Abstract:
A method for estimating an electrophysiologic response contained in a measured signal includes obtaining a plurality of samples and defining a plurality of bins, each of which corresponds to a range of values of a sorting parameter associated with each of the samples. Each sample of the measured signal is then classified into one of the bins on the basis of a value of a sorting parameter associated with that sample. Then, for each bin, a statistic indicative of samples classified into that bin is maintained. On the basis of these bin statistics, the desired electrophysiologic response can then be estimated.

Description:
RELATED APPLICATIONS 
   This application is a divisional of copending U.S. application Ser. No. 10/014,274 now U.S. Pat. No. 6,718,199 filed on Oct. 26, 2001, which claims the benefit of the priority date of U.S. Provisional Application 60/243,682, filed on Oct. 27, 2000, the contents of which are herein incorporated by reference. 

   FIELD OF INVENTION 
   The invention relates to the measurement of electrophysiologic responses, and more particularly to enhancing the signal-to-noise ratio in such measurements. 
   BACKGROUND 
   In making a diagnosis, it is often useful to have the patient&#39;s cooperation. This is particularly true in the diagnosis of disease involving sensory pathways to the brain. For example, a straightforward way to assess a patient&#39;s hearing is to simply ask the patient whether he can hear particular tones having various frequencies and amplitudes. 
   In many cases, one takes for granted that a patient will be able to answer such questions. However, in some cases, a patient cannot communicate his perception. This occurs most frequently when the patient is an infant, or when the patient is unconscious. In a veterinary setting, it is rare to encounter a patient that can accurately communicate perception at all. 
   One approach to evaluating an infant&#39;s hearing is to make a sound and to then measure an evoked response associated with that sound. This evoked response is typically an electrophysiologic signal generated in response to the sound and traveling between the inner ear and the brain along various neural pathways, one of which includes the auditory brainstem. This signal is thus referred to as the “auditory brainstem-response,” hereafter referred to as the “ABR.” 
   The ABR is typically only a small component of any measured electrophysiologic signal. In most cases, a noise component arising from other, predominantly myogenic, activity within the patient dwarfs the ABR. The amplitude of the ABR typically ranges from approximately 1 microvolt, for easily audible sounds, to as low as 20 nanovolts, for sounds at the threshold of normal hearing. The noise amplitude present in a measured electrophysiologic signal, however, is typically much larger. Typical noise levels range from between 2 microvolts to as much as 2 millivolts. The resulting signal-to-noise ratio is thus between −6 dB and 100 dB 
   One approach to increasing the signal-to-noise ratio is to exploit differences between the additive properties of the ABR and that of the background noise. This typically includes applying a repetitive auditory stimulus (a series of clicks, for example) and sampling the electrophysiologic signal following each such stimulus. The resulting samples are then averaged. The ABR component of the samples add linearly, whereas the background electrophysiologic noise, being essentially random, does not. As a result, the effect of noise tends to diminish with the number of samples. The number of samples required to reach a specified signal-to-noise level depends on the noise level present in the samples. In principle, therefore, one can achieve a specified signal-to-noise ratio either with a small number of relatively quiet samples or with a large number of relatively noisy samples. 
   In practice, signal averaging techniques such as that described above are unlikely to work when the signal-to-noise ratio is worse than −48 dB. Since a minimally acceptable 5% confidence level requires a signal-to-noise ratio of at least −4 dB, this signal-averaging approach is prone to inaccuracy. 
   Signal averaging methods as described above perform best when the background noise is relatively constant. For example, the steady drone of an air-conditioner can readily be separated from a signal of interest. Such background noise is referred to as “stationary” noise. 
   The noise component of an electrophysiologic signal is often non-stationary. For example, after a few minutes of taking measurements, an infant may begin to stir, thereby momentarily increasing the background electrophysiologic noise level. The infant might then return to a deep sleep, thereby reducing the background electrophysiologic noise level. 
   The non-stationary nature of the noise component poses a dilemma for a clinician attempting to measure the ABR. For example, if the infant begins to stir, the clinician might suspend taking measurements to avoid contaminating data already collected with noisy data. This might prove to be a good decision if the infant were to fall back into a deep sleep, since one could then acquire additional quiet samples. However, even noisy samples can improve signal-to-noise ratio, provided that there are enough of them available. Hence, this might also prove to be a poor decision if the infant were to continue stirring. In such a case, it would have been better to have acquired the additional, albeit noisy samples. Because the behavior of an infant is, to a great extent, unpredictable, the clinician occasionally makes an incorrect guess, thereby either wasting time or needlessly corrupting acquired data. 
   SUMMARY 
   The invention is based on the recognition that, by dividing the sequence of samples that make up the signal into subsequences of samples, one can reduce the signal-to-noise ratio of an electrophysiologic signal and avoid many difficulties posed by the presence of non-stationary noise. The samples within a particular subsequence are characterized by a common range of values of a sorting parameter. Each subsequence of samples yields a statistic that is independent of corresponding statistics yielded by other subsequences of samples. These statistics, each of which corresponds to a subsequence, can then be combined in different ways to derive an estimate of an electrophysiologic response contained in the signal. The presence of non-stationary noise can, to a great extent, be compensated for by appropriately combining the statistics associated with each subsequence. 
   In one practice of the invention, a plurality of samples of a measured electrophysiologic signal is obtained. The electrophysiologic signal typically includes an electrophysiologic response to a stimulus. The method of the invention seeks to estimate the value of this response. 
   The method includes defining a plurality of bins, each of which corresponds to a range of values of a sorting parameter associated with each of the samples. Preferably, the range of values for each bin is such that each value of the sorting parameter is associated with at most one bin. 
   Each sample of the measured signal is then classified into one of the bins on the basis of a value of a sorting parameter associated with that sample. Then, for each bin, a statistic indicative of samples classified into that bin is maintained. On the basis of these bin statistics, the desired electrophysiologic response can then be estimated. In one particular practice of the invention, maintaining the bin statistic includes maintaining a moving average of samples in the bin. 
   In one practice of the invention, the sorting parameter includes a measure of noise present in the samples. The noise might be electrophysiologic noise, ambient acoustic noise, or any other noise process. The sorting parameter can also be derived from a combination of noise processes. 
   The estimation of electrophysiologic response can include combining the bin statistics to derive a quantity indicative of the electrophysiologic response. This might include averaging the bin statistics, or evaluating a weighted averaging of the bin statistics, with the weights being manually or automatically selected. In one practice, the weight assigned to a statistic for samples in a particular bin might be indicative of a quality of the samples in the bin. For example, the weight can be inversely proportional to a noise level associated with the particular bin. Alternatively, the weights can be selected to optimize a measure of an extent to which the quantity approximates the electrophysiologic response. The assignment of weights in a weighted average can also include excluding bin statistics associated with particular bins from being considered in evaluating the quantity indicative of the electrophysiologic response. 
   In another practice of the invention, a sequence of samples is decomposed into a plurality of subsequences, each of which includes samples selected on the basis of a value of a sorting parameter associated with each of the samples. The samples from each subsequence are then used to evaluate a plurality of subsequence statistics, each of which is associated with a corresponding subsequence. A subset of these subsequence statistics is then selected. The subset can include some or all of the subsequence statistics. On the basis of subsequence statistics from this set, the electrophysiologic response is then estimated. 
   In one practice of the invention, the subsequences are selected by selecting a noise threshold. Subsequence statistics that are associated with subsequences having noise levels above this threshold are then excluded from the subset. 
   The extent to which each of the selected subsequence statistics contributes to an estimate of the electrophysiologic response can be controlled. For example, one or more subsequence statistics can be weighted by an amount indicative of noise present in the corresponding subsequence. In this optional practice of the invention, subsequences statistics from subsequences that contain exceptionally noisy samples can be made to contribute less to the estimate than subsequence statistics from subsequences having samples that are not as noisy. 
   The method of the invention is applicable to various types of physiological stimuli. These stimuli include auditory, visual, olfactory, and gustatory stimuli, or combinations thereof. 
   These and other features and advantages of the invention will better understood from the following detailed description and the accompanying figures, in which: 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a block diagram of a system for acquiring electrophysiologic data; and 
       FIGS. 2 and 3  illustrate the data acquisition process. 
   

   DETAILED DESCRIPTION 
   Referring to  FIG. 1 , a system  10  for acquiring electrophysiologic data for measurement of auditory brainstem response (“ABR”) includes a sensor  12  attached to an infant&#39;s scalp. The sensors  12 , which are typically scalp electrodes, are configured to detect an analog signal  13  representing ongoing electrical activity. This analog signal  13  is provided to first and second band-pass filters  14   a–b  that generate first and second filtered signals  15   a–b,  respectively. In one embodiment, the first band-pass filter  14   a  has a passband between 180 Hz and 2000 Hz and the second band-pass filter  14   b  has a passband between 30 Hz and 2000 Hz. The resulting first and second filtered signals  15   a–b  are then passed to first and second analog-to-digital (A/D) converters  18   a–b  for conversion into a corresponding first and second digital signals  19   a–b . These digital signals  19   a–b  are then provided to a digital signal processor  20 . 
   Referring now to  FIG. 2 , on the basis of noise measurements derived from the first digital signal  19   a,  the digital signal processor  20  sorts the samples that make up the second digital signal  19   b  into a plurality of bins  22   a–j  each of which is associated with a band of noise amplitudes. The amplitude bands of the bins  22   a–j  are selected to be non-overlapping. For the application described herein, there are ten bins. However, the number of bins  22   a–j , and the amplitude ranges associated with each bin  22   a–j , depend on the specific application of the data-acquisition system  10 . Each bin  22   a–j  has an associated averaging accumulator  24   a–j  that maintains a moving average  25   a–j  of the samples in its corresponding bin  22   a–j.  Each bin  22   a–j  also has an associated counter  27   a–j  that contains the number of samples N i  in its associated bin  22   a–j.  Referring back to  FIG. 1 , the moving averages  25   a–j  and the counters  27   a–j  are maintained in a data buffer  26  that is available to a processing system  28 . 
   Note that the first and second digital signals  19   a–b  need not use the same time-base. For example, the first A/D converter  18   a  might sample the first filtered signal  15   a  at a sampling rate that differs from that used by the second A/D converter  18   b  to sample the second filtered signal  15   b.  In another example, the noise analysis may be made over a portion of the first filtered signal  15   a  that corresponds to a time interval that precedes and/or follows the portion of the second filtered signal  15   b  that corresponds to a time interval including the data being sorted into one of the bins. Additionally, noise analysis of a portion of the first filtered signal  15   a  can impact the sorting of samples from several portions of the second filtered signal  15   b.  The method of the invention can thus be used with any manner of noise analysis. 
   During data acquisition, each averaging accumulator  24   a  averages only those samples within its associated bin  22   a.  Since all samples are within one of the bins  22   a–j,  each sample can affect no more than one moving average  25   a–j.  Since the samples in any one bin  22   a  are averaged independently of samples in other bins  22   b–j,  samples from one bin  22   a  are prevented from contaminating the moving averages  25   b–j  obtained by averaging samples from other bins  22   b–j.    
   Referring now to  FIG. 3 , the clinician can, at any time select which of the moving averages  25   a–j  available for each band are to be combined into a single average representative of an ABR measurement  38 . As shown in  FIG. 3 , the clinician controls switches u i    29   a–j  that selectively exclude selected bands (hereafter referred to as “excluded bands”) from consideration in evaluating the ABR measurement  38 . These switches  29   a–j  are typically set to exclude from consideration all bands having a noise power above a selected threshold. 
   The clinician also controls weighting coefficients  30   a–j  associated with each of the remaining bands (hereafter referred to as the “included” bands). These weighting coefficients  30   a–j  can be controlled manually, or automatically. In either case, weighting coefficients  30   a–j  can be controlled individually, or as a group. Additionally, particular combinations of weighting coefficients  30   a–j  can be pre-programmed and selectively applied. 
   The moving averages  25   a–j  of each included band, which are available in the accumulators  24   a–j,  are then multiplied by the corresponding number of samples N i  in each band. The results are then scaled by their corresponding weighting coefficients  30   a–j  at corresponding mixers  32   a–j.  The outputs  35   a–j  of the mixers  32   a–j,  which are proportional to the weighted averages  34   a–j  corresponding to each band, the accumulated number of samples summed across all included bands, and the sum of the weighting coefficients of the included bands, are then provided to an output averaging-element  36 , the output of which is the desired ABR measurement  38 . This ABR measurement  38  is obtained by summing the outputs of the mixers  32   a–j  and normalizing the result by both the sum of the weighting coefficients of the included bands and the accumulated number of samples summed across the included bands. 
   In the illustrated embodiment, the processing system  28  carries out the function of mixing the moving averages  25   a–j  with the weighting coefficients  30   a–c,  averaging the resulting products, and normalizing the result to obtain the desired ABR measurement  38 . However, without loss of generality, these functions can also be carried out by special-purpose hardware. 
   In one practice of the invention, the data associated with each included band is weighted by the reciprocal of the noise amplitude associated with that band. As a result, data from noisier included bands will contribute less to the ABR measurement  38  than data from less noisy included bands. This reduces the possibility that contributions from noisier included bands will excessively degrade the accuracy of the ABR measurement  38 . 
   In addition to processing the amplified signal received from the sensors, the digital signal processor  20  also generates repetitive auditory stimuli. These auditory stimuli are communicated to the infant through an earphone  40  in communication with the digital signal processor  20  by way of a digital-to-analog (D/A) converter  42 , as shown in  FIG. 1 . The auditory stimuli can be adaptively controlled by the digital signal processor  20  in response to the measurements obtained by the data-acquisition system  10 . For example, if no ABR response appears to be evoked, the digital signal processor  20  may gradually increase the amplitude of the auditory stimuli to identify the infant&#39;s hearing threshold. 
   The processing system  28  also executes user-interface software for displaying, on a display monitor  48 , the results of data manipulation performed by the digital signal processor  20 . In the illustrated embodiment, the processing system  28  uses a Windows NT® operating system to execute user-interface software necessary for convenient display of data. 
   The data-acquisition system  10  permits retrospective control over which bands to incorporate into the ABR measurement  38  and the extent to which each band contributes to the ABR measurement  38 . By judiciously selecting the weighting coefficients  30   a–j,  the signal-to-noise ratio of the ABR measurement can be optimized even in the presence of non-stationary electrophysiologic noise. As the ABR measurement  38  unfolds during the data acquisition process, the weighting coefficients  30   a–j  can be adjusted in an effort to maximize the signal-to-noise ratio of the ABR measurement  38 . These adjustments can be made either in real-time, while the test is being conducted, or after the test has been terminated. The clinician conducting the test can thus experiment with different weighting coefficients  30   a–j  without discarding valuable data and/or unnecessarily replicating data. 
   Clinical ABR testing often results in multiple tests of the same stimulus condition, with measurements from each test being contaminated by different patterns of background nose. For example, in the middle of one test, a doctor&#39;s pager may suddenly go off, while in the middle of another test, the infant may cough or sneeze. 
   Previously, it was counterproductive to combine data from a relatively noiseless test with data from a test having greater average noise. The data-acquisition system  10  described herein, however, permits data to be combined band by band across several such tests in a manner that optimizes the signal-to-noise ratio of the resulting ABR measurement  38 . 
   In conventional data-acquisition systems, weighted averaging requires a priori selection of weighting coefficients. Thus, the weighting coefficients cannot be adaptively optimized in response to the signal-to-noise ratio of the resulting ABR measurement. In contrast, the data-acquisition system  10  described herein enables weighting coefficients  30   a–j  to be assigned dynamically or after the fact, thereby providing considerably more flexibility in the selection of methods for optimizing signal-to-noise ratio of the ABR measurement  38 . 
   The data-acquisition system  10  and method described herein are generally applicable to all clinical ABR testing, whether manual or automated. Such ABR testing can include neuro-diagnostic procedures, audiometric threshold estimation, and newborn screening. 
   The invention has been described in the context of measuring auditory response. However, evoked responses can arise from other stimuli, such as visual, tactile, olfactory, or gustatory stimuli. The principles described herein are applicable to measurement of evoked response resulting from whatever stimuli. 
   As described herein, samples are sorted into bins  22   a–j  on the basis of electrophysiologic noise amplitudes. However, sorting parameters other than electrophysiologic noise amplitude can be used. Additionally, the sorting parameter can also be a multi-dimensional quantity. For example, the digital signal processor  20  may have a second input for measuring ambient acoustic noise level. In such a case, the digital signal processor  20  can assign samples to bins  22   a–j  on the basis of both an electrophysiologic quantity, namely the sample amplitude, and on an acoustic quantity, namely the measured ambient acoustic noise level in the testing room. In this case, the sorting parameter is a two dimensional quantity and the bins  22   a–j  can be viewed as a two-dimensional array. While this might complicate the implementation of the data-acquisition system  10 , the principle of the invention is itself unchanged. 
   Alternatively, the sorting parameter can be made a function of more than one variable. For example, a measurement of ambient acoustic noise in the room might be converted into an equivalent electrophysiologic noise level. This equivalent electrophysiologic noise level could then be added to corresponding samples from the digital signal before those signals are sorted into bins  22   a–j.    
   It is to be understood that the foregoing description is intended to illustrate and not limit the scope of the invention. The invention is defined by the scope of the following claims. Other aspects, advantages, and modifications are within the scope of the following claims.