GB2599719A

GB2599719A - Event related optical signal neuroimaging and analysis systems and methods

Info

Publication number: GB2599719A
Application number: GB2016093.3A
Authority: GB
Inventors: Dench Jonathan
Original assignee: Comind Technologies Ltd
Current assignee: Comind Technologies Ltd
Priority date: 2020-10-09
Filing date: 2020-10-09
Publication date: 2022-04-13
Also published as: WO2022074403A1; GB202016093D0

Abstract

An event related optical signal (EROS) neuroimaging and analysis system 100 for monitoring a subject’s brain activity includes one or more light sources 101 and light detection circuitry 120 arranged adjacent the subject’s head, wherein light, e.g. modulated IR light, is emitted through the subject’s head and brain tissue 110, and the light detection circuitry outputs a detection radio frequency (RF) signal based on light incident on a detection surface 124 of the circuitry. Analogue radiofrequency mixing of the detection RF signal with a local oscillator (LO) 141 RF signal is used to provide a mixed RF signal, and a phase of the mixed RF signal is used for neuroimaging and analysis. The analogue RF mixer 130 includes a first port 131 for receiving the LO RF signal, a second port 132 for receiving the detection RF signal, and a third port 133 for outputting the mixed RF signal. There may additionally be a second light source (102, fig 2) and second local oscillator (142, fig 2).

Description

Event Related Optical Signal Neuroimaging and Analysis Systems and Methods

Technical Field

The present disclosure relates to the field of event related optical signal (EROS') systems and methods for neuroimaging and analysis.

Background

Existing neuroimaging techniques include diffuse optical imaging and near-infrared spectroscopy.

Such techniques are designed for measuring haemodynamic effects, such as those associated with oxygenation state of haemoglobin in the brain and other effects which manifest in optical absorption characteristics of brain tissue.

These techniques may therefore enable an indication of properties of cerebral blood flow to be obtained. While cerebral blood flow may be used to provide an indication of activity occurring in the brain, cerebral blood flow is an indirect indicator of underlying neuronal activity.

It may be preferable to be able to reliably monitor brain activity in other ways, for example to provide additional and/or alternative information to that which may be obtained by monitoring haemodynamic effects.

Summary

Aspects of the disclosure are set out in the independent claims and optional features are set out in the dependent claims. Aspects of the disclosure may be provided in conjunction with each other, and features of one aspect may be applied to other aspects.

In an aspect, there is provided an event related optical signal, EROS, neuroimaging and analysis system for monitoring activity of a subject's brain. The system comprises: one or more light sources each configured to emit modulated light; light detection circuitry comprising a light detector, the light detection circuitry configured to output a detection radio frequency, RF, signal based on light incident on a detection surface of the detector; an analogue RF mixer having: (i) a first port connected to one or more local oscillators, LOs, to receive one or more LO electrical RF signals therefrom; (ii) a second port connected to the light detection circuitry to receive the detection RF signal therefrom, wherein the analogue RF mixer is configured to mix the LO RF signal and the detection RF signal to obtain a mixed RF signal, and the analogue RF mixer further comprises (iii) a third port configured to output the mixed RF signal; and wherein the system further comprises a controller configured to provide neuroimaging and analysis based on a phase of the mixed RE signal.

Embodiments may enable the mixed SF signal to be analysed for determining one or more properties of the light incident on the detector, and thus of activity occurring within the subject's brain. Analysing the mixed SF signal may be advantageous as this mixed SF signal may include different component parts (as compared to just the detection RE signal on its own), and one or more of these different component parts may facilitate easier analysis, as compared to the detection SF signal. For example, embodiments may enable a lower frequency signal to be measured for determining properties of the light incident on the detector, such as phase information for the light received on the detector. Phase information obtained from the mixed SF signal may comprise a phase offset between the detection RE signal and the LO RE signal. For example, the phase offset may comprise an offset between amplitude modulation of the detection SF signal (as originally imparted by the first light source) and the LO SF signal (as imparted by the first LO). The phase information may provide an indication about optical path length, penetration depth and/or time of flight for photons travelling from the light source to the detector via the subject's brain tissue. This information may be used to infer properties of neural activity.

The analogue SF mixer may be configured to mix the LO SF signal and the detection SF signal so that the mixed SF signal comprises: (i) a first component corresponding to a difference frequency for the LO RE and detection RE signals input to the analogue RE mixer, and (ii) a second component corresponding to the sum frequency for the LO SF and detection SF signals input to the analogue SF mixer. The analogue SF mixer may comprise a non-linear circuit configured to mix the LO SF signal and the detection RE signal so that the mixed RE signal comprises the first and second component. For example, the non-linear circuit may comprise a circuit configured to output a mixed SF signal which is an approximation to a multiplication of the LO SF signal and the detection SF signal. For example, the non-linear circuit may be arranged to provide circuitry which break's Ohm's law.

The analogue SF mixer may be configured to suppress, in the mixed SF signal, the LO SF and detection SF signals input to the analogue SF mixer. The analogue SF mixer may comprise a double balanced SF mixer. The SF mixer (e.g. the double balanced SF mixer) may be configured to suppress, in the mixed SF signal, harmonics, such as even order products, of the LO RE and detection SF signals input to the analogue SF mixer. The SF mixer (e.g. the double balance SF mixer) may comprise a diode ring and one or more switches. Each switch may comprise a transistor switch, such as a field effect transistor switch.

The controller may be configured to provide neuroimaging and analysis based on the phase of the first component of the mixed RF signal. For example, the phase of the first component of the mixed RF signal may comprise a phase offset as evident in the mixed RF signal. The phase offset may comprise a phase offset between a phase of the detection RF signal and a phase of the LO RF signal. The phase of the two signals may correspond to phases brought about by amplitude modulation at the first light source and at the first LO respectively. The phase offset may provide an indication of at least one of: co an optical path length for the light from the light source to the detector through the subject's brain tissue, 00 a time of flight for the light from the light source to the detector through the subject's brain tissue, and (iii) a penetration depth of the light into the brain tissue during travel of the light from the light source to the detector through the subject's brain tissue.

The system may further comprises signal processing circuitry configured to perform a low-pass filter of the mixed RF signal to provide a filtered RF signal in which the second component of the mixed RF signal has been removed. The system may comprise an amplifier configured to provide amplification to the filtered RF signal. The controller may be configured to provide the neuroimaging and analysis based on the phase of the first component as present in the filtered RF signal.

The one or more LOs may be configured to provide the LO RF signal input to the analogue RF mixer at a first LO RF frequency. The first LO RF frequency may be selected based on an expected frequency for the detection RF signal input to the analogue RF mixer. The expected frequency for the detection RF signal input to the analogue RF mixer may comprise an expected frequency for a component of interest within the detection RF signal input to the analogue RF mixer. Said expected frequency, and/or said component of interest may correspond to a frequency of the modulation scheme (or modulated waveform, e.g. amplitude modulation) applied to the light from the first light source, e.g. a frequency of the modulated waveform. For example, the expected frequency for the detection RF signal input to the analogue RF mixer may correspond to a frequency of the amplitude modulation scheme applied at the first light source (e.g. the frequency of the modulated waveform), and/or an expected wavelength of an output from the light detector brought about by the light incident on the detector.

The one or more LOs may be selectively operable to provide the LO RF signal input to the analogue RF mixer at one of a plurality of different frequencies. For example, both [Os could be left on, with filtering and/or switches used to only provide one LO RF signal at a time. The controller may be configured to select which of the plurality of different frequencies is used for the LO RF signal input to the RF analogue mixer based on the expected frequency for the detection RF signal input to the RF analogue mixer. The controller may be configured to select the frequency for the LO RF signal input to the RF analogue mixer to be the closest of the plurality of frequencies to the expected frequency. The one or more light sources may be selectively operable to emit modulated light at one of a plurality of different wavelengths.

The system may be configured to control operation of the one or more LOs so that the frequency of the LO RE signal input to the analogue RE mixer is selected based on the modulation frequency of light emitted from the one or more light sources. The system may be configured to provide time multiplexing of both: (i) the modulation frequency of the light emitted from the one or more light sources (e.g. the frequency of the light which is emitted according to a modulation waveform having a modulation frequency), and (ii) the frequency of the LO RF signal input to the analogue RE mixer (e.g. the frequency of the signal from the LO which is modulated according to a modulation waveform having a modulation frequency).

The system may be configured to operate so that: (i) in a first time window, the frequency of the LO SF signal input to the analogue SF mixer is selected to correspond to the modulation frequency of light emitted by the light source, and (ii) in a second time window in which the frequency of light emitted by the light source is different to that in the first window, the frequency of the LO SF signal input to the analogue SF mixer is selected to correspond to the modulation frequency of light emitted by the light source and is different to that in the first time window. The LOs may be controlled so that, in each time window, the frequency of the LO SF input to the analogue SF mixer is selected to be the closest of the plurality of LO SF input frequency to the modulation frequency of light emitted in that time period. The one or more light sources may be configured to emit amplitude modulated light at one or more selected wavelengths (where that light is modulated according to a frequency of the modulation waveform). The one or more light sources may comprise: (i) a first light source configured to emit light at a first light source modulation frequency, and (ii) a second light source configured to emit light at a second light source modulation frequency. One or both light sources may comprise of lasers.

The light detection circuitry may comprise a pre-amplifier configured to provide amplification to SF signals output from the detector to provide the detection SF signal. The one or more LOs may comprise: (i) a first LO configured to provide a first LO SF signal input frequency, and (ii) a second LO configured to provide a second LO SF signal input frequency different to the first LO SF signal input frequency. The one or more LOs may be selected to be operable to provide an LO SF signal input frequency of within 1 MHz of the expected frequency. The system may be configured to control the one or more light sources to first emit light at one wavelength and to then emit light at a different wavelength. The system may comprise a head support configured to be placed onto the subject's head so that the one or more light sources and the light detector are arranged adjacent to the subject's head.

In an aspect, there is provided a method of event related optical signal, EROS, neuroimaging an analysis for monitoring activity of a subject's brain. The method comprises: arranging both: (i) one or more light sources, and (ii) light detection circuitry adjacent to a subject's head; emitting modulated light from the one or more light sources through the subject's head; using the light detection circuitry to output a detection RF signal based on light incident on a detection surface of a detector of the light detection circuitry; performing analog radiofrequency mixing of the detection RF signal with a local oscillator, LO, RF signal to provide a mixed RF signal; and providing neuroimaging and analysis based on a phase of the mixed RF signal.

Providing neuroimaging and analysis based on a phase of the mixed RF signal may comprise providing neuroimaging and analysis based on a phase of a first component of the mixed RF signal. Said first component may correspond to a difference frequency for: (i) the LO RF signal input for the RF mixing, and (ii) the detection RF signal input for the RF mixing. The method may comprise performing a low-pass filter of the mixed RF signal to provide a filtered RF signal in which a second component of the mixed RF signal has been removed, wherein said second component corresponds to a sum frequency for: (i) the LO RF signal input for the RF mixing, and (ii) the detection RF signal input for the RE mixing. Methods may comprise providing the neuroimaging and analysis based on the phase of the first component as present in the filtered RF signal.

Aspects of the present disclosure provide computer program products comprising computer program instructions configured to program a controller to perform any of the methods disclosed herein.

Figures Some examples of the present disclosure will now be described, by way of example only, with reference to the figures, in which: Fig. 1 shows a schematic diagram of an exemplary Event Related Optical Signal (EROS') system.

Fig. 2 shows a schematic diagram of an exemplary Event Related Optical Signal ('EROS') system.

In the drawings like reference numerals are used to indicate like elements.

Specific Description

Embodiments of the present disclosure are directed to Event Related Optical Signal (EROS') systems and methods. For these, light from one or more light sources is directed towards a subject's brain tissue, and back scattered light from that brain tissue is detected. Embodiments relate to signal processing approaches which enable information about events occurring in the subject's brain tissue to be obtained based on properties of the back scattered light measured at the detector. In particular, signals detected by the detector (which may carry such information about events occurring in the subject's brain tissue) are mixed with signals from a local oscillator in an analogue radio frequency mixer. The analogue radio frequency mixer outputs a signal having a component at a frequency corresponding to the difference in frequency between a frequency in the signal from the detector and a frequency in the signal from the local oscillator.

Information about events occurring in the subject's brain tissue may then be determined based on properties of the signal component having this difference frequency, such as its phase information. This phase information is maintained from the original high frequency signal, where the phase of the difference frequency is the same as that of the original high frequency signal. This may enable e.g. phase information to be extracted from the backscattered signal with sufficiently high precision and time resolution that events due to neuronal activity in the brain can be resolved in the detected signal.

Basic principle of EROS system EROS systems of the present disclosure may direct amplitude modulated light to regions of the subject's brain tissue. Light signals caused by scattering of this light from the subject's brain tissue can then be detected by one or more detectors. The phase of the amplitude modulated waveform carried by the detected light can be used to infer information about the scattering events which scattered the light back towards the detectors. For example, it may provide information about the optical path length from the source to the detector, which can be used to determine the depth in the tissue at which the scattering took place.

Liciht sources EROS systems of the present disclosure are arranged to direct light from one or more light sources towards a subject's brain tissue through the scalp and skull. These light sources will typically be positioned on the subject's scalp. The light sources provide light which is amplitude modulated with a waveform (e.g. a sinusoid or pulse train). This waveform may be provided from an oscillator connected to the light source. The modulated light from the one or more light sources is directed towards the subject's brain tissue so that it may pass through their scalp, skull and into their brain tissue. It is to be appreciated that the penetration depth of this light may vary depending on a number of factors, such as the wavelength of the light, as well as material properties (e.g. density) of the medium through which the light is passing. Typically, light used in EROS systems of the present disclosure has near-infrared (NIR) wavelengths (e.g. 800 to 2500 nm). At these wavelengths, it can be expected that at least some of the light emitted from the light source will pass into the brain tissue of the subject (i.e. it will not all be blocked by the scalp/skull), and also some of the light will penetrate more deeply into the brain tissue to enable information to be obtained from a greater volume of brain tissue.

Optical paths of photons directed towards the subject's brain tissue As light from the one or more light sources passes through the subject's scalp, skull and/or brain tissue, light scattering events will occur as the light interacts with the medium through which it is travelling. It will be appreciated that there may be a plurality of different causes for a scattering event to occur, and the causes for these different scattering events to occur may also depend on properties of the light and/or the medium through which it is travelling. As a consequence of a scattering event, the light will change direction. Photons of light entering the brain tissue will diffuse, moving in random walks due to optical scattering until they are either absorbed or exit the brain tissue. The random nature of this diffusion means that although individual scattered photons have unpredictable paths, bulk photon movements can be accurately understood probabilistically.

The paths followed by masses of photons launched into the brain tissue from one light source and scattered back out onto a photodetector are well understood probabilistically. On average, the trajectories for photons from source to detector are arc-shaped, e.g. a plot of the different trajectories may have a banana shape.

Detectors, and the spatial arrangement of the detectors relative to the light sources The scattering of light within brain tissue and towards a detector will be referred to as 'back scattering of light'. EROS systems of the present disclosure may utilise one or more light detectors, such as photodiodes, to measure this backscattered light. It will be appreciated that back scattered light will not always travel directly back towards any given location on the scalp, but instead, this light may travel in one of a plurality of different directions (e.g. back scattered light from one light source may be detected at a plurality of different locations on the subject's scalp). Light may be scattered a plurality of times before it reaches a detector. The depth reached by photons emitted from the source and picked up by the detector will be proportional to the distance between the source and detector. For example, short source-detector distances typically cover shallow tissue depths, whereas longer source-detector distances contain photons which travel deeper into the brain tissue. Embodiments of the present disclosure may utilise a plurality of source-detector pairs, each pair being spatially arranged to be associated with a selected depth of light penetration into the subject's brain.

Some of the back scattered light signals may carry information about activity occurring within the brain. The detectors may be operable to determine one or more properties of the back scattered light which they detect. The system may be configured to determine an indication of the intensity of light incident on the detector and/or phase information associated with light incident on the detector -such phase information may be provided by the phase of the waveform carried as amplitude modulation on the scattered light. In particular, such phase information may be used to identify a time of flight (TOF') for photons. Phase information in detected light may be used to provide an indication of the temporal offset of that light as compared to light which would have reached the detector along a path of known length. This difference in phase (and thus difference in time of flight from source to detector) will provide an indication of the distance that photon has travelled to get from the source to detector (e.g. its optical path length). EROS systems of the present disclosure may utilise probabilistic models to estimate the photon path from source to detector, and/or the penetration depth of that photon within the brain tissue.

Neuroimaging and analysis based on detected signals EROS systems of the present disclosure may be configured to detect an indication of fast optical signals (FOS') occurring in the subject's brain tissue. These fast optical signals relate to neural activity, such activity can cause changes in optical scattering properties of the brain tissue in which that activity occurs. As such, scattering properties of light in brain tissue will vary concurrently with neural activity in that brain tissue, and so an indication of the neural activity occurring may be obtained based on information contained within scattered light signals measured by detectors. The physiological mechanisms responsible for such fast optical signals comprise cell swelling and membrane conformation changes. These changes may occur during the transfer of ions and water that happen during electrical neuronal events such as action potentials in the brain.

As a result of the fast optical signals occurring (or not occurring), different regions within the brain tissue will cause light scattering events at different rates. For example, when a region of the brain is active (e.g. when fast optical signals are being transmitted through that region of the brain), the activity in that region will lead to a different number and/or type of scattering events occurring, as compared to a region which is dormant (e.g. when no, or not many, fast optical signals are being transmitted through that region of the brain). This will be evident in the measured phase offsets, as either a change in phase offsets will indicate an event occurring (e.g. which caused the scattering to occur), or an absolute value of the phase offset itself will indicate a depth at which an event (e.g. a scattering) occurred.

Temporal monitoring/temporal neuroimaging and analysis EROS systems of the present disclosure are configured to repeatedly (e.g. continuously) pass photons from the one or more light sources through intervening brain tissue to detectors of the system. By monitoring properties of the back scattered light received at the one or more detectors, systems of the present disclosure may determine whether any neural events are occurring (e.g. whether the detected signals correspond to regions of the brain through which fast optical signals are being transmitted). For example, neural activity in a volume of brain tissue may be inferred based on a change in the rate of scattering of light associated with that volume of brain tissue (e.g. light which has passed through that volume of brain tissue). EROS systems of the present disclosure may utilise a plurality of different source-detector pairs arranged to enable activity in different regions of the brain to be monitored at the same time.

By monitoring lots of detected photons, and having an estimate for their expected trajectories through the brain tissue, changes in neural activity may be identified based on measured phase offsets at the detector. For example, where a source-detector pair initially receives photons having a consistent phase offset (and thus consistent time of flight), and then photons are suddenly received having less of a phase offset (e.g. indicating a smaller time of flight), this may suggest that neural activity has occurred somewhere on that expected trajectory causing earlier scattering than expected. Based on this shorter time of flight, an indication of penetration depth for the scattering event may be determined, and this provides an indication of activity in a certain region of the brain tissue. Using these probabilistic methods, it is possible to filter out photons which did not reach the brain tissue, as these will have probabilistically travelled shorter paths from their source to a detector.

One specific example of an EROS system will now be described with reference to Fig. 1. Some alternative and/or additional features of EROS systems of the present disclosure will be described later with reference to Fig. 2.

Fig. 1 shows an EROS system 100. The EROS system 100 includes a first light source 101. Fig. 1 also shows a subject's brain tissue 110. The EROS system 100 also includes light detection circuitry 120 which includes a light detector 124.The EROS system 100 includes an analogue radiofrequency ('RE') mixer 130 having a first port 131 (also referred to as an 10 port'), a second port 132 (also referred to as an IRF port'), and a third port 133. The EROS system 100 also includes a first local oscillator 141 and a controller 150.

The light source 101 will be located proximal to the subject's brain tissue 110 in use. Typically, the light source 101 will be placed on, or proximal, to the subject's scalp. Likewise, the light detection circuitry 120 (and the light detector 124) will be located on, or proximal to, the subject's scalp in use. There are occasions where these may be located off the head and coupled with light guides. The light detection circuitry 120 is connected to the second port 132 of the analogue SF mixer 130. The first local oscillator 141 is connected to the first port 131 of the analogue SF mixer 130. The controller 150 is connected to the third port 133 of the analogue SF mixer 130.

The first light source 101 is configured to emit modulated light. The first light source 101 is configured to emit light at a first wavelength, and to provide amplitude modulation of the light. In this example, the first light source 101 comprises a laser for emitting light at the first wavelength.

The first light source 101 is configured to emit light at near infrared wavelengths (such as between 800 and 2500 nm). The first light source 101 is configured to direct the modulated light towards the subject's brain tissue 110. The amplitude modulated light will comprise light at the first wavelength amplitude modulated according to a selected modulation pattern, referred to herein as a waveform. The selected modulation pattern may be sinusoidal, or it may provide another suitable and detectable waveform for the emitted light. The selected modulation may have a modulation frequency (e.g. a frequency of the modulated waveform applied to the light from the first light source 101), and the modulation frequency may be a frequency which is expected to be evident in light incident on the detectors (for example it may be selected based on a bandwidth of the detectors). Typically, the modulation waveform may have a frequency between 50 MHz - 750 MHz, usually 100-300 MHz.

The light detector 124 is arranged in a region to which it is statistically likely for light from the first light source 101 to be back scattered. The light detector 124 is arranged a selected distance away from the first light source 101 (the source-detector distance). The source-detector distance is selected based on the properties of the light-material interaction of the wavelength of light being emitted by the light source 101 and the power that can be safely used at that wavelength. The source-detector distance will typically be smaller for lower wavelength light sources, and higher for higher wavelength light sources. Typical maximum values would be < 7 cm for 830 and <8.5 cm for 1064 nm & 1310 nm.

The light detector 124 may comprise one or more photodetectors such as an avalanche photodiode. The light detection circuitry 120 is configured to output a detection radiofrequency ('SF') signal based on light incident on the light detector 124. The light detection circuitry 120 is configured so that the detection SF signal provides a representation of the light incident on a detection surface of the detector 124. The light detection circuitry 120 is configured so that the detection SF signal will retain phase information that was present in the light incident on the detector 124. This includes phase information associated with light from the first light source 101 that has back scattered from brain tissue 110 and travelled to the detection surface of the tissue 110. In particular, a portion of the light incident on the detector 124 will have travelled from the first light source 101 to the detector 124 via a trajectory which passes into the subject's brain tissue 110. This light will have been amplitude modulated at the first light source 101, and so an amplitude of the total light incident on the detector 124 will also correspond (at least in part) to the amplitude modulation waveform applied at the first light source 101. This will provide some phase information, as at any given moment in time, the amplitude of light incident on the detector 124 will provide an indication of the phase of the amplitude modulation waveform(e.g. how far through once cycle of amplitude modulation the light incident on the detector 124 is). For example, the detection RF signal may provide an indication of the instantaneous intensity of light incident on the detector 124.

The first local oscillator 141 (10') is configured to output a local oscillator radiofrequency (10 RF') signal at a selected frequency. The first LO 141 is configured to output an LO RF signal at a frequency which is close, but not identical, to the frequency of the modulation waveform (e.g. the waveform modulated on to the light provided by the first light source 101). The LO RF signal provides a reference having a fixed offset in frequency from the waveform which is modulated on to the light provided by the first light source 101. The LO RF signal from the first LO 141 is configured to correspond to the amplitude modulation waveform, but with a small frequency offset. For example, the LO RF signal may have a frequency within 1 MHz of the frequency of the waveform which is modulated on to the light provided by the first light source 101, such as within 250 kHz, for example within 150 kHz, for example within 100 kHz, for example within 75 kHz, for example within 50 kHz, for example within 25 kHz, for example within 10 kHz. This sets the lower limit for temporal resolution (the best). 1-100 kHz IF would be typical with approximately 5 MHz being the upper limit.

The analogue RF mixer 130 is configured to receive the LO RF signal at its first port 131, and to receive the detection RF signal at its second port 132. The RF mixer 130 is configured to combine these two signals to provide a mixed RF signal. As will be appreciated by the skilled addressee in the context of the present disclosure, the mixed RF signal will include a component at a sum frequency and a component at a difference (or intermediate) frequency (e.g. beats). Phase information for the amplitude modulation waveform from the detection RF signal will be preserved in the mixed signal, as will phase information for the LO RF signal. For instance, phase information for the two input signals to the RF mixer 130 will be preserved in the mixed RF signal (at both sum and difference frequencies). That is, any phase information for the amplitude modulated light, as received at the detector 124 (and thus provided to the RF mixer 130 in the detection RF signal), and any phase information for the LO RF signal from the first LO 141 (as provided to the RF mixer 130), will be preserved in the mixed RF signal. As such, an indication of the phase information carried by light incident on the detector 124 as compared to the phase information provided by the first LO 141 will be preserved in the mixed RF signal. The mixed RF signal may provide an indication of a phase offset between the two input signals. The RF mixer 130 is configured to output the mixed RF signal through its third port 133.

The analogue RF mixer 130 may comprise a nonlinear electrical circuit such as IC Analogue Devices AD831 or Linear Technology LT5526, with prototyping being done using Anzac MD-108 & Analogue Devices AD831. The RF mixer 130 may be configured to combine the LO RF signal and the detection RF signal so that a component of the mixed RF signal comprises a product of the two input signals (e.g. the two input signals are multiplied). The RF mixer 130 may be configured to suppress other components produced by the mixing, such as components at either of the input frequencies, or harmonics thereof. For example, the RF mixer 130 may be configured to suppress even order products of the input signals.

The RF mixer 130 may comprise a passive RF mixer. The passive RF mixer may comprise one or more diodes (or field effect transistors). The diodes (or transistors) may be configured to provide a non-linear relationship between voltage and current, thereby to provide mixing. The RF mixer 130 may comprise an unbalanced mixer, or a single or double balanced RF mixer may be used (to provide filtering of one or both of the input signals from the mixed RF signal). For example, the double balanced mixer may comprise a diode double balanced mixer. The diode double balanced mixer may comprise two unbalanced to balanced transformers, and a diode ring.

The diode ring may comprise four diodes, such as Schottky barrier diodes. The diode forward voltage drop may be selected based on a drive level for the LO RF signal input. The RF mixer 130 may comprise a field effect transistor (FET') switching RF mixer. For example, the RF mixer 130 may comprise one or more FETs arranged to provide switching to provide the mixed RF signal. For example, the RF mixer 130 may comprise a Gilbert cell mixer. The RF mixer may be arranged to receive the detection RF signal as a current signal or a voltage signal. Typically, the detection RF signal will be provided as a voltage signal. The mixer 130 may be provided in an integrated circuit.

The controller 150 is configured to identify phase information associated with the light incident on the detector 124 based on the mixed RF signal (optionally this may include use of additional signal processing circuitry). The controller 150 is configured to identify a phase offset for the detected light based on the mixed RF signal. The controller 150 is configured to determine a phase offset between: (i) the detection RF signal (e.g. the phase associated with the amplitude modulation scheme applied to light from the first light source 101, as evident in the light detected at the detector 124), and (ii) the LO RF signal (e.g. the phase of the LO RF signal as provided to the RF mixer). The controller 150 may be configured to determine a time of flight associated with that phase offset. For example, the controller may be configured to monitor such determined phase offsets to determine when events occur. The controller may be configured to determine an expected penetration depth based on the wavelength of the light being emitted by the first light source.

The phase offset, and a determined time of flight, may provide an indication of the path length for the light incident on the detector 124 from the light source 101 (and an indication of the depth of penetration into the subject's brain tissue 110). Based on this information, the controller 150 is configured to determine at what depth any scattering events occurred and/or whether fast optical signals within the brain tissue 110 were responsible for that scattering. The controller 150 may be configured to determine this phase information based on the difference frequency in the mixed RF signal generated by the RF mixer 130. The difference frequency may be at a substantially lower frequency than the detection RF signal. This may enable the phase information carried by the difference frequency to be measured and processed without the need for high bandwidth detectors, because the difference frequency may be relatively low as compared to the RF signals at the mixer's inputs.

In operation, the first light source 101 is placed adjacent to the subject's head. Typically, the first light source 101 will be placed on, or as close as possible to, the subject's scalp. The detector 124 is also placed adjacent to the subject's head. Typically, the detector 124 will be placed on, or as close as possible to, the subject's scalp. The detector 124 will be located a selected distance away from the light source 101. This selected distance will vary depending on the wavelength of light being emitted by the first light source 101. Often, the detector 124 will be placed adjacent to the first light source 101, e.g. the detector 124 may be adjacent the first light source 101 on the subject's scalp.

The first light source 101 is then operated to emit modulated light. The light will be emitted from the first light source 101 at a selected wavelength, and with an amplitude modulation scheme applied thereto so that the amplitude modulated light will have an amplitude which varies cyclically according to a modulation frequency (e.g. to enable phase information to be easily identified in that amplitude modulated light). The modulated light emitted from the first light source 101 is directed towards the subject's brain tissue 110. Each individual photon of light will follow its own individual path from the first light source 101. Typically, a large number of photons will travel from the first light source 101 through the subject's scalp and skull and into their brain tissue 110, where one or more scattering events will occur before they travel onto the detection surface of the detector 124.

The detector 124 is configured to measure the number of photons incident on its detection surface, and the light detection circuitry 120 will output a signal which indicates this information. In particular, the light detection circuitry 120 outputs a detection RF signal which corresponds to the intensity of light incident on the detector 124 (e.g. the number of incident photons). This detection RF signal may therefore retain an indication of the amplitude modulation scheme as applied to the light emitted from the first light source 101. The detection SF signal may therefore carry phase information corresponding to the amplitude modulation scheme (as evident in photons incident on the detector 124). This detection RE signal is provided to the second port 132 (the SF port) of the SF mixer 130.

At the same time, the first LO 141 is operated to provide the LO SF signal. The LO SF signal is provided at a frequency which is similar, but not identical, to the modulation frequency of the first light source (e.g. as evident in the detection RE signal). The LO RE signal is provided to the first port 131 (the LO port) of the SF mixer 130.

The RE mixer 130 mixes these two electrical signals (the detection RE signal and the LO RE signal). The SF mixer 130 outputs a mixed SF signal which is based on a combination of the two electrical signals provided to it. In particular, the mixed SF signal will include a first component at a difference frequency (the difference between the two input frequencies) and a sum frequency (the sum of the two input frequencies). The mixed SF signal is output through the third port 133 of the SF mixer 130 (the output port).

The mixed SF signal will provide an indication of a phase offset between the detection SF signal and the LO RE signal. Due to the time taken for modulated light to travel from the first light source 101 to the detector 124 through the subject's brain tissue 110, the indication of the amplitude modulation scheme of the first light source 101, as evident in the light received at the detector 124, may vary in its temporal offset from the LO RE signal. As such, there may be a difference in phase between the detection RE signal and the LO RE signal, and this difference in phase may vary depending on the time of flight of photon's through the subject's brain (this difference in phase may also vary according to the difference between the two frequencies, but this varying phase difference will be known, as the two input frequencies will be known). This phase difference will be evident in the mixed SF signal. This difference in phase will correspond to the delay brought about by the travel of photons from the source to the detector 124. The extent and/or variation of the phase difference will therefore provide an indication of the extent of the distance travelled by the photons.

To provide neuroimaging and/or analysis, the controller 150 will measure the phase difference, as evident in the mixed SF signal. In particular, the controller 150 will measure the phase difference as present in the component of the difference frequency present in the mixed SF signal. For example, a low pass filter may be used to extract this component. The controller 150 will determine a time of flight for the light travelling from the source to the detector 124 via the subject's brain based on this phase offset. The time of flight is then used to determine a penetration depth. This time of flight/penetration depth information is then compared to known values for light emitted from the source to identify whether this time of flight/penetration depth corresponds to an event occurring in the subject's brain tissue 110, or whether it corresponds to expected scattering in the absence of any events occurring.

This penetration depth/time of flight information is monitored over time (e.g. continuously). In the event that any change in penetration depth/time of flight occurs (as evident in a change of phase difference in the mixed RF signal), then this may indicate that an event has occurred, or has stopped occurring. For example, a change in phase information (for a small time period) may indicate that an event has occurred. Typically, if the phase information suggests a decreased time of flight/penetration depth, this may suggest that an event has occurred somewhere in the brain tissue 110 closer to the light source 101 than the usual penetration depth (and that this event has caused the change in scattering to occur). Using the time of flight/penetration depth information obtained from the phase information in the mixed RF signal, it may de determined the location of the event in the brain tissue 110. Imaging of this event may be provided based on this information and/or an analysis of this event occurring may be performed (e.g. information about this event may be determined based on a comparison with previous data indicating what an event of that nature/at that depth signifies).

Some alternative and/or additional features of EROS systems of the present disclosure will now be described with reference to Fig. 2.

Fig. 2 shows an EROS system 100. As with the EROS system 100 shown in Fig. 1, the EROS system 100 of Fig. 2 includes a first light source 101, and Fig. 2 also shows a subject's brain tissue 110. Likewise, the EROS system 100 of Fig. 2 also includes light detection circuitry 120 which includes a light detector 124, as well as an analogue radiofrequency mixer 130 having a first port 131, a second port 132, and a third port 133. As with Fig. 1, the EROS system 100 of Fig. 2 also includes a first local oscillator 141 and a controller 150.

Additionally, the EROS system 100 of Fig. 2 further includes a second light source 102, a first light source switch 106 and a second light source switch 107. The light detection circuitry 120 of the EROS system 100 of Fig. 2 also includes a lens 122 and a pre-amplifier 126. The EROS system 100 of Fig. 2 also includes a second local oscillator 142 and an oscillator switch 146. Also included is a band pass filter switch 166, along with a first band pass filter 161, a second band pass filter 162 and a signal amplifier 170.

The features of Fig. 2 which have previously been described with reference to Fig. 1 will not be described, but it is to be appreciated that the description of these features above also applies here.

The second light source 102 may also be located adjacent to the subject's scalp, but in a different location to the first light source 101. For example, the second light source 102 may be arranged so that light detected at the detector 124 from the second light source 102 may enable additional information about activity in the subject's brain tissue 110 to be obtained (as compared to the information obtain by using light from the first light source 101 alone). The second light source 102 may be functionally similar to the first light source 101, but the combination of light sources may enable additional information to be obtained. For example, the second light source 102 may be configured to emit light at a selected wavelength and apply a selected amplitude modulation scheme to the light. The selected wavelength for the second light may be the same as the selected wavelength of the first light, or it may be different. The selected amplitude modulation scheme for the second light source 102 may be the same as that applied to light from the first light source 101, or it may be different, e.g. the two may have different modulation frequencies.

The system 100 may be arranged to control which of the light sources is emitting modulated light towards the subject's brain. For example, only one light source may be operated at a time, or both may be operated simultaneously, but at different wavelengths and/or modulation frequencies. The first and second light source switches 106, 107 are shown to illustrate this functionality. For example, the switches 106, 107 may be configured to control whether their respective light source emits light. Each switch 106, 107 may comprise a cover for blocking, or filtering, light emitted from that light source (e.g. so that the light sources may be left on during operation, but that light only travels to the subject's brain tissue 110 during certain windows, as controlled by the switches 106, 107).

The lens or other optical light coupling system 122 may be arranged between the subject's scalp and the light detector 124. The lens 122 may be arranged to focus light from a plurality of different regions and/or directions towards the detection surface of the detector 124. The lens 122 may enable the light detector 124 to receive more incident light from the subject's brain tissue 110.

The pre-amplifier 126 may be arranged to provide amplification of an output signal from the light detector 124. For example, the pre-amplifier 126 may be arranged to receive an output signal from the light detector 124 and to amplify this output signal to provide the detection RF signal.

The second LO 142 may also be operable to provide an LO RF signal to the first port 131 of the RF mixer 130. The second LO 142 may be functionally similar to the first LO 141, but the inclusion of the second LO 142 may improve the performance of the RF mixing. For example, the second LO 142 may be configured to output a second LO RF signal which is at a different frequency to that of the first LO RF signal.

The first LO 141 may be configured to output the first LO RF signal at a frequency which is similar, but not identical, to a modulation frequency of the light output from the first light source 101. The second LO 142 may be configured to output the second LO RF signal at a frequency which is similar, but not identical, to a modulation frequency of the light output from the second light source 102. For example, if the first and second light sources output light at a different frequency to one another, then the system 100 may switch between the first and second LO 142, so that the LO RF signal input to the RF mixer 130 is the one which corresponds to the light source whose light is intended to be measured. The system 100 may be configured to select which LO RF signal to use based on an expected frequency of the detection RF signal, e.g. so that the difference frequency in the mixed RF signal is at a lower frequency. For example, the LO RF signal input may be chosen so that the RF mixer 130 outputs a mixed RF signal frequency with the lowest difference frequency available. This may be particularly advantageous where the frequency of the first light source 101 differs substantially from the frequency of the second light source 102.

The oscillator switch 146 is shown to illustrate functionality for controlling which of the LOs provides the input signal to the first port 131 of the RF mixer 130. As with the light source switches 106, 107 described above, the oscillator switch 146 may comprise a switch operable to selectively direct the output from only one of the LOs to the RF mixer 130 (e.g. so that both [Os may remain on while only one is used to provide the LO RF signal input).

The LO RF input signal to the mixer 130 may be selected to correspond to which of the light sources is active, or is intended to be measured. The [Os may be controlled so that the LO RF signal applied to the RF mixer 130 at any one time is that which will enable a relevant phase offset to be measured.

In other words, where it is expected that the detector 124 will be receiving incident light primarily from the first light source 101, which carries with it an indication of the amplitude modulation scheme applied by the first light source 101, the first LO 141 may be used, as it provides the first LO RF input signal at the frequency closest to the modulation frequency applied by the first light source. Where it is expected that the detector 124 will be receiving incident light primarily from the second light source 102, which carries with it an indication of the amplitude modulation scheme applied by the second light source 102, the second LO 142 may be used, as it provides the second LO RF input signal at the frequency closest to the modulation frequency applied by the second light source.

The system 100 may provide time multiplexing for the operation of the light sources and the [Os.

The first light source 101 may be operated to direct modulated light to the subject's brain tissue 110 for a first time period (while light is not directed from the second light source 102 to the subject's brain tissue 110). During this first time period, the first LO 141 is selected to provide the LO RF signal input to the RF mixer 130 (where the first LO RF signal input is selected to operate in combination with the first light source 101 output). Then, the second light source 102 may be operated to direct modulated light to the subject's brain tissue 110 for a second time period (while light is not directed from the first light source 101 to the subject's brain tissue 110). During this first time period, the second LO 142 is selected to provide the LO RF signal input to the RF mixer 130 (where the second LO RF signal input is selected to operate in combination with the second light source 102 output). In this manner, the LO RF signal input provided to the RF mixer 130 at any one time may be the one at a frequency closest to the modulation frequency evident in the detection RF signal (so that the resulting intermediate frequency is lower).

As disclosed herein, processing circuitry may comprise one or more band pass filters configured to remove components from the mixed RF signal at certain frequencies. For example, a low-pass filter may be provided to remove higher frequency components from the mixed RF signal. In particular, a low-pass filter may be used to remove frequencies above a selected value, where that selected value is greater than the difference frequency, e.g. so that signal processing and analysing of measured signals can be based on lower frequency components in the signal (i.e. the difference frequency). In the example shown in Fig. 2, two band pass filters are shown. The two band pass filters may have different filtering frequencies, e.g. they may filter at different frequencies. Also shown in Fig. 2 is the band pass filter switch 166 which is configured to selectively apply the mixed RF signal to one of the two band pass filters. The switch 166 may be configured to select which band pass filter is used based on expected frequencies for components in the mixed RF signal and/or based on which of the first/second light source is being used/which of the first/second LO is used to provide the LO RF signal.

The system 100 may be configured to control which of the band pass filters to apply. The first band pass filter 161 may perform a low pass filter to a first frequency, and the second band pass filter 162 may perform a low pass filter to a second frequency which is higher than the first frequency. The system 100 may be configured so that in the event that the intermediate frequency of interest is likely to be below the first frequency, then the first band pass filter 161 is used, and/or if the frequency of interest is likely to be above the first frequency but below the second frequency, then the second band pass filter 162 is used.

The system 100 may be configured to use the one or more bandpass filters to filter (e.g. to low pass filter) the mixed RF signal from the RF mixer 130 to provide a filtered RF signal. The system 100 of Fig. 2 also shows the signal amplifier 170. The signal amplifier 170 may be configured to receive a signal and to amplify that signal. For example, if one or more band pass filters are used to provide a filtered RF signal, then the signal amplifier 170 is configured to amplify the filtered RF signal. Alternatively, where no band pass filters are provided, the signal amplifier 170 is configured to amplify the mixed RF signal. It will be appreciated that both the band pass filters, the band pass switch 166 and the signal amplifier 170 are optional. The controller 150 may be configured to perform neuroimaging and analysis based on the mixed RF signal, the filtered RF and the amplified RF signal, as relevant.

In some examples of the present disclosure, such as where multiple light sources are provided and operated at the same time, the detection RF signal may comprise components at different frequencies (e.g. according to different modulation schemes applied by different light sources). In such cases, the mixed RF signal may also comprise an indication of a plurality of difference frequencies. The controller 150 may be configured to perform a discrete Fourier analysis of the mixed RF signal to identify the different constituent frequencies, such as using a Fast Fourier Transform ('FFT') algorithm. For example, where different frequencies in the detection RF signal are separated by more than approximately 100 Hz, the different resulting peaks may be identified using the discrete Fourier analysis. Alternatively, or in addition, the band pass filters may be configured to filter above or below a selected frequency or frequency range (e.g. if one band pass filter is applied, frequencies above the selected frequency will pass, but it the other band pass filter is used, frequencies below the selected frequency will pass). For example, the system 100 may be configured to process mixed RF signals which comprise components indicative of multiple difference frequencies. The system 100 may be configured to select which LO RF signal is input to the RF mixer 130 based on an expected frequency for the signal which is intended to be measured (e.g. to provide as lower difference frequency as possible).

It will be appreciated from the discussion above that the examples shown in the figures are merely exemplary, and include features which may be generalised, removed or replaced as described herein and as set out in the claims. With reference to the drawings in general, it will be appreciated that schematic functional block diagrams are used to indicate functionality of systems and apparatus described herein. In addition, the processing functionality may also be provided by devices which are supported by an electronic device. It will be appreciated however that the functionality need not be divided in this way, and should not be taken to imply any particular structure of hardware other than that described and claimed below. The function of one or more of the elements shown in the drawings may be further subdivided, and/or distributed throughout apparatus of the disclosure. In some examples the function of one or more elements shown in the drawings may be integrated into a single functional unit.

As will be appreciated by the skilled reader in the context of the present disclosure, each of the examples described herein may be implemented in a variety of different ways. Any feature of any aspects of the disclosure may be combined with any of the other aspects of the disclosure. For example method aspects may be combined with apparatus aspects, and features described with reference to the operation of particular elements of apparatus may be provided in methods which do not use those particular types of apparatus. In addition, each of the features of each of the examples is intended to be separable from the features which it is described in combination with, unless it is expressly stated that some other feature is essential to its operation. Each of these separable features may of course be combined with any of the other features of the examples in which it is described, or with any of the other features or combination of features of any of the other examples described herein. Furthermore, equivalents and modifications not described above may also be employed without departing from the invention.

Certain features of the methods described herein may be implemented in hardware, and one or more functions of the apparatus may be implemented in method steps. It will also be appreciated in the context of the present disclosure that 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 drawings. Accordingly, aspects of the disclosure which are described with reference to products or apparatus are also intended to be implemented as methods and vice versa. The methods described herein may be implemented in computer programs, or in hardware or in any combination thereof. Computer programs include software, middleware, firmware, and any combination thereof. Such programs may be provided as signals or network messages and may be recorded on computer readable media such as tangible computer readable media which may store the computer programs in non-transitory form. Hardware includes computers, handheld devices, programmable processors, general purpose processors, application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), and arrays of logic gates.

Any controller described herein may be provided by any control apparatus such as a general purpose processor configured with a computer program product configured to program the processor to operate according to any one of the methods described herein. In addition, the functionality of the controller may be provided by an application specific integrated circuit, ASIC, or by a field programmable gate array, FPGA, or by a configuration of logic gates, or by any other control apparatus.

Other examples and variations of the disclosure will be apparent to the skilled addressee in the

context of the present disclosure.

Claims

Claims 1. An event related optical signal, EROS, neuroimaging and analysis system for monitoring activity of a subject's brain, the system comprising: one or more light sources each configured to emit modulated light; light detection circuitry comprising a light detector, the light detection circuitry configured to output a detection radio frequency, RF, signal based on light incident on a detection surface of the detector; an analogue SF mixer having: a first port connected to one or more local oscillators, LOs, to receive one or more LO electrical SF signals therefrom; (ii) a second port connected to the light detection circuitry to receive the detection RE signal therefrom, wherein the analogue SF mixer is configured to mix the LO SF signal and the detection SF signal to obtain a mixed SF signal, and the analogue RE mixer further comprises (iii) a third port configured to output the mixed SF signal; and wherein the system further comprises a controller configured to provide neuroimaging and analysis based on a phase of the mixed SF signal.
2. The EROS system of claim 1, wherein the analogue RE mixer is configured to mix the LO SF signal and the detection SF signal so that the mixed SF signal comprises: (i) a first component corresponding to a difference frequency for the LO SF and detection RE signals input to the analogue RE mixer, and (ii) a second component corresponding to the sum frequency for the LO RE and detection SF signals input to the analogue SF mixer.
3. The EROS system of claim 2, wherein the analogue RE mixer is configured to suppress, in the mixed SF signal, the LO SF and detection SF signals input to the analogue SF mixer.
4. The EROS system of claim 3, wherein the SF mixer is configured to suppress, in the mixed SF signal, even order products of the LO SF and detection SF signals input to the analogue SF mixer.
5. The EROS system of any of claims 3 or 4, wherein the SF mixer comprises a diode ring and one or more switches.
6. The EROS system of claim 2, or any claim dependent thereon, wherein the controller is configured to provide neuroimaging and analysis based on the phase of the first component of the mixed RF signal.
7. The EROS system of claim 2, or any claim dependent thereon, wherein the system further comprises signal processing circuitry configured to perform a low-pass filter of the mixed RF signal to provide a filtered RF signal in which the second component of the mixed RF signal has been removed, for example wherein the system comprises an amplifier configured to provide amplification to the filtered RF signal..
8. The EROS system of claim 7, wherein the controller is configured to provide the neuroimaging and analysis based on the phase of the first component as present in the filtered RF signal.
9. The EROS system of any preceding claim, wherein the one or more LOs are configured to provide the LO RF signal input to the analogue RF mixer at a first LO RF frequency, wherein the first LO RF frequency is selected based on an expected frequency for the detection RF signal input to the analogue RF mixer.
10. The EROS system of claim 9, wherein the expected frequency for the detection RF signal input to the analogue RF mixer comprises a frequency of the amplitude modulation scheme applied at the first light source.
11. The EROS system of claim 9 or claim 10, wherein the one or more LOs are selectively operable to provide the LO RF signal input to the analogue RF mixer at one of a plurality of different frequencies; and wherein the controller is configured to select which of the plurality of different frequencies is used for the LO RF signal input to the RF analogue mixer based on the expected frequency for the detection RE signal input to the RF analogue mixer.
12. The EROS system of claim 11, wherein the controller is configured to select the frequency for the LO RF signal input to the RF analogue mixer to be the closest of the plurality of frequencies to the expected frequency.
13. The EROS system of any of claims 11 or 12, wherein the one or more light sources are selectively operable to emit modulated light at one of a plurality of different frequencies; and wherein the system is configured to control operation of the one or more LOs so that the frequency of the LO RF signal input to the analogue RF mixer is selected based on the frequency of modulated light emitted from the one or more light sources.
14. The EROS system of claim 13, wherein the system is configured to provide time multiplexing of both: (i) the frequency of the light emitted from the one or more light sources, and (ii) the frequency of the LO RF signal input to the analogue RF mixer.
15. The EROS system of claim 14, wherein the system is configured to operate so that: (i) in a first time window, the frequency of the LO RE signal input to the analogue RF mixer is selected to correspond to a modulation frequency of light emitted by the one or more light sources, and (ii) in a second time window in which a modulation frequency of light emitted by the one or more light sources is different to that in the first window, the frequency of the LO RF signal input to the analogue RF mixer is selected to correspond to the modulation frequency of the light emitted by the one or more light sources and is different to that in the first time window.
16. The EROS system of claim 15, wherein the LOs are controlled so that, in each time window, the frequency of the LO RF input to the analogue RF mixer is selected to be the closest of the plurality of LO RF input frequencies to the modulation frequency of light emitted in that time period.
17. The EROS system of any preceding claim, wherein the light detection circuitry comprises a pre-amplifier configured to provide amplification to RF signals output from the detector to provide the detection RF signal.
18. The EROS system of any preceding claim, wherein the one or more LOs comprise: (i) a first LO configured to provide a first LO RF signal input frequency, and (ii) a second LO configured to provide a second LO RF signal input frequency different to the first LO RF signal input frequency.
19. The EROS system of claim 9, or any claim dependent thereon, wherein the one or more LOs are selected to be operable to provide an LO RF signal input frequency of within 1 MHz of the expected frequency.
20. The EROS system of any preceding claim, wherein the system is configured to control the one or more light sources to first emit light at one wavelength and to then emit light at a different wavelength.
21. The EROS system of any preceding claim wherein the system comprises a head support configured to be placed onto the subject's head so that the one or more light sources and the light detector are arranged adjacent to the subject's head.
22. A method of event related optical signal, EROS, neuroimaging an analysis for monitoring activity of a subject's brain, the method comprising: arranging both: (i) one or more light sources, and (ii) light detection circuitry adjacent to a subject's head; emitting modulated light from the one or more light sources through the subject's head; using the light detection circuitry to output a detection RF signal based on light incident on a detection surface of a detector of the light detection circuitry; performing analogue radiofrequency mixing of the detection RF signal with a local oscillator, LO, RF signal to provide a mixed RF signal; and providing neuroimaging and analysis based on a phase of the mixed RF signal.
23. The method of claim 22, wherein providing neuroimaging and analysis based on a phase of the mixed RF signal comprises providing neuroimaging and analysis based on a phase of a first component of the mixed RF signal, wherein said first component corresponds to a difference frequency for: (i) the LO RF signal input for the RF mixing, and (ii) the detection RF signal input for the RF mixing.
24. The method of claim 23, further comprising performing a low-pass filter of the mixed RF signal to provide a filtered RF signal in which a second component of the mixed RF signal has been removed, wherein said second component corresponds to a sum frequency for: (i) the LO RF signal input for the RF mixing, and (h) the detection RF signal input for the RF mixing, for example wherein the method comprises providing the neuroimaging and analysis based on the phase of the first component as present in the filtered RF signal.
25. A computer program product comprising computer program instructions configured to program a controller to perform the method of any of claims 22 to 24.