The present invention relates generally to physiological monitoring and diagnosis, and specifically to sleep recording and analysis.
Human sleep is generally described as a succession of five recurring stages (plus waking, which is sometimes classified as a sixth stage). Sleep stages are typically monitored using a polysomnograph to collect physiological signals from the sleeping subject, including brain waves (EEG), eye movements (EOG), muscle activity (EMG), heartbeat (ECG), blood oxygen levels (SpO2) and respiration. The commonly-recognized stages include:
Although sleep staging is most often performed by a human operator, who reads and scores the polysomnogram, there are also methods known in the art for computerized sleep staging. Penzel et al review such methods in “Computer Based Sleep Recording and Analysis,” Sleep Medicine Reviews 4:2 (2000), pages 131-148, which is incorporated herein by reference.
Although sleep staging is widely accepted as the standard method for diagnosis and classification of sleep disorders, this method provides only coarse resolution and fails to exploit the wealth of information in the polysomnogram signals. The inventors have found many cases in which traditional sleep stage analysis fails to uncover underlying sleep pathologies. In response to the shortcomings of conventional methods, the inventors have developed a family of sleep quality indicators, which assist the diagnostician in recognizing sleep-related disorders.
In some embodiments of the present invention, a sleep analysis system acquires physiological signals, such as EEG signals, during sleep, and adaptively segments the signals to identify quasi-stationary segments. The system automatically analyzes each segment to determine the relative energy in each of a number of frequency bands, and thus assigns the segments to different frequency states. Typically, the states are defined for each patient by fuzzy clustering of features extracted from each segments; and each segment is assigned a degree of membership with respect to each of the states. Based on the fuzzy clustering and membership levels, the system determines and displays sleep quality indicators relating to the distribution of the segments among the clusters.
In some embodiments, the system displays the results of the analysis so that changes in the distribution of states over time, in the course of a period of sleep, can be readily visualized by a caregiver, such as a medical sleep specialist. Additionally or alternatively, the system may display characteristic patterns of transition between different states.
Further additionally or alternatively, the system may calculate the fundamental frequency of each segment, typically expressed as the moment of the EEG power spectrum. The fundamental frequency is then displayed so as to enable the caregiver to visualize changes in the trend and standard deviation of the fundamental frequency, which are indicative of continuous changes in the patient's sleep quality.
Although the embodiments described herein relate mainly to analysis and visualization of EEG signals, the principles of the present invention may similarly be applied to polysomnogram signals of other types, such as respiration and ECG signals.
There is therefore provided, in accordance with an embodiment of the present invention, a method for diagnosis, including:
acquiring a physiological signal from a patient during a period of sleep;
segmenting the signal to define a time sequence of quasi-stationary segments, each of the segments having a respective frequency spectrum;
computing respective levels of membership of the segments in a plurality of frequency states responsively to the respective frequency spectrum; and
displaying a plot indicative of the levels of membership of the segments in the sequence over time.
In disclosed embodiments, computing the respective levels includes applying fuzzy clustering to the segments so as to define the states.
In one embodiment, displaying the plot includes displaying a density plot, in which the levels of membership are represented by color variations. In another embodiment, displaying the plot includes displaying an accumulation plot, showing cumulative levels of membership of the segments in the plurality of frequency states over the sequence. In yet another embodiment, displaying the plot includes displaying an accumulation plot showing cumulative durations of the segments in each of the plurality of frequency states. Typically, the method includes determining and comparing respective accumulation rates of the cumulative durations in at least two of the frequency states.
In some embodiments, displaying the plot includes assigning each of at least some of the segments to one of a waking state and a sleep state responsively to the frequency spectrum, and displaying an accumulation plot showing a cumulative assignment of the segments to the waking and sleep states over time.
There is also provided, in accordance with an embodiment of the present invention, a method for diagnosis, including:
acquiring a physiological signal from a patient during a period of sleep;
segmenting the signal to define a time sequence of quasi-stationary segments, each of the segments having a respective frequency spectrum;
computing a fundamental frequency of each segment in the time sequence responsively to a moment of the respective frequency spectrum of the segment; and
displaying a plot showing the fundamental frequency of the segments in the sequence over time.
Displaying the plot may include showing at least one of a trend and a variance of the fundamental frequency.
There is additionally provided, in accordance with an embodiment of the present invention, a method for diagnosis, including:
acquiring a physiological signal from a patient during a period of sleep;
segmenting the signal to define a time sequence of quasi-stationary segments, each of the segments having a respective frequency spectrum;
computing respective levels of membership of the segments in a plurality of frequency states responsively to the respective frequency spectrum;
based on the respective levels of membership, determining a sleep quality indicator responsively to a statistical characteristic of the segments; and
displaying the sleep quality indicator.
In disclosed embodiments, the statistical characteristic includes at least one of:
a cumulative duration of the segments associated with each of the frequency clusters;
a relative duration of the segments associated with each of the frequency clusters;
a mean duration of the segments associated with each of the frequency clusters;
a variance of a duration of the segments associated with each of the frequency clusters;
a total number of the segments associated with each of the frequency clusters; and
a relative duration of the segments associated with each of the frequency clusters.
In some embodiments, the method includes assigning the segments to predefined sleep stages responsively to the frequency spectrum, and determining the sleep quality indicator includes computing the statistical characteristic with respect to each of the sleep stages.
In one embodiment, displaying the sleep quality indicator includes displaying a plot indicative of the levels of membership of the segments in the sequence over time. In another embodiment, displaying the sleep quality indicator includes displaying a plot showing a fundamental frequency of the segments in the sequence over time. In yet another embodiment, computing the respective levels of membership includes assigning the segments in the time sequence to respective frequency states, and determining the sleep quality indicator includes computing probabilities of transition among the frequency states.
In some embodiments, the physiological signal includes an electroencephalogram (EEG) signal. Optionally, the method includes identifying transient phenomena in the EEG signal, and computing an index quantifying a frequency of occurrence of the transient phenomena. The transient phenomena may include one or more of K-complexes and spindles.
Additionally or alternatively, the physiological signal may include a respiration signal. In one embodiment, the method includes identifying respiratory events occurring during the period of sleep, and computing statistical characteristics of the respiratory events. Typically, computing the statistical characteristics includes computing and displaying a respiratory event histogram.
In another embodiment, the method includes measuring a heart rate of the patient, and computing the statistical characteristics includes computing a relative heart rate index indicative of changes in the heart rate associated with the respiratory events.
In yet another embodiment, computing the statistical characteristics includes assigning respective confidence levels to the respiratory events, and displaying the confidence levels as a function of respiration state.
There is further provided, in accordance with an embodiment of the present invention, a method for diagnosis, including:
acquiring a physiological signal from a patient during a period of sleep;
segmenting the signal to define a time sequence of quasi-stationary segments, each of the segments having a respective frequency spectrum;
computing respective levels of membership of the segments in a plurality of frequency states responsively to the respective frequency spectrum;
responsively to the respective levels of membership, assigning each of at least some of the segments to one of a waking state and a sleep state responsively to the frequency spectrum; and
displaying an accumulation plot showing a cumulative assignment of the segments to the waking and sleep states over time.
The method may include determining and comparing respective accumulation rates of the waking and sleep states.
There is moreover provided, in accordance with an embodiment of the present invention, diagnostic apparatus, including a sensor, which is adapted to acquire a physiological signal from a patient during a period of sleep, and a diagnostic processor, which is adapted to carry out the functions described above. In some embodiments, the sensor includes at least one electrode, and the physiological signal includes an electroencephalogram (EEG) signal. Additionally or alternatively, the sensor may include a respiration sensor and/or a heart rate sensor.
There is furthermore provided, in accordance with an embodiment of the present invention, a computer software product, including a computer-readable medium in which program instructions are stored, which instructions, when read by a computer, cause the computer to carry out the functions described above.
The present invention will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings in which:
The signals from electrodes 23, 24 and sensor 26 are collected, amplified and digitized by a console 28. Console 28 may process and analyze the signals locally, using the methods described hereinbelow. Alternatively or additionally, console 28 may be coupled to communicate over a network 30, such as a telephone network or the Internet, with a diagnostic processor 32. This configuration permits sleep studies to be performed simultaneously in multiple different locations. Processor 32 typically comprises a general-purpose computer with suitable software for carrying out the functions described herein. This software may be downloaded to processor 32 in electronic form, or it may alternatively be provided on tangible media, such as optical, magnetic or non-volatile electronic memory. Processor 32 analyzes the signals conveyed by console 28 in order to identify sleep states of patient 22 and to extract sleep quality indicators. The results of the analysis are presented to an operator 34, such as a physician, on an output device 36, such as a display or printer.
Processor 32 acquires an EEG signal from patient 22, at a signal acquisition step 40. Typically, for sleep studies, the signal is acquired over the course of at least several hours. The processor then adaptively segments the signal into quasi-stationary segments, at a segmentation step 42. Adaptive segmentation is described at length in the above-mentioned U.S. patent applications. Briefly, processor 32 advances a sliding window, of variable size, through the EEG signal and evaluates statistical features of the signal within the window. The statistical features typically include aspects of the frequency spectrum of each segment, which are determined by methods of spectral analysis known in the art. The processor optimizes the window boundaries so as to envelope a segment that is statistically stationary to within a predefined bound. In consequence, the EEG signal is divided into a time sequence of quasi-stationary segments of varying length, separated by shorter transient periods. This sort of adaptive segmentation is advantageous in that the segments that are chosen represent actual physiological states of the patient, as opposed to the arbitrary 30-second epochs that are used in conventional sleep scoring.
EEG signals normally comprise five major types of waves: (1) δ-wave (1.0-3.5 Hz), (2) θ-wave (4.0-7.0 Hz), (3) α-wave (7.5-12 Hz), (4) σ-wave (12-15 Hz); and (5) β-wave (15-35 Hz). Each quasi-stationary segment typically comprises one dominant wave and possibly other frequency components superimposed on the dominant wave. The frequency composition of the different types of segments determined at step 42 typically varies from patient to patient. Therefore, in order to classify the segments for each individual patient, processor 32 applies a fuzzy clustering algorithm to divide the segments into clusters, at a clustering step 44. Each cluster has a characteristic distribution of features, such as frequency components and overall segment energy. Methods of fuzzy clustering are likewise described in the above-mentioned patent applications.
In the representation of
Returning now to
wherein K is the number of clusters and D is a scalar function of distance between xn and μk. For example, D can be an Euclidian distance, given by D(xn, μk)=(xn−μk)H(xn−μk), wherein H denotes the conjugate transpose operator. Alternatively, other methods known in the art may be used for computing cluster membership. The membership levels may be advantageously displayed as a function of time, as illustrated below in
The membership values determined at step 46 may be used by processor 32 in automatically assigning each 30-sec epoch during the monitoring period to one of the accepted sleep stages, at a sleep staging step 48. For example, the following scheme may be used, combining the states of the segments in the EEG signal with additional information from EMG and EOG signals:
1) Stage wake—Epochs more than 50% of whose duration are occupied by high-frequency EEG and/or body movements and/or eye blinks are classified as stage wake. Epochs that are not classified as stage wake are classified as sleep.
2) Sleep stages 2-4—Epochs classified as sleep, in which:
Alternatively or additionally, sleep stages may be determined using cardiovascular, respiratory or other physiological indicators. For example, a method for sleep staging based on cardio-respiratory signals is described in U.S. patent application Ser. No. 10/995,817, filed Nov. 22, 2004, whose disclosure is incorporated herein by reference.
In addition to or instead of standard sleep staging at step 48, processor 32 typically computes sleep quality indicators, at a sleep quality assessment step 50. For example, for each of clusters 60, 62, 64 and 66 (referred to respectively as HF, MF1, MF2 and LF states), the processor may compute the following sleep quality parameters:
Furthermore, processor 32 may combine the segmentation data with the sleep staging performed at step 48 in order to compute the above parameters separately for each identified sleep stage or group of sleep stages. For example, the relative duration of the HF state in REM may be calculated as follows:
As another example, the relative number of HF segments in REM may be calculated as follows:
References is now made to
The term “density plot” is used herein to denote a plot in which the color at a given point is indicative of the relative value of a parameter referred to the Cartesian coordinates of the point. In other words, as can be seen in
It can be seen in
As in the case of the density plot shown above, the fundamental frequency correlates well with the hypnogram sleep stages, but provides richer information that is lost in the discrete hypnogram. This information may be further brought out, for example, by displaying a trend line and a range of standard deviation of the fundamental frequency over time (omitted from
Like other sleep quality indicators, the fundamental frequency may be correlated with the patient's sleep stages. For example, processor 32 may calculate the average fundamental frequency, and possibly the variance of the fundamental frequency, over each of the sleep stages identified at step 48.
wherein D denotes the duration in seconds, and T is the total duration of all EEG segments. In other words, for each successive segment, the duration of the segment is added to the cumulative duration of the state to which the segment belongs, while the cumulative durations of the other states remains unchanged.
Alternatively or additionally, cumulative membership values may be computed and displayed by integrating the above-mentioned membership function wkn over successive segments. Parameters that can be extracted in this manner include:
1. Total Membership Index Up to Segment N:
2. Cumulative Membership Index of Segment N:
The accumulation rate of each frequency state can be modeled by fitting an exponential function g(t)=1−e−μt to the accumulation function, using least squares fitting, for example. The estimated accumulation rate μ for each curve is shown in the figure.
Changing trends in the state accumulation plot are indicative of changes and/or fragmentation of sleep states. For example, a knee 88 in HF curve 80 marks the point of transition from wakeful to sleeping states (occurring in this case about one hour after the beginning of the trial). The accumulation rate of HF states is markedly lower following the wake/sleep transition in normal patients, as can be seen in
wherein Ni,j is the number of transitions from state i to state j.
The transition matrix shows a pattern of frequency state dynamics during sleep, which can be used as a measure of sleep quality. For example, the inventors found that in a group of patients suffering from fragmented sleep (who nonetheless presented apparently normal hypnograms), the transition probability from state MF2 to LF state was substantially lower than in normal patients. This result reflects a deficiency in low-frequency (LF) activity that characterizes fragmented sleep.
Various other sleep quality indicators may be derived from the EEG signal and calculated over the entire sleep period or for selected sleep stages. For example, the sleep quality indicators may relate to transient phenomena in the EEG, such as K-complexes and/or spindles. A K-complex index, which quantifies the frequency of K-complex episodes during sleep, may be calculated as follows:
A spindle index, quantifying the frequency of EEG spindles during sleep, may be calculated in like fashion. (K-complexes and spindles are well-known phenomena in EEG. Techniques for automatic identification and monitoring of these phenomena are described in the above-mentioned related patent applications.)
Although the embodiments described above relate mainly to analysis of EEG signals, the principles of these embodiments may similarly be applied to other physiological indicators. For example, a snoring index (based on identification of snoring episodes by audio analysis) may be used to indicate the number or duration of snores during one or more sleep stages.
As another example, a transition matrix of the type shown in
Furthermore, processor 32 may generate respiratory event histograms to describe the distribution of the duration of respiratory events during different sleep stages. (Methods for identifying respiratory events are likewise described in the above-mentioned related applications.) Additionally or alternatively, respiratory event histograms may be presented as a function of body position, time of night, or pressure titration levels of a respiratory assist device. The processor may also assign a confidence level to each suspected respiratory event (for example, from 0 for non-events to 1 for events that are certain), and the confidence levels may be displayed as a function of respiration state in a density plot similar to that shown in
Respiratory events are typically accompanied by a drop in heart rate (bradycardia), followed by heart rate elevation (tachycardia). Processor 32 may calculate sleep quality indicators based on these phenomena. For example, a relative heart rate index RHR, indicating the change (drop and/or elevation) of the heart rate associated with respiratory events, may be calculated as follows:
Here HR(t) is the HR in the time interval of interest, and BHR is the baseline heart rate.
It will be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art.
1. Definition of Features
If Sxx(f) denotes the estimated power spectrum of an EEG segment, then
is the relative energy in the frequency band that is bounded by frequencies f1 and f2.
Let V(xk) denote the energy variance of the samples within the kth EEG segment (denoted xk). The normalized variance is then
wherein K is the total number of segments.
The fundamental frequency of an EEG segment is the moment of the frequency spectrum, calculated as follows:
2. Initial Classification Using Fuzzy Clustering
The EEG segments are classified into the following classes in the feature space defined by f1, f2 and f3:
C1—high frequency.
C2—mixed frequency.
C3—Low frequency.
The segments may be classified according to the criterion: C(xn)=arg mkax (wnk), wherein xn is the feature vector of segment n, and wnk is the membership level of the segment in cluster k. In this case k=1, 2, 3.
3. Unification: {tilde over (C)}2←C2 ∪C3
4. Partitioning of {tilde over (C)}2 by Fundamental Frequency:
f4,n>5 Hzε{tilde over (C)}2
f4,n≦5 Hzε{tilde over (C)}3
(Here f4,n is the fundamental Frequency of Segment n.)
5. Partitioning of {tilde over (C)}3 Using Fuzzy Clustering in the Feature Space Defined by f4 and f5
Features corresponding to the maximal centroid of f5 are returned to {tilde over (C)}2 in two subclasses. Feature vectors classified in the subclass characterized by minimal f5 value of the centroid are returned to {tilde over (C)}2.
6. Definition of Validation Rules
7. Implementation of Rules
8. Partitioning of {tilde over (C)}2 Using Hierarchical Fuzzy Clustering in the Feature Space Defined by f6 into Ĉ2 and C4.
Hierarchical fuzzy clustering partitions the feature space in a recursive manner. Each level of recursion generates a new hierarchy level, in which a portion of the feature space attributed to one selected cluster is subdivided into M groups. In the present case, at each hierarchy level, the cluster with minimal centroid value is partitioned into two new clusters until the diversity level between clusters at the same hierarchy level drops below a predetermined threshold. The diversity level D is given by:
In one embodiment, the threshold on D is 2, i.e., when D<2 the recursion stops.
The feature vectors attributed to the cluster with minimal centroid value are assigned to C4, while the rest of the feature vectors are assigned to Ĉ2. C4 corresponds to MF1, while Ĉ2 corresponds to MF2.
| Number | Date | Country | Kind |
|---|---|---|---|
| 155955 | May 2003 | IL | national |
This application claims the benefit of U.S. Provisional Patent Application 60/590,375, filed Jul. 21, 2004. It is a continuation-in-part of U.S. patent application Ser. No. 10/678,773, filed Oct. 3, 2003 (published as US 2004/0230105 A1), and is also related to co-pending U.S. patent application Ser. No. 10/677,176, filed Oct. 2, 2003 (published as US 2004/0073098 A1). The disclosures of all these related applications are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IL05/00776 | 7/21/2005 | WO | 00 | 5/8/2007 |