Patent Grant
12334105
The present invention is related to the diagnosis and treatment of physiological disorders.
During exhalation, carbon dioxide (CO2) diffuses from the pulmonary capillaries into the lungs, while oxygen (O2) diffuses from the lungs into the pulmonary capillaries. For each of these gases, equilibrium is reached (i.e., the exchange of the gas stops) when the partial pressure of the gas in the lungs equals the partial pressure of the gas in the pulmonary capillaries. In general, equilibrium for CO2 is reached prior to equilibrium for O2.
The main components in exhaled air are nitrogen (N2), Oi water (H2O), and CO2. Hence, the molecular mass MA(t) of exhaled air, as a function of a time variable t, is approximately equal to CN
At any time during an exhalation, in approximation:
MA(t)=(1−C′O
where −C′O
ME=MA(tE)=MI+C′CCO
(The approximation MCO
In general, two physical mechanisms govern the changes in the concentrations of CO2 and O2 during exhalation: diffusion and perfusion. Diffusion causes the gases to move across the alveolar walls, from the side of higher concentration to the side of lower concentration. The rate of diffusion is proportional to the concentration gradient across the alveolar walls and to a diffusion constant. Perfusion refers to the flow of blood through the alveolar capillaries.
In some subjects, the flow of blood through the alveolar capillaries is sufficiently fast so as not to inhibit the rate of diffusion. In other words, the rate of change of the concentration of each of the gases is diffusion-constrained. In general, for diffusion-constrained gas exchange, C′O
MC=MA(tE0)≈(1−C′CO
Given two molecular masses MA(t1) and MA(t2) where t1<t2≤tE0, it follows, from equation (1), that:
C′CO2(t2)−C′CO
For t2>t1≥tE0, it follows, from equation (1), that:
C′O
From the above, it may be deduced that, for diffusion-constrained gas exchange, MA(t) changes in two stages. In the first stage, MA(t) increases until reaching a maximum of MC at t=tE0. In the second stage, MA(t) drops exponentially to ME, which is typically closer to MC than to MI. The rate at which MA(t) changes in each stage depends on the rate of diffusion, which may be impaired in some subjects.
In other subjects, on the other hand, the blood flow rate through the alveolar capillaries limits the rate of diffusion; in other words, the rate of concentration change is perfusion-constrained. For such subjects, the rate of concentration change is capped by a maximum value, which is a function of the rate of blood flow.
In particular, for perfusion-constrained gas exchange, C′CO
C′CO
Thus, perfusion-constrained gas exchange takes place in a single stage, in which MA(t) increases linearly until reaching ME.
In yet other subjects, the exchange of O2 is diffusion-constrained, but the exchange of CO2 is perfusion-constrained. In this case, there are two stages, as in the case of complete diffusion constraint. However, the first stage is relatively long, and MC is relatively close to ME.
The speed “v” of sound in a gas is a function of the molecular mass “M” of the gas. (In this context, the term “gas” includes, within its scope, a mixture of gases such as CO2, O2, N2, and water vapor.) For example, for an ideal gas,
where γ is the adiabatic constant of the gas, R is the universal gas constant, and T is the temperature of the gas in Kelvins.
U.S. Pat. No. 8,689,606 describes a sensor chip for gas having cells for emitting and receiving ultrasound and being configured for a sufficiently large frequency range and for measuring concentration of at least one of the gas components based on at least two responses within the range. The frequency range can be achieved by varying the size of cell membranes, varying bias voltages, and/or varying air pressure for an array of cMUTs or MEMS microphones. The sensor chip can be applied in, for example, capnography. A measurement air chamber is implemented in the respiratory pathway, and it and/or the pathway may be designed to reduce turbulence in the exhaled breath subject to ultrasound interrogation. The chip can be implemented as self-contained in the monitoring of parameters, obviating the need for off-chip sensors.
US Patent Application Publication 2019/0080803 describes an apparatus including a network interface and a processor. The processor is configured to receive, via the network interface, speech of a subject who suffers from a pulmonary condition related to accumulation of excess fluid, to identify, by analyzing the speech, one or more speech-related parameters of the speech, to assess, in response to the speech-related parameters, a status of the pulmonary condition, and to generate, in response thereto, an output indicative of the status of the pulmonary condition.
West, John B., et al., “Measurements of pulmonary gas exchange efficiency using expired gas and oximetry: results in normal subjects,” American Journal of Physiology-Lung Cellular and Molecular Physiology 314.4 (2018): L686-L689 describes a noninvasive method for measuring the efficiency of pulmonary gas exchange in patients with lung disease. The patient wears an oximeter, and the partial pressures of oxygen and carbon dioxide in inspired and expired gas is measured using miniature analyzers.
West, John B., and G. Kim Prisk. “A new method for noninvasive measurement of pulmonary gas exchange using expired gas,” Respiratory physiology & neurobiology 247 (2018): 112-115 describes how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency.
There is provided, in accordance with some embodiments of the present invention, a system including an output device and one or more processors. The processors are configured to cooperatively carry out a process that includes computing one or more values of at least one parameter at respective times during an exhalation of a subject, based on one or more properties of sound passing through air exhaled by the subject during the exhalation, the parameter being related to a concentration of a gas in the air, and generating an output, via the output device, in response to the values.
In some embodiments, the system further includes a sensor configured to measure a speed of the sound, and the process includes computing the values based on the speed.
In some embodiments, the system further includes a sensor configured to measure a baseline concentration of the gas in other exhaled air, and the process includes computing the values based on the baseline concentration.
There is further provided, in accordance with some embodiments of the present invention, a method including computing one or more values of at least one parameter at respective times during an exhalation of a subject, based on one or more properties of sound passing through air exhaled by the subject during the exhalation, the parameter being related to a concentration of a gas in the air, and generating an output in response to the values.
In some embodiments, the output indicates a state of the subject with respect to a physiological condition selected from the group of conditions consisting of: heart failure, asthma, hypobaropathy, hypercapnia, Chronic Obstructive Pulmonary Disease (COPD), and Interstitial Lung Disease (ILD).
In some embodiments, the method further includes, based on the values, identifying an extent to which a rate of change in the concentration is perfusion-constrained, and the output indicates the extent to which the rate of change is perfusion-constrained.
In some embodiments,
In some embodiments, generating the output includes generating the output in response to comparing the rate of change to a baseline rate of change.
In some embodiments,
In some embodiments, computing the rate of change includes computing the rate of change as a function of:
In some embodiments, the one or more values include an equilibrium value of the parameter.
In some embodiments, the equilibrium value includes a CO2-equilibrium value of a CO2-concentration of CO2 in the air.
In some embodiments, computing the CO2-equilibrium value includes computing the CO2-equilibrium value based on a baseline CO2-equilibrium value that was measured prior to the exhalation.
In some embodiments, the sound is emitted by the subject while producing the exhalation.
In some embodiments, the sound belongs to speech of the subject, and computing the values includes computing the values based on a speech signal representing the speech.
In some embodiments, computing the values includes:
In some embodiments, the values include respective expansion factors that quantify the expansions or contractions.
In some embodiments, the baseline spectral envelopes belong to respective baseline signal-portions corresponding to the portions of the signal, respectively.
In some embodiments, the baseline signal-portions are other portions of the speech signal.
In some embodiments, the baseline signal-portions belong to a reference speech signal.
In some embodiments, the reference speech signal represents other speech uttered while in a known physiological state, and the output indicates a physiological state of the subject relative to the known physiological state.
In some embodiments, the reference speech signal represents other speech, and computing the values includes computing the values based on one or more measured properties of other air exhaled during the other speech.
In some embodiments, the reference speech signal represents other speech uttered by the subject.
In some embodiments, computing the values includes computing the values while identifying the correspondence between the baseline signal-portions and the portions of the speech signal, by varying the correspondence and expanding or contracting the spectral envelopes or the baseline spectral envelopes so as to minimize a sum of respective distance measures for the portions, the distance measure for each of the portions being a distance between (i) spectral coefficients of the portion and (ii) baseline spectral coefficients of the baseline signal-portion to which the portion corresponds, following the expansion or contraction.
In some embodiments, computing the values includes computing the values under a constraint that the values vary in accordance with a predefined function.
In some embodiments, the method further includes, prior to computing the values, identifying the correspondence between the portions and the baseline signal-portions by minimizing a sum of respective distance measures for the portions, the distance measure for each of the portions being a distance between (i) spectral coefficients of the portion and (ii) baseline spectral coefficients of the baseline signal-portion to which the portion corresponds.
In some embodiments, computing the values includes computing the values based on, for each of the portions, a statistic of respective ratios between (i) one or more formant frequencies of the portion, and (ii) corresponding formant frequencies in the baseline spectrum for the portion.
In some embodiments, the values include respective expansion factors that quantify the expansions or contractions, and the expansion factor for each portion minimizes a distance between (i) spectral coefficients of the portion and (ii) baseline spectral coefficients of the baseline spectrum for the portion, following an application of the expansion factor to the spectral coefficients or to the baseline spectral coefficients.
In some embodiments, computing the values includes computing the values based on respective measured speeds of the sound.
There is further provided, in accordance with some embodiments of the present invention, a computer software product including a tangible non-transitory computer-readable medium in which program instructions are stored. The instructions, when read by one or more processors, cause the processors to cooperatively carry out a process that includes computing one or more values of at least one parameter at respective times during an exhalation of a subject, based on one or more properties of sound passing through air exhaled by the subject during the exhalation, the parameter being related to a concentration of a gas in the air, and generating an output in response to the values.
The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which:
Many conventional techniques for assessing impaired cardiovascular or pulmonary function in a subject require the subject to visit a hospital or clinic, and/or require the use of a specialized device. Testing for such physiological problems may thus be inconvenient and/or expensive.
Embodiments of the present invention therefore provide improved techniques for diagnosing such physiological problems. These techniques capitalize on the fact that the physiological state of a subject may affect the concentrations of gases in the air exhaled by the subject, and hence, the properties of sound passing through the air, such as sound produced by the subject during the exhalation. Advantageously, using these techniques, the subject may be tested at home using no more than a simple microphone, such as a microphone belonging to a smartphone or personal computer.
More specifically, in embodiments of the present invention, a processor computes one or more values of at least one parameter related to a concentration of a gas (e.g., O2 or CO2) in the exhaled air (which, in general, is the same as the concentration of the gas in the subject's lungs) at respective times during an exhalation of the subject, based on one or more properties of sound passing through the air at these times. The properties may include, for example, the speed of the sound (which may be measured directly) and/or spectral properties of the sound. Subsequently, the processor generates an output in response to the values.
For example, based on the values, the processor may compute a rate of change in the parameter and/or an equilibrium value of the parameter. Subsequently, based on the rate of change and/or the equilibrium value (e.g., based on comparing the rate of change and/or the equilibrium value to a suitable baseline), the processor may ascertain the subject's physiological state and then generate an output indicating the state. For example, in response to identifying an abnormality in the rate of change and/or the equilibrium value, the processor may generate an alert indicating that the subject's state with respect to a physiological condition may be unstable. Alternatively or additionally, the output may indicate the rate of change, the equilibrium value, and/or the values themselves, such that a physician may ascertain the subject's physiological state in response thereto.
In some embodiments, the processor computes the values of the parameter based on a speech signal representing speech of the subject. For example, the processor may select one or more portions of the speech signal, compute respective spectral envelopes of the portions, and compute the values of the parameter based on respective expansions or contractions of the spectral envelopes relative to respective corresponding baseline spectral envelopes. As described in detail below, these embodiments capitalize on the relationship between the concentration of CO2 in (and hence, the molecular mass of) the air exhaled while the speech is uttered, and the spectrum of the speech signal representing this speech. For example, per this relationship, a higher concentration of CO2 causes the spectral envelope of the signal to be more contracted (i.e., less expanded), relative to a lower concentration of CO2.
In some embodiments, the parameter includes an “expansion-factor parameter,” whose values, referred to herein as “expansion factors,” quantify the relative expansions or contractions of the spectral envelopes. The expansion factor for each spectral envelope may be computed from the ratios between the formant frequencies in the spectral envelope and the corresponding formant frequencies in the baseline envelope. Alternatively, the expansion factor may be computed directly from spectral coefficients representing the spectral envelope.
Alternatively or additionally, the parameter may include the concentration of the gas. Alternatively or additionally, the parameter may include the molecular mass of the exhaled air. The values of the concentration, and/or the values of the molecular mass, may be derived from the expansion factors.
In other embodiments, the processor computes the values of the parameter based on measured speeds of sound passing through the exhaled air. The sound—which does not necessarily include speech sound, and is not even necessarily within an audible range of frequencies—may be produced by the subject during the exhalation, or it may be produced by another source, such as a speaker or an ultrasound transducer. The speeds may be measured by any suitable sensor, such as the aforementioned ultrasound transducer.
Reference is initially made to
System 20 comprises an audio-receiving device 32, which is used by subject 22. Device 32 comprises circuitry, typically comprising an audio sensor 38 (e.g., a microphone), which converts sound waves to analog electrical signals, an analog-to-digital (A/D) converter 42, a processor 36, and a network interface, such as a network interface controller (NIC) 34. Typically, device 32 further comprises a storage device (e.g., a solid-state drive), a screen (e.g., a touchscreen), and/or other user interface components, such as a keyboard or a speaker. In some embodiments, device 32 comprises a mobile phone, a tablet computer, a laptop computer, a desktop computer, a voice-controlled personal assistant (such as an Amazon Echo™ or a Google Home™ device), a smart speaker device, or a dedicated medical device.
In some embodiments, audio sensor 38 (and, optionally, A/D converter 42) belong to a unit that is external to device 32. For example, audio sensor 38 may belong to a headset that is connected to device 32 by a wired or wireless connection, such as a Bluetooth connection.
In some embodiments, system 20 further comprises a temperature sensor configured to measure the temperature of the exhaled air of subject 22. The measured temperatures are received by processor 36, and are used by the processor to calculate the values of a relevant parameter related to a concentration of a gas in air in lungs of the subject, as further described below with reference to the subsequent figures.
For example, for embodiments in which audio sensor 38 belongs to a microphone in a headset, the temperature sensor may be mounted onto the microphone. The output signal of the temperature sensor may be encoded as an acoustic signal, e.g., by frequency modulation, such that A/D converter 42 receives a bi-channel stereo audio signal including both the output from the microphone and the acoustic signal from the temperature sensor.
Typically, system 20 further comprises a server 40, comprising circuitry comprising a processor 28, a storage device 30, such as a hard drive or flash drive, and a network interface, such as a network interface controller (NIC) 26.
Server 40 may further comprise a screen, a keyboard, and/or any other user interface components. Typically, server 40 is located remotely from device 32, e.g., in a control center, and server 40 and device 32 communicate with one another, via their respective network interfaces, over a network 24, which may include a cellular network and/or the Internet.
System 20 is configured to facilitate evaluating the subject's physiological state with respect to heart failure, asthma, hypobaropathy, hypercapnia (e.g., due to changes in altitude or air quality), Chronic Obstructive Pulmonary Disease (COPD), Interstitial Lung Disease (ILD), or any other physiological condition that affects the concentration of gases in the subject's lungs.
Typically, the system performs this function by processing one or more speech signals (also referred to herein as “speech samples”) representing speech uttered by the subject during an exhalation. As further described below with reference to the subsequent figures, the system, based on the speech signals, computes one or more values of at least one parameter associated with the air in the lungs of the subject at respective times during the exhalation. The parameter may include, for example, the molecular mass of the air or the concentration of a gas, such as CO2 or O2, in the air.
In other embodiments, the system is configured to compute the values of the parameter based on measured speeds of sound in the exhaled air at the respective times during the exhalation. The speeds may be measured by any suitable sensor.
In some such embodiments, the sound is produced by the subject during the exhalation. Although the sound need not necessarily include speech, an advantage of speech is that, by virtue of the speech imposing a pattern of short inhalations and long exhalations, equilibrium concentrations are generally reached during the exhalations.
In other such embodiments, the sound is produced by another source. For example, the system may comprise an ultrasonic transducer 33 configured to emit sound (in the form of ultrasonic waves) into the exhaled air and to measure the speed of the sound, e.g., as described in Huang, Y. S., et al., “An accurate air temperature measurement system based on an envelope pulsed ultrasonic time-of-flight technique,” Review of Scientific Instruments 78.11 (2007): 115102 or in Jedrusyna, A., “An Ultrasonic Air Temperature Meter,” Recent Advances in Mechatronics, Springer, Berlin, Heidelberg, 2010, 85-89, the respective disclosures of which are incorporated herein by reference. While the speed of the sound is measured, the subject need not speak or produce any sound at all; nonetheless, speech may be advantageous by virtue of imposing a pattern of short inhalations and long exhalations, as described above.
The measured speeds of sound may be communicated, via any suitable communication interface, to processor 36 and/or processor 28. In response to the speeds, the processor may compute values of the molecular mass per equation (7). (For embodiments in which a temperature sensor is not used, an approximation for the temperature of the exhaled air, such as 307.5 K, may be used.) Subsequently, the processor may derive values of a gas concentration from the values of the molecular mass, e.g., per equation (2).
In yet other embodiments, the system, during a registration procedure, measures one or more properties of air exhaled by the subject or another subject. For example, the system may measure the speed of sound in the air, e.g., using the ultrasonic techniques described above. Alternatively or additionally, a baseline concentration of a gas (e.g., CO2) in the air may be measured directly using any suitable sensor, e.g., as described in J. B. West et al., “Measurements of pulmonary gas exchange efficiency using expired gas and oximetry: results in normal subjects,” Am. J. Physiol. Cell. Mol. Physiol., vol. 314, no. 4, pp. L686-L689, April 2018, whose disclosure is incorporated herein by reference. During this registration procedure, the subject need not speak or produce any sound at all; nonetheless, speech may be advantageous by virtue of imposing a pattern of short inhalations and long exhalations, as described above.
Subsequently to the registration, based on the measured properties, the processor computes parameter values (e.g., gas concentrations) with respect to the subject's test speech signals, as described below with reference to the subsequent figures. For example, for embodiments in which the speed of sound is measured during the registration, the processor may compute baseline values of the parameter based on the measured speeds of sound, and then compute the parameter values based on the baseline values.
In response to the values of the parameter, the system generates an output via any suitable output device, such as a display or a speaker. For example, based on the values of the parameter, the processor may estimate the state of the subject with respect to a physiological condition. Subsequently, the processor may include the estimated state, optionally with a likelihood associated with the estimation, in the output. Thus, for example, the output may indicate a likelihood that the subject is in a stable state, and/or a likelihood that the subject is in an unstable state, with respect to the condition. Alternatively or additionally, the output may include a score indicating the degree to which the subject's state appears to be unstable.
Typically, processor 36 of device 32 and processor 28 of server 40 cooperatively perform the receiving and processing of the speech samples. For example, as the subject speaks into device 32, the sound waves of the subject's speech may be converted to an analog signal by audio sensor 38, which may in turn be sampled and digitized by A/D converter 42. (In general, the subject's speech may be sampled at any suitable rate, such as a rate of between 8 and 45 kHz.) The resulting digital speech signal may be received by processor 36. Subsequently, processor 36 may communicate the speech signal, via NIC 34, to server 40, such that processor 28 receives the speech signal via NIC 26 and then processes the speech signal. Alternatively, processor 36 may process the speech signal, in which case the system need not necessarily comprise server 40. (Notwithstanding the above, the remainder of the present description, for simplicity, generally assumes that processor 28—also referred to hereinbelow simply as “the processor”—performs the processing.)
Subsequently to generating the aforementioned output, system 20 may communicate the output to the subject, to another person (e.g., the subject's physician), and/or to an electronic patient management system, which may integrate the output with other subject-specific information and take appropriate action.
For example, processor 28 may communicate the output to processor 36, and processor 36 may then communicate the output to the subject, e.g., by displaying a visual message on the display of device 32 and/or by playing an audio message using a speaker of device 32. Alternatively or additionally, in response to the output indicating a relatively high likelihood that the subject's state is unstable, the processor may communicate an alert indicating that the subject should take medication or visit a physician. The alert may be communicated by placing a call or sending a message (e.g., a text message) to the subject, to the subject's physician, and/or to a monitoring center. Alternatively or additionally, in response to the output, the processor may control a medication-administering device so as to adjust an amount of medication administered to the subject.
In some embodiments, device 32 comprises an analog telephone that does not comprise an A/D converter or a processor. In such embodiments, device 32 sends the analog audio signal from audio sensor 38 to server 40 over a telephone network. Typically, in the telephone network, the audio signal is digitized, communicated digitally, and then converted back to analog before reaching server 40. Accordingly, server 40 may comprise an A/D converter, which converts the incoming analog audio signal—received via a suitable telephone-network interface—to a digital speech signal. Processor 28 receives the digital speech signal from the A/D converter, and then processes the signal as described above. Alternatively, server 40 may receive the signal from the telephone network before the signal is converted back to analog, such that the server need not necessarily comprise an A/D converter.
As further described below with reference to the subsequent figures, processor 28, in processing the speech samples, may compare the spectral envelopes of the samples to baseline spectral envelopes. The baseline spectral envelopes, and/or reference speech signals to which the baseline spectral envelopes belong, may be received by processor 28 via NIC 26 and/or any other suitable communication interface, such as a flash-drive interface.
Processor 28 may be embodied as a single processor, or as a cooperatively networked or clustered set of processors. For example, a control center may include a plurality of interconnected servers comprising respective processors, which cooperatively perform the techniques described herein. In some embodiments, processor 28 belongs to a virtual machine.
In some embodiments, the functionality of processor 28 and/or of processor 36, as described herein, is implemented solely in hardware, e.g., using one or more Application-Specific Integrated Circuits (ASICs) or Field-Programmable Gate Arrays (FPGAs). Alternatively or additionally, the functionality of processor 28 and/or of processor 36 is implemented at least partly in software. For example, in some embodiments, processor 28 and/or processor 36 is embodied as a programmed digital computing device comprising at least a central processing unit (CPU) and random access memory (RAM). Program code, including software programs, and/or data are loaded into the RAM for execution and processing by the CPU. The program code and/or data may be downloaded to the processor in electronic form, over a network, for example. Alternatively or additionally, the program code and/or data may be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory. Such program code and/or data, when provided to the processor, produce a machine or special-purpose computer, configured to perform the tasks described herein.
Reference is now made to
The center of
CO2 has a significantly higher molecular mass than that of the other main gaseous components of exhaled air. Hence, in general, exhaled air having a higher concentration of CO2 has a higher molecular mass than exhaled air having a lower concentration, such that, per equation (7), the speed of sound in the former is less than the speed of sound in the latter. (Although the exhaled air of the subject is generally not an ideal gas, embodiments of the present invention generally assume equation (7) to hold. Other, more complex formulae for non-ideal gases that may be used are described, for example, in O. Cramer, “The variation of the specific heat ratio and the speed of sound in air with temperature, pressure, humidity, and CO2 concentration,” J. Acoust. Soc. Am., vol. 93, no. 5, pp. 2510-2516, May 1993, whose disclosure is incorporated herein by reference.) The relationship between the speed of sound and the frequency “f” of the sound for a given wavelength “X” is given by the formula f=vλ. Thus, for any given subject, speech uttered with a greater speed of sound will generally have higher frequency content, relative to speech containing the same verbal content but uttered with a lesser speed of sound.
It follows, therefore, that the spectral properties of speech are affected by the level of CO2 concentration in the air exhaled during the speech. This effect is illustrated in the left and right portions of
More formally, letting w denote frequency, letting H0(ω) denote spectral envelope 48, and letting H1(ω) denote spectral envelope 50, it follows from the above that H1(ω)=H0(ω/β), where β=v1/v0, i.e., the ratio of the speed of sound in the unstable-state exhalation to the speed of sound in the stable-state exhalation. Per equation (7), this ratio is equivalent to
where M0 and M1 are the respective molecular masses of the air exhaled in the stable and unstable states, and T0 and T1 are the respective temperatures of the exhaled air. Hence:
β is referred to below as the “expansion factor” of H1(ω) relative to H0(ω); β>1 indicates expansion, as at the left of
As described in detail below with reference to the subsequent figures, the processor is configured to identify the degree to which the spectral envelopes of one or more portions of the speech signal received from subject 22 (
Reference is now made to
Typically, the processor begins to process test signal 52 by identifying any breathing pauses 54 in signal 52, e.g., using voice activity detection (VAD). Subsequently, the processor divides the signal into segments 56, which are separated from each other by breathing pauses 54. The processor then selects one of segments 56 for further processing. Typically, subsequently to selecting the segment, the processor divides the segment into smaller portions referred to herein as “frames,” the length of each frame typically being between 10 and 50 ms. By way of example,
Subsequently, the processor computes respective values of a parameter, such as the expansion-factor parameter or the molecular mass of the exhaled air, for the selected one or more portions (e.g., frames) of the test signal, by comparing the spectral envelopes of the portions to corresponding baseline spectral envelopes. Typically, the baseline spectral envelopes belong to respective baseline signal-portions corresponding to the selected portions of the test signal, respectively.
In some cases, the baseline signal-portions belong to a reference speech signal, i.e., a reference signal representing other speech uttered by the subject or by a different subject. (The reference signal may be stored, for example, in storage device 30 (
In some such cases, the reference utterance is uttered by a speaker in a known physiological state, e.g., a stable state with respect to a physiological condition. Thus, the output generated by the processor (as described above with reference to
In other cases, the baseline signal-portions belong to the test signal. For example, when recording the test signal, the subject may repeat a word, or a short series of words, several times. Any portion of the test signal, such as a portion assumed to be at equilibrium, may then be designated as the baseline.
In some embodiments, the processor computes the values by executing a two-stage technique. First, the processor identifies a correspondence between the portions of the test signal and the baseline signal-portions. Next, the processor computes the expansion factors and, optionally, the values of another parameter responsively to the correspondence. In other embodiments, the processor executes a one-stage technique, per which the processor computes the values while finding the correspondence. Each of these techniques is described below.
By way of example,
The Two-Stage Technique
Per the two-stage technique, the processor first identifies the correspondence, using any suitable algorithm such as the Dynamic Time Warping (DTW) algorithm described in Sakoe and Chiba, “Dynamic Programming Algorithm Optimization for Spoken Word Recognition,” IEEE Transactions on Acoustics, Speech, and Signal Processing 26.2 (1978): 43-49, whose disclosure is incorporated herein by reference.
Typically, the correspondence-finding algorithm minimizes a sum of respective distance measures between corresponding pairs of frames, subject to one or more suitable constraints. The distance measure between two frames may be defined, for example, as the distance (e.g., the Euclidean distance) between the spectral coefficients of the first frame and the spectral coefficients of the second frame. (The spectral coefficients, which represent the spectral envelope of the frame, may be computed using linear prediction, cepstral analysis, or any other suitable technique for short-time spectrum computation.) By way of example,
For example, the processor may first select a sequence of Nt test-signal frames for which expansion factors are to be calculated. The processor may further calculate a sequence {v[nt]} for nt=1 . . . Nt, each v[nt] being a vector of spectral coefficients for the ntth test-signal frame of the sequence. The processor may further identify Nb baseline frames from which corresponding frames are to be found. The processor may also calculate a sequence {u[nb]} for nb=1 . . . Nb, each u[nb] being a vector of spectral coefficients for the nbth baseline frame.
Subsequently, the processor may identify the correspondence between the test-signal frames and the baseline frames, by identifying the mapping (nt1, nb1), (nt2, nb2), . . . , (ntK, nbK) that pairs the ntkth test-signal frame with the nbkth baseline frame for k=1 . . . K such that the sum of distances between the pairs is minimized subject to one or more constraints. In other words, the processor may identify the mapping that minimizes Σk=1Kw[k]*d(u[nbk], v[ntk]), where d(u[nbk], v[ntk]) is the distance between u[nbk] and v[ntk] and {w[k]} are respective weights for the pairs of frames. (Typically, at least some of the weights are different from each other.) Typically, d(u[nbk], v[ntk])=∥u[nbk]−v[ntk]∥p, p being greater than or equal to one, where ∥x∥p indicates the LP norm of x. (The Euclidean distance is obtained for p=2.)
The constraints may include, for example, one or more of the following:
Subsequently to identifying the correspondence, the processor calculates the expansion factors for the K test-signal frames relative to the K baseline frames, respectively. By way of example,
It is noted that, in some cases, the same test-signal frame may correspond to multiple baseline frames, such that multiple expansion factors may be computed for the test-signal frame. In such a case, the processor may average the multiple expansion factors, or simply select one of the expansion factors.
For further details regarding the computation of the expansion factors, reference is now made to
In some embodiments, the processor computes each expansion factor by computing a statistic (e.g., an average, such as a weighted average, or a median) of respective ratios between (i) one or more formant frequencies of the portion of the test signal for which the expansion factor is computed, and (ii) corresponding formant frequencies in the baseline spectrum for the portion.
By way of illustration,
In other embodiments, rather than considering ratios between formant frequencies, the processor computes the expansion factor by utilizing a mathematical relationship between the expansion factor and the spectral coefficients that represent the spectral envelopes. As an example of such a relationship, expansion of a spectral envelope by a factor of 0 causes the nth cepstral coefficient cn′ of the expanded envelope to have the value
where ck is the kth cepstral coefficient of the original envelope. (In practice, the above summation may be performed over values of k between n−j and n+j, j being an integer such as five, for example, without significant loss of precision.) In other words, applying the expansion factor β to the cepstral coefficient cn yields a new cepstral coefficient
Similar relationships exist for other types of spectral coefficients, such as Discrete Fourier Transform (DFT) coefficients.
In particular, in such embodiments, the processor computes the expansion factors such that the expansion factor for each of the test-signal portions minimizes a distance between (i) spectral coefficients v of the test-signal portion and (ii) baseline spectral coefficients u of the baseline spectrum for the test-signal portion, following an application of the expansion factor to u or v. In other words, the processor calculates each expansion factor such that the expansion factor minimizes the distance d(u′, v), u′ being the vector u following the application of β thereto, or the distance d(u, v′), v′ being the vector v following the application of 1/β thereto. The distance d(x, y) between the two vectors of spectral coefficients may be calculated, for example, as ∥x−y∥p, p being greater than or equal to one.
In some embodiments, the processor minimizes the distance using an iterative optimization technique, such as the Newton-Raphson method. In other embodiments, the processor performs an exhaustive search for the optimal expansion factor over a discrete set of values within an expected range. For example, the processor may compute d(u′, v) (or d(u, v′)) for β=1±jδ, j=0, . . . , J, where δ is a small step size, and then select the β yielding the minimum distance. In yet other embodiments, the processor executes the above two techniques in combination: first an exhaustive search is performed, and then the selected β is used as a starting point for an iterative optimization technique.
In some embodiments, the processor outputs the values of β without explicitly deriving values of any other parameter from the values of β.
In other embodiments, the processor derives one or more values of another parameter from the values of β, based on equation (8). Examples are hereby provided.
(a) An Equilibrium Molecular Mass or Gas Concentration
Provided the frames represent speech uttered after equilibrium was reached, the processor may compute an equilibrium molecular mass or concentration of a gas from the expansion factors. The processor may assume that equilibrium is reached after a threshold time from the start of the segment, the threshold time being between one and four seconds, for example.
For example, the processor may first compute a single equilibrium value SE from the individual values of β, e.g., by averaging the individual values. Subsequently, based on βE, the processor may compute Mtest,E, the equilibrium molecular mass of the air exhaled by the subject while uttering the test signal, and/or CCO
In particular, for embodiments in which a temperature sensor is used as described above with reference to
Mref,E may be computed, for example, from the speed of sound measured (e.g., using the ultrasonic techniques described above with reference to
For CCO
Alternatively, for embodiments in which a baseline concentration of CO2 is measured during the utterance of the reference signal as described above with reference to
(b) A Rate of Change in a Gas Concentration
Alternatively or additionally to computing an equilibrium value, the processor may compute a rate of change in the concentration of a gas, such as CO2 or O2, in the expired air. In particular, the processor may first compute multiple values of the concentration at different respective times. Subsequently, the processor may compute the rate of change based on the multiple values.
For example, the processor may first compute multiple values of the molecular mass, {Mtestk}, for at least some of the K test-signal frames for which the correspondence to the baseline was found. In particular, each Mtestk may be computed as (Mrefk*Mtestk)/((βk)2*Trefk) or, for embodiments in which a temperature sensor is not used, as Mrefk/(βk)2, where βk is the expansion factor for the kth pair of frames. (Mrefk may be computed as described above for Mref,E.)
Subsequently, based on {Mtestk}, the processor may identify the extent to which the rate of change in the concentration is perfusion-constrained. Subsequently, the processor may compute the rate of change in the concentration in response to identifying the extent to which the rate of change is perfusion-constrained. For example, the processor may compute M′test, the discrete-time derivative of {Mtestk}. Next, the processor may compute the rate of change in the concentration based on M′test and at least one constant that depends on the extent to which the rate of change is perfusion-constrained.
For example, the processor may compute the rate of change as C*M′test, where C is a constant depending on the extent to which the rate of change is perfusion-constrained. In this regard, reference is now made to
In some embodiments, respective predefined values of C are assigned to multiple functions 61, which represent the change over time in the molecular mass of exhaled air, or in the expansion factor, in various cases. For example,
By comparing {Mtestk} or {βk} to functions 61, the processor identifies the extent to which the gas exchange is perfusion constrained, and selects C responsively thereto. For example, the processor may regress {Mtestk} or {βk} to sets of function parameters that define functions 61, respectively. (The sets of function parameters may be stored in storage device 30 (
(As a purely illustrative example, the function β(t)=√{square root over (βE2+K1e−t/τ
Thus, for example:
Optionally, prior to computing M′test, the processor may smooth {Mtestk} or {βk} such that the regression error is reduced to zero.
In other embodiments (e.g., based on the regression described above), the processor outputs an indication of the extent to which the rate of change in the gas concentration is perfusion constrained, without necessarily computing the rate of change.
In some embodiments, values of the relevant parameter, such as the equilibrium CO2 concentration, are calculated for multiple segments 56, as further described below with reference to
The One-Stage Technique
Per the one-stage technique, the processor uses a modified form of the aforementioned correspondence-finding algorithm (e.g., DTW), which computes the values of the parameter while identifying the correspondence between the baseline signal-portions and the portions of the speech signal. In particular, the modified algorithm varies the correspondence and expands or contracts the spectral envelopes or the baseline spectral envelopes (i.e., applies an expansion factor β or 1/β to each of the spectral envelopes or baseline spectral envelopes) so as to minimize a sum (e.g., a weighted sum) of respective distance measures for the portions. The distance measure for each of the portions is the distance between the spectral coefficients of the portion and the spectral coefficients of the baseline signal-portion to which the portion corresponds, following the expansion or contraction.
Typically, the minimization is performed under the constraints described above for the two-stage technique. Moreover, one or more additional constraints are imposed. For example, for cases in which the test frames were produced at equilibrium, the processor may require that the same expansion factor is applied to each of the frames, such that the resulting molecular mass is constant.
For example, after calculating v[1], . . . , v[Nt] and u[1], . . . , u[Nb], the processor may identify the mapping (nt1, nb1, β1, r1), (nt2, nb2, β2, r2), . . . , (ntK, nbK, βK, rK) that minimizes Σk=1Kw[k]*d(u[nbk], v[ntk], βk) subject to the constraints described above for the two-stage technique along with the additional constraints described below, where r is a binary “direction” variable indicating whether the molecular mass is increasing or decreasing, and d(u[nbk],v[ntk], βk)=d(u[nbk]′,v[ntk]) or d(u[nbk],v[ntk]′), where the “′” appendage indicates modification of the vector by βk or 1/βk (respectively) as described above. (Each βk may be selected from a discrete set of potential values.) The additional constraints may be as follows. (The description below assumes a convention in which r=0 corresponds to an increase in the molecular mass, while r=1 corresponds to a decrease. In some embodiments, the opposite convention is used.)
Alternatively or additionally to the latter constraint, for cases in which the test frames were produced prior to equilibrium, the processor may require that the resulting molecular mass or expansion factor vary in accordance with a predefined parametric function, such as any one of functions 61 or a linear combination thereof.
Subsequently, the processor may generate an output responsively to the parameter values that were computed while finding the correspondence. Alternatively or additionally, the processor may compute the values of another parameter; for example, the processor may compute gas concentrations from {βk} or {Mtestk}, as described above for the one-stage technique. Subsequently, the output may be generated responsively to these additional parameter values.
Reference is now made to
Algorithm 62 begins with a signal-receiving step 64, at which the processor receives a test signal from the subject, e.g., over network 24 (
Next, at a segment-selecting step 68, the processor selects one of the segments (or a portion thereof). Subsequently, at a dividing step 70, the processor divides the selected segment into frames. The processor then computes the rate of change of CO2 concentration over the period of time spanned by the selected segment.
For example, using the two-stage technique, the processor may, at an optimizing step 72, find the optimal correspondence of the test-signal frames to baseline frames. (As described above with reference to
Subsequently, at another computing step 19, the processor computes a statistic, such as an average or maximum, of the rate of change over the frames.
Subsequently, the processor checks, at a checking step 78, whether any unselected segments remain. If yes, the processor returns to segment-selecting step 68.
Following the computation of the statistic for each segment, the processor, at an averaging step 80, computes the average of the statistic over the segments. In doing so, the processor may weight the segments differently, discard outliers, and/or use any other techniques known in the art for increasing the reliability of the average. (Alternatively to an average, the processor may compute a median or any other suitable statistic.)
Next, the processor, at a comparing step 82, compares the average to a suitable predefined threshold. If the average passes the threshold, the value of the parameter is deemed to be abnormal. (Depending on the parameter and on the physiological condition with respect to which the subject is being tested, an abnormal value may either be less than or greater than the threshold.) In response to identifying the abnormality, the processor generates an alert at an alert-generating step 84. Otherwise, algorithm 62 ends without the generation of an alert.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of embodiments of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description. Documents incorporated by reference in the present patent application are to be considered an integral part of the application except that to the extent any terms are defined in these incorporated documents in a manner that conflicts with the definitions made explicitly or implicitly in the present specification, only the definitions in the present specification should be considered.
The present application claims the benefit of U.S. Provisional Application 63/116,949, entitled “Detecting impaired physiological function by speech analysis,” filed Nov. 23, 2020, whose disclosure is incorporated herein by reference.
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| Number | Date | Country | |
|---|---|---|---|
| 20220165295 A1 | May 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| 63116949 | Nov 2020 | US |
