Patent Description:
Plethysmography, be it pneumatic-based or optics-based, is a measurement technique commonly used to monitor changes in blood volume in the macrovascular and the microvascular system of an individual and, more specifically, to monitor changes in the blood volume comprised in the arteries or arterioles. The changes in the arterial blood volume are further affected by the contractions of the muscular walls of the arteries or arterioles. Monitoring the changes in the arterial blood volume with plethysmography therefore empirically provides information on relative changes in muscle tension or 'tone' of the smooth muscle tissue of the arterioles, also referred to as peripheral arterial tone, PAT.

Optical plethysmography or photoplethysmography measures the arterial blood volume changes by shining light from one or more light sources, such as LEDs, onto an investigated volume and by detecting collected light corresponding to the light being reflected or transmitted in the investigated volume on a sensor, wherein the sensor may, for example, comprise or correspond to a photodetector, such as for example a photodiode. The light sources and the sensor form the so-called plethysmography probe and can for example be arranged on opposite sides of the investigated volume, e.g., a finger, a nostril, an ear, a forehead, the inside of a mouth, a toe, a wrist, an ankle, etc., of an individual, hereby allowing the measurement of a transmission mode photo-plethysmogram, PPG, or at the same side of the investigated volume, hereby allowing the measurement of a reflectance mode PPG. Irrespective of the employed measurement technique, both the transmission mode PPG and the reflectance mode PPG capture the cyclic fluctuations of arterial blood volume in the investigated volume and, thus, changes in the peripheral arterial tone of the individual.

Because arterial blood flow to the investigated volume can be modulated by multiple other physiological phenomena such as breathing and heart rate, plethysmography can also be used for monitoring respiratory and circulatory conditions, hypovolemia, and even for detecting sleep-disturbing events leading to or caused by sleep disorders. Sleep disorder diagnosis is a medical field wherein a patient's sleep is monitored during a certain time, e.g., one or more nights. Based on the monitoring, different sleep-related or, better, sleep-disturbing events may be identified such as apneic events, snoring, limb movements, or others. For example, the reuptake of breathing at the end of a sleep apnea event usually coincides with a norepinephrine release. Norepinephrine is released in the bloodstream and binds to adrenergic receptors in the arterioles in the investigated volume, which triggers an increase in muscle tension of the arterioles resulting in a reduction of the arteriole diameter and a reduction of arterial blood volume in the investigated volume. Monitoring peripheral arterial tone, PAT, through plethysmography, for example, can therefore provide valuable information on the occurrence of these sleep-disturbing events such as, for example, sleep apnea. This observation is widely reported in the last century and explained in detail in the scientific publication entitled "<NPL>, where the authors describe that the Pulse PlethysmoGraphic Amplitude, or PPGA, of the photoplethysmograph is due to pulsatile changes in tissue volume, mainly arterial blood and that during sympathetic activation, or vasoconstriction, the PPGA decreases.

However, due to the effect of gravity, when some part of the body is situated below heart level, a hydrostatic pressure gradient is automatically generated. Hydrostatic pressure gradients affect the venous system, an innately low-pressure system, causing venous distention also known as venous blood pooling. Venous pooling can invoke a reflex constrictory response in the arteries supplying blood to the veins, thus imposing an additional physiological change that can obscure the desired arterial vasomotor response which is investigated by the plethysmography. This reflex is commonly referred to as venoarteriolar reflex or VAR and is described in detail in PART A of the whitepaper "<NPL> et al. To solve this problem, <CIT> proposes a plethysmography probe capable of completely covering the surface of the distal end of the finger and providing a uniform pressure field that extends all the way to the terminal end of the finger. <CIT> proposes a probe with an internal membrane and an external membrane with the inner membrane that applies a predetermined static pressure to the body part and the outer membrane that assures the predetermined static pressure applied by the inner membrane is substantially unaffected by volume changes of the body part. The external counter-pressure exerted by the outer membrane, thus, is claimed to reduce venous blood pooling and distension within the measurement site and is claimed to reduce distal venous pooling. This is claimed to reduce the likelihood of the induction of venoarteriolar reflex vasoconstriction, which can otherwise lead to the development of an indeterminate degree of vasoconstriction. The prior art, therefore, describes a complex and costly probe for providing a uniform pressure probe to reduce issues related to an indeterminate degree of vasoconstriction.

It is an object of embodiments of the present disclosure to provide a solution capable of detecting sleep-disturbing events leading to or caused by sleep disorders overcoming the shortcomings on the conventional solutions, and, more specifically, to provide a solution capable of detecting sleep-disturbing events including sleep disorders in an accurate and robust way based on physiological information acquired by means of conventional, off-the-shelf medical equipment. It is a further object of embodiments of the present disclosure to provide a solution capable of detecting sleep-disturbing events including sleep disorders in an accurate and robust way based on a signal indicative of the peripheral tone of an individual acquired by conventional, off-the-shelf medical equipment such as plethysmography probes not providing uniform pressure.

These objects are achieved, according to a first example aspect of the present disclosure, by a computer-implemented method for detecting sleep-disturbing events as defined by claim <NUM>. In particular, the computer-implemented method is capable of detecting sleep-disturbing events from a signal indicative of a peripheral arterial tone, PAT, of an individual affected by a venoarteriolar reflex, VAR. The signal may be obtained by conventional, off-the-shelf medical equipment, as long as the obtained signal provides information indicative of the PAT and the effects on the signal caused by the venoarteriolar reflex, VAR. Examples of such medical equipment include standard probes employing pneumatic-plethysmography or photo-plethysmography, PPG, probes capable of obtaining a PAT signal affected by VAR. The method, thus, comprises processing that signal obtained from the PPG probe to derive therefrom sleep-disturbing events. More specifically, the method comprises determining one or more vasoconstriction events from changes in the signal. The method further comprises deriving a reference amplitude value and a baseline amplitude value for the determined vasoconstriction event. The reference amplitude value and the baseline amplitude value are different from each other. The reference and baseline amplitude values correspond to the amplitude values of characteristics points in the signal for the vasoconstriction event which allow characterization of the vasoconstriction event. The obtained reference and baseline amplitude values are then related to each other to obtain a measure indicative of the magnitude of the vasoconstriction event, i.e., a magnitude measure characterizing the intensity or significance of the vasoconstriction event and, therefore, the intensity or significance of the observed physiological event. Once the magnitude of the detected physiological event is obtained, the method proceeds to detect, therefrom, a sleep-disturbing event. Relating the reference amplitude value to a baseline amplitude value allows for adequately reducing the effects of more slowly varying, i.e., steady-state changes, observed in the signal. Steady-state changes are effects observed in the signal that are varying at a slower rate than the changes of the signal resulting from the vasoconstriction events. As detailed above, such steady-state changes may, for example, be caused by a venoarteriolar reflex. In other words, the reference and baseline amplitude values are related to each other such that the steady-changes in the signal are taken into account and, thus, the venoarteriolar reflex, when determining the magnitude of a vasoconstriction event. Doing so assures a correct assessment of the magnitude of the vasoconstriction events and, in turn, correct detection and characterization of the sleep-disturbing events, therefrom. As a result, false positive and false negative detection of sleep-disturbing events is substantially eliminated.

The reference and baseline amplitude values for the vasoconstriction event are preferably derived from a baseline-invariant version of the signal. This baseline-invariant signal may be calculated specifically for the vasoconstriction event or for the complete signal. That is, a partial baseline-invariant signal for the vasoconstriction event or a baseline-invariant signal for the complete signal can be calculated. From the baseline-invariant signal, the reference amplitude value and the baseline value for the vasoconstriction event are then selected. As detailed above, the reference and baseline amplitude values correspond to the amplitude values of characteristics points in the signal for the vasoconstriction event which allow characterization of the vasoconstriction event. The selection of the reference and baseline amplitude values is thus preferably done in a way that allows the calculation of the magnitude measure for the vasoconstriction event.

The baseline-invariant signal is preferably calculated by dividing the obtained signal with a baseline. The dividing can be performed with respect to the portion of the signal corresponding to the vasoconstriction event or the complete signal. In the first case, the baseline-invariant signal for the vasoconstriction event is calculated by dividing the portion of the signal corresponding to the vasoconstriction event with the baseline for the event. The baseline is a baseline level which may be a baseline value or a signal portion for the corresponding vasoconstriction event. In the second case, the baseline-invariant signal is obtained by dividing the complete signal with a baseline for the complete signal. Herein, the baseline is a baseline signal. Doing so results in removing the venoarteriolar reflex effect on the arterial tone for at least the vasoconstriction event, thus assuring correct assessment of the magnitude of the vasoconstriction events and therefore a correct detection and characterization of the sleep-disturbing events. The reference amplitude value and baseline amplitude value are then be derived from the baseline-invariant signal. For example, the maximum amplitude value observed in the portion of the baseline-invariant signal corresponding to the vasoconstriction event can be selected as the reference amplitude value and the mean amplitude value observed in the portion of the baseline-invariant signal corresponding to the vasoconstriction event can be selected as the baseline amplitude value.

The thus selected reference amplitude value and baseline amplitude value are related to each other to obtain the magnitude measure for the vasoconstriction event. Preferably, the reference amplitude value is related to the baseline amplitude value by calculating, from the reference amplitude value and the baseline amplitude value, an absolute magnitude for the vasoconstriction event. As the reference and the baseline amplitude values are selected from the baseline-invariant version of the signal, the magnitude for the vasoconstriction event can be derived, for example, as the difference between them. The thus calculated magnitude measure is an absolute value that allows quantifying the intensity of the vasoconstriction event on an absolute scale.

The baseline for the vasoconstriction event is preferably derived by calculating an envelope of the signal. Calculating the envelope of the signal allows extracting the venoarteriolar reflex observed in the signal. In other words, the calculated signal's envelope characterizes the venoarteriolar reflex throughout the complete signal. A peak envelope, a troughs envelope, a peak-to-troughs average envelope, a percentile value-based envelope, or a smoothed version of the signal can, for example, be calculated and used as the envelope of the signal. Alternatively, instead of calculating the envelope of the complete signal, an amplitude value for the vasoconstriction event may be calculated which can be used as a baseline for the vasoconstriction event. For example, a peak amplitude, a through amplitude, a peak-to-trough average amplitude, or a percentile value for the vasoconstriction event can be calculated and used as the baseline for the vasoconstriction event.

Alternatively, the reference amplitude value and the baseline amplitude value for the vasoconstriction event can be directly derived from the obtained signal. This can be done by, for example, calculating a peak amplitude, a through amplitude, a peak-to-trough average amplitude, or a percentile value for the vasoconstriction event directly from the obtained signal. These amplitude values may serve as a baseline amplitude value or a reference amplitude value for the vasoconstriction event as long as the baseline and reference amplitude values are selected to differ from one another. For example, the peak amplitude for the vasoconstriction event can be selected as the reference amplitude value and any of other amplitude values characterizing the vasoconstriction event, i.e., through amplitude, peak-to-though average amplitude, or average amplitude, as the baseline amplitude value.

The thus selected reference amplitude value and baseline amplitude values are then related to each other to obtain the magnitude measure for the vasoconstriction event. Preferably, the reference amplitude value is related to the baseline amplitude value by calculating, from the reference amplitude value and the baseline amplitude value for the vasoconstriction event, a relative magnitude for the vasoconstriction event. The relative magnitude for the vasoconstriction event can be derived, for example, as their relative difference or relative change or any other substantially relative magnitude measure. The, thus calculated magnitude measure is a relative value that allows quantifying the intensity of the vasoconstriction event on a relative scale.

The detecting of the sleep-disturbing event preferably comprises identifying a vasoconstriction event characterized by a magnitude measure above a pre-determined value. In other words, vasoconstriction events with a certain magnitude measure are considered as sleep disturbing events. The pre-determined value can be determined based on, for example, measurements obtained during clinical trials. It is preferred that the step of detecting sleep-disturbing events includes using a classifier trained or developed for said detecting. Any conventional classifier, such as a neural network, a decision tree, or a support vector machine, may be trained.

Preferably, the step of identifying further takes into account at least one of a duration of the vasoconstriction event, a duration of an amplitude drop period and/or a duration amplitude rise period of the vasoconstriction event, steepness of the amplitude drop period, and/or steepness of the amplitude rise period of the vasoconstriction event. The duration of the vasoconstriction event, the duration of the amplitude drop period, and/or the duration of the amplitude rise period are additional measures that can be used to improve the quantification of the intensity of the vasoconstriction event. Similarly, the steepness of the amplitude drop and/or the steepness of the amplitude rise are other additional measures that can be also used to improve the quantification of the intensity of the vasoconstriction event. Taking any of these additional measures in combination with the magnitude measure allows quantification of the intensity of the vasoconstriction event in terms of various signal properties and, thus, improving the detection of the sleep-disturbing events and as well as their better characterization.

The determining of a vasoconstriction event preferably comprises identifying a portion of the signal characterized by an amplitude drop followed by an amplitude increase. In other words, to identify vasoconstriction events, the method searches for changes in the signal characterized by an amplitude drop followed by an amplitude increase. The determining can be performed by any suitable for the purpose signal processing technique.

Preferably, the determining further takes into account at least one of a duration of the amplitude drop period and the amplitude rise period of the signal portion, a duration of an amplitude drop period and/or a duration amplitude rise period of the signal portion, steepness of the amplitude drop period, and/or steepness of the amplitude rise period of the signal portion. Taking into account the duration of the amplitude drop and/or rise period, and the steepness of these respective periods allows quantification of the amplitude in terms of various signal properties and, thus, improving the determination of vasoconstriction events from the obtained signal.

The signal indicative of the peripheral arterial tone of the individual affected by a venoarteriolar reflex is preferably obtained by means of plethysmography. Plethysmography allows to obtain a signal, i.e., a plethysmography signal or plethysmogram, which is indicative of the changes in blood volume such as pulsatile blood volume changes, at a selected anatomical location of the patient, for example, a finger, a nostril, an ear, a forehead, the inside of a mouth, a toe, a wrist, an ankle, etc. A plethysmography signal can be obtained by so-called plethysmography probes which can employ pneumatic-based or optics-based plethysmography. As this plethysmography signal empirically provides information on relative changes in the muscle tension or 'tone' of the muscle tissue of the arterioles as well as information on the venoarteriolar reflex, the plethysmography signal allows deriving, therefrom, the signal indicative of changes in peripheral arterial tone which is affected by a venoarteriolar reflex.

Preferably, the signal indicative of the peripheral arterial tone is derived from an optical plethysmography signal measured at an investigated volume of the individual and light intensities acquired by means of optical plethysmography at two or more points in time along the optical plethysmography signal. Therefrom, changes in arterial blood volume in the investigated volume between the two or more points in time are derived by determining a logarithm or a function approximation thereof of a function of the light intensities, thereby assessing the peripheral arterial tone, PAT, of the individual. The logarithm or the function approximation of the function of the light intensities is herein referred to as an evaluation function. Preferably, this evaluation function corresponds to the logarithm of the ratio of the light intensities and the evaluation function depends on one or more of the following: an optical path length; a function of the oxygen saturation estimate or SpO2; and the changes in arterial blood volume in the investigated volume. Preferably, at least one of the points in time corresponds to the diastole in a cardiac cycle of the individual and/or wherein at least one of the points in time corresponds to the systole in a cardiac cycle of the individual.

According to a second example aspect, an apparatus configured to detect sleep-disturbing events from a signal indicative of a peripheral arterial tone of an individual affected by a venoarteriolar reflex is disclosed characterized by the features of claim <NUM>. The apparatus comprises at least one processor and at least one memory including computer program code, where the at least one memory and computer program code are configured to, with the at least one processor, cause the apparatus to perform the steps of the first example aspect. Such an apparatus can thus provide one or more of the advantages mentioned with respect to the first example aspect.

According to a third example aspect, a system is disclosed comprising the apparatus according to the second example aspect. Preferably, the system further comprises a plethysmography probe. Preferably, the plethysmography probe is an optical plethysmography probe which comprises a light source configured to emit light and a sensor configured to collect by optical plethysmography propagated light corresponding to the light being transmitted or reflected when propagating in the investigated volume of the individual at the two or more points in time. The sensor is further configured to determine the light intensities of the propagated light at the two or more points in time. Optionally, the probe is further provided with an accelerometer to detect the position of the investigated volume. Optionally, the system can further comprise a wireless transmitter comprising a wireless communication interface, wherein the wireless transmitter is configured to transmit the determined peripheral arterial tone wirelessly for further processing by the apparatus. The wireless communication interface is preferably a low-power communication interface, e.g., a Bluetooth Low Energy, BLE, wireless interface. Such a system can thus provide one or more of the advantages with respect to the first example aspect.

According to a fourth example aspect, a use of a logarithm or a function approximation thereof for assessing a signal indicative of the peripheral arterial tone, PAT, of an individual monitored by optical plethysmography, is provided, wherein assessing the signal indicative of the peripheral arterial tone comprises: obtaining an optical plethysmography signal measured at an investigated volume of the individual and light intensities acquired by optical plethysmography at two or more points in time along the optical plethysmography signal; and determining changes in arterial blood volume in the investigated volume between the two or more points in time by determining a logarithm or a function approximation thereof of a function of the light intensities, thereby assessing PAT of the individual. The use of the logarithm or the function approximation allows obtaining a signal indicative of the PAT of an individual based on light intensities measured by means of optical plethysmography.

According to a fifth example aspect, a computer program product is disclosed comprising computer-executable instructions for causing a computer to perform the method according to the first example aspect.

According to a sixth example aspect, a computer readable storage medium is disclosed comprising computer-executable instructions for causing a computer to perform the method according to the first example aspect.

Such a computer program product and a computer readable storage medium can provide one or more of the advantages with respect to the first example aspect.

The present disclosure generally relates, amongst others, to a method and an apparatus for assessing a signal indicative of the peripheral arterial tone, PAT, of an individual for detecting sleep-related or, better, sleep-disturbing events. More particularly, the assessment of the signal is performed in such a way as to ensure substantial invariance to any steady-state changes observed in the signal, which may for example be caused by physiological phenomena such as a venoarteriolar reflex, thus ensuring accurate and robust detection of the sleep-disturbing events.

In the context of the present disclosure, an investigated volume of an individual is for example a volume defined in an investigated tissue of the individual which is monitored by pneumatic-based or optics-based plethysmography. Optical plethysmography is a measurement technique in which emitted light is collected on a sensor by optical plethysmography. In other words, an investigated volume of an individual is for example a volume defined in an investigated tissue of the individual for which an optical plethysmography signal is acquired. For example, the investigated volume is a peripheral tissue volume of the individual. For example, the investigated volume is a volume defined in finger, a tip of a finger, a distal end of a digit of the individual, a nostril, an ear, a forehead, the inside of a mouth, a toe, a tip of a toe, a wrist, an ankle of the individual. In the context of the present disclosure, the investigated volume of an individual comprises the skin of the individual comprised in the investigated volume and further comprises the blood volume present in the investigated volume.

In the context of the present disclosure, arterial blood volume is to be understood as the arterial blood volume in the investigated volume. In the context of the present disclosure, peripheral arterial tone or PAT is understood as arterial tone changes in investigated arterial beds in the investigated volume of an individual. In other words, determining pulsatile volume changes in the vascular beds of the investigated volume of the individual allows determining or assessing information indicative for muscle tension or 'tone' of the smooth muscle tissue of the arterioles in the investigated volume and therefore allows determining or assessing peripheral arterial tone which is modulated by the sympathetic nervous system. Determining peripheral arterial tone is non-invasive and can for example be used to detect heart diseases, erectile dysfunction, sleep apnea, obstructive sleep apnea, cardiovascular conditions, etc..

In the context of the present disclosure, an optical plethysmography signal is a signal measured by optical plethysmography. For example, the optical plethysmography signal is an optical plethysmogram. For example, the optical plethysmography signal is a PPG signal. The optical plethysmography signal is for example measured at the tip of a finger of the individual by an optical plethysmography setup comprising at least one light source and a sensor. In the context of the present disclosure, a light intensity corresponds to the intensity of light collected on the sensor of the optical plethysmography setup, wherein the light collected on the sensor corresponds to light generated by one or more light sources being transmitted through or reflected in the investigated volume of the individual.

In the context of the present disclosure, the oxygen saturation estimate or SpO2 or hemoglobin composition corresponds to a fraction of oxygenated hemoglobin related to a total amount of hemoglobin in the arterial blood volume in the investigated volume. For example, the oxygen saturation estimate or SpO2 or hemoglobin composition corresponds to a ratio of the concentration of oxygenated hemoglobin on the sum of the concentrations of oxygenated and deoxygenated hemoglobin in the arterial blood volume being monitored in the investigated volume. Alternatively, the oxygen saturation estimate or SpO2 or hemoglobin composition corresponds to a ratio of the volume fraction of oxygenated hemoglobin on the sum of the volume fractions of oxygenated and deoxygenated hemoglobin in the arterial blood volume being monitored in the investigated volume.

In the context of the present disclosure, deoxygenated hemoglobin is defined as the form of hemoglobin without the bound oxygen, and without any other bound molecule such as for example carbon monoxide, carbon dioxide, or iron. In the context of the present disclosure, oxygenated hemoglobin is defined as the form of hemoglobin with the bound oxygen. In the context of the present disclosure, light emitted by the light sources of an optical plethysmography setup comprises photons that reach the sensor through a probabilistic path of one or multiple scattering events. This optical path is not straight and is often assumed to follow a curved spatial probability distribution. The investigated volume along this curved optical path forms the volume which is sampled or investigated by optical plethysmography.

In the context of the present disclosure, one or more changes in arterial blood volume in the investigated volume between the two or more points in time are evaluated, thus assessing PAT of the individual. In the context of the present disclosure, a change in arterial blood volume in the investigated volume between two points in time corresponds to a relative change between the volume of arterial blood present in the investigated volume at a first point in time and the volume of arterial blood present in the investigated volume at a second point in time different from the first point in time.

In the context of the present disclosure, a chromophore is a molecular unit that absorbs or scatters light in the investigated volume. For example, in the context of the present disclosure, examples of chromophores are melanin molecules, oxygenated hemoglobin, deoxygenated hemoglobin, etc. In the investigated volume, the decay in light intensity of the incident light emitted by a light source of an optical plethysmography setup follows the Beer-Lambert law which can be formulated as in equation (<NUM>): <MAT> wherein:.

the Beer-Lambert law as formulated in Equation (<NUM>) can be evaluated at the first point in time and at the second point in time. When taking a ratio of both expressions, Equation (<NUM>) is obtained: <MAT>.

Then, Equation (<NUM>) is obtained by taking the natural logarithm of both sides of equation (<NUM>), as follows: <MAT>.

If a logarithm with another base b that Euler's number e is used, Equation (<NUM>) then becomes: <MAT>.

It can be seen that Equation (<NUM>') is equal to Equation (<NUM>) up to the constant <MAT>.

Equation (<NUM>) can be simplified to Equation (<NUM>) when the difference Vi,s - Vi,d is being renamed to ΔVi, thereby obtaining: <MAT>.

From Equation (<NUM>), it can be seen that the logarithm of the fraction of light intensities at the first point in time and at the second point in time is linearly related to the difference in either volume fraction or concentration of chromophore i between the first point in time and the second point in time.

Some chromophores remain attached to the epidermis of the individual between the two points in time along the optical plethysmography signal. For example, melanin molecules remain fixed to the investigated volume between the two points in time along the optical plethysmography signal. The difference in either volume fraction or concentration of such chromophores, such as for example melanin molecules, between the two points in time is therefore null. Hence, the contribution to the righthand side of Equation (<NUM>) of such chromophores is also null.

The main chromophores of which either the volume fraction or the concentration fluctuates between the two points in time along the optical plethysmography signal are the oxygenated and deoxygenated hemoglobin in the arterial blood volume. The two predominant forms of hemoglobin in the context of the present disclosure, i.e. oxygenated hemoglobin and deoxygenated hemoglobin, demonstrate absorption and scattering coefficients which are significantly different for most wavelengths of light.

The effect of all other chromophores, wherein all other chromophores are not oxygenated hemoglobin nor deoxygenated hemoglobin, of which either the volume fraction or the concentration fluctuates between the two points in time along the optical plethysmography signal can be written as the product of their combined extinction coefficient, εother, and one minus the sum of either the volume fractions or the concentrations of oxygenated hemoglobin and deoxygenated hemoglobin, wherein the sum of either all volume fractions or all concentrations equals <NUM>.

Taking the above considerations into account, Equation (<NUM>) can then be rewritten as follows into Equation (<NUM>): <MAT>.

It is known that the oxygen saturation estimate can be defined according to Equation (<NUM>): <MAT> wherein:.

Additionally, Vblood is defined as the total volume fraction or the total concentration of oxygenated and deoxygenated hemoglobin comprised within the arterial blood in the investigated volume and is defined as follows in Equation (<NUM>): <MAT>.

It is assumed that under normal circumstances, the sum of the volume fractions or the concentrations of oxygenated and deoxygenated hemoglobin within the arterial blood volume or the sum of the concentrations of oxygenated and deoxygenated hemoglobin within the arterial blood volume remains approximately constant throughout the measurement of the optical plethysmography signal. Indeed, only the ratio of oxygenated hemoglobin and deoxygenated hemoglobin, i.e., only the oxygen saturation estimate, might significantly change during the monitoring of the individual by optical plethysmography, for example during sleep apnea.

From Equation (<NUM>) and (<NUM>), the following can be obtained: <MAT>.

By substituting expression (<NUM>) into Equation (<NUM>), the following can be obtained: <MAT>.

Two predetermined calibration coefficients Q<NUM> and Q<NUM>, which are two constants, can be defined as follows:
<MAT>.

After rewriting Equation (<NUM>) in view of the two predetermined calibration coefficients Q<NUM> and Q<NUM>, Equation (<NUM>) can be obtained, wherein the left-hand side of Equation (<NUM>) corresponds to an evaluation function, and wherein Q<NUM>SpO<NUM> +Q<NUM> corresponds to a compensation function which is a function of the oxygen saturation estimate: <MAT>.

Equation (<NUM>) highlights a term on the left-hand side, referred to as the evaluation function, which shows a linear relationship with:.

Under the assumption of a constant volume fraction or concentration of the sum of oxygenated and deoxygenated hemoglobin in the arterial blood, ΔVbood is a linear proxy for arterial blood volume fluctuations within the investigated volume, and hence corresponds to a measurement of peripheral arterial tone.

For a constant value of the oxygen saturation estimate, i.e., SpO<NUM> = const, a change in arterial blood volume in the investigated volume between two points in time is thus evaluated when determining the logarithm of the ratio of the light intensities collected on the sensor when measuring with optical plethysmography at said two points in time. Mathematically, this can be represented as <MAT>.

As only a linear relationship between a measurable parameter and ΔVblood is relevant to investigate relative changes in ΔVblood rather than the exact ΔVbood value, determination of ΔVbood up to a constant factor is sufficient, as is performed by determining the evaluation function.

If the SpO<NUM> is not constant, the evaluation function will also change with changes in SpO<NUM>. However, compensation methods can be used to compensate for the effect of changes in SpO<NUM>. For example, one can determine a compensation function fλ<NUM>, in which case Equation (<NUM>) can be re-written as: <MAT>.

As a result, the PATchannel is a signal indicative of the peripheral arterial tone of the investigated volume of the individual. The PATchannel signal is thus a signal which can be obtained from the light intensities measured with optical plethysmography and the optical plethysmography signal by determining a logarithm or a function approximation thereof of a function of the light intensities which may be optionally divided by a function which depends on the SpO2, where the function of the light intensities corresponds to a ratio of the light intensities.

According to Equation (<NUM>), the evaluation function corresponds to the natural logarithm of a function of the light intensities. Alternatively, starting from Equation (<NUM>), any other evaluation function defined as a function of the light intensities could be used, for example, a linear approximation of the logarithm of a function of the light intensities, or for example a Taylor series approximation of a function of the light intensities, or for example a linear approximation of other base logarithms of a function of the light intensities. Alternatively, the evaluation function corresponds approximately to the ratio of the pulsatile waveform or AC component of the optical plethysmography signal and of the slowly varying baseline or DC component of the optical plethysmography signal, resulting in equation (<NUM>): <MAT>.

The evaluation function thus corresponds to a logarithm of a ratio of the light intensities; and the evaluation function depends on one or more of the following:.

Further, at least one of the points in time corresponds to the diastole in a cardiac cycle of the individual and/or wherein at least one of the points in time corresponds to the systole in a cardiac cycle of the individual.

During systole, the volume of arterial blood in the investigated volume of the individual is maximum, resulting in the largest absorption and scattering of light of any point in time within a cardiac cycle, i.e., the period between two heart beats, since hemoglobin is one of the main absorbers and scatters of photons in the investigated volume, hence resulting in the lowest measured light intensity on the sensor of the optical plethysmography setup. Conversely, during diastole, the volume of arterial blood in the investigated volume of the individual is minimum, resulting in the lowest absorption and scattering of light of any point in time within a cardiac cycle and hence highest measured light intensity on the sensor of the optical plethysmography setup. At least one first point in time corresponds for example to the diastole in a first cardiac cycle and/or at least one second point in time corresponds for example to the systole in a second cardiac cycle different from the first cardiac cycle. Alternatively, at least one first point in time corresponds for example to the systole in a first cardiac cycle and/or at least one second point in time corresponds for example to the diastole in a second cardiac cycle different from the first cardiac cycle. Alternatively, at least one first point in time corresponds for example to the systole or to the diastole in a cardiac cycle and at least one second point in time corresponds to any point in time within the same cardiac cycle or within a different cardiac cycle.

As mentioned above the light intensities can be obtained by means of optical plethysmography by:.

Optical plethysmography technology uses a simple and non-invasive setup probe or biosensor. The optical plethysmography biosensor non-invasively measures pulsatile volume changes in the investigated volume, and thereby assesses PAT, by collecting the optical plethysmography signal. The light source is for example a LED or any other suitable light source which can be miniaturized to fit in the optical plethysmography biosensor. The wavelength is for example comprised in the red spectrum. Alternatively, the wavelength is comprised in the infra-red spectrum. A physical distance between the light sources and the sensor is for example a few millimeters, such as for example less than <NUM>.

The assessment of the signal indicative of the peripheral arterial tone, PAT, of an individual for detecting sleep-disturbing events will be now described in detail with reference to figures.

<FIG> shows a simplified block scheme of a system according to an example embodiment of the present disclosure. The system <NUM> comprises a device <NUM> configured to measure fluctuations in arterial blood volume of an investigated volume of an individual by means of optical plethysmography and an apparatus <NUM> configured to obtain the light intensities measured by the device <NUM> and to process the obtained light intensities to detect, therefrom, sleep-disturbing events <NUM>. The device <NUM> is for example placed on the finger of an individual. The device <NUM> thus measures the light intensity of the light propagated through the finger of the individual over time. As detailed above and illustrated in Equation (<NUM>) for example, the measured light intensities reflect the fluctuations in the arterial blood volume of the individual. Further, as detailed above and illustrated in Equations (<NUM>) and (<NUM>), the measured light intensities empirically provide information on the peripheral arterial tone of the individual. The device <NUM> thus outputs light intensities <NUM> measured over time reflecting the peripheral arterial tone of the individual. The measured light intensities are fed to the apparatus <NUM>. The apparatus <NUM> comprises at least one processor and at least one memory configured to store algorithms to operate the apparatus stored in the form of software or program instructions in the at least one memory. In addition to storing the software, the at least one memory may further store any data generated by the apparatus and any other data required for its proper operation. This data may however be stored in another memory external to the apparatus. The at least one processor can execute the program instructions stored in the at least one memory and thus controls the operation of the apparatus. Otherwise said, in an embodiment, the apparatus <NUM> comprises a computing system that comprises hardware and software components for processing the obtained measured light intensities <NUM> and for determining therefrom sleep-disturbing events <NUM>.

<FIG> shows various steps performed by the apparatus <NUM> to detect sleep-disturbing events <NUM>. In the first step, i.e., step <NUM>, the peripheral arterial tone signal, i.e., the PATchannel signal, is derived from the obtained light intensities and the measured optical plethysmography signal as detailed above and illustrated in Equations (<NUM>) and (<NUM>). Summarized, the apparatus <NUM> obtains the light intensities <NUM> acquired over time by the device <NUM> by means of optical plethysmography, for example, at two or more points in time. From the obtained light intensities <NUM> the apparatus <NUM> then determines the changes in arterial blood volume in the investigated volume between the two or more points in time. This is done by determining a logarithm or a function approximation thereof of a function of the light intensities which may be optionally divided by a function that depends on the SpO2. The result is the PATchannel signal of the individual as illustrated in Equations (<NUM>) and (<NUM>).

In the next step, i.e., step <NUM>, vasoconstriction events are determined from the PATchannel signal. As detailed above, vasoconstriction events are characterized by fluctuation in the PATchannel signal's amplitude. More specifically, a vasoconstriction event in the PATchannel signal is characterized with an amplitude drop followed by an amplitude increase. Vasoconstriction events in the PATchannel signal may be determined by means of any suitable for the purpose signal processing algorithms. Summarized, in this step, the PATchannel signal is segmented into event segments characterized by a drop, followed by an increase in the signal's amplitude. Each of these event segments reflects a vasoconstriction, i.e., constriction of the arteries in the investigated volume. In other words, the event segments correspond to the vasoconstriction events observed in the PATchannel signal. These vasoconstriction events may for example be related to sleep-disturbing events such as a respiratory event such as apnea or hypopnea, respiratory-related-arousal event or RERA event, periodic or non-periodic limb movement, bruxism event, or snore.

<FIG> shows an example of the signal indicative of the peripheral arterial tone, PAT, of the individual with highlighted episodes of sudden arterial tone changes characterized by amplitude decreases followed by amplitude increases. As it can be seen, each of the detected event segments is characterized with an amplitude drop followed by an amplitude increase. The figure further shows that the fluctuations in the peripheral arterial tone of the respective event segments somewhat correlate to the fluctuations in oxygen saturation estimate and the SpO2 of the individual.

In the next step, i.e., step <NUM>, the apparatus proceeds to characterize the respective event segments, i.e., the vasoconstriction events, in terms of characterizing features. The characterizing features comprise features such as for example: a magnitude of the event segment, i.e., the difference between the minimum and maximum amplitude values of the event segment; a duration of the event segment; a duration of the amplitude drop period and/or a duration of the amplitude rise period of the event segment; a steepness of the amplitude drop period and/or a steepness of the amplitude rise period of the event segment; the full width at half maximum of the event segment; and so on. The characterizing features of the respective event segments, however, need to be calculated so that the effect of the VAR episode on the amplitude in the event segments is substantially reduced.

To do so, the apparatus calculates in step <NUM> a baseline-invariant version of the PATchannel signal, i.e., a baseline-invariant signal. The baseline-invariant signal can be derived by relating the amplitude of the PATchannel signal to a baseline level, for example, by dividing the PATchannel signal by:.

In case the baseline signal is any one of the smoothed signals mentioned above, it is important to ensure that the time-variation, for example, characterized by a time constant, of the smoothed signal is slow enough such that the resulting smoothed signal does not follow the shape of the event segment to such extent that the event segment's or PATchannel signal division by this smoothed signal results in a baseline-invariant signal with significant loss of information pertaining to the morphology of the original event segment. In other words, the fluctuations in the derived baseline-invariant signal caused by the peripheral arterial tone should be substantially preserved while the fluctuations caused by the VAR episode should be substantially reduced.

<FIG> shows an example of the signal indicative of the peripheral arterial tone, PAT, of the individual affected by a VAR episode caused by venous blood pooling triggered by the lowering of the arm of the finger at which the optical plethysmography, PPG, signal is measured below the heart level, and highlights how the PAT channel amplitude is depressed during the VAR. More specifically, the top two plots show how the amplitude of the PPG signal <NUM> and the amplitude of its filtered and normalized version <NUM> become depressed during the VAR episode. The third plot shows how the amplitude of the PAT channel <NUM> derived as illustrated in Equations (<NUM>) or (<NUM>) drops during the VAR episode. The fourth plot shows how dividing each sample of the PAT channel by a baseline value results in a baseline-invariant version of the PAT channel <NUM> for which the effect of the VAR amplitude modulation is substantially eliminated. From the figure, it can be seen that the amplitude variations caused by the peripheral arterial tone in the event segments 110_1 to 110_3 and 110_n in the original PAT channel <NUM> and the baseline-invariant version of the PAT channel <NUM> are preserved while the amplitude modulation caused by the VAR episode is substantially eliminated in the baseline-invariant version of the PAT channel <NUM>.

<FIG> illustrates a detailed view of the effect of dividing each sample of the PATchannel signal <NUM> with the samples of the extracted peak envelope <NUM>, throughs envelope, peaks-throughs average envelope, and a smoothed version of the PATchannel signal. The peak or troughs envelope corresponds to the local maxima and local minima amplitude values in the PATchannel signal, while the peak-troughs average envelope corresponds to the mean of the peak and troughs envelope. As it can be seen, the baseline-invariant signal <NUM> resulting from dividing the samples of the original PATchannel signal <NUM> with the upper or lower amplitude, the mean of the upper and lower amplitude, or the amplitude of the smoothed version of the signal substantially eliminates the amplitude depression caused by the VAR, while it maintains the integrity of the morphology and the relative amplitude variations of the respective event segments.

Once a baseline-invariant signal is calculated, the apparatus proceeds to characterize the event segments. To do so, the apparatus derives various features characterizing the event segments from the baseline-invariant version of the signal. The characterizing features comprise features such as for example: a maximum and/or a minimum amplitude of the event segment, a magnitude of the event segment; a median and/or a mean amplitude of the event segment; a quartile amplitude of the event segment; a duration of the vasoconstriction event; a duration of the amplitude drop period; a duration of the amplitude rise period of the vasoconstriction event; a steepness of the amplitude drop period; a steepness of the amplitude rise period of the vasoconstriction event; the full width at half maximum of the event segment, and so on.

To derive these features, the apparatus calculates in step <NUM> various characteristics points from the portion of the baseline-invariant signal corresponding to the event segment. The characteristic points are described in terms of amplitude and/or time. For example, characteristics points could be the sample of the event segment with the maximum amplitude value, the sample of the event segment with a minimum amplitude value, the first and last samples of the event segment, and so on.

The apparatus then uses the information obtained from the derived characteristic points to derive the various features characterising the event segment. To do so, in step <NUM>, the apparatus relates the obtained information to derive the various features. For example, the magnitude of the event segment can be calculated as the difference between the maximum and the minimum amplitude values observed in the event segment. In other words, the magnitude of the amplitude drop of the event segment can be calculated as the difference between the amplitude value of the first sample or the sample with the maximum amplitude value and the amplitude value of the sample with the minimum amplitude value. Typically, the first sample coincides or substantially coincides with the sample with the maximum amplitude value. Herein, the first sample or the sample with maximum amplitude value acts as a reference point, while the sample with minimum amplitude value acts as a baseline point, and their respective amplitude values as a reference amplitude value and a baseline amplitude value. The duration of the event segment can be calculated as the difference in time between the first and the last samples of the event segment. The steepness of the amplitude drop of the event segment can be calculated as the ratio of the amplitude difference and the time difference of the first sample or the sample with the maximum amplitude value and the sample with the minimum amplitude value, and so on.

<FIG> shows an example of event segment <NUM> of the baseline-invariant signal <NUM> illustrating various characteristic points allowing the calculation of various features characterizing the event segment. In this example, the reference amplitude value and the baseline amplitude values correspond to the signal's samples <NUM> and <NUM> with a maximum and minimum amplitude values, respectively. The duration <NUM> of the event segment is identified by the samples <NUM> and <NUM> corresponding to the first and the last samples in the event segment. The amplitude drop portion of the event segment and the amplitude rise portion of the event segment correspond to the slopes <NUM> and <NUM> with respective duration <NUM> and <NUM>. In this example, the steepness of the amplitude drop is simplistically illustrated as the absolute magnitude <NUM> of the amplitude drop. Similarly, the steepness of the amplitude rise period is herein illustrated as the absolute magnitude between the samples <NUM> and <NUM>.

Alternatively, the features characterising the event segment on an absolute scale can be derived by relating the amplitude of the signal portion corresponding to the event segment to a baseline level. For example, this can be done by dividing PATchannel signal portion corresponding to an event segment, by a baseline level for the event segment. For example, the baseline level for the event segment can be:.

As can be seen from this list, the baseline level for the event segments can be a baseline value or a baseline signal. <FIG> illustrates an example of possible baseline values for two event segments which can be used to relate the amplitude of the event segment to a baseline level, e.g., by dividing the portion of the PATchannel signal by the baseline level corresponding to the event segment. In this figure, each event segment is indicated by a pair of dashed lines. The amplitude values indicating the maximum amplitude value, the minimum amplitude value, the mean amplitude value, the median amplitude value, as well as the lower quartile amplitude value, Iqr, and the amplitude values at the maximum and the minimum slope of the event segments, are illustrated.

Dividing the portion of the PATchannel signal corresponding to the event segment by the baseline amplitude value for the event segment results in obtaining a baseline-invariant portion for the respective event segment. Thus, the output in step <NUM> is the baseline-invariant signal portion for the respective event segments. Once the baseline-invariant signal portions for the respective event segments are calculated, the apparatus proceeds to perform step <NUM> and step <NUM> as described above to derive the characteristics features for the respective events. That is, in step <NUM> the apparatus derives various characteristic points from the respective baseline-invariant signal portions corresponding to the respective event segments. Then, in step <NUM>, the apparatus uses the information obtained from the characteristic points for the respective event segments to derive the various features characterising the respective event segments in the same manner as described above. For example, the magnitude of the event segment can be calculated as the difference between the maximum and the minimum amplitude values. The magnitude of the amplitude drop of the event segment can be calculated as the difference between the amplitude value of the first sample or the sample with the maximum amplitude value and the amplitude value of the sample with the minimum amplitude value, and so on.

Alternatively, any magnitude-related characteristic features such as features calculated using one or more amplitude values of the signal portion corresponding to the event segment can be obtained on a relative scale rather than on an absolute scale. In this case, step <NUM> is omitted and the apparatus derives the various characteristics features from the original, unmodified PATchannel signal <NUM> as shown in the third plot of <FIG>. In this case, to correct for the amplitude fluctuations caused by the VAR episode, the characteristics features affected by the VAR such as the magnitude and the steepness features, are calculated on a relative scale. To do so, the characteristic amplitude points for the event segment such as the peak amplitude, the trough amplitude, the peak-to-trough average amplitude, or the percentile value are derived as detailed above with reference to <FIG>. Differently from above, herein, the magnitude of the event segment is derived by, for example, calculating a relative difference between the reference and baseline amplitude values. Similarly, other amplitude-related features characterising the event segment which are derived based on one or more amplitude values derived from the signal portion corresponding to the event segment such as the steepness features can be derived on a relative scale.

The output of step <NUM> is, thus, one or more features characterizing the event segments by means of at least a magnitude measure characterizing the intensity of the event segment, and, possibly, one or more additional features such as a duration of the event segment, a duration of the amplitude drop period of the event segment; a duration of the amplitude rise period of the event segment, a steepness of the amplitude drop period of the event segment, a steepness of the amplitude rise period of the event segment, and a full width at half maximum of the event segment.

In the last step of the method, i.e., step <NUM>, the method proceeds to detect sleep-disturbing events <NUM> based on the determined one or more features characterizing the vasoconstriction events. A sleep-disturbing event can be detected for example based on at least the magnitude measure of the vasoconstriction event. If the magnitude measure is above a predetermined threshold value, the vasoconstriction event is considered to be a sleep-disturbing event. In addition to the magnitude measure, other features characterizing the vasoconstriction event can be also taken into account. These additional features can further characterize the vasoconstriction event in terms of its morphological profile. A morphological profile may for example be linked to the shape of the vasoconstriction event. For example, at least one or a combination of the duration of the event segment, the duration of the amplitude drop period of the event segment; a duration of the amplitude rise period of the event segment, a steepness of the amplitude drop period of the event segment, a steepness of the amplitude rise period of the event segment, and a full width at half maximum of the event segment may be further taken into account. In such a case, a parameterized cost function can be evaluated which takes the considered features into account to evaluate whether a vasoconstriction event is a sleep-disturbing event.

This step of detecting sleep-disturbing events can be implemented by means of a classifier that has been developed to perform the step for detecting a sleep-disturbing event. The classifier thus implements the parameterized cost function by designing and inputting a set of rules for the detection. These rules can, as detailed above, be based on threshold values for the respective one or more features or for a respective combination of features that examine how well the features of an event comply with the criteria defined by the rules. The threshold values for the respective features can for example be derived based on measurements obtained during a clinical trial. From these measurements, first sleep-disturbing events are identified by means of manual or computer-aided scoring and then threshold values for the respective features are determined from the identified sleep-disturbing events. Further, the features can be ordered according to their accuracy in detecting a certain sleep-disturbing event, and then one or more most optimal features can be selected for the detection of a respective sleep-disturbing event. Using only the most optimal features for the detection of the sleep-disturbing events allows simplifying the classifier implementation without sacrificing detection accuracy. The thus developed classifier can then evaluate the parameterized cost function implementing these rules to determine whether an event is a sleep-disturbing event or not.

The apparatus <NUM> can further provide an indication of certain medical conditions and physiological states based upon the concurrence of sleep-disturbing events characterized with specific features. For example, by analyzing the concurrence of vasoconstriction events with certain features such as a certain minimum event duration and a certain minimum distance between the minimum and maximum sample value, i.e., the duration of the amplitude drop of the event, and/or features observed in other physiological signals, such as an increase in pulse rate or heart rate and/or a decrease in blood oxygen saturation and/or a limb movement during the event. The limb movement can be voluntary or involuntary movement and can for example be picked up by an accelerometer. This concurrence of the sleep-disturbing events and the additional physiological features can further aid the medical personnel in determining certain medical conditions and physiological states of the individual.

<FIG> illustrates an example of a respiratory event, in this example an apnea event. As it can be seen from the figure, the end-stage of the apnea event coincides with a decrease in the PATchannel signal amplitude and/or an increase in pulse rate, PR, and/or a decrease in SpO<NUM>.

As described above, the present solution can improve the accuracy of determining various characterizing features from the physiological signal indicative of the peripheral arterial tone and, thus, can improve the accuracy of detecting sleep-disturbing events from such a physiological signal. Further, as described above, the method can provide an indication of the concurrence of the sleep-disturbing events and, possibly, features observed in other physiological signals to provide additional information which can aid the medical personnel in determining certain medical conditions and physiological states of the individual.

Furthermore, although the above-presented observations and methodology are described with respect to optical plethysmography, the skilled person will recognize that the same observations and methodology can be readily applied to a physiological signal obtained by means of pneumatic plethysmography.

<FIG> shows a suitable computing system <NUM> enabling to implement embodiments of the method for detecting sleep-disturbing events according to the invention. Computing system <NUM> may, in general, be formed as a suitable general-purpose computer and comprise a bus <NUM>, a processor <NUM>, a local memory <NUM>, one or more optional input interfaces <NUM>, one or more optional output interfaces <NUM>, a communication interface <NUM>, a storage element interface <NUM>, and one or more storage elements <NUM>. Bus <NUM> may comprise one or more conductors that permit communication among the components of the computing system <NUM>. Processor <NUM> may include any type of conventional processor or microprocessor that interprets and executes programming instructions. Local memory <NUM> may include a random-access memory, RAM, or another type of dynamic storage device that stores information and instructions for execution by processor <NUM> and/or a read-only memory, ROM, or another type of static storage device that stores static information and instructions for use by processor <NUM>. The processor may thus execute the instructions stored in the local memory to perform various steps of the method described above. Input interface <NUM> may comprise one or more conventional mechanisms that permit an operator or user to input information to the computing device <NUM>, such as a keyboard <NUM>, a mouse <NUM>, a pen, voice recognition, etc. and/or one or more PPG sensors. Output interface <NUM> may comprise one or more conventional mechanisms that output information to the operator or user, such as a display <NUM>, etc. Communication interface <NUM> may comprise any transceiver-like mechanism such as for example one or more Ethernet interfaces that enables computing system <NUM> to communicate with other devices and/or systems, for example with other computing devices <NUM>, <NUM>, <NUM>. The processing of the signal obtained from the one or more PPG sensors may thus be processed remotely by the other computing devices. The communication interface <NUM> of computing system <NUM> may be connected to such another computing system by means of a local area network, LAN, or a wide area network, WAN, such as for example the internet. Storage element interface <NUM> may comprise a storage interface such as for example a Serial Advanced Technology Attachment, SATA, interface or a Small Computer System Interface, SCSI, for connecting bus <NUM> to one or more storage elements <NUM>, such as one or more local disks, for example, SATA disk drives, and control the reading and writing of data to and/or from these storage elements <NUM>. Although the storage element(s) <NUM> above is/are described as a local disk, in general, any other suitable computer-readable media such as a removable magnetic disk, optical storage media such as a CD or DVD, -ROM disk, solid state drives, flash memory cards,. could be used. Computing system <NUM> could thus correspond to a circuitry for processing the signal obtained from one or more PPG sensors to detect, therefrom, sleep-disturbing events as described above with reference to <FIG>.

The term circuitry also covers, for example, and if applicable to the particular claim element, a baseband integrated circuit or processor integrated circuit for a mobile device or a similar integrated circuit in a server, a cellular network device, or other computing or network device.

Claim 1:
A computer-implemented method for detecting sleep-disturbing events from a signal (<NUM>) indicative of a peripheral arterial tone of an individual, the signal being affected by a venoarteriolar reflex, the method comprises:
- determining (<NUM>) a vasoconstriction event (<NUM>, 110_1 - 110_n) from changes in the signal (<NUM>, <NUM>);
- deriving (<NUM>) a reference amplitude value (<NUM>) and a baseline amplitude value (<NUM>) for the vasoconstriction event (<NUM>, 110_1 - 110_n), the reference amplitude value being different from the baseline amplitude value;
- relating (<NUM>) the reference amplitude value (<NUM>) for the vasoconstriction event to the baseline amplitude value (<NUM>) for the vasoconstriction event, thereby obtaining a magnitude measure (<NUM>) for the vasoconstriction event; and
- detecting (<NUM>), therefrom, a sleep-disturbing event.