detector interval may be selected such that photodetector 30 receives deep-penetrating photons from the subject's brain tissue. These photons may have a longer flight time from the light source to the detector compared to photons that penetrate shallower and undergo fewer scattering events.

[0047] Detectors 30 can be positioned spatially close to each other on the subject's scalp. The arrangement of detectors 30 can be chosen such that they image similar regions of the subject's brain. For example, detectors 30 can be positioned within a threshold distance from each other on the subject's scalp, such that the data acquired by these detectors 30 can be averaged (e.g., providing an average for the same volume of the subject's brain). That is, detectors 30 can be configured to spatially detect the same volume of tissue within the subject's brain. For example, detectors can be positioned within a tissue attenuation length from each other (e.g., within the sum of absorption and scattering coefficients).

[0048] Light source 20 is configured to generate light and direct it (via a reference channel) to the subject's scalp and light detector 30. Beam splitter 24 is configured to receive the light generated by light source 20 and split it into two channels: (i) directing the light to the subject's scalp using sample delivery channel 25 and sample delivery probe 25', and (ii) directing the light to light detector 30 using reference delivery channel 26 and reference receiving channel 36. The beam splitter is used to direct most of the light to the subject's scalp. For example, the beam splitter could be a 90:10 beam splitter or a 99:1 beam splitter. Sample delivery channel 25 is configured to receive sample light from the beam splitter and deliver it to the subject's scalp (via sample delivery probe 25'). Reference delivery channel 26 is configured to receive reference light from the beam splitter and deliver it to one or more detectors 30 (via reference receiving channel 36).

[0049] Each reference transmission connection 28 is configured to transmit a portion of the reference light traveling along the reference transmission channel 26 to one of the reference receiving channels 36. Each reference receiving channel 36 is configured to transmit the reference light to the photodetector 30 corresponding to that reference receiving channel 36. Sample receiving probes are configured to receive sample light from the subject's brain tissue. Each sample receiving probe can focus the received sample light onto the sample receiving channel associated with that probe. Each sample receiving channel can be configured to transmit the received sample light to the photodetector 30 corresponding to that sample receiving channel. The sample receiving probes can be arranged close together on the subject's scalp.

[0050] for Figure 1 The iNIRS system does not require a detector coupled to the subject's scalp via only one sample receiving channel 35 (and associated sample receiving probe 35'). This detector is shown as an example to illustrate that multiple detectors can be coupled to the subject's scalp (and not all detectors need to be coupled to the subject's scalp via two or more sample receiving channels). However, for the purposes of the following description, reference will be primarily made to detector 30 coupled to the subject's scalp via two or more sample receiving channels.

[0051] Detector 30 is coupled to light source 20 via reference receiving channel 36 (and reference transmitting channel 26). Detector 30 is also coupled to the subject's scalp via two separate optical channels: a first sample receiving channel 351 and a second sample receiving channel 352. Each of these sample receiving channels can be coupled to the subject's scalp via sample receiving probes (first and second sample receiving probes, respectively). The first sample receiving channel 351 has a different length than the second sample receiving channel 352. For this purpose, the second sample receiving channel 352 includes an additional optical channel length 352a (e.g., ...). Figure 1 (As shown). Given the additional optical channel length 352a, the distance required for light to travel from the subject's scalp to the detector 30 through the second sample receiving channel 352 is less than the distance required for light to travel through the first sample receiving channel 351.

[0052] The first sample receiving channel 351 can be coupled to the subject's scalp at a location close to where the second sample receiving channel 352 is coupled (e.g., via the first sample receiving probe 351'). Therefore, the first sample receiving channel 351 can be configured to image regions of the subject's brain that are substantially similar (e.g., identical) to those of the second sample receiving channel 352. That is, on average, light entering the first sample receiving channel 351 and traveling parallel to the detector 30 may represent the same region of the subject's brain as light entering the second sample receiving channel 352 and traveling parallel to the detector 30. The difference is that light traveling via the second sample receiving channel 352 to the detector 30 will travel a longer distance between the subject's scalp and the detector (due to the additional optical channel length 352a).

[0053] Detector 30 is configured to receive three inputs: (i) reference light directly from light source 20, (ii) sample light indirectly from light source 20, which has traveled via a first sample receiving channel 351 (e.g., via the subject's brain tissue and through the subject's scalp and skull), and (iii) sample light indirectly from light source 20, which has traveled via a second sample receiving channel 352 along a longer optical path than the first sample receiving channel 351. For example, detector 30 may include three or more input ports. A first input port of detector 30 may be coupled to a reference transmission channel 26 for which detector 30 is used. A second input port of detector 30 may be coupled to the first sample receiving channel 351 for which detector 30 is used. A third input port of detector 30 may be coupled to the second sample receiving channel 352 for which detector 30 is used. The detector is configured to combine the reference light with the sample light (as an interferometer). The iNIRS system 10 (e.g., detector 30 and controller 40) can be configured to determine one or more properties of a subject's brain tissue based on the combination of reference light and sample light (as described in more detail below). It should be understood that, in the context of this disclosure, the combination of different lights can be provided by a single component, or the combination of different lights can be staggered. For example, first and second sample lights can be combined into a single channel, which can then be combined with a reference light-carrying channel, or three different channels can be combined into a single channel by a single component.

[0054] From this point onward, the sample light received at detector 30 from the object to be imaged (e.g., the subject's brain) and traveling along the first sample receiving channel 351 will be referred to as the "first sample light". Similarly, the sample light received at detector 30 but traveling along the second sample receiving channel 352 will be referred to as the "second sample light". Because the second sample receiving channel 352 has an additional optical channel length 352a, the second sample light will take longer to travel from the subject's scalp to detector 30 than the first sample light. The reference light is the light that travels directly through one or more optical channels (reference channels) from light source 20 to detector 30 (e.g., without passing through the object to be imaged).

[0055] Light source 20 is used to provide wavelength-scanning light emission. For this purpose, light source 20 can be used to generate a series of pulsed emission lights. During each pulse, the wavelength of the light can be “scanned” within a wavelength range. For example, the scan can take the form of chirped pulses. Multiple different wavelengths of light will be emitted during one pulse. For example, the wavelength can be continuously increased or decreased during one pulse (the rate of change of wavelength can be constant or variable). A series of chirped pulses can be continuous (e.g., the time interval between pulses is zero). Light source 20 can be used to continuously emit a series of pulses, where each pulse has a wavelength scan. However, it should be understood that light source 20 does not need to provide continuous scanning. For example, the light source can be tuned in a stepwise manner rather than continuously, such that light source 20 emits light of different wavelengths at different time intervals (e.g., discrete time intervals for emission at each of multiple wavelengths). Light source 20 can scan unidirectionally (e.g., increasing or decreasing the wavelength only during a wavelength scan), or light source 20 can scan bidirectionally (e.g., increasing and decreasing the wavelength both during a wavelength scan). Unidirectional scanning can be beneficial because it increases the number of photons detected per scan.

[0056] The controller 40 can be used to selectively control the wavelength scanning of the light source 20. The light source modifier 22 can be configured to control the wavelength of light emitted from the light source 20. For example, the light source modifier 22 can be configured to apply a selected current (or voltage) to the light source 20 to select the wavelength of light emitted from the light source 20. The wavelength scanning of the light source 20 can be controlled by applying a corresponding electrical signal to the light source 20 using the light source modifier 22. The controller 40 can be configured to use the light source modifier 22 to control the current / voltage applied to the light source 20 to provide a selected pattern of the wavelengths of the light emitted by the light source 20.

[0057] Light source 20 can be controlled to perform wavelength scanning according to a selected pattern used for scanning. For example, light source 20 can scan a selected range of light wavelengths and / or light source 20 can scan light wavelengths according to a selected scanning profile (e.g., linearly increasing, sinusoidal, triangular, etc.). For example, light source 20 can scan according to a selected scanning rate or a selected total scanning time. Light source 20 is used to emit wavelength scanning light such that during a single wavelength scan, light is guided to the subject's brain tissue at multiple different wavelengths through a sample delivery channel (and to the detector via a reference channel). The wavelength of the light emitted by light source 20 will vary over time. Therefore, the timing of light emission from light source 20 can be determined based on the wavelength of the light.

[0058] Light source 20 is used for scanning within a selected wavelength range. For example, light source 20 can be used for optical frequency scanning within a 50 GHz range. This allows light source 20 to emit modulated light of multiple different wavelengths between 829.94 nm and 830.06 nm, for example, centered at 830 nm, or between 1309.857 nm and 1310.143 nm, for example, centered at 1310 nm. Light source 20 can be used for wavelength scanning within a wavelength range of at least 0.025 nm, such as 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 (e.g., relative to its centered wavelength). Light source 20 can have high output power, long coherence time, and wide mode-hop-free wavelength tuning. Light source 20 can have a narrower linewidth and a longer coherence length, for example, because light source 20 will not scan within a particularly large bandwidth.

[0059] The light source disclosed herein can be used to emit highly coherent light (e.g., substantially coherent light). It should be understood that the light source may not be able to both emit perfectly coherent light and provide wavelength-scanning light emission, for example, because light of different wavelengths changes phase at different rates. The light source of this disclosure can be controlled to scan within a relatively narrow wavelength range compared to the absolute wavelength of the light source. In other words, the difference between the maximum and minimum wavelengths in a single wavelength scan is small relative to these wavelengths. Each light source can be used to emit light (i.e., an electric field) whose phase changes little over time.

[0060] The iNIRS system of this disclosure receives a first sample light, a second sample light, and a reference light, all originating from the same light source (i.e., light source 20). The light source of this disclosure is used to provide a wavelength scan of emitted light with sufficient coherence such that the sample light and reference light received at optical detector 30 will be in relatively similar (e.g., substantially similar) phases relative to each other. Therefore, combining the sample light with the reference light will result in a fundamental constructive interference between the two waves (e.g., a series of sample light waves will have a phase sufficiently similar to the corresponding series of reference light waves, such that the resulting combined optical signal will contain a constructive combination of the two light waves). In other words, the coherence length of the light source is such that multiple scattering in the tissue will not reduce the coherence or fringe contrast below the noise floor of the measurement.

[0061] For example, each light source in this disclosure may include a laser. The laser can be selected based on its coherence length, for example, to enable the aforementioned constructive interference between the sample light and the reference light. In other words, the iNIRS system can be configured such that the maximum expected time-of-flight delay of the sample light photons (which have traveled through the subject's brain tissue and been received at the optical detector), such as a second sample light (described in more detail below), relative to the reference light photons (which have traveled along one or more reference channels and been received at the optical detector), is within the coherence time period of the laser (e.g., the difference in the length of the optical path between the sample light and the reference light is within the coherence length of the laser). Within this coherence time period, the phase of the light emitted by the laser is substantially stable (although the wavelength of the emitted light changes). Therefore, the combined optical signal at the optical detector may be free of amplitude loss (e.g., the interference occurring at the detector may be substantially entirely constructive).

[0062] For example, an iNIRS system can be used with a coherence length or range of approximately 50 m in air—for instance, a light source with 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 specific range is not intended to limit, but rather to illustrate a general range of light sources. A light source can be selected such that it has a coherence length two or more times greater than the maximum expected optical path length difference; for example, the coherence length can be three or four times greater or more. A light source with a coherence length significantly greater than the optical path length can increase the accuracy of measuring sample photons that have undergone numerous scattering interactions within the subject's brain tissue.

[0063] The iNIRS system 10 is configured such that the source-detector path length of the reference light is different from the source-detector path length of the sample light. In other words, the iNIRS system 10 is configured such that the average or expected optical path length of the light traveling from the source 20 through the subject's brain tissue to each detector will be different from the optical path length of the light traveling from the source 20 through the reference channel to the detector.

[0064] The iNIRS system 10 is configured such that sample light can travel along two or more distinct optical pathways as it travels from the light source 20 to the detector 30. Therefore, the sample light can travel along different paths through the optical channels (except for traveling through the subject's head via a different path). The iNIRS system 10 includes at least two distinct optical pathways through which the sample light can travel from the light source 20 to the detector 30 (except for traveling through the subject's brain). Figure 1 In the example shown, the different optical pathways are those paths extending from the object to be imaged (e.g., the subject's scalp) to the detector 30. That is, sample light can be directed from the light source 20 to the object (along the sample transport path 25), and this sample light can travel through the object and reach the detector 30, where the route from the object to the detector 30 is either along a first sample receiving path 351 or a second sample receiving path 352. In other words, the iNIRS system 10 is configured to provide two or more different light source-detector optical path lengths to the sample light (regardless of the path the sample light takes as it travels through the object to be imaged).

[0065] As will be understood in the context of this disclosure, sample light photons directed to the subject's brain tissue can travel from the light source 20 to the photodetector 30 via virtually an infinite number of different paths. The sample light photons may experience numerous scattering events, thus following a highly tortuous path between the sample delivery probe 25' and the sample receiving probe 35'. The iNIRS system 10 can be configured to perform neuroimaging and analysis based at least in part on activity within the subject's brain tissue. The flight time of the sample light photons from the light source 20 to the photodetector 30 will, of course, increase with the increase in the path length taken by the sample light photons. Therefore, photons traveling longer paths and penetrating deeper into the subject's brain tissue will take even longer to reach the photodetector 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 can be configured such that the shortest flight time for photons of light to travel from the light source 20 to the photodetector 30 will be the flight time of the reference light photons along the reference channel. Sample light photons will have a longer flight time than the reference light. Sample light photons that penetrate deeper into the subject's brain tissue are likely to be those with longer flight times to the photodetector 30. The additional optical channel length 352a is configured such that the difference in optical path length between the first sample receiving channel 351 and the second sample receiving channel 352 means that the first sample light photons will have a shorter flight time than the second sample light photons.

[0067] As will be understood in the context of this disclosure, the path taken by each individual sample photon across the object to be imaged (between the sample delivery channel and the sample receiving channel) is unpredictable. However, given a large number of these sample photons, the overall time-of-flight distribution of these sample photons can be statistically modeled. Therefore, for a given source-detector pair, one or more expected characteristics of the sample photon time-of-flight distribution may be known. For example, for each source-detector pair, the expected time difference (e.g., spectral width) between the shortest and longest time-of-flight photons may be known. This can be derived, for example, based on the signals of the earliest and latest detectable photons previously observed. In other words, for any given source-detector pair, there may be a known maximum expected spectral width in the resulting time-of-flight distribution of the sample photons.

[0068] In other words, the photons from the first and second sample lights will each provide a photon distribution from the earliest arriving photon to the latest arriving photon. No incident photons can be resolved over the system's noise floor before the earliest photon and after the latest photon. The time difference between the first and last detected incident photons (and thus the associated frequency difference between the lowest and highest beat frequencies) defines the width or range of the incident photon distribution. Additional channel lengths can be selected based on this time width / range of the sample light photons from the first and second lights. For example, this could be based on D4. σ The width is selected (e.g., according to the beam diameter measurement standard ISO 11146).

[0069] The iNIRS system 10 can actually provide two light-detector pairs between the same light source 20 and detector 30. Figure 1In the example, this is due to the two distinct optical paths provided between the object and detector 30 (e.g., due to the first and second sample receiving channels 351, 352). A known expected spectral width will exist for the flight time distribution of the first sample photons (e.g., a known time interval between the shortest and longest flight times of the first sample photons). For example, this spectral width could be some value between 0.5 and 2 ns. An additional optical channel length 352a can increase the additional distance of the optical channel along which the second sample photons must travel to reach detector 30, where this additional distance corresponds at least to the expected spectral width of the first sample photons. For example, the additional optical channel length 352a could have a distance at least as long as a combination of: (i) the expected spectral width of the first sample light, and (ii) an additional buffer period (selected such that an unusually long flight time for the first sample photons still arrives at the detector before any second sample photons).

[0070] In other words, the additional optical channel length 352a increases the additional distance of the optical channel, such that the time taken for the second sample light photon to travel along the optical channel of this additional length will be at least as long as the expected spectral width of the flight time distribution of the first sample light photon. The additional optical channel length 352a is configured such that the detectable photons of the first sample light can always have a shorter flight time than the detectable photons of the second sample light. For example, the first sample light photon with the longest flight time that passes through the object to be imaged and is detected by detector 30 will still have a shorter overall flight time from light source 20 to detector 30 than the second sample light photon with the shortest flight time that passes through the object to be imaged.

[0071] The iNIRS system 10 is configured such that detector 30 receives three inputs: a reference beam (from reference receiving channel 36), a first sample beam (from first sample receiving channel 351), and a second sample beam (from second sample receiving channel 352). Detector 30 is used to combine these three inputs using a beam combiner. For example, the detector may provide an interferometer assembly (combined with the first and second sample channels and the reference channel) for combining the reference beam and the sample beam to obtain an interference pattern. The obtained interference pattern may include contributions associated with the first sample beam (and first sample receiving channel 351) and contributions associated with the second sample beam (and second sample receiving channel 352).

[0072] Light source 20 is used to emit substantially coherent light. The resulting interference pattern of the light from light source 20 (obtained at each detector) may include a combined signal having a beat frequency (or intermediate frequency / difference frequency) component corresponding to the following wavelength differences: (i) the wavelength of the sample light photon received at photodetector 30 at a given moment, and (ii) the wavelength of the reference light photon received at photodetector 30 at the same moment. Since the received photons of the reference light will travel the same distance (through the reference channel) from light source 20 to photodetector 30, the reference light should have a substantially narrow and uniform wavelength within a single sampling interval, limited by the laser's own linewidth and optical frequency scan rate.

[0073] The sample light received at detector 30 (to be combined with the reference light) will include photons from the first sample light and photons from the second sample light. These received photons will have different wavelengths. The photons from the first sample light received at detector 30 will take different, distinct paths through the object to be imaged. Therefore, these photons from the first sample light received at detector 30 will have different times of flight, and thus these photons will have different wavelengths (due to wavelength scanning emission from light source 20). Similarly, the photons from the second sample light received at detector 30 will have different times of flight through the object, and thus these photons will have different wavelengths.

[0074] The additional optical channel length 352a is configured such that photons of the first sample light received at detector 30 will be included in the first wavelength range, and photons of the second sample light received at detector 30 will be included in the second wavelength range. The length of the additional optical channel length 352a can be selected such that there is no overlap between the first and second wavelength ranges.

[0075] Therefore, the resulting interferogram obtained by detector 30 will contain multiple different beat frequencies (due to the different wavelength differences). The detected second sample light will have a higher beat frequency than the detected first sample light (because the photons of the second sample light will have a longer flight time). Within the range of beat frequencies obtained for each of the first and second sample lights, a higher beat frequency can correspond to a photon with a longer flight time (e.g., a photon that penetrates deeper). It should be understood that, in this example, the reference light will travel a shorter distance than the sample light to reach the detector. Of course, alternatives can be provided where the sample light travels a shorter distance than the reference light—in which case a higher beat frequency would be associated with the shortest flight time. However, in this example, it will be assumed that the reference light travels a shorter distance than the sample light.

[0076] The iNIRS system 10 can be used to obtain a digital representation of each resulting interferogram. For example, detector 30 may include an analog-to-digital converter (ADC) for obtaining interferogram data from each interferogram provided by detector 30. The following will combine... Figure 1 Illustration A illustrates an example of a circuit used to obtain such interferogram data. Fourier analysis (e.g., using FFT or inverse Fourier transform (IFT)) can be performed on each obtained interferogram to obtain an indication of the time-of-flight (DTOF) distribution of sample light photons incident on photodetector 30. Each determined DTOF can provide a distribution showing the time-of-flight of all sample light photons incident on photodetector 30 at a given moment. A DTOF can contain an ensemble average representing a large number of incident photons (in each of several distinct time-of-flight (TOF) bins). The intensity of each TOF bin indicates the number of incident photons in that TOF bin (e.g., all incident photons with time-of-flight within the range of time-of-flight covered by that TOF bin). The phase of the TOF bin (e.g., obtained using Fourier analysis) can represent the average phase of all photons arriving within that TOF bin.

[0077] exist Figure 1 In the example, detector 30 will obtain an interferogram that actually contains two separate DTOFs: one DTOF corresponding to the photons of the first sample light that have traveled through the object to be imaged, and the other DTOF corresponding to the photons of the second sample light that have traveled through the object to be imaged. Figure 2 An example of interferogram data obtained in this way is shown.

[0078] Figure 2 The curve 400 shows the relationship between the amplitude of the photons of the sample light received at detector 30 and the time of flight. Figure 2 The data shown can be obtained by performing an FFT on the acquired interferogram data. The amplitude can provide an indication of the total number of photons detected at each flight time. Curve 400 includes: first sample light data 401, which contains photons of a first sample light received within a first flight time range 401a, and second sample light data 402, which contains photons of a second sample light received within a second flight time range 402a. Figure 2 The data shown may have been obtained using a single digitizer channel of the ADC. For example... Figure 2As shown, the first sample light data 401 is contained within a much smaller time-of-flight range than the second sample light data 402. Curve 400 actually contains two separable DTOFs: one corresponding to the first sample light and one corresponding to the second sample light.

[0079] Each DTOF follows a similar distribution. This distribution includes an initial spike followed by a gradually decreasing tail. The end of a DTOF can be defined by a point where it is no longer possible to distinguish any signal associated with that DTOF from the background noise. In other words, for detected sample light, the start and end points of a DTOF are points where the number of received sample light photons is sufficiently small (or nonexistent) such that the detection amplitude at those beat frequencies (i.e., time of flight) is no longer significantly (e.g., statistically significant) greater than the detection amplitude associated only with background noise (and not with incident sample light photons). That is, the amplitude detected at those beat frequencies no longer consistently exceeds the system's noise floor (e.g., the average number of incident photons at that frequency is less than one per measurement).

[0080] Figure 2 The two DTOFs shown in curve 400 are separated from each other by a separation time 410. Separation time 410 is the time offset between the first DTOF (of the first sample light) and the second DTOF (of the second sample light) included in the data. Figure 2 In this context, the separation time 410 is represented as the time offset between the peak value of the first sample light data 401 and the peak value of the second sample light data 402. However, it should be understood that the separation time 410 can be the time offset between other suitable points in each time-of-flight distribution, such as the time offset between the lowest flight times of the first and second sample lights, the time offset between the longest flight times of the first and second sample lights, and / or the time offset between the average flight times of the first and second sample lights (e.g., the average flight time of the first and second sample lights). In other words, the separation time 410 represents the difference in the detected flight times of the photons from the first and second sample lights.

[0081] The separation time 410 corresponds to the additional optical channel length 352a associated with the second sample light received at detector 30. The separation time 410 is longer than the spectral width of the first sample light data 401 (e.g., the separation time 410 is greater than the amount of time that separates the beginning and end of the first time-of-flight range 401a). Figure 2As shown, there is no spectral overlap between the first sample light data 401 and the second sample light data 402. The first sample light data 401 can be separated from the second sample light data 402. In other words, two separate DTOFs (one corresponding to the first sample light and one corresponding to the second sample light) can be extracted from the obtained interferogram. Each of these separate, extractable DTOFs may not contain any time-of-flight data corresponding to photons from the other sample light.

[0082] The controller 40 of the iNIRS system 10 can be used to process interferogram data. The controller 40 can be used to process the interferogram data obtained from the detector 30 (and the ADC) to obtain DTOF data of a first sample light and DTOF data of a second sample light. As described above, the DTOF data can indicate beat frequency data. That is, the first DTOF data can correspond to a first beat frequency, and the second DTOF data can correspond to a second beat frequency. The controller 40 can be used to extract the first and second DTOF data. This can include separating the two DTOFs contained in the interferogram. The controller 40 can be used to perform separation based on an indication of time-of-flight. The indication of time-of-flight can include an indication of the beat frequency value (e.g., before processing the data to obtain the DTOF data), or an indication of the time of flight (e.g., obtained from the processed DTOF data).

[0083] Controller 40 can be used to process interferogram data to obtain two distinct DTOFs. Controller 40 can be used to image an object (e.g., neuroimaging of a subject's brain) based on the two distinct DTOFs obtained from the same interferogram data. Controller 40 can be used to first separate the two distinct DTOFs from the interferogram data. This can include identifying the first DTOF data as all data points with a time-of-flight below a first threshold time-of-flight (and optionally above a lower threshold time-of-flight, which is less than the first threshold time-of-flight), and identifying the second DTOF data as all data points with a time-of-flight above a second threshold time-of-flight (and optionally below an upper threshold time-of-flight, which is greater than the second threshold time-of-flight). The first and second threshold times of flight can be the same time, or the first and second threshold times of flight can be different (where the second threshold time-of-flight is greater than the first time-of-flight).

[0084] In other words, controller 40 can be used to obtain: (i) first DTOF data containing the distribution of the first sample light time-of-flight values, and (ii) second DTOF data containing the distribution of the second sample light time-of-flight values. The time-of-flight values ​​derived from the interferogram data can indicate that the time of flight of the first sample light is shorter than that of the second sample light. However, as will be understood, this difference in time-of-flight values ​​is at least in part due to the additional optical channel length 352a that the second sample light must travel compared to the first sample light.

[0085] The controller 40 can be used to compensate for this significant difference in flight time between the first and second sample lights. For this purpose, the controller 40 can be used to align the first DTOF (corresponding to the first sample light) with the second DTOF (corresponding to the second sample light). The iNIRS system 10 is used to image the object to be imaged based on time-of-flight data associated with the photons' flight time, and how these flight times change as the photons travel through the object to be imaged (e.g., through the subject's brain). Therefore, the controller 40 can be used to process the acquired DTOF data to obtain data describing the different flight times of the photons traveling through the object (e.g., between the point where the sample light leaves the sample delivery channel 25 and the point where the sample light enters the first / second sample receiving channels 351, 352).

[0086] Controller 40 can be used to align first DTOF data with second DTOF data. For example, controller 40 can apply a time offset to one or both of the first and second DTOF data. The time offset can be selected to eliminate the influence of the additional optical channel length 352a on the time-of-flight data of the second DTOF. For example, controller 40 can align the first and second DTOFs so that both contain only information about the time of flight of photons passing through the object (but not also through the channel between the light source and the object and / or through the channel between the object and the detector). Controller 40 can be used to align the first and second DTOFs by applying a fixed time offset associated with the difference in the duration taken for light to travel along the first and second sample receiving channels. Controller 40 can be used to align the first and second DTOFs by applying a time offset based on aligning one or more features in the first time-of-flight data with corresponding features in the second time-of-flight data, such as alignment based on the TOF peak, average TOF value, and / or maximum or minimum TOF value of each of the two DTOFs.

[0087] Therefore, the controller 40 of the iNIRS system 10 can be used to acquire two sets of DTOF data (e.g., first and second DTOF data) using a light source 20 and a photodetector 30. The controller 40 can acquire these two sets of DTOF data using only one ADC, for example, the ADC can simultaneously digitize the two DTOF distributions within the same interferogram acquired by the detector 30. Thus, the iNIRS system 10 can be used to acquire twice the data for each such light source-detector pair. The first and second sample receiving channels 351, 352 can be arranged close to each other on the object to be imaged. The controller 40 can be used to average the first and second DTOF data of the object. For example, the iNIRS system 10 can be used to sequentially acquire a series of interferograms (and thus acquire interferogram data). For each interferogram data, the controller 40 can be used to acquire the first and second DTOF data. The controller 40 can be used to image the object (e.g., neuroimaging of a subject's brain) based on the temporal evolution of the DTOF data (e.g., based on how the time-of-flight distribution evolves over time). Therefore, the first and second DTOF data in each interferogram data can be combined to provide average DTOF data, and the object can be imaged based on the temporal evolution of the consecutive terms of the average DTOF data.

[0088] Figure 1 Illustration A shows an example of an arrangement for converting a received optical signal into digital data. Illustration A also shows an arrangement of components that can be used as part of the photodetector 30 of this disclosure. Figure 1 As shown in the iNIRS system 10, the detector 30 is configured to receive three inputs: (i) reference light that has traveled along the reference transmission channel 26 and the reference reception channel 36, (ii) a first sample light that has been received through the first sample reception channel 351, and (iii) a second sample light that has been received through the second sample reception channel 352.

[0089] As shown in the figure, the detector may include a beam combiner / 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 configured to provide a digital signal output 307.

[0090] A beam combiner / splitter 301 is coupled to a reference receiving channel 36, a first sample receiving channel 351, and a second sample receiving channel 352. The beam combiner / splitter 301 is configured to receive the first sample light, the second sample light, and the reference light, and to combine these lights to provide a combined optical signal. For example, the first and second sample receiving channels 351 and 352 can be combined into a beam combining element. This combination can be implemented using, for example, fused fiber couplers, polarization combiners, beam splitter cubes, diffraction gratings, or other splitting / combining optical elements (such as photonic lanterns and fiber-to-free-space-to-fiber multiplexing optics).

[0091] Each sample receiving channel may include a single-mode fiber (SMF) or a few-mode fiber (FMF). Each sample receiving channel may be coupled to an additional fiber in the form of a multi-mode fiber (MMF) or an FMF. Each sample receiving channel may be coupled to this additional fiber and configured such that each sample receiving channel (e.g., each SMF or FMF) excites its own unique mode within the additional fiber. A reference channel may be provided by an SMF or an FMF (typically an SMF). The reference channel may be coupled to the additional fiber, for example, to excite the fundamental mode of the additional fiber. The additional fiber may be configured to combine light in an FMF or MMF fiber coupler. Alternatively, one or more free-space beam combining elements, such as a beam splitter cube, may be used to combine the sample light in the FMF / MMF with the reference light.

[0092] The beam combiner / splitter 301 can be configured to separate the resulting combined optical signal into two separate channels: a first optical channel 302a and a second optical channel 302b. For example, this could be a 50:50 split (or close to that ratio). The first optical channel 302a and the second optical channel 302b can be coupled to a balanced photodetector 303. Each optical channel can be configured to guide light to an associated photodiode. The balanced detector can be configured to provide an output based on the difference between the outputs of the two photodetectors. These two photodetectors are typically configured such that the beat frequency signals on each photodiode are 180° out of phase with each other, and therefore the coherent AC terms will be positively superimposed on each other. The balanced photodetector 303 can be configured to output a current corresponding to the difference between the output currents of the two photodetectors. The balanced photodetector 303 can remove any unwanted DC terms from the signal, such as slow fluctuations from the light source 20 or other common-mode effects such as noise.

[0093] The photodetector 30 can be used to convert the current output from the balanced photodetector 303 into a corresponding voltage using a current-to-voltage converter. For example... Figure 1As shown in Illustration A, the converter may include a transimpedance amplifier 304. The voltage output from the transimpedance amplifier 304 can then be amplified using an amplifier 305. The amplifier can be used to scale the output signal to the full range of the ADC and limit the electronic frequency of the circuitry to further maximize the SNR. This amplified voltage is then provided to the ADC 306 for digitization. The ADC 306 includes a digitizer with sufficient bandwidth to allow the entire signal bandwidth containing time-of-flight information to be digitized without attenuation. As will be understood in the context of this disclosure and as described in more detail below, the ADC can have a digitization bandwidth much larger than that of a single DTOF. In fact, by providing more DTOFs in each interferogram to be digitized, the iNIRS system 10 can utilize a larger proportion of the digitization bandwidth of each ADC 306 of the system 10.

[0094] For example, the digitizer bandwidth can be at least as large as the bandwidth of the combined optical signal (e.g., the digitizer bandwidth can be large enough to handle multiple different DTOF distributions included in an interferogram). For example, a digitizer with a sufficiently high sampling rate can be selected such that the bandwidth of the signal to be processed satisfies the Nyquist criterion. The digitizer can be provided as part of each photodetector 30, or the digitizer can be part of a controller 40, and the controller 40 can be coupled to each photodetector 30 to receive the electrical signal to be digitized from that photodetector 30. For each combined optical signal, a digital signal output 307 is provided, which gives a digital representation of the combined optical signal (and thus represents the sample light incident on the photodetector 30 at the moment the combined optical signal is generated and measured).

[0095] The iNIRS system 10 is used to obtain a plurality of digital signal outputs 307 indicating sample light incident on a photodetector 30. Specifically, each photodetector 30 is used to repeatedly combine optical signals (a first sample, a second sample, and a reference) to provide a digital signal output 307 representing each combined optical signal. For example, for each photodetector 30, a time series of digital signal outputs 307 can be obtained, where each subsequent digital signal output 307 corresponds to a subsequent time point in the acquisition and measurement of the combined optical signal (and the digital signal output 307 represents the acquired and measured combined optical signal). As described above, each digital signal output 307 can be in the form of interferogram data indicating an interferogram obtained using the detector 30 (from which two or more sample light DTOFs at that time point can be obtained from the detector 30).

[0096] In the example described herein, the iNIRS system 10 is used to acquire interferogram data that actually contains indications of two separate DTOF signals (one corresponding to the first sample light and one corresponding to the second sample light). Figure 1 In the example provided, two sample receiving channels are given, one of which has a delay, allowing two separate DTOFs to be obtained using a source 20 and a detector 30. However, it should be understood that, within the context of this disclosure, similar functionality can be provided by introducing a delay into one of the two or more sample delivery channels (as a complement or alternative to introducing a delay into one of the two or more sample receiving channels). Reference will now be made to... Figure 3a An example describing this arrangement.

[0097] Figure 3a The iNIRS system is shown. (Compared to...) Figure 1 The system is similar, containing a light source 20, a detector 30, and an object to be imaged. However, in Figure 3a The system includes a first sample transport channel 251 and a second sample transport channel 252. Each sample transport channel 251, 252 couples the light source 20 to the object to be imaged. The iNIRS system also includes a sample receiving channel and a reference channel 26. Figure 3a (Only one of each channel is shown in the diagram). Detector 30 is configured to combine the reference light carried on reference channel 26 with the sample light carried on sample receiving channel.

[0098] exist Figure 3a In the middle, the second sample transmission channel 252 is provided with an additional optical channel length 252a. Figure 3a The additional optical channel length 252a shown is configured to provide with Figure 1 The additional optical channel length 352a shown serves the same function. That is, the additional optical channel length 252a is configured such that the portion of the sample light incident at the detector will have a significantly longer flight time compared to the other sample light incident at the detector (wherein this additional flight time is due to the sample light traveling along the additional length of the optical channel). Figure 3a In this configuration, light source 20 guides a first sample light to the object via a first sample delivery channel 251, and a second sample light to the object via a second sample delivery channel 252. Both the first and second sample lights can be received at the same sample receiving channel. Each of the first and second sample lights can then be combined with a reference light to provide first and second beat frequencies. Figure 1As in the example, the additional optical channel length 252a is selected to suppress spectral overlap between the beat frequency associated with the first sample light and the beat frequency associated with the second sample light. The light source 20 may be coupled to a beam splitter for splitting the light from the light source 20 into: (i) first sample light directed to the object along the first sample transport channel 251, (ii) second sample light directed to the object along the second sample transport channel 252 (and via the additional optical channel length 252a), and (iii) reference light directed to the detector 30 along one or more reference channels.

[0099] Now refer to Figure 3b Describe another example iNIRS system. Figure 1 The system (and) Figure 3a One advantage of this system compared to others is that if more light sources are added to the system, these light sources can be combined with the existing two sample receiving channels, so that for each light source, first and second sample light (where the second sample light has an optical delay compared to the first sample light) can be provided to detector 30. Alternatively, as in... Figure 3a In the case of adding multiple different detectors, each detector may have only one sample receiving channel, but the detector can receive first and second sample light from the light source.

[0100] Figure 3b An iNIRS system including a first light source 20a and a second light source 20b is shown. The first light source 20a is coupled to the object via a sample transfer channel 25a and (ii) to the detector (e.g., a combiner 301 for the detector) via a reference channel 26a. The second light source 20b is coupled to the object via a sample transfer channel 25b and (ii) to the detector (e.g., a combiner 301 for the detector) via the reference channel 26b. The system includes the components described above... Figure 1 The first and second sample receiving channels 351 and 352 of the described type (e.g., having an additional optical channel length 352a in the second optical channel 352). The iNIRS system can be configured such that the first sample receiving channel 351 can receive a first sample light from a first light source 20a and a first sample light from a second light source 20b, and that the second sample receiving channel 352 can receive a second sample light from the first light source 20a and a second sample light from the second light source 20b.

[0101] This system can be configured to suppress spectral overlap between four distinct received optical signals. For example, one of the reference channels 26a and 26b can have an additional optical channel length designed to introduce a time-of-flight delay into that reference channel. Figure 3bThis is illustrated by the reference additional channel length 262b in the second reference channel 26b. This reference additional channel length 262b of the reference channel (second reference channel 26b) and the additional optical channel length 352a of the second sample receiving channel 352 can be selected such that all four beat frequency distributions can fit onto the same interferogram without spectral overlap. Alternatively, the system can be used for temporal multiplexing of the operation of the two light sources, so that only one light source is operated at a time (and therefore the additional optical channel length 352a itself can suppress spectral overlap in the interferogram, e.g., the reference additional channel length 262b is not required).

[0102] Figure 3c Another example iNIRS system is shown. Figure 3c In the iNIRS system, there is a light source 20 and a detector (although only the combiner 301 of the detector is shown). The light source 20 is coupled to the object via a sample transfer channel 25 and to the detector (combiner 301) via a reference channel 26. Figure 3c The system and Figure 1 The system is similar, the difference is that... Figure 3c The system includes a third sample receiving channel 353. The third sample receiving channel 353 includes an additional optical channel length 353a, which has a different length than the additional optical channel length 352a of the second optical channel 352. The three sample receiving channels are configured with different lengths such that three separate beat frequency distributions can be contained in a single interferogram without spectral overlap. For example, one of the additional optical channel lengths 352a and 353a can be significantly larger than the other to further increase the flight time of sample photons traveling along that channel.

[0103] Figure 3d Another example iNIRS system is shown. Figure 3d The iNIRS system is similar to Figure 3b The iNIRS system. However, in Figure 3b The diagram shows a single beam splitter to split light from light source 20 into the following paths: (i) a first sample transport channel 251, (ii) a second sample transport channel 252, and (iii) a reference channel 26. For the iNIRS system of this disclosure, combining or separating three or more individual optical channels can be achieved by a single component (such as...). Figure 1 and Figures 3a to 3c (as shown), or it can be implemented by multiple components. In Figure 3d The system provides two beam splitters: a first beam splitter 24a and a second beam splitter 24b.

[0104] A first beam splitter 24a is coupled to a light source 20 to receive light from the light source 20. The first beam splitter 24a is configured to split the light into a sample optical channel and a reference optical channel. A reference channel 26 extends from the first beam splitter 24a toward a detector, where it is coupled to the system's sample receiving channel. The sample optical channel extends from the first beam splitter 24a to a second beam splitter 24b. The second beam splitter 24b is a separate component from the first beam splitter 24a. The second beam splitter 24b is configured to split the sample light received from the first beam splitter 24a into two sample delivery channels: a first sample delivery channel 251 and a second sample delivery channel 252 (wherein the second sample delivery channel 252 has an additional optical channel length 252a as described herein). It should be understood that, for the example system, a similar arrangement can be provided where the two sample receiving channels are first combined into a single sample channel, and then this single sample channel is combined with the reference channel (e.g., via a separate component), and / or where one sample receiving channel is first combined with the reference channel, and then the other sample receiving channel is combined with the combined channel.

[0105] Figure 3e Another example iNIRS system is shown. Figure 3e The system includes two detectors: a first detector 30a and a second detector 30b. For simplicity, the combiner of each detector is shown as a separate component from the detector; however, it should be understood that these combiners can form part of the detector. Figure 3e A light source 20 is shown. Light from the light source 20 is split into two paths: (i) a sample delivery channel 25 for delivering sample light to the object to be imaged, and (ii) a reference delivery channel 26 for providing reference light to detectors 30a and 30b. Each detector 30a and 30b has an associated reference receiving channel 36a and 36b, respectively. Each reference receiving channel 36a and 36b is configured to provide light from the reference channel 26 to the detector corresponding to that reference receiving channel. For example, the reference channel 26 may have a beam splitter for splitting the reference light from the reference channel 26 into each of the two reference receiving channels 36a and 36b.

[0106] Each of detectors 30a and 30b is coupled to the object to be imaged via two sample receiving channels. As shown, the first detector 30a is coupled to the object via a first sample receiving channel 3510a and a second sample receiving channel 3520a. One of these channels 3510a and 3520a includes an additional optical channel length as disclosed herein (e.g., Figure 3e(As shown in channel 3510a). Similarly, the second detector 30b is coupled to the object via the second detector first sample receiving channel 3510b and the second detector second sample receiving channel 3520b. Likewise, one of these channels 3510b, 3520b includes an additional optical channel length as disclosed herein (e.g., Figure 3e (As shown in channel 3520b). Therefore, as described herein, each of the first and second detectors 30a and 30b can receive the first and second sample light, wherein the time-of-flight difference between the two sample receiving channels of each detector 30a and 30b is such that the resulting first beat frequency will not have spectral overlap with the resulting second beat frequency.

[0107] For each of detectors 30a and 30b, two beam combiners are provided: (i) one for combining light from the two sample receiving channels onto a single combined sample channel, and (ii) one for combining light from the single combined sample channel with reference light from a reference receiving channel. Each detector may include these two beam combiners.

[0108] For the first detector 30a, a first detector first combiner 3011a is coupled to both first detector sample receiving channels 3510a and 3520a, and is used to combine light from these two channels 3510a and 3520a onto the first detector combined sample channel. A first detector second combiner 3012a is coupled to the first reference receiving channel 36a and the first detector combined sample channel to combine the combined sample light with the reference light. The first detector 30a is coupled to the first detector second combiner 3012a to receive the combined light from the first detector second combiner 3012a. For the second detector 30b, a second detector first combiner 3011b is coupled to both first and second detector sample receiving channels 3510b and 3520b, and is used to combine light from these two channels 3510b and 3520b onto the second detector combined sample channel. The second detector second combiner 3012b is coupled to the second reference receiving channel 36b and the second detector combined sample channel to combine the combined sample light with the reference light. The second detector 30b is coupled to the second detector second combiner 3012b to receive combined light from the second detector second combiner 3012b. Therefore, combinations of different light can be provided in stages (e.g., through multiple different components).

[0109] Figure 3eDifferent example functions of the iNIRS system are also illustrated. As described herein, each detector is used to receive and process first and second sample light data. Thus, each detector can effectively obtain information about two (or more) different photon distributions of the sample light passing through the object to be imaged. For example, each detector can use a digitizer channel, and the resulting data obtained from that digitizer channel can indicate two different beat frequency distributions (i.e., the resulting data can contain the first sample light photon distribution and the second sample light photon distribution). In other words, the iNIRS system of this disclosure can be configured to better utilize the full bandwidth of the digitizer channel (e.g., to obtain more usable data from each digitizer channel). Sample delivery channels and / or sample receiving channels can be configured on the object such that the system is used to obtain two or more photon distributions of similar volumes within the object, and / or such that at least partially obtained photon distributions are for different volumes within the object.

[0110] As an example, such as Figure 3e As shown, the sample receiving channels 3510a and 3520a of the first detector 30a can be located at the same position on the object. That is, the sample receiving channels 3510a and 3520a can be adjacent to each other (e.g., within a threshold distance of each other). Therefore, on average, the sample photons traveling from the sample delivery channel 25 to the first detector 30a via the two sample receiving channels 3510a and 3520a can travel through substantially similar volumes of the object (e.g., such as...). Figure 3e (The photon paths are shown in the diagram). In other words, the sample light passing through each of these sample receiving channels of the first detector 30a can actually be used to image the same region of the object. Therefore, the first detector 30a can actually simultaneously acquire two (or more) photon distributions of the same region of the object (e.g., using a single digitizer channel). The system can be used to process different photon distributions together, such as averaging the data obtained from each distribution (i.e., averaging based on the distributions obtained using two sample receiving channels).

[0111] As another example, such as Figure 3e As shown, the sample receiving channels 3510b and 3520b of the second detector 30b can be spaced apart on the object. In this case, the same detector (second detector 30b) can be used to simultaneously image two different volumes within the object. Figure 3e As shown, on average, the sample photons received at each channel can travel through substantially different volumes within the image. Therefore, the first sample photon distribution can represent a portion of the object, while the second sample photon distribution can represent different portions of the object.

[0112] It should be understood that, within the context of this disclosure, different examples can be combined with each other. For example, an iNIRS system can be provided, in which there are two sample delivery channels (of different lengths) and two sample receiving channels (of different lengths). These channels can be configured (e.g., having selected lengths) such that all combinations of different sample optical channel paths will fit within their respective regions on the resulting interferogram. That is, the channels can be configured to stack all different beat frequency distributions within a single interferogram, with no spectral overlap between the distributions. Similarly, multiple light sources can be used, wherein some or all of these light sources are coupled to the object via two or more sample delivery channels. Likewise, there can be three or more sample delivery channels and / or sample receiving channels.

[0113] Therefore, this disclosure provides an iNIRS system in which sample light can travel from a light source to an object along two or more distinct optical paths, and from the object to a detector (regardless of the path taken across the object between the sample delivery channel and the sample receiving channel). These distinct optical paths can have different lengths, such that the resulting beat frequency distributions of different combinations of sample light and reference light can be fitted onto the same interferogram without spectral overlap. Thus, one digitizer channel of the ADC can be used to digitize an interferogram containing information indicating two or more distinct DTOFs of the sample light. This arrangement allows more imaging data about the object to be acquired. In other words, this arrangement allows more data to be acquired without increasing the number of digitizers in the system. For example, the iNIRS system of this disclosure can be configured to maximize the number of distinct beat frequency distributions provided within an interferogram to be digitized. That is, for a given digitizer bandwidth, the iNIRS system can be configured to present the maximum number of distinct distributions within an interferogram, with no spectral overlap between those distributions.

[0114] In each example described herein, each interferogram can provide an indication of all sample light photons incident on detector 30 at a given time. Within this interferogram, there may be two or more distinct beat frequency distributions associated with different sample light incident on (first / second, etc.) detectors. A controller can be used to extract the DTOF for each of these sample light beat frequency distributions. Each determined DTOF can provide a distribution showing the time of flight of all relevant sample light photons incident on photodetector 30 at a given time. Each DTOF may contain an ensemble average representing a large number of incident photons (in each of several distinct TOF intervals). The intensity of each TOF interval will provide an indication of the number of incident photons at that TOF. The phase of the TOF interval (e.g., obtained using Fourier analysis) can represent the average phase of all photons arriving at that TOF interval. As described in more detail below, many characteristics of a subject's brain tissue can be determined based on such DTOF data obtained from the subject's brain tissue.

[0115] The iNIRS system 10 can be used to obtain multiple time-ordered DTOFs from the photodetector 30. This can include averaging the DTOFs (whereby the DTOFs of the first and second sample lights obtained simultaneously are averaged). The digitizer can provide digital output indications of different measurements and can optionally process this digital output in various ways to provide and / or use such DTOF data. An example of such a process will now be described.

[0116] Controller 40 can be used to receive raw digital interferogram data (e.g., data representing an interferogram obtained by converting combined optical signals into digital data). This raw interferogram can be divided into individual scans for wavelength scanning emission from light source 20. For example, the scan rate of light source 20 and the start time of the first scan can be used to determine the scan period. The data can then be grouped, with each group representing a separate scan. An optional Hilber transform can be performed on the data at this stage. Data windowing processing (e.g., using Hann or Blackman-Harris windows) can be performed to reduce sidelobes in the data. Fourier analysis, either inverse Fourier analysis or regular Fourier analysis, can be performed on the data. For example, an inverse Fourier transform can be performed. Fourier analysis can be performed for each wavelength scan of light source 20. The resulting data can be in the form of a series of temporal point spread functions (TPSFs), where each TPSF corresponds to an associated wavelength scan. The TPSF data can be processed to remove the instrument response function (IRF) to provide DTOF data. For example, post-processing can be used to filter out (e.g., deconvolution and / or subtract) IRF.

[0117] In other words, the iNIRS system 10 can be used to determine the time-of-flight distribution sequence of sample light photons incident on one or more detectors. When the object to be imaged is the brain of a subject, this DTOF data can be processed to provide information related to multiple 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 traveled. Each TOF interval 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 the brain tissue through which the photons have traveled, as well as properties of other tissues such as the scalp and skull). Optical properties include the 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 how specific properties change over time. This includes how optical properties evolve over time, as well as properties that indicate motion within the subject's brain tissue (e.g., due to blood flow).

[0118] The controller 40 can store data that correlates the time-of-flight of a sample photon (or a TOF interval) with an indication of the average path trajectory of that photon. This can include an indication of the depth to which the photon penetrates into the subject's brain tissue, and / or an indication of the region of the subject's brain tissue through which the photon travels from the light source 20 to the photodetector 30. The controller 40 can be used to process DTOF data by dividing the data into selected TOF intervals. Within each TOF interval, the data can provide depth-resolved evolution data of the subject's brain tissue. That is, since TOF can be associated with certain penetration depths or regions, each TOF interval can contain data showing characteristics associated with a particular penetration depth or region. Therefore, the evolution of the data within each TOF interval can provide an indication of how one or more characteristics of the subject's brain tissue evolve. For example, if the evolution indicates a change in motion (e.g., blood flow), the motion and the region where the motion occurs can be identified. For this purpose, the TOF-resolved decay slope can be used to identify how the curve of a particular TOF (e.g., for a particular penetration depth / region) decays over time.

[0119] In other words, the iNIRS system 10 can be used to perform autocorrelation, where DTOF scans of consecutive wavelengths are combined to assess the time-of-flight fluctuations of the light field at the photodetector 30. Due to the time-dependent fluctuations of the DTOF, these fluctuations can be quantified. The fluctuations can also be resolved in depth by identifying the associated TOFs (and associated penetration depths / regions) in which these fluctuations occur. The controller 40 can be used to process the data received from the photodetector 30 to provide depth-resolved autocorrelated time-of-flight information of the subject's brain tissue. The controller 40 can use this information to obtain indications of multiple different properties of the subject's brain tissue, such as intracranial pressure (ICP), blood flow index, arterial elasticity, etc. These properties of the subject's brain tissue can be used for various forms of neuroimaging and analysis, such as in brain-computer interfaces, for imaging brain regions to identify potential localized damage or stroke, and / or monitoring neural responses to substances such as drugs.

[0120] As will be understood in the context of this disclosure, when using a square-law detector, the intensity at the detector can be proportional to the square of the superimposed electric field intensity. The rate of change of the optical frequency multiplied by the time delay can produce the frequencies of the interference fringes present in each interferogram. In other words, a Fourier transform interferogram containing multiple beat frequencies can be used to indicate the photon flight time associated with those beat frequencies present in the interferogram. In other words, the iNIRS system 10 is configured to measure the phase shift or frequency shift between photons in the two inputs (reference and sample) of the detector and attribute this difference to the properties of the intermediate brain tissue through which the sample light passes.

[0121] For this purpose, the photodetector 30 may include a beam combiner configured to combine the received light and provide the combined light (which includes components of the first and / or second sample light at different beat frequencies) to signal processing circuitry. The detector 30 may be used to generate interference patterns based on the optical frequency difference between an incident sample electric field and a reference electric field, for example, where 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 electric field and the reference electric field. Therefore, the detected intensity or power (in the form of photocurrent) may be equal to the square of the sum of the incident sample electric field and the reference electric field. Such a detector may include a photodiode, an avalanche photodiode, and / or a fast linear array camera, a streak camera, and a fast charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) sensor. The detector 30 may be a high-bandwidth detector. For example, the detector 30 may be used to resolve interference fringes of 100 MHz or higher, such as up to 1 GHz. The detector 30 may include a single speckle detector. For example, the optical fiber used in the detector may be single-mode. If a multi-mode detector is used, it can include a square-law detector array, such as a photodiode array, focal plane array, fast line scan camera, or fast CCD array. The detector can also include a balanced detector array. A balanced detector array can be used, for example, with a 4-port (2 inputs, 2 outputs, 50:50 ratio) fiber coupler or beam splitter cube, such that the reference light and scattered light are combined and (e.g., uniformly) beamed onto a pair of out-of-phase detectors. The balanced detector can enhance the signal-to-noise ratio of the detected signal by suppressing the incoherent components of the signal. This balanced photodetector can also make full use of all the light transmitted through the interferometer and suppress common noise such as laser intensity noise.

[0122] It should be understood that the examples described herein are not intended to be limiting in the context of this disclosure. Rather, these examples illustrate some possible ways of implementing the claimed techniques. For example, iNIRS system 10 is described as having a series of optical cables provided with channels and probes for coupling these channels to the subject's scalp. However, it should be understood that these probes may be part of the optical channels themselves, or may not be provided at all. Similarly, the arrangement of reference channels is only intended to show that reference light is transmitted from the light source to the photodetector via the optical channels (rather than via the subject's brain tissue). For example, in the case of providing multiple light sources, each light source may include a reference channel for each photodetector, wherein the reference channel directly connects the light source to the photodetector. In this case, there may not be a reference connection at all in the system. Alternatively, in the case of using multiple light sources, the reference light may be transmitted over a common reference optical channel, wherein a portion of the reference light is directed from the common reference optical channel to each photodetector. The light source may also be configured to deliver light to one of a number of different locations on the subject's scalp. For example, the light source may be coupled to a number of different sample delivery channels, each sample delivery channel (e.g., from a beam splitter) extending toward the subject's scalp.

[0123] It should be understood that the specific arrangements of the signal processing circuitry for the detectors shown are not intended to be limiting. Each photodetector can be used to combine a first sample light, a second sample light, and a reference light to provide a combined optical signal having one or more first beat frequencies and one or more second beat frequencies, and to process those combined optical signals to determine one or more properties of the subject's brain tissue. Any suitable signal processing and / or conversion circuitry can be used for the above purposes. For example, a transimpedance amplifier may not be necessary (e.g., depending on the photodetector or ADC, a current-to-voltage conversion may not be necessary, or the conversion may be performed differently). Similarly, a balanced photodetector is not required; a single photodetector, such as a photodiode, can be used. Similarly, the arrangements with ADCs shown in the figures are not intended to be limiting. For example, multiple ADCs can be used (e.g., one ADC for each detector output stream), or all detector output streams can be fed into a common ADC.

[0124] As will be understood from the above discussion, the examples shown in the accompanying drawings are merely exemplary and include features that can be generalized, removed, or replaced as set forth herein and in the claims. Referring generally to the accompanying drawings, it should be understood that the schematic functional block diagrams are used to indicate the functions of the systems and apparatus described herein. Additionally, processing functions may also be provided by devices supported by electronic equipment. However, it should be understood that functions do not need to be divided in this way and should not be construed as implying any particular hardware structure other than the hardware described and claimed below. The functions of one or more of the elements shown in the accompanying drawings may be further subdivided and / or distributed within the apparatus of this disclosure. In some examples, the functions of one or more elements shown in the accompanying drawings may be integrated into a single functional unit.

[0125] As those skilled in the art will understand in the context of this disclosure, each of the examples described herein can be implemented in a variety of different ways. Any feature of any aspect of this disclosure can be combined with any other aspect of this disclosure. For example, a method aspect can be combined with an apparatus aspect, and features described in reference to the operation of specific elements of an apparatus can be provided in a method that does not use those specific types of apparatus. Furthermore, each feature of each example is intended to be separable from the features described therewith, unless it is explicitly stated that some other feature is essential for its operation. Each of these separable features can, of course, be combined with any other feature of the example describing that feature, or with any other feature or combination of features of any other example described herein. In addition, equivalents and modifications not described above may be employed without departing from the invention.

[0126] Some features of the methods described herein can be implemented in hardware, and one or more functions of the apparatus can be implemented in the method steps. It will also be understood that, in the context of this disclosure, the methods described herein need not be performed in the order in which they are described, nor necessarily in the order in which they are depicted in the accompanying drawings. Therefore, aspects of this disclosure described with reference to a product or apparatus are also intended to be implemented as methods, and vice versa. The methods described herein can be implemented as computer programs, or as hardware, or any combination thereof. Computer programs include software, middleware, firmware, and any combination thereof. Such programs can be provided as signals or network messages and can be recorded on a computer-readable medium, such as a tangible computer-readable medium that stores the computer program in a non-transitory 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.

[0127] Any controller disclosed herein may be implemented using fixed logic such as logic gate components or programmable logic such as software and / or computer program instructions executed by a processor. The controller may include a central processing unit (CPU) and associated memory 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 memory (EPROMs), electrically erasable programmable read-only memory (EEPROMs), application-specific integrated circuits (ASICs), or any other type of digital logic, software, code, electronic instructions, flash memory, optical discs, 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). In particular, any controller disclosed herein may be provided by an ASIC.

[0128] Other examples and variations of this disclosure will be apparent to those skilled in the art in the context of this disclosure.

Claims

1. A method for operating an interferometric near-infrared spectroscopy (iNIRS) system, the iNIRS system comprising: Light-emitting device, including a light source; Optical detection devices, including interferometric optical detectors; The iNIRS system includes multiple optical channels, which are configured as follows: The first optical channel path is configured to extend between the light source and the object, and (ii) extend between the object and the detector; The second optical channel path is configured to extend between the light source and the object, and (ii) extend between the object and the detector; as well as The reference optical path is configured to extend between the light source and the detector; The method includes: The light source provides wavelength-scanning light emission; The first sample light is transmitted from the light source to the object through the first optical channel path, and the first sample light received from the object is transmitted to the detector. The second sample light is transmitted from the light source to the object through the second optical channel path, and the second sample light received from the object is transmitted to the detector; Reference light is transmitted from the light source to the detector along the reference channel via the reference optical channel path; and Through the detector: The reference light and the first sample light are combined to provide optical signals with multiple first beat frequencies between the first sample light and the reference light; and The reference light and the second sample light are combined to provide optical signals with multiple second beat frequencies between the second sample light and the reference light; The first optical channel path has a different length than the second optical channel path to suppress spectral overlap between the first beat frequency and the second beat frequency.

2. The method according to claim 1, wherein, A portion of the first optical channel path shares a common optical channel with a portion of the second optical channel path.

3. The method according to claim 1 or 2, wherein, The plurality of optical channels include: A sample delivery channel, coupled to the light source and configured to be coupled to the object, guides a first sample light and a second sample light from the light source to the object; A first sample receiving channel is configured to be coupled to the object to receive a first sample light from the object; and A second sample receiving channel is configured to be coupled to the object to receive a second sample light from the object; The first optical channel path includes the sample transmission channel and the first sample receiving channel; The second optical channel path includes the sample transmission channel and the second sample receiving channel; and The first sample receiving channel has a different length than the second sample receiving channel, thereby providing a length difference between the first optical channel path and the second optical channel path.

4. The method according to claim 1 or 2, wherein, The iNIRS system includes an analog-to-digital converter (ADC), and the method further includes: Sample data is obtained through the ADC, the sample data including indications of the first beat frequency and the second beat frequency detected by the optical detector.

5. The method according to claim 4, wherein, The process of obtaining sample data through the ADC includes: The sample data for the first beat frequency and the second beat frequency are obtained using a single ADC channel.

6. The method according to claim 4, wherein, The iNIRS system includes a controller, and the method further includes: The controller processes the sample data to obtain: (i) first sample data, including an indication of the first beat frequency detected by the optical detector, and (ii) second sample data, including an indication of the second beat frequency detected by the optical detector.

7. The method according to claim 6, wherein, The method further includes: The controller obtains the first time-of-flight data of the first sample light based on the first sample data; and The controller obtains the second time-of-flight data of the second sample light based on the second sample data.

8. The method according to claim 1 or 2, wherein, The light source is a first light source, the light-emitting device includes a second light source, and the method further includes: The interferometric optical detector receives a first sample light from the second light source, a second sample light from the second light source, and a second reference light from the second light source.

9. The method according to claim 1 or 2, wherein, The optical detection device is a first optical detection device, and the iNIRS system includes a second optical detection device, the second optical detection device including a second detector, wherein the plurality of optical channels are configured as follows: The third optical channel path is configured to extend between the light source and the object, and (ii) extend between the object and the second detector; The fourth optical channel path is configured to extend between the light source and the object, and (ii) extend between the object and the second detector; as well as The second reference optical channel path is configured to extend between the light source and the second detector; The method further includes: The third sample light is transmitted from the light source to the object through the third optical channel path, and the third sample light received from the object is transmitted to the second detector; The fourth sample light is transmitted from the light source to the object through the fourth optical channel path, and the fourth sample light received from the object is transmitted to the second detector; Reference light is transmitted from the light source to the second detector via the second reference optical channel path along the second reference channel; and Through the second detector: The reference light and the third sample light are combined to provide optical signals with multiple third beat frequencies between the third sample light and the reference light; and The reference light and the fourth sample light are combined to provide optical signals with multiple fourth beat frequencies between the fourth sample light and the reference light; The third optical channel path has a different length than the fourth optical channel path to suppress spectral overlap between the third beat frequency and the fourth beat frequency.

10. The method according to claim 1 or 2, wherein, The plurality of optical channels include: A first sample delivery channel is coupled to the light source and configured to be coupled to the object to guide first sample light from the light source to the object; A second sample delivery channel, coupled to the light source and configured to be coupled to the object, guides second sample light from the light source to the object; and A sample receiving channel is configured to be coupled to the object to receive a first sample light and a second sample light from the object; The first optical channel path includes the first sample transmission channel and the sample receiving channel; The second optical channel path includes the second sample transmission channel and the sample receiving channel; and The first sample transport channel has a different length than the second sample transport channel, thereby providing a length difference between the first optical channel path and the second optical channel path.

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