# Patent

## Title
System and method for estimating physiological parameters by deconvolving artifacts

## Abstract

There is disclosed a system and methods to estimate physiological parameters. In accordance with embodiments a method is disclosed which includes generating distribution data for a plurality of signals. The method may also include deconvolving one of the plurality of signals from the other plurality of signals to produce clean signals. The clean signals may then be used to calculate physiological parameters.

## Background
RELATED APPLICATIONS
This application claims priority to U.S. Provisional Application No. 61/009,399, filed Dec. 28, 2007, and is incorporated herein by reference in its entirety.


BACKGROUND
The present disclosure relates generally to medical devices and, more particularly, to non-invasive medical devices and methods used for determining physiological parameters.
This section is intended to introduce the reader to various aspects that may be related to various aspects of the present disclosure, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
In the field of medicine, doctors often desire to monitor certain physiological characteristics of their patients. Accordingly, a wide variety of devices may have been developed for monitoring many such characteristics of a patient. Such devices may provide doctors and other healthcare personnel with the information they need to provide the best possible healthcare for their patients. As a result, such monitoring devices have become useful in treating patients.
Non-invasive medical devices may be particularly useful and desirable, as they generally provide immediate feedback and do not traumatize a patient. Generally, non-invasive sensors may transmit electromagnetic radiation, such as light, through a patient's tissue. The sensor may photoelectrically detect the absorption and scattering of the transmitted light in such tissue. The light passed through the tissue may be selected to be of one or more wavelengths that may be absorbed and scattered by particular tissue constituents, such as blood, for example. One or more physiological characteristics may then be calculated based upon the amount of light absorbed and/or scattered.
One non-invasive technique for monitoring certain physiological characteristics of a patient is commonly referred to as pulse oximetry, and the devices built based upon pulse oximetry techniques are commonly referred to as pulse oximeters. Pulse oximetry may be used to measure various blood flow characteristics, such as the blood-oxygen saturation of hemoglobin in arterial blood, the volume of individual blood pulsations supplying the tissue, and/or the rate of blood pulsations corresponding to each heartbeat of a patient. In fact, the “pulse” in pulse oximetry refers to the time varying amount of arterial blood in the tissue during each cardiac cycle.
Pulse oximetry readings may measure the pulsatile, dynamic changes in amount and type of blood constituents in tissue. However, events other than the pulsing of arterial blood, such as noise received by the sensor, for example, may lead to modulation of the light path, direction, and the amount of light detected by the sensor, introducing error to the measurements. As such, various types of noise are primary causes of artifacts that may obscure determination of the blood constituent signal and make it difficult to obtain accurate measurements.
SUMMARY
Certain aspects commensurate in scope with the disclosure are set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the embodiments might take and, these aspects are not intended to limit the scope of the disclosure. Indeed, the disclosure may encompass a variety of aspects that may not be set forth below.
In an embodiment, there is provided a method for non-invasively estimating physiological parameters. The method may include detecting light from a plurality of light sources and generating respective distributions for the detected light of each of the plurality of light sources. The distribution for the detected light of one of the plurality of light sources may be deconvolved from each of the other distributions for the detected light from the other plurality of light sources to produce clean distributions. Physiological parameters may then be estimated using the clean distributions.
In an embodiment, there is provided a system for estimating the physiological parameters. The system may include a sensor comprising a plurality of light sources and a detector configured to generate signals based on light detected from the plurality of light sources. The system also includes a monitor coupled to the sensor. The monitor may be configured to generate distribution data for each of the plurality of light sources and deconvolve distribution data of one of the plurality of light sources from the distribution data of each of the other plurality of light sources.
In an embodiment, there is provided a method of calibration. The method of calibration may include collecting data during two time intervals and generating normalized density estimators representing the data collected during the two time intervals. The calibration method may also include finding a transform function such that the equality f2*h1=f1*h2 is true, wherein f1 is a vector representing data collected during the first time interval, f2 is a vector representing data collected during the second time interval, h1 is a density estimator representing the data from the first time interval, h2 is a density estimator representing data from the second time interval, and “*” is the convolution operator.



BRIEF DESCRIPTION OF THE DRAWINGS
Advantages of embodiments may become apparent upon reading the following detailed description and upon reference to the drawings in which:
FIG. 1 illustrates a pulse oximeter in accordance with an embodiment;
FIG. 2 illustrates a cross-sectional view of a pulse oximeter sensor in accordance with an embodiment;
FIG. 3 is a flow chart illustrating an exemplary technique for estimating physiological parameters in accordance with an embodiment;
FIG. 4 illustrates a clean density estimator for an IR signal in accordance with an embodiment;
FIG. 5 illustrates a clean density estimator for a red signal in accordance with an embodiment;
FIG. 6 illustrates a clean density estimator for a noise signal in accordance with an embodiment;
FIG. 7 illustrates a noisy density estimator for an IR signal in accordance with an embodiment;
FIG. 8 illustrates a noisy density estimator for a red signal in accordance with an embodiment;
FIG. 9 illustrates a noisy density estimator for a noise signal in accordance with an embodiment;
FIG. 10 is a flow chart illustrating a technique for distribution calibration in accordance with an embodiment;
FIG. 11 illustrates a calibration of a linear transform wherein a linear parameter is too large, according to an embodiment;
FIG. 12 illustrates a calibration of a linear transform wherein the linear parameter is too small, according to an embodiment; and
FIG. 13 illustrates a calibration of a linear transform wherein the linear parameter is nearly optimal, in accordance with an embodiment.



DETAILED DESCRIPTION
One or more specific embodiments will be described below. In an effort to provide a concise description of these embodiments, not all features of an actual implementation are described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.
In accordance with the present disclosure, a system and method are disclosed for estimating physiological parameters after deconvolving artifacts. In particular, in accordance with an embodiment, techniques for estimating percent oxygen saturation are disclosed using a third channel to estimate the distribution of noise. Specifically, distributions for an IR spectrum and a red spectrum may be generated after they have passed through blood perfused tissue. An estimated artifact distribution may be obtained using a third wavelength. In an embodiment, the estimated artifact distribution may be deconvolved from the distributions for the IR and red signals, thus, cleaning artifacts from the IR and red distributions. In an embodiment, once the artifact distribution is deconvolved from the IR and the red signals, the ratio-of-ratios, or “ratrat”, can be calculated to determine the percent saturation of oxygen in hemoglobin.
Using the present techniques, the distribution of the artifacts may be estimated and not the artifact signal itself. Additionally, the clean IR and red signals may not be de-noised signals, rather a de-noised distribution. As such, consistent saturation readings may be provided even in situations providing highly artifacted signals, and the system and methods disclosed herein may be useful to provide distributions to a maximum likelihood saturation estimator.
Referring to the figures and turning initially to FIG. 1, a pulse oximeter system is illustrated in accordance with an embodiment and is generally designated by the reference numeral 10. In an embodiment, the system 10 includes a monitor 12 which may house hardware and software configured to compute various physiological parameters. The monitor 12 may include a display 14 to display the various physiological parameters. For example, the display 14 may display the percent oxygen saturation of hemoglobin and the pulse rate.
In an embodiment, a sensor 16 may be communicatively coupled to the monitor 12 via a cable 18 and a connector 20. A cross-sectional view of the sensor 16 is illustrated in FIG. 2. As can be seen, the sensor 16 may have three emitters 20a-c capable of directing electromagnetic radiation, or light, toward a detector 22. In an embodiment, each emitter 20a-c may emit light at a unique wavelength.
In an embodiment, the first emitter 20a may emit light in the red region of the electromagnetic spectrum and the second emitter 20b may emit light in the infrared (IR) region of the electromagnetic spectrum. The third emitter 20c may emit light having a wavelength selected to maximize the detection of noise that is introduced to the sensor signal. In accordance with an embodiment, the third emitter 20c may operate at about 1250 nm to 1350 nm, for example. Alternatively, the third emitter 20c may operate in the blue region of the electromagnetic spectrum at approximately 450 nm to 550 nm, for example. In other words, the third wavelength may be in the IR, red, blue, or other regions of the electromagnetic spectrum depending upon the wavelength range that may be best suited to address the expected noise. Additionally, in an embodiment, a combination of more than one wavelength may be used to estimate the distribution of noise, as will be discussed in greater detail below.
According to an embodiment, FIG. 3 illustrates a flow chart 30 for operating a non-invasive medical device, such as the pulse oximeter 10 shown in FIG. 1. In an embodiment, light from a plurality of light sources, i.e., the emitters 20a and 20b, is detected, as indicated at block 32. As discussed above, light from the emitters 20a-b passes through blood perfused tissue before being detected at the detector 22. The constituent parts of the blood perfused tissue reflect and absorb the light. In an embodiment, the detector 22 produces an electrical signal indicative of the light that arrives at the detector 22 which may be correlative to an optical density (OD) of the blood perfused tissue relative to the respective wavelengths. Generally, the optical density represents the absorbance of a material, in this case, blood perfused tissue. The electrical signal is transmitted to the monitor 12 for processing and calculation of physiological parameters.
In an embodiment, the optical density of the light emitted by emitters 20a-b, with respect to the pulse oximeter 10, detected at the detector 22, may be correlated to each other according to the equation:

vk=skuk,  (1)

where vk represents the optical density of a first signal, such as the red signal, for example, and uk represents the optical density for a second signal, such an IR signal, for example, at time k. The sk is the ratio of the two signals or ratrat at time k. The red and IR optical density signals may be scaled versions of underlying signals:

vk=αktk, and  (2)

uk=βktk,  (3)

where tk is e.g., the change in blood volume due to pulse. Thus, the ratrat is given by sk=αk/βk, and αk, and βk can be referred to as scale parameters or scales of the red and IR optical density signals, respectively.

The measurements of the red and IR optical density signals may be corrupted by non-signal artifact. As mentioned above, the non-signal artifacts may be induced by various types of noise received by the sensor. Because of the non-signal artifacts, in an embodiment, the measurements actually reflect:

vk=αktk,+εk, and  (4)

uk=βktk,+ζk,  (5)

where the variables εk and ζk are random noise artifacts. The relation of scales still holds, but equation 1 is replaced by:

vk=sk(uk−ζk)+εk.  (6)

If εk and ζk are large compared to the signal values, then attempts to estimate the scale of the red and IR signals can fail. If εk and ζk are nearly equal and change over time with greater variation than the cardiac signal tk, then the estimated scale parameters will converge to the same number, giving unity ratrat, or saturation nearly 80.
Therefore, in an embodiment, the scale parameters for the red and IR signals αk and βk can be estimated accurately only if the influence of the random noise artifacts εk and ζk can be ignored. To do so, physical observations at wavelengths other than the red and IR signal wavelength may be used, such as those from a third wavelength. Alternatively, second order observations of the red and IR signals themselves may provide sufficient information to ignore the artifacts.
Referring again to FIG. 3, in an embodiment, distributions for the plurality of light sources is determined, as indicated at block 34. The distribution of one of the plurality of light sources, such as the third source, can be deconvolved from the distributions of the other light sources, i.e., the red and IR signals, as indicated at block 36, to generate clean distributions. The clean distributions may then be used to compute physiological parameters, as indicated at block 38. For example, the clean red and IR signals may be used to compute the ratrat.
The technique illustrated in FIG. 3 may be advantageous in several aspects. For example, as a saturation signal changes very slowly compared to sampling rate, signal reconstruction provides much more information than needed. Noise deconvolution, however, is not a signal reconstruction technique, as it does not attempt to find the underlying signal tk or the true IR and red signals. It is, however, an easier problem to solve than reconstruction, and its solution would be implied by a good reconstruction algorithm. Furthermore, it occurs in probability space instead of frequency space. The following provides a theoretical basis for the present techniques.
A Convolution of Sequences
In an embodiment, a bi-infinite sequence is an indexed collection of numbers: . . . , g-3, g-2, g-1, g0, g1, g2, . . . Such a sequence can be written like a vector, e.g., g. The sequences considered herein have compact support, meaning that only a finite number of nonzero elements are present. Thus, the only functional difference between the sequences considered herein and vectors are that the sequences can have variable length, and indexing matters.
Given two such sequences, f, g, their convolution is defined as:




  
    
      
        H
        =
        
          
            
              f
              ⋆
              g
            
            ⇒
            
              h
              i
            
          
          =
          
            
              ∑
              j
            
            ⁢
            
              
                f
                j
              
              ⁢
              
                
                  g
                  
                    i
                    -
                    j
                  
                
                .
              
            
          
        
      
    
    
      
        (
        7
        )
      
    
  




When f and g have compact support, so does f*g. Additionally, convolutions on sequences have associative and commutative properties, such that f*g=g*f and (f*g) *h=f*(g*h). Moreover, the summing of two random variables is equivalent to convolving their distribution functions. For example, suppose X and Y are discrete-valued random variables, and that x and y are associated discrete probability density functions. This means that there is an atomic unit of measurement, Δv such that xi=Pr{X=iΔv}, and yi=Pr{Y=iΔv}. Then the discrete probability density function of Z=X+Y is x*y, or z=x*y.

A Density Estimator

In an embodiment, if G is a finite set of real numbers, the density estimator, H(G) is the bi-infinite sequence h, whose ith element, hi is the number of elements of G which are in the ith bin. The bins are implicitly understood. Generally, the ith bin is defined as [iΔx, (I+1)Δx), so that each bin is of equal width, where Δx is implicitly understood. Because G is finite, h=H(G) has compact support.
The normalized {tilde over (H)}(G), is the sequence {tilde over (h)} defined as:




  
    
      
        
          
            
              h
              ~
            
            i
          
          =
          
            
              h
              i
            
            /
            
              
                ∑
                j
              
              ⁢
              
                h
                i
              
            
          
        
        ,
      
    
    
      
        (
        8
        )
      
    
  




where h=H(G). That is {tilde over (H)}(G) is a scaled version H(G) which sums to 1. If G represents a number of independent draws from a random variable, then {tilde over (H)}(G) gives an estimate of the probability distribution function of the random variable, subject to the width of the bins and the number of draws.

Accordingly, let V1:l and U1:l denote the collections of red and IR optical density observations, respectively, from timestep 1 to l. The normalized density estimators {tilde over (H)}(V1:l) and {tilde over (H)}(U1:l) approximate the probability density functions of the red and IR signals as random variables. This means that if an integer k is selected uniformly at random from 1, 2, 3, . . . , l, and uk and vk are then viewed, the probability of those random variables would be described by the normalized density estimators {tilde over (H)}(V1:l) and {tilde over (H)}(U1:l). Such normalized density estimators are shown in FIGS. 4, 5, 6, 7, 8 and 9. Specifically, FIGS. 4, 5 and 6 illustrate noiseless collects of a normalized density estimator 40 of the IR optical density, a normalized density estimator 42 of the red optical density, and a normalized density estimator 44 of a noise signal nk optical density, respectively. FIGS. 7, 8 and 9 illustrate noisy collects of a normalized density estimator 50 of the IR optical density, a normalized density estimator 52 of the red optical density and a normalized density estimator 54 of the noise signal nk, respectively.
According to various embodiments, each density estimator in FIGS. 4, 5, 6, 7, 8 and 9 represents 3200 data points sampled at 53 Hz. The density estimator for the noiseless and noisy collects, however, do not resemble each other, and the density estimators 44 and 56 have larger support by about half an order of magnitude. The density estimators 40, 42, 44, 50, 52, and 54 in all have the same scale in the value axis (y-axis) to emphasize the spread caused by artifact. However, as can be seen, the IR density estimator 40 and the red density estimator 42 have the same shape, as do the IR density estimator 50 and the red density estimator 52, subject to scaling differences in the x-axis. This is expected, as the saturation is not expected to change much during sampling. Additionally, the scaling difference between the value red and IR plots approximates the ratrat, as it is indicative of the ratio between the red optical density and IR optical density signals.
Additionally, each of the density estimators 40, 42 and 44 have a well defined peak. Alternatively, the density estimators 50, 52 and 54 are significantly more distributed due to the noise. Because of the distribution it is difficult to see similarities between the density estimators 50, 52 and 54 of the noisy collects and the density estimators 40, 42 and 44 of the noiseless collects. As such, the density estimators for the clean and noisy collects do not resemble each other and the density estimators for the noisy collects have larger support by about a half an order of magnitude. Therefore, the removal of the noise from the signals during noisy collects may help in achieving a more accurate estimation of physiological parameters.
For additional information regarding scale functions and density estimators, the book Introduction to Robust Estimation and Hypothesis Testing, second edition, R and R. Wilcox, Elsevier, Amsterdam (2005), may be referenced and is incorporated herein in its entirety and for all purposes.
The Algorithm and Calibration
In an embodiment, the proposed algorithm for estimating physiological parameters by deconvolving artifacts relies on the third channel, which can be an independent wavelength or a number of wavelengths combined together, and has been denoted nk. Observations of the noise signal nk allow for estimation of random processes that generate {εk}k and {ζk}k. Specifically, the distributions of the noise signal nk can be deconvolved from the normalized density estimators of observed red and IR signals, afterwhich, the scale parameters can be accurately estimated.
The simplest way to generate distributions of εk and ζk is to apply two functions to the collection values N1:l and take the normalized density estimator. Let the functions be Ør and Øi. The simplest model for functions Ør and Øi are of two linear functions such as:

Ør(x)=crx, and  (9)

Øi(x)=cix,  (10)

where the two constants cr and ci are to be determined. The noise signal nk of the third channel corresponds directly to the artifact parts εk and ζk, but needs to be translated into the right units. The third channel is not purely corrupting noise, rather, it is only related is some way to the corrupting noise. For example, if the third signal is an optical signal, and the corrupting noise comes from decoupling of the optical sensor (e.g., the oximeter sensor moves around on the finger), this decoupling will affect all three signals similarly but not identically, as it may depend on several factors, such as, the efficiencies of the detectors, their apertures, etc., for example. In this case, to translate the signal of the third wavelength into something equivalent to the corrupting noise, one may have to perform a scale transform(s), or make a nonlinear transform of some kind (listed in equation (23)). Alternatively, if the third signal is non-optical (such as a piezo electric sensor, or a magnetic induction sensor, etc. for example), the signal may be considered in terms of standard units such as pounds per square-inch, ohms, etch, which may be converted or translated into optical density unit equivalents in the red and IR wavelengths.

In an embodiment, a noise deconvolution saturation estimator may operate as shown in Algorithm 1 below. Note that since the values are grouped into density estimators before being deconvolved, there is some inherent loss of accuracy. Thus, accuracy of the method is affected by the bin-width. Moreover, the assumption that the density estimator represents the probability distribution function only works for a large sample size, such as, more than 100 samples, for example. As such, a meaningful result at rates lower than 1 Hz may be difficult to achieve.










Algorithm 1 - Saturation estimator algorithm


with artifact deconvolved.















Input: Sequences of red, IR, and noise signals, the posting rate


Output: the estimated saturation


DECONVOLVESAT (v1:k, u1:k, n1:k, prate)








(1)
Let lo ← 1, hi ← prate


(2)
while lo < k








(3)
let hi ← min (k, hi).


(4)
Let V ← {tilde over (H)} (vlo:hi), U ← {tilde over (H)} (ulo:hi), Nr ← {tilde over (H)} (Ør(nlo:hi)), Ni



← {tilde over (H)} (Øi(nlo:hi))


(5)
Deconvolve: R ← DECON (V, Nr), I ← DECON (U, Ni).


(6)
Compute the appropriate scale parameters of R and I. Let



ŝlo:hi be the ratio



of the scale parameters.


(7)
let lo ← hi + 1.


(8)
let hi ← hi + prate.








(9)
return ŝ1:k









The actual deconvolution may be performed by applying a least squares framework. A least squares framework is represented in Algorithm 2 and discussed in greater detail below.










Algorithm 2 - Least Squares Nonnegative Deconvolver.

















DECON (f, h)










(1)
Formulate the toeplitz matrix A associated with f.



(2)
Find vector g with nonnegative elements such that









(Ag − f)T (Ag − f) is minimized.










(3)
return g.









Deconvolution

Given the sequences f and h, finding the sequence g such that h=f*g presents some complications. Specifically:

    
    
        1. There may not be a sequence g that solves this problem and which has compact support. That is, the solution has an infinite number of nonzero elements. This solution is found by using the Fourier Transform and dividing but is typically ‘unstable’ because the elements become increasingly large in magnitude as the index diverges.
        2. By switching to a least-squares framework and restricting the search to compact sequences of a bounded number of nonzero elements, the solution may have negative elements, which cannot currently be interpreted as (scaled) density estimator values.

The least squares problem may be formulated as follows: find g with at most n+1 nonzero elements such that ∥h−f*g∥2 is minimized. Let I be the lowest index of a nonzero element of f, I+m be the highest index of a nonzero element of f, and j be the lowest index of g.

    
    


A matrix A may be written:




  
    
      
        
          
            
              
                f
                ⋆
                g
              
              =
              
              ⁢
              
                [
                
                  
                    
                      fi
                    
                    
                      0
                    
                    
                      0
                    
                    
                      ...
                    
                    
                      0
                    
                  
                  
                    
                      
                        fi
                        +
                        1
                      
                    
                    
                      fi
                    
                    
                      0
                    
                    
                      ...
                    
                    
                      0
                    
                  
                  
                    
                      
                        fi
                        +
                        2
                      
                    
                    
                      
                        fi
                        +
                        1
                      
                    
                    
                      fi
                    
                    
                      ...
                    
                    
                      0
                    
                  
                  
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                  
                  
                    
                      
                        fi
                        +
                        n
                      
                    
                    
                      
                        fi
                        +
                        n
                        -
                        1
                      
                    
                    
                      
                        fi
                        +
                        n
                        -
                        2
                      
                    
                    
                      ...
                    
                    
                      fi
                    
                  
                  
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                  
                  
                    
                      
                        fi
                        +
                        m
                      
                    
                    
                      
                        fi
                        +
                        m
                        -
                        1
                      
                    
                    
                      
                        fi
                        +
                        m
                        -
                        2
                      
                    
                    
                      ...
                    
                    
                      
                        fi
                        +
                        m
                        -
                        n
                      
                    
                  
                  
                    
                      0
                    
                    
                      
                        fi
                        +
                        m
                      
                    
                    
                      
                        fi
                        +
                        m
                        -
                        1
                      
                    
                    
                      ...
                    
                    
                      
                        fi
                        +
                        m
                        -
                        n
                        +
                        1
                      
                    
                  
                  
                    
                      0
                    
                    
                      0
                    
                    
                      
                        fi
                        +
                        m
                      
                    
                    
                      ...
                    
                    
                      
                        fi
                        +
                        m
                        -
                        n
                        +
                        2
                      
                    
                  
                  
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                    
                      ...
                    
                  
                  
                    
                      0
                    
                    
                      0
                    
                    
                      0
                    
                    
                      ...
                    
                    
                      
                        fi
                        +
                        m
                      
                    
                  
                
                ]
              
            
          
        
        
          
            
              
              ⁢
              
                [
                
                  
                    
                      gj
                    
                  
                  
                    
                      
                        gj
                        +
                        1
                      
                    
                  
                  
                    
                      
                        gj
                        +
                        2
                      
                    
                  
                  
                    
                      ...
                    
                  
                  
                    
                      
                        gj
                        +
                        n
                      
                    
                  
                
                ]
              
            
          
        
        
          
            
              
                =
                
                ⁢
                Ag
              
              ,
            
          
        
      
    
    
      
        (
        12
        )
      
    
  




where the matrix A is Toeplitz matrix. The least-squares formulation, without the non-negativity constraint in g, is described by the normal equation: ATAg=ATh. Because of the special structure of A, we have:





  
    
      
        
          ATA
          =
          
            [
            
              
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    0
                  
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    1
                  
                
                
                  γ2
                
                
                  ...
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    n
                  
                
              
              
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    l
                  
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    0
                  
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    1
                  
                
                
                  ...
                
                
                  
                    
                      γ
                      ⁢
                      
                        
                      
                      ⁢
                      n
                    
                    -
                    1
                  
                
              
              
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    2
                  
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    1
                  
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    0
                  
                
                
                  ...
                
                
                  
                    
                      γ
                      ⁢
                      
                        
                      
                      ⁢
                      n
                    
                    -
                    2
                  
                
              
              
                
                  ...
                
                
                  ...
                
                
                  ...
                
                
                  ...
                
                
                  ...
                
              
              
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    n
                  
                
                
                  
                    
                      γ
                      ⁢
                      
                        
                      
                      ⁢
                      n
                    
                    -
                    1
                  
                
                
                  
                    
                      γ
                      ⁢
                      
                        
                      
                      ⁢
                      n
                    
                    -
                    2
                  
                
                
                  ...
                
                
                  
                    γ
                    ⁢
                    
                      
                    
                    ⁢
                    0
                  
                
              
            
            ]
          
        
        ,
      
    
    
      
        (
        13
        )
      
    
  




where γi is the sample autocovariance of the sequence. (An actual sample autocovariance typically involves a subtraction of the first moment which is ignored here.) The matrix ATA is symmetric, positive, definite, and Toeplitz, which makes the unconstrained least squares problem amenable to specialized techniques such as the Levinson-Durbin algorithm or the Anderson-Bitmead algorithm, which speed up the computation considerably from the usual O(n3) runtimes for Gaussian Elimination [1]. It is not clear if these algorithms can be altered for the constrained system, however. It may be easier to adapt the scale estimator to the case of negative density estimator values.

A constrained least squares deconvolution problem can be formulated as a bounded quadratic programming problem:




  
    
      
        
          g
          ∈
          
            R
            
              n
              +
              1
            
            min
          
        
        ,
        
          g
          ≥
          
            0
            ⁢
            
              
                
                  
                  
                    Ag
                    -
                    h
                  
                  
                
                2
                2
              
              .
            
          
        
      
    
    
      
        (
        14
        )
      
    
  




The objective function is





  
    
      
        
        
          Ag
          -
          h
        
        
      
      2
      2
    
    =
    
      
        
          g
          T
        
        ⁢
        
          A
          T
        
        ⁢
        Ag
      
      -
      
        2
        ⁢
        
          
        
        ⁢
        
          h
          T
        
        ⁢
        Ag
      
      +
      
        
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which is quadratic in g. As implemented for a calibration study, the deconvolution routine formulates this problem and delegates the solution to a quadratic programming algorithm, which is computationally expensive, even when seeded with the unconstrained optimal solution as an initial guess.

Calibration

In an embodiment, the functions Ør and Øi of equations (9) and (10), and Algorithm 1 are found through a calibration process. The calibration may be difficult, however, as the noise channel is not identically zero during the “noiseless” collects, as illustrated by the density estimator 44 in FIG. 6. To account for this, in calibrating for Øi, two time intervals for the same subject are taken and then calibrated so that the sampling from the two time intervals are equivalent. FIG. 10 illustrates a flow chart representation of a technique 60 for calibration in accordance with an exemplary embodiment of the present invention.
In an embodiment, the technique 60 begins by collecting data during a first time period from a single source, as indicated in block 62. A second set of data is collect from the source during a second time period, as indicated at block 64. For example, two samples for the IR or red signal may be taken. For convenience, call them 1:n and n+1:m. The time steps 1:n may be considered “clean,” and n+1:m may be considered “noisy,” although there need not be such a distinction. The normalized density estimators then are:

h1=Ĥ(U1:n),  (15)

f1=Ĥ(Øi(N1:n)),  (16)

h1=Ĥ(Un+1:m),  (17)

f1=Ĥ(Øi(Nn+1:m)),  (18)

where the function Øi is a candidate function. Assuming that the subject's cardiac characteristics are the same for the two collects, the density estimators may be presented as:

h1=f1*g,  (19)

h2=f2*g,  (20)

where g is the normalized density estimator representing the discrete probability density function of the cardiac signal. Referring again to FIG. 10, a scaling parameter is found to calibrate the first and second data so that they are approximately equal, or so that they exhibit approximately equal distributions, as indicated in block 66. Specifically, manipulation of the equations (19) and (20) using commutative and associative properties produces:

f2*h1=f2*f1*g,  (21)

f1*h2=f1*f2*g=f2*f1*g,  (22)

Thus, calibration for the data sets consists of finding Øi such that

f2*h1=f1*h2  (23)

If Øi is parameterized by a single parameter, for example, if Øi is linear, then finding the optimal parameter can be easily achieved with a brute-force search, since the range of the parameter can be bounded in advance by inspection. That is, for an particular signal's optical density, the scale of noise should not be larger than the observed signals, but should be larger than zero.
In an embodiment, the selection of an appropriate scaling parameter ci is graphically illustrated in plots 70, 72, and 74 of FIGS. 11, 12 and 13, respectively, which show three choices of the parameter for a linear transform Øi. In each of the FIGS. 11, 12 and 13, a first plot line 76 represents a first observed IR distribution which may be described as an underlying IR distribution convoluted with a noise distribution. A second plot line 78 represents a second observed IR distribution representing an underlying IR distribution convoluted with a noise distribution. A third plot line 80 represents a scaled noise distribution. In FIG. 11, the plot 70 shows the third plot line 80 as indicating that the scaling parameter of the noise distribution is too large, as the scaling factor does not allow for equation 23 to be true. This is shown by the first plot line 76 having a more concentrated or less spread distribution the plot line 78.
In FIG. 12, the plot 72 shows the third plot line 80 as being inverted, indicating that the scaling parameter for the noise signal is too small. This is illustrated further by the plot line 76 having a wider distribution than the plot line 78. In FIG. 13, the plot 74 shows the third plot line 80 as being nearly optimal, as the plot lines 76 and 78 have nearly the same distribution and, thus, the two sides of equation 23 are approximately equivalent. The calibration using a linear transform was attempted and the experiment is discussed in detail below.
Linear Calibration Experiment
The basic experiment includes:

    
    
        1. Gathering red and noise signals over two separate periods;
        2. Compute the density estimators of the red signal over both periods) call them f1 and f2;
        3. Use the translation to translate the noise signal in to the red equivalent and construct density estimators h1 and h2; and
        4. As indicated in equation (23), and because of the commutative and associative properties of convolution, f2*h1=f1*h1 should be met regardless of the presence of strong noise if the cardiac signals are relatively constant over the two time periods. This equation (and the same equation for the IR signal and the translation of the third signal into IR equivalent) is satisfied when the technique is properly estimating the distribution of noise in the distributed signals.
    
    


Consider the calibration of two different parts of the same collect data. That is, as above, consider the three time intervals 1:n, n+1:n, and m+1:l. In laboratory experiments, the first interval was clean, while the other two intervals had different kinds of artifacting (scratching versus tapping). Using the same language as above, a linear calibration was attempted to get

f2*h1=f1*h2,  (24)

then another calibration was attempted to get

f3*h1=f1*h3.  (25)

The same calibration was expected, but the results were different by a factor of two. The results are tabulated in Table 1. Specifically, Table 1 shows













Noise Interval
ci
cr







Interval 2
1.63590393
1.33100586


Interval 3
4.08316895
2.53460938









The scaling factors in the Red and IR form a devonvolution calibration on two different noise intervals. The parameters were found with a Nelder Mead brute-force search to minimize the L∞ norm. The density estimators had 80 bins.

Theoretically, any proposed choice of transforms Øi and Ør should produce the same results when calibrated multiple times under the following procedure: Randomly partition a collect into three equal-sized sets, numbered 1, 2, 3, and then calibrate the functions to get f2*h1=f1*h2.
There are a number of reasons the calibration may have been off by the factor of two. For example:

    
    
        The additive model of equation (4) may not apply. This may have profound effects on any attempt at noise-deconvolved saturation estimation.
        The linear model for Øi and Ør is not appropriate. This may be corrected by finding an appropriate calibration model for the Øi and Øi.
        The noise channel used in the experiments was not appropriate.
    
    


Because of the inherent non-linearity of the calibration problem, the transforms Øi and Ør may be kept simple, e.g., parametrized by a single parameter each, Any of the following proposed transforms might be applicable, although there is no theoretical reason for proposing any of them other than simplicity:




  
    
      
        
          
            
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As far as other noise channels, the obvious suspects are: another optical channel at a different wavelength or combination of wavelengths; a Cauchy distribution (or a Gaussian) whose width is determined by the second moment of the signal of an optical channel or by the width of the biggest peak in the Fourier Transform of the optical signals; the residual of a linear least squares fit or other fit.
While the disclosure may be conducive to various modifications and alternative forms, embodiments have been shown by way of example in the drawings and have been described in detail herein. However, it should be understood that the disclosure is not intended to be limited to the particular forms disclosed. Rather, the disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the following appended claims.

## Claims

1. A method for non-invasively estimating a physiological parameter comprising:
detecting light over a period of time from a plurality of light sources comprising at least three light sources;
generating respective distributions for the detected light of each of the plurality of light sources for the period of time;
deconvolving the distribution for the detected light of one of the plurality of light sources from each of the other distributions for the detected light from the other plurality of light sources to produce clean distributions for the period of time; and
estimating a physiological parameter based at least in part upon the clean distributions;
wherein deconvolving the distribution for the detected light of one of the plurality of light sources comprises using a least squares algorithm, wherein the least squares algorithm comprises:
formulating a toeplitz matrix A associated with f; and
finding a vector g with nonnegative elements such that (Ag-f)T(Ag-f) is minimized, wherein g and f are bi-infinite sequences.

2. The method of claim 1, wherein the distribution for the detected light of the one of the plurality of light sources is utilized to estimate the distribution of noise artifacts in a detected signal.

3. The method of claim 1, wherein the plurality of light sources comprises a first light source operating in the red region of the electromagnetic spectrum, a second light source operating in the infrared region of the electromagnetic spectrum, and a third light source operating in region of the electromagnetic spectrum that is selected to detect noise.

4. The method of claim 3, wherein the third light source operates in a blue region of the electromagnetic spectrum.

5. The method of claim 3, wherein the third light source operates in a region comprising the wavelengths approximately in the range of 1250 to 1350 nm.

6. The method of claim 1, wherein deconvolving the distribution for the detected light of the one of the plurality of light sources comprises using a least squares algorithm, wherein the least squares algorithm is solved using non-negative matrix factorization relaxation steps.

7. The method of claim 1, wherein the method further comprises calibrating functions representative of the distribution of a noise signal.

8. The method of claim 7, wherein calibrating functions representative of the distribution of the noise signal comprises:
collecting a first set of data for each of the plurality light sources;
collecting a second set of data for each of the plurality of light sources; and
parameterizing the functions representative of the distribution of the noise signal, wherein parameterizing the functions comprises finding a parameter to produce approximately equal distributions of the first and second sets of data.

9. The method of claim 4, wherein computing physiological parameters comprises determining a scaling difference between distributions of detected light for the red and infrared light sources.

10. The method of claim 1, wherein estimating the physiological parameter comprises estimating a blood oxygen saturation.

11. The method of claim 10, further comprising displaying the blood oxygen saturation on the monitor.

12. The method of claim 1, wherein the three light sources operate at different wavelengths from each other.

13. The method of claim 1, further comprising passing light from the three light sources through blood-perfused tissue, prior to detecting the light.

14. A system for estimating a physiological parameter comprising:
a sensor comprising:
a plurality of light sources; and
a detector configured to generate signals based on detected light from the plurality of light sources over a period of time; and

a monitor coupled to the sensor configured to:
generate distribution data based on the detected light for the period of time for each of the plurality of light sources; and
deconvolve distribution data for the period of time of one of the plurality of light sources from the distribution data of each of the other plurality of light sources for the period of time, to produce clean distributions;
wherein deconvolving the distribution data comprises the monitor using a least squares algorithm, wherein the least squares algorithm comprises:
formulating a toeplitz matrix A associated with f; and
finding a vector g with nonnegative elements such that (Ag-f)T(Ag-f) is minimized, wherein q and f are bi-infinite sequences.

15. The system of claim 14, wherein the plurality of light sources comprises three light sources operating at different wavelengths.

16. The system of claim 15, wherein the three light sources comprise:
a first light source operating in the red region of the electromagnetic spectrum; and
a second light source operating in the IR region of the electromagnetic spectrum.

17. The system of claim 14, wherein at least one of the plurality of light sources is used to obtain data related to artifacts.

18. The system of claim 17, wherein the monitor is configured to find functions representative of the artifacts through a calibration process, wherein the calibration process comprises parameterization of the functions.

19. The system of claim 14, wherein the monitor is further configured to estimate a physiological parameter based at least in part on the clean distributions.

20. The system of claim 19, wherein the parameter comprises blood oxygen saturation.

21. A method for non-invasively estimating a physiological parameter comprising:
detecting light over a period of time from a plurality of light sources comprising at least three light sources;
generating respective distributions for the detected light of each of the plurality of light sources for the period of time;
calibrating functions representative of a distribution of a noise signal,
wherein calibrating functions representative of the distribution of the noise signal comprises:
collecting a first set of data for each of the plurality light sources;
collecting a second set of data for each of the plurality of light sources; and
parameterizing the functions representative of the distribution of the noise signal, wherein parameterizing the functions comprises finding a parameter to produce approximately equal distributions of the first and second sets of data;

deconvolving the distribution for the detected light of one of the plurality of light sources from each of the other distributions for the detected light from the other plurality of light sources to produce clean distributions for the period of time; and
estimating a physiological parameter based at least in part upon the clean distributions.

22. A system for estimating a physiological parameter comprising:
a sensor comprising:
a plurality of light sources; and
a detector configured to generate signals based on detected light from the plurality of light sources over a period of time; and

a monitor coupled to the sensor configured to:
generate distribution data based on the detected light for the period of time for each of the plurality of light sources;
calibrate functions representative of a distribution of a noise signal, wherein calibrating functions representative of the distribution of the noise signal comprises:
collecting a first set of data for each of the plurality light sources;
collecting a second set of data for each of the plurality of light sources; and
parameterizing the functions representative of the distribution of the noise signal, wherein parameterizing the functions comprises finding a parameter to produce approximately equal distributions of the first and second sets of data; and

deconvolve distribution data for the period of time of one of the plurality of light sources from the distribution data of each of the other plurality of light sources for the period of time, to produce clean distributions.