Patent Publication Number: US-2022225881-A1

Title: Infrared otoscope for characterization of effusion

Description:
CROSS-REFERENCE 
     This is a continuation-in-part of U.S. application Ser. No. 16/438,603, filed Jun. 12, 2019, which is a continuation of U.S. application Ser. No. 15/609,015, filed May 31, 2017, now U.S. Pat. No. 10,357,161, issued Jul. 23, 2019, the full disclosures of which are incorporated herein by reference in their entirety; this application is also a continuation-in-part of U.S. application Ser. No. 16/043,584, filed Jul. 24, 2018, which is a continuation of U.S. application Ser. No. 15/188,750, filed Jun. 21, 2016, now U.S. Pat. No. 10,568,515, issued Feb. 25, 2020, the full disclosures of which are incorporated herein by reference in their entirety. 
    
    
     BACKGROUND 
     Acute Otitis Media (AOM) is a common disease of the inner ear, involving tissue inflammation and fluidic pressure which impinges on the tympanic membrane. Acute Otitis Media may be caused by a viral infection, which generally resolves without treatment, or it may be caused by a bacterial infection, which may progress and cause hearing loss or other deleterious and irreversible effects. Unfortunately, it is difficult to distinguish between viral or bacterial infection using currently available diagnostic devices, and the treatment methods for the two underlying infections are quite different. For bacterial infections, antibiotics are the treatment of choice, whereas for viral infections, the infection tends to self-resolve, and antibiotics are not only ineffective, but may result in an antibiotic resistance which would make them less effective in treating a subsequent bacterial infection. It is important to accurately diagnose acute otitis media, as AOM can be a precursor to chronic otitis media with effusion (COME), for which surgical drainage of the effusion and insertion of a tube in the tympanic membrane is indicated. 
     The definitive diagnostic tool for inner ear infections is myringotomy, an invasive procedure which involves incisions into the tympanic membrane, withdrawal of fluid, and examination of the effusion fluid under a microscope to identify the infectious agent in the effusion. Because of complications from this procedure, it is only used in severe cases. This presents a dilemma for medical practitioners, as the prescription of antibiotics for a viral infection is believed to be responsible for the evolution of antibiotic resistance in bacteria, which may result in more serious consequences later in life, and with no efficacious treatment outcome, as treatment of viral infectious agents with antibiotics is ineffective. An improved diagnostic tool for the diagnosis of acute otitis media is desired. 
     SUMMARY 
     In an aspect, an optical coherence tomography (OCT) device has a low coherence optical source generating optical energy coupled through a first splitter, thereafter to a second splitter, the second splitter having a measurement optical path to a tympanic membrane and also a reference optical path to a reflector which returns the optical energy to the first splitter, where the reflected optical energy is added to the optical energy reflected from the measurement optical path. The combined reflected optical energy is then provided to the first splitter, which directs the optical energy to a detector. The reflector is spatially modulated in displacement along the axis of the reference optical path such that the detector is presented with an optical intensity and optionally a continuum of optical spectral density from a particular measurement path depth, when the measurement optical path and reference optical path are equal in path length. When the device is positioned with the measurement path directed into an ear canal and directing optical energy to a tympanic membrane, by varying the reference optical path length through translation of the location of the reflector along the axis of the reference optical path, a measurement of optical and spectral characteristics of the tympanic membrane may be performed. Additionally, an external pressure excitation may be applied to provide an impulsive or steady state periodic excitation of the tympanic membrane during the OCT measurement, and a peak response and associated time of the peak response identified. The temporal characteristics and positional displacement of the tympanic membrane can be thereafter examined to determine the tympanic membrane response to the external pressure excitation. The evaluation of the tympanic membrane response from the OCT detector data may subsequently be correlated to a particular viscosity or biofilm characteristic. By examination of the temporal characteristic, an estimate of the viscosity of a fluid adjacent to a tympanic membrane may be determined, and the viscosity subsequently correlated to the likelihood of a treatable bacterial infection. 
     A first object of the invention is a non-invasive medical device for the identification of fluid type adjacent to a tympanic membrane. 
     A second object of the invention is a method for identification of a fluid adjacent to a tympanic membrane. 
     A third object of the invention is a method for performing optical coherence tomography for identification of a film characteristic adjacent to a tympanic membrane. 
     A fourth object of the invention is an apparatus for performing optical coherence tomography for identification of a fluid characteristic adjacent to a tympanic membrane. 
     An fifth object of the invention is an apparatus and method for characterization of a tympanic membrane and adjacent materials by coupling a pressure excitation source to a tympanic membrane, where the tympanic membrane is illuminated through a measurement path by an optical source having low coherence, the low coherent optical source also coupled to a reference path and to a mirror, where reflections from the mirror and reflections from the tympanic membrane are summed and presented to a detector, the reference path length modulated over a range which includes the tympanic membrane, the detector thereby receiving reflected optical energy from the tympanic membrane through the measurement path and also from the mirror through the reference path, such that modulation of the reference path length at a sufficiently high rate allows for estimation of the tympanic membrane position in response to the pressure excitation, thereby providing characterization of the tympanic membrane and adjacent fluid. 
     A sixth object of the invention is an optical coherence tomography system having a measurement path and a reference path, the reference path modulated in length, the measurement path and reference path coupled through an optical splitter to an optical source having low coherence, where reflected optical energy from the reference optical path and reflected optical energy from the measurement optical path are summed and provided to a wavelength splitter and thereafter to a plurality of detectors, one detector for each sub-range of wavelengths within the wavelength spectrum of the low coherence optical source, the plurality of detectors coupled to a controller discriminating by wavelength characteristics the detector response for at least two different reflective materials. 
     In a second aspect, a controller enables one of a first plurality of optical sources, or alternatively a single first optical source at a wavelength for bacterial absorption, and one of a second plurality of optical sources, or alternatively a second optical source operative at an adjacent wavelength which is non-absorptive for bacteria, an optional third source operative at a wavelength absorptive for watery fluid and an optional fourth source operative at an adjacent non-absorptive wavelength for watery fluid, each optical source or sources optionally operative at alternating or exclusive intervals of time. Each wavelength source is optically coupled through a tapered speculum which is inserted into the ear canal of a subject to be examined. The optical beam from each optical source may be carried as a directed beam, or the optical beam may be carried in an annular light guide or light pipe which surrounds the speculum, the optical energy from the illumination configuration impinging onto a front (distal) surface of a tympanic membrane, the tympanic membrane having a bacterial film or bacterial fluid on an opposite (proximal) surface of the tympanic membrane to be characterized. Reflected optical energy is coupled into the speculum tip to a single detector having a first wavelength response for energy reflected from the first source and a second wavelength response for energy reflected from the second wavelength source, or to separate detectors which are operative in each optical wavelength range of a respective optical source. The first wavelength response and second wavelength response are averaged over the associated interval the respective optical source is enabled to form an average measurement for each first wavelength response and each second wavelength response, and a ratio is formed from the two measurements. A first wavelength is in an absorption or scattering range of wavelengths for a bacterium to be characterized, and a second of the wavelengths is adjacent to the first wavelength and outside of the bacterial scattering or absorption wavelength. The response ratio for the first and second wavelength is applied to a polynomial or to a look-up table which provides an estimate of bacterial load from the ratio of power in the first wavelength to the power in the second wavelength, optionally compensating for the wavelength specific attenuation when absorptive or scattering fluid is not present, for example by using a stored wavelength scaling coefficient which compensates for scattering alone. A similar ratio for the detector responses associated with the third and fourth wavelength sources which are in adjacent absorptive and non-absorptive wavelengths, respectively, for water may be formed as well. 
     In a third aspect providing axial extent specificity over the region of measurement, the first and second wavelength sources are selected as adjacent wavelengths for absorption response and non-absorption response for bacteria, and also have a short coherence length, with the optical output of each source directed to the proximal surface of the tympanic membrane and middle ear to be characterized after splitting the optical energy into a measurement path and a reference path. The measurement path directs optical energy to the fluid to be characterized having a length equal to the reference path, the reflected optical energy from the measured path and reflected path are combined, thereby forming a coherent response over a narrow depth range, which is set to include the proximal surface of the tympanic membrane and middle ear region to be characterized. The first wavelength source and second wavelength source are enabled during exclusive intervals of time, and the combined measurement path and reference path optical energy directed to a detector response to the associated wavelengths. The first wavelength detector response and second wavelength detector response form a ratio which is used as a bacterial load metric, the ratio metric acting as a proxy for detection of the presence of bacteria. The third and fourth wavelengths are selected as in the first example to be adjacent but comparatively scattering and non-scattering for watery fluid, and used to form a second ratio which acts as a proxy for detection of watery fluid in the selected axial extent. 
     For the second or third aspect, by combining the second metric (presence of watery fluid) with the first metric (presence of bacteria), a more complete survey of the scope of acute otitis media may be determined. 
     A seventh object of the invention is a device for measurement of infectious agents present in an individual suspected of suffering from acute otitis media, the device having a plurality of optical sources, each optical source operative at a unique wavelength or range of wavelengths, each optical source operative within a particular range of wavelengths for an interval of time which is exclusive from the interval of time when optical sources at other wavelengths are operative, the device having a detector for measurement of reflected optical energy, the detector measuring a ratio of detected optical energy at a first wavelength to detected optical energy at a second or third wavelength, thereafter forming a ratio metric value as a proxy for estimated bacterial load. 
     An eighth object of the invention is a method for determination of bacterial concentration by successively illuminating a first surface of a membrane using a first and second wavelength at exclusive time intervals, measuring the reflected optical energy from the opposite surface of the membrane during each associated interval, forming a ratio of the first wavelength and second wavelength detector responses from the associated illumination events, each illumination event at a unique wavelength or range of wavelengths, where at least one of the illumination wavelengths corresponds to a bacterial absorption band, and another of the illumination wavelengths is in a wavelength with non-absorption or non-scattering characteristic for a bacterial colony or group of dispersed bacterium. 
     A ninth object of the invention is a speculum tip for insertion into an ear canal, one or more pairs of optical sources, each optical source coupling an optical output through the speculum tip, each optical source operative in a unique wavelength or range of wavelengths, each pair of optical sources generating a first optical output at a first wavelength selected for reflective attenuation for either watery fluid or bacteria, and also generating a second wavelength selected for comparative non-attenuation reflection for either watery fluid or bacteria, the second wavelength operative near the first wavelength, where reflected optical energy from the tympanic membrane is directed to a detector responsive to each optical source wavelength for optical energy reflected into the speculum tip, the detector coupled to a controller measuring a ratio of detector response from said first and said second wavelength, thereby forming a metric indicating the presence of bacteria and/or watery fluid from the detector response ratio associated with each pair of emitters. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: 
         FIG. 1  shows a block diagram of an infrared spectroscopy system for making measurements of a tympanic membrane. 
         FIG. 2  shows a detail view of a speculum tip and optical components with respect to a tympanic membrane. 
         FIG. 3  shows a plot of scattered IR spectral response vs wavelength from a tympanic membrane. 
         FIG. 4  shows a plot of waveforms for measurement of reflected optical energy from a first and second optical source. 
         FIG. 5  shows a block diagram of an OCT measurement system for dual wavelength measurements. 
         FIG. 6A  and  FIG. 6B  shows a block diagram for a multi-wavelength detector. 
         FIG. 7A ,  FIG. 7B ,  FIG. 7C ,  FIG. 7D ,  FIG. 7E , and  FIG. 7F  show waveform plots for a normal tympanic membrane. 
         FIG. 8A ,  FIG. 8B ,  FIG. 8C ,  FIG. 8D ,  FIG. 8E , and  FIG. 8F  show waveform plots for viral effusion in a tympanic membrane. 
         FIG. 9A ,  FIG. 9B ,  FIG. 9C ,  FIG. 9D ,  FIG. 9E , and  FIG. 9F  show waveform plots for bacterial effusion in a tympanic membrane. 
         FIG. 10  shows a block diagram of an optical fiber based OCT system for dual wavelength in-fiber dual spectroscopy. 
         FIG. 11  shows a block diagram of an optical coherence tomography characterization system. 
         FIG. 12A  shows a plot of mechanical actuator displacement vs actuator voltage. 
         FIG. 12B  shows a plot of reference path length over time, as controlled by actuator voltage or current. 
         FIG. 13  shows a block diagram for an optical coherence tomography characterization system for use examining a tympanic membrane. 
         FIG. 14  shows a polychromatic detector. 
         FIG. 15A  shows a plot of an example excitation waveform for modulation of a reference length. 
         FIG. 15B  shows a detector signal for a tympanic membrane adjacent to fluid such as from OME and a detector signal for a normal tympanic membrane. 
         FIG. 16  shows an optical waveguide system for measurement of a tympanic membrane. 
         FIG. 17  shows an optical waveguide system for measurement of a tympanic membrane with an excitation source. 
         FIG. 18A  shows a plot for a sinusoidal excitation applied to deformable surface or membrane with a reflected response signal. 
         FIG. 18B  shows a plot for a step excitation applied to a deformable surface or membrane, and a response to the step excitation. 
     
    
    
     DETAILED DESCRIPTION 
     The present provides an otoscope for characterization of fluid in an ear. The present provides methods, systems, and devices relating to the use of optical coherence tomography (OCT). For example, the OCT may be used in the diagnosis of otitis media (OM). For example, the present disclosure provides methods, systems, and devices related to the detection of bacteria in a fluid opposite a membrane using a measurement of optical properties of the fluid and bacteria using one or more dual wavelength optical sources and a detector which is responsive to a particular source during a particular time interval. 
       FIG. 1  shows a block diagram for an infrared (IR) spectroscopy system with an expanded view of the speculum tip in  FIG. 2 . A controller  134  is coupled to a detector response processor  130  and dual source controller  132 . The dual source controller  132  enables and provides power to a first optical source (not shown) at a first wavelength λ 1  and a second wavelength source (not shown) at a second wavelength λ 2  during alternating intervals. The optical energy from the sources is directed through a speculum tip  102  and onto the front (distal) surface of a tympanic membrane  120  to be characterized, with the speculum tip  120  minimizing the reflected optical energy from inside the speculum tip  120  to the detector  106  through paths other than those which first reflect from the tympanic membrane  120 . The reflected optical energy is sensed by an optical detector  106  and provided to image processor  130 , which compares the reflected optical energy at a first wavelength to reflected optical energy at a second wavelength, and forms a metric such as ratio of reflected optical power measured at the detector in each wavelength 
     
       
         
           
             
               
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     The wavelength metric may be used to estimate the likelihood of presence of bacteria or bacterial load in the inner ear fluid on the opposite (proximal) surface of the tympanic membrane  120 . 
       FIG. 2  shows an example detailed view of IR speculum tip  102  with respect to other elements of an example embodiment. For bacterial measurement, first wavelength  21  and adjacent second wavelength  22  optical energy  212  may be coupled to the speculum tip  102  in any known manner which then couples to an annular light pipe, such as with a plurality of optical fibers positioned around the circumference of speculum tip  102 , thereby coupling optical energy  200  to tympanic membrane  120  and to fluid  204  which may be on the proximal side of tympanic membrane  120 , but without directly coupling to detector  106  until after reflection from tympanic membrane  120  and any fluid  204  which may lie opposite the tympanic membrane  120  distal surface which is facing the speculum tip  102 . It may be additionally advantageous to add structure which exclude optical energy from sources other than tympanic membrane reflection. Reflected optical energy, which includes responses from tympanic membrane  120  and any fluid  204  which may be present, is focused by lens  206  into a dual range wavelength detector  106 . In one example embodiment, the inner surfaces of speculum tip  212  are reflective and no lens or focusing mechanism  206  is present to guide unfocused reflected light to detector  106 . Where a lens  206  is not present, the detector  106  is responsive to optical energy traveling directly from the tympanic membrane, as well as optical energy which has reflected from the inner reflective surface of the speculum tip  212 . In this embodiment, identification of the selection region may be accomplished using a laser pointer (not shown) or other optical viewing system. The laser pointer emitter may optionally be disabled during measurement intervals to avoid contributing unwanted detector response from the laser pointer scattered reflection. A similar set of third and fourth wavelengths may be used to measure water content with adjacent wavelengths in absorption and non-absorption wavelengths. In another example embodiment, lens system  206  is present with the detector  106  having a small extent and comparatively small number of pixels and positioned at focal point  207 , or alternatively it may be placed at an image plane as shown in  FIG. 2  with a large number of pixels, such as 50×50 or 100×100, or a resolution which is governed by the pixel pitch and available inner diameter of speculum  102  at the image or focal plane. 
       FIG. 3  shows a spectral response for energy reflected from a tympanic membrane with and without bacterial/watery fluid. The reflection characteristic has a characteristic 
     
       
         
           
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     absorption falloff associated with Rayleigh scattering, whereby longer wavelengths have fewer scattering interactions and lower absorption than shorter wavelengths. The absorption plot  302  is generally reciprocal with increasing wavelength, however bacteria having a physical length which interacts with optical energy at an associated wavelength, such as the range  309  which has a greater absorption  312 , 314  for various bacterium in region  309  of the plot for bacterial fluid compared to non-bacterial fluid in response plot  302 . Particular bacteria which are absorptive in range  309  include  Haemophilus Influenzae, Moraxella Catarrhalis , and  Streptococcus Pneumoniae . Similarly, an elevated absorption peak  306  is found associated with water absorption in a different range of wavelengths. In the present invention, the detector is responsive to reflected optical energy in a first wavelength range  309  such as 1050 nm to 1150 nm which provides for a decreased response at the detector due to bacterial scattering, and the detector uses absorption in an adjacent wavelength  322  such as 1000 nm or the visible optical range  308  of 400 to 800 nm, which may also be used as a fifth wavelength λ 5  for pointing and illuminating the region of examination used for forming the λ 1  and λ 2  or λ 3  and  4  metric ratios. In this case, λ 5  may be in a visible range or detection wavelength range for a 2D detector  106 , with the λ 5  source having a narrow dispersion laser (not shown) for illuminating the region of examination and indicating a landmark region such as the “cone of light” of the tympanic membrane for locating the measurement region. 
     In an illustrative example,  FIG. 3  shows a first wavelength  326  with an increased absorption when bacteria is present (region  309 ) compared to second wavelength  322  which is unaffected by the presence of bacteria, and third wavelength  326  has greater absorption when watery fluid is present compared to fourth wavelength  324  which is adjacent to the absorptive wavelength for watery fluid. These examples are given for illustrative purposes, wavelengths for absorption by bacteria or water may vary from those shown in the example of  FIG. 3 . In the context of the present specification, wavelength specific absorption may also be referred to as scattering or reflective attenuation. In one example of the invention, a first wavelength operative for increased absorption or scattering in the presence of bacteria is in the range 1050 nm to 1150 nm, and an adjacent wavelength is one below 1050 nm or above 1150 nm. In another example of the invention, a third wavelength operative for increased absorption or scattering in the presence of watery fluid is the range  310  from 1450 nm to 1600 nm, and a fourth wavelength which is adjacent to the third wavelength is below 1450 nm or above 1600 nm. 
       FIG. 4  shows a plot of waveforms for operation of the device of  FIGS. 1 and 2 , which uses two optical sources such as λ 1  and λ 2 , although the commutation (also known as time multiplexing) for four wavelengths may be done in any order. A first wavelength λ 1  optical source  402  is commutated on during intervals  408 ,  416 , and  424  and off during exclusive intervals  412 ,  420  when the second wavelength λ 2  optical source is enabled. Intermediate gaps  410 ,  414 ,  418 ,  422  may be used for ambient light corrections at the detector, which may be used to estimate an ambient light and detector offset value, and thereafter subtracted from the detector response during intervals  408 ,  416 ,  424  of λ 1 , and intervals  412  and  420  of λ 2 . The detector response  406  includes detector noise, which may be averaged over the measurement interval  408 ,  416 ,  424  for the first wavelength λ 1 , or  412 ,  420  for the second wavelength λ 2 . In one example of the invention extended from the one shown in  FIG. 4 , λ 1  is a wavelength of increased bacterial absorption, λ 2  is a nearby reference wavelength which is outside the bacterial absorption wavelength of λ 1 , λ 3  is a wavelength for water absorption, λ 4  is a wavelength near to λ 3  but not affected by water absorption, and λ 5  is an optical wavelength for visualization, each wavelength λ 1  and  22  are commutated on during exclusive intervals as waveforms  402  and  404  of  FIG. 4  for forming a bacterial metric 
     
       
         
           
             
               
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     optionally after which each wavelength λ 3  and λ 4  are commutated during exclusive intervals  402  and  404  to form fluid metric 
     
       
         
           
             
               
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     Each corresponding metric may then be compared with a threshold for each metric to arrive at an estimated likelihood of presence of fluid or presence of bacteria. In one example of the invention, the respective bacterial or water fluid detector wavelength responses may be corrected for wavelength-specific attenuation or scattering (in the absence of watery fluid or bacteria) so that each pair of wavelengths (pathogen specific and adjacent) provide a unity metric ratio 
     
       
         
           
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     when bacteria or watery fluid, respectively, are not present. 
       FIG. 5  shows a block diagram for an optical coherence tomography (OCT) characterization system, which has the benefit of narrow depth of axial specificity, which allows the response being measured to be restricted to a particular axial depth and range of depth, such as the proximal surface of the tympanic membrane and middle ear region. A low coherence source  514  having a plurality of wavelength range outputs includes a first wavelength λ 1  and a second wavelength λ 2  which are directed along path  518  to first splitter  516 , and thereafter to second splitter  526 . Half of the optical energy is thereafter directed to the measurement optical path  528 , and half to mirror  512  and movable reflector  508 , which adjusts the length of the reference path to be equal to the measurement path length which includes the proximal surface of the tympanic membrane and middle ear region. The optical energy returned from the reflector  508  and returned from tympanic membrane  532  combine at second splitter  526 , and the summed optical energy continues to first splitter  516  and thereafter to mirror  524  and detector  520 . Where the reference optical path (optical distance from splitter  526  to reflector  508 ) is exactly the same length as measurement optical path (from second splitter  526  to tympanic membrane  532 ), the coherently summed reference optical energy and reflected optical energy is directed, in sequence, to second splitter  526 , first splitter  516 , mirror  524 , and to detector  520 . The short coherence length of source  514  provides depth specificity, which allows measurement of bacterial response, typically with specificity of less than an optical wavelength in depth on the proximal side of tympanic membrane  532 . Schematic  FIG. 5  is shown for illustration only, other configurations of optical mirrors and splitters may be used. 
       FIG. 6A  shows a first example of a multi-wavelength detector  520 A, where a first wavelength λ 1  detector  602  is responsive to λ 1  and transparent for second wavelength λ 2  associated with second detector  604 . By bonding a first detector  602  and second detector  604  together using an optically transparent adhesive, the front-facing detector  602  is transparent for the optical energy λ 2  of the detector  604  behind it. This construction of the detector  602 / 604  may require commutation of the various optical sources as was described in  FIG. 4 , particularly where one of the detectors has an out-of-band response to adjacent wavelength optical energy used for a different measurement, such as water vs bacterial absorption. 
       FIG. 6B  shows another embodiment of a multi-wavelength detector  520 A, which utilizes a diffraction grating  608  to separate the various wavelengths λ 1 , λ 2 , λ 3 , λ 4 , etc. to detector  606  for spatial isolation of each wavelength. Because the various wavelengths are spatially separated, this configuration of detector may permit the four optical sources to be operated continuously and simultaneously, as they are inherently non-interfering because of the spatial separation by wavelength not present in the detector configuration of  FIG. 6A . Dark current detector response (the detector response in the absence of optical energy used to establish a baseline response level which is subtracted from a reading when optical energy is present) may be made before or after the optical sources are enabled. 
       FIGS. 7A, 7B, 7C, 7D, 7E, and 7F  show associated waveforms for positional drive  701  and  703 , which modulate the axial position of reflector  508  of  FIG. 5 , where the position “0” corresponds to position  536   b  of  FIG. 5 , the position “−0.5” indicates position  536   a, “+ 0.5” indicates position  536   c , and “+1.0” indicates position  536   d.    
     For the attenuation plot of  FIG. 3 , and using λ 1  at an exemplar maximum viral attenuation wavelength of 1100 nm and λ 2  at an exemplar adjacent wavelength 1000 nm, and λ 3  at an exemplar water absorption wavelength of 1500 nm and λ 4  at an exemplar nearby wavelength of 1400 nm which is outside the water absorption wavelength, it is possible to compare the relative responses of λ 1  with λ 2 , and λ 3  with λ 4  to determine the three conditions of clinical interest: absence of watery fluid, presence of effusion fluid without bacteria, and presence of effusion fluid with bacteria, as is desired for subjects suffering from ear discomfort. The apparatus and method thereby providing a diagnostic tool for viral vs bacterial infection, as well as determining that no fluid is present proximal to the tympanic membrane. 
       FIGS. 7A and 7D  are plots of axial position for the reflector  508  of  FIG. 5 ,  FIGS. 7B and 7C  show the λ 1  and λ 2  responses, respectively, which are differential for bacteria, and  FIGS. 7E and 7F  show the λ 3  and λ 4  responses, respectively, which are differential for presence of watery fluid. The waveforms  702 ,  740 ,  703 , and  741  show equal amplitude detector responses  714  and  750  where no fluid is present proximal to the tympanic membrane. Responses  706 ,  744 ,  718 , and  754  are minimal coherent reflections due to patches of ear wax, ear follicles, or other minor structures distal to the tympanic membrane, and responses  712 ,  713 ,  722 , and  758  are the respective detector responses for λ 1  through λ 4 , respectively at the tympanic membrane. The short duration of the responses  708 ,  748 ,  721 , and  757  at position +0.5 near the tympanic membrane also indicates that only the tympanic membrane is providing return signal, and only over the short duration of coherent reflection from the tympanic membrane. As minimal differential attenuation is present which is specific to wavelength, the response amplitudes  714 ,  750 ,  724 , and  756  are all equivalent amplitude. 
       FIGS. 8A and 8D  similarly show a plot of reflector position  801  and  803 , respectively, corresponding to the region of coherence about the tympanic membrane, as was described for  FIGS. 7A and 7D . The plots of  FIGS. 8B and 8C  show the OCT responses from viral (watery) fluid proximal to the tympanic membrane. The responses  806 ,  844 ,  818 , and  854  distal to the tympanic membrane are minimal, as before. The tympanic membrane responses and proximal responses  812 ,  841 ,  822 , and  858  have an extended duration of response associated with the fluid boundary proximal to the tympanic membrane, and include a longer time extent  808  and  848  of response, related to the spatially expanded response from fluid adjacent to the tympanic membrane, compared to the narrow tympanic membrane detector response such as  712  of  FIG. 7 . The peak amplitude detector responses  814  (λ 1 ) and  850  (λ 2 ) are similar in amplitude, whereas the peak response  824  (λ 3 ) is reduced compared to  856  (λ 4 ) because of the differential absorption of water at λ 3  compared to λ 4 . 
       FIGS. 9A and 9D  show the reflector position plots with responses of  FIGS. 9B, 9C, 9E, and 9F  for bacterial effusion proximal to the tympanic membrane. The amplitude  914  of OCT detector response  912  to λ 1  is reduced compared to the detector amplitude response  947  at λ 2 , which is not as absorptive for bacteria. The extent of OCT response  908  and  948  is lengthened, as before, due to the bacterial concentration which may be adjacent to the tympanic membrane. The water attenuation of λ 3  compared to λ 4  is shown in plots  903  and  941 , with responses  922  attenuated at amplitude  924  compared to plot  958  at greater amplitude  956 . 
     As described in the previous response plots, the ratio of reflected signal λ 1 /λ 2  may be used to estimate bacterial concentration, and the ratio of reflected signal λ 3 /λ 4  may be used to estimate fluid presence adjacent to the tympanic membrane, and the ratio may compensate for lower amplitude response from shorter wavelengths (having more Rayleigh scattering) of each pair of wavelengths such that the ratio is normalized to 1 for the absence of either bacteria or watery fluid in each respective ratio. 
       FIG. 10  shows a fiber optic architecture for performing OCT to form a differential measurements previously described. Low coherence source  1002  generates λ 1 , λ 2 , λ 3 , λ 4  in a commutated sequence (for detector  1022  of  FIG. 6A , or concurrently for the detector of  FIG. 6B ), which is applied to first splitter  1006 , the low coherence source being coupled to optical fiber  1008  and to second splitter  1010 , half of the optical source power directed thereafter to optical fiber  1012  and lens  1013 , which directs the beam through the speculum tip (not shown), to tympanic membrane  1051 , with reflections from the tympanic membrane and adjacent structures directed back along Lmeas path to lens  1013 , optical fiber  1012 , and back to second splitter  1010 . The other half of the power traveling from the source  1002  through splitter  1004  to second splitter  1010  is directed to reference path  1017  with length Lref terminating in a polished fiber end  1019 , which reflects optical energy in a counter-propagating direction and back to second splitter  1010 . The reference path length Lref is equal to the total measurement length from second splitter  1010  to the tympanic membrane  1050 . By adjusting Lref using the PZT modulator  1014  which changes the length of the optical fiber by stretching it longitudinally, the region of optical coherence can be modulated axially about the tympanic membrane. 
     An optical coherence tomography (OCT) device has a low coherence optical source generating optical energy coupled through a first splitter, thereafter to a second splitter, the second splitter having a measurement optical path to a tympanic membrane and also a reference optical path to a reflector which returns the optical energy to the first splitter, where the reflected optical energy is added to the optical energy reflected from the measurement optical path. The combined reflected optical energy is then provided to the first splitter, which directs the optical energy to a detector. The reflector is spatially modulated in displacement along the axis of the reference optical path such that the detector is presented with an optical intensity and optionally a continuum of optical spectral density from a particular measurement path depth, when the measurement optical path and reference optical path are equal in path length. When the device is positioned with the measurement path directed into an ear canal and directing optical energy to a tympanic membrane, by varying the reference optical path length through translation of the location of the reflector along the axis of the reference optical path, a measurement of optical and spectral characteristics of the tympanic membrane may be performed. Additionally, an external pressure excitation may be applied to provide an impulsive or steady state periodic excitation of the tympanic membrane during the OCT measurement, and a peak response and associated time of the peak response identified. The temporal characteristics and positional displacement of the tympanic membrane can be thereafter examined to determine the tympanic membrane response to the external pressure excitation. The evaluation of the tympanic membrane response from the OCT detector data may subsequently be correlated to a particular viscosity or biofilm characteristic. By examination of the temporal characteristic, an estimate of the viscosity of a fluid adjacent to a tympanic membrane may be determined, and the viscosity subsequently correlated to the likelihood of a treatable bacterial infection. 
       FIG. 11  shows a block diagram for an optical coherence tomography (OCT) device  1100  according to one example of the invention. Each reference number which appears in one drawing figure is understood to have the same function when presented in a different drawing figure. A low coherence source  1102  such as a broadband light emitting diode (LED) with a collimated output generates optical energy along path  1104  to first optical splitter  1106 , and optical energy continues to second optical splitter  1108 , where the optical energy divides into a measurement optical path  1118  and a reference optical path  1112 , which include the segment from second splitter  1108  to mirror  1110  to path length modulator  1114 . The optical energy in the measurement optical path  1118  interacts with the tympanic membrane  1120 , and reflected optical energy counter-propagates to the detector via path  1118 , where it is joined by optical energy from reference optical path  1112  reflected from mirror  1110  and splitter  1108 , and the combined reflected optical energy propagates to first splitter  1106 , thereafter to mirror  1105 , and to detector  1124  via path  1122 . Detector  1124  generates an electrical signal corresponding to the intensity of detected optical energy on path  1122 , which is a steady state maximum when the path length for reflected optical energy from the tympanic membrane is exactly the same length as the reference optical path, and a temporal maximum if the reference optical path length is swept over a range, such as by actuating path length modulator  1114  over time. Each type of reflective membrane will produce a characteristic detector signal. For example, as the reference path length traverses through a thin membrane boundary such as a healthy tympanic membrane, a single peak will result corresponding to the single reflective region of the tympanic membrane. If the reference path length is through a fluidic ear such as one containing low-viscosity infectious effusion, an initial peak of the tympanic membrane reflection will subsequently generate a region of extended reflection with an amplitude that drops from optical attenuation of the reflected signal. If the reference path length traverses through the tympanic membrane with a bacterial infection, a bacterial film may be present on the opposite surface of the tympanic membrane, which may produce a greater axial extent of reflection, followed by a pedestal indicating a high scattering coefficient and corresponding increased attenuation. Additionally, the three types of fluid viscosities behind the tympanic membrane (air vs thin fluid vs thick fluid) will respond differently to pressure excitations generated on the tympanic membrane. Accordingly, is possible to modulate the reference optical path length and optionally the pressure adjacent to the tympanic membrane, and examine the nature of the detector output signal and response to excitation pressure to determine the presence or absence of fluid adjacent to the tympanic membrane, the presence or absence of a biofilm such as bacteria adjacent to the tympanic membrane, and the viscosity of fluid adjacent to the tympanic membrane, all from movement of the tympanic membrane on the measurement optical path as presented at the detector output. 
     In one example of the present invention, the path length modulator  1114  varies the reference path length by a distance corresponding to the measurement path length from  1126   a ,  1126   b ,  1121   c , and  1121   d  of  FIG. 11 , corresponding to a region of movement of a tympanic membrane  1115  to be characterized. As modulator  1114  increases the reference path length, the signal delivered to the detector is closer to region  1126   d  and when modulator  1114  decreases the distance of the reference path length, the region signal delivered to the detector is in region  1126   a.    
       FIG. 12A  shows an example relationship between actuator voltage or current and axial displacement of path length modulator  1114 , which is driven by a mechanical driver circuit  1116 , which may be a voice coil driver for a voice coil actuator coupled to mirror  1114 , modulating the mirror about the optical axis of  1112 . The type of driver and path length modulator  1114  is dependent on the highest frequency of displacement modulation, since the energy to displace path length modulator  1114  is related to the mass of the path length modulator  1114 , such as the case of a moving mirror. The mirror and actuator may be micro electrical machined system (MEMS) for lower reflector mass and correspondingly faster mirror response. It may be possible to utilize a variety of other path length modulators without limitation to the use of mirrors. 
       FIG. 12B  shows the controller  1117  generating an actuator voltage in a step-wise manner, with the actuator stopping momentarily at each depth. For example, if increased actuator drive results in a longer reference path length, then from T 1  to T 2 , the actuator voltage may be  1202   a , corresponding to the displacement position  1126   a  of  FIG. 11 , and the other voltages  1202   b ,  1202   c , and  1202   d  may correspond to positions adjacent to the tympanic membrane of  1126   b ,  1126   c , and  1126   d , respectively. 
       FIG. 13  shows an example OCT tympanic membrane characterization system  302  with the elements arranged to provide a single measurement output. For the case of free-space optics (optical energy which is not confined within a waveguide such as an optical fiber), the system splitters and combiners of  FIGS. 11 and 13  are partially reflective mirrors. The principal elements show in  FIG. 13  correspond to the same functional elements of  FIG. 11 . By rearrangement of the reference optical path, the elements of the system may be enclosed, as shown. 
     In one example of the invention, detector  1124  may be a single omni-wavelength optical detector responsive to the total applied optical intensity, and having a characteristic response. In another example of the invention detector  1124  may include a single wavelength filter, or a chromatic splitter and a plurality of detector elements, such that each reflected optical wavelength may be separately detected.  FIG. 14  shows collimated optical energy  1122  entering chromatic detector  1124 A, where it is split into different wavelengths by refractive prism  1124 B, which separates the wavelengths λ 1 , λ 2 , λ 3 , λ 4  onto a linear or 2D detector  1124 C, which is then able to provide an intensity map for the reflected optical energy by wavelength. Individual detection of wavelengths may be useful where the signature of wavelength absorption is specific to a particular type of bacteria or tympanic membrane pathology. The spectrum of detector response is typically tailored to the reflected optical energy response, which may be in the IR range for an OCT system with more than a few mm of depth measurement capability. In one example of the invention, the detector spectral response for various biological materials is maintained in a memory and compared to the superposition of responses from the plurality of optical detectors. For example, the optical reflective characteristics of cerumen (earwax), a healthy tympanic membrane, an inflamed tympanic membrane (a tympanic membrane which is infused with blood), a bacterial fluid, an effusion fluid, and an adhesive fluid may be maintained in a template memory and compared to the spectral distribution of a measured tympanic membrane response over the axial depth of data acquisition. The detector response at each axial depth over the range of reference optical path length can then be compared to the spectral characteristics of each of the template memory spectral patterns by a controller, with the controller examining the detector responses for each wavelength and the contents of the template memory and estimating the type of material providing the measurement path reflection based on this determination. The detection of a spectral pattern for cerumen may result in the subtraction of a cerumen spectral response from the detector response, and/or it may result in an indication to the user that earwax has been detected in the response, which the user may eliminate by pointing the measurement optical path in a different region of the tympanic membrane. 
     Because the axial resolution of the optical coherence tomography is fractions of an optical wavelength, it is possible to characterize each of the structures separately on the basis of optical spectrum, even though each of the structures being imaged is only on the order of a hundred microns in axial thickness. The axial resolution of the system may be improved by providing a very narrow optical beam with high spatial energy along the measurement axis and over the axial extent of the tympanic membrane. 
       FIGS. 15A and 15B  show an example of the invention for use in detecting position of a tympanic membrane over time. The controller  1117  generates a triangle waveform  1502  for use by the path length modulator, which directs the optical energy to the tympanic membrane, which may have fluid adjacent to it, and the fluid may have a particular viscosity, which may be known to increase during the progression of a bacterial infection. Bacterial infections are known to provide a biological film on the surface of a membrane, such as the tympanic membrane, with specific optical reflection characteristics. The optical signal is directed through the outer ear canal towards the tympanic membrane to be characterized, and the detector responses of  FIG. 15B  are examined by controller  1117  of  FIG. 13 . A first set of waveforms  1509  shows a time domain response which includes an initial peak  1507  associated with the strong reflection of the sharp reflective optical interface provided by the tympanic membrane at a first reflective interface, and the fluid behind the tympanic membrane also generates a signal which attenuates with depth, shown as a sloped pedestal  1508 . The presence of pedestal  1508  indicates the presence of fluid behind the tympanic membrane. This may be contrasted with the second set of responses  1511  for a normal tympanic membrane, such as the peak of waveform  1522 , which is comparatively narrow and of shortened duration  1520 , as reflective fluid is not present behind the tympanic membrane. 
     In an additional embodiment of the invention, the tympanic membrane itself may be modulated by an external excitation source, such as an air puff, or a source of air pressure which is modulated over time. Where an external pressure excitation source is provided, and the pressure excitation is selected to provide less than 1% displacement of the tympanic membrane, for example, the relative temporal position of the peak optical signal will indicate the position of the tympanic membrane. Because the refresh rate of the system is optical, rather than acoustic of prior art ultrasound devices, the speed of interrogation of the tympanic membrane is only limited by the rate of modulation of the path length modulator  1114 , which may be several orders of magnitude faster than an ultrasound system. Additionally, the axial resolution of an optical system relying on optical interferometry is much greater than the axial resolution of an ultrasound system which is governed by transducer ringdown. Additionally, because the acoustic impedance boundary between air and the tympanic membrane is extremely large, the ultrasound penetration depth of ultrasound to structures beyond the tympanic membrane is very limited. By contrast, the optical index of refraction ratio from air to tympanic membrane is many orders of magnitude lower than the ultrasound index of refraction ratio across this boundary, so the optical energy loss at the interface is lower. The optical penetration is primarily bounded by the scattering losses associated with the tympanic membrane and structures beyond the tympanic membrane interface, and these losses may be mediated in part by using a very high optical energy which is pulsed with a duty cycle modulation to maintain the average power applied to the tympanic membrane in a reasonable average power range. 
       FIG. 16  shows a fiber-optic example of an optical coherence tomography system  1600 . Controller  1618  coordinates the various subsystems, including enabling low coherence source  1602 , which couples optical energy to an optical fiber  1604 , which delivers this optical energy thereafter to a first splitter  1606 , thereafter to optical fiber  1608  and to second splitter  1610 . Optical energy from second splitter  1610  is directed down two paths, one a measurement path  1612  with length Lmeas  1615  to a tympanic membrane, and the other to reference optical path  1617  with length Lref and terminating into an open reflective fiber end  1619 , which may alternatively be a mirrored polished end or optical reflective termination, with the optical path  1617  including an optical fiber wrapped around a PZT modulator  1614 , which changes dimensional shape and diameter when an excitation voltage is applied to the PZT. When the PZT modulator  1614  is fed with a sine wave or square wave excitation, the PZT modulator  1614  increases and decreases in diameter, thereby providing a variable length Lref. The PZT modulator  1614  is also capable of high speed fiber length modulation in excess of 100 Khz in frequency. Other fiber length modulators known in the art may be used for rapidly changing the length of optical fiber on the Lref path, with the PZT modulator  1614  shown for reference only. The combined optical energy from the Lmeas path and Lref path reach the second splitter  1610  and return on fiber  1608 , comprising the sum of optical energy reflected from PZT modulator  1614  and reflected from the tympanic membrane  1650 . The combined optical energy travels down path  1608  to first splitter  1606 , through fiber  1620 , and to detector  1622 , where the coherent optical energy superimposes and subtracts, forming a detector  1622  output accordingly, which is fed to the controller  1618  for analysis. The controller  1618  also generates the PZT modulator excitation voltage  1616 , such as the voltage or current waveform  1502  of  FIG. 5A , and may also generate a signal to enable the low coherence source  1602 , and perform analysis of the detector  1622  response, which may be a single intensity value over the wavelength response of the detector  1622 , or the individual wavelength output provided by the sensor of  FIG. 14 . The controller acts on the detector responses in combination with the Lref modulation function to determine an effusion metric which may be correlated to the likelihood of fluid being present adjacent to a tympanic membrane, and also provide an indication of the viscosity of the fluid adjacent to the tympanic membrane. 
       FIG. 17  shows an extension of  FIG. 16  with an external tympanic membrane excitation generator  1704  which delivers miniscule pressure changes such is actuated by a voice coil actuator or other pressure source, preferably with peak pressures below 50 deka-pascals (daPa) for application to a tympanic membrane. The modulation of the reference path length by the PZT modulator  1614  is at a rate which exceeds the highest frequency content of the excitation generator  1704  by at least a factor of 2 to satisfy the Nyquist sampling requirement. 
     In one example of the invention, the reference path length is modulated by a first modulator and second modulator operative sequentially, where the first modulator provides a large but comparatively slow reference path length change, and the second modulator provides a small but comparatively fast reference path length change. In this manner, the first modulator is capable of placing the region of OCT examination within a region of interest such as centered about a tympanic membrane, and the second modulator is capable of quickly varying the path length to provide a high rate of change of path length (and accordingly, a high sampling rate) for estimation of tympanic membrane movement in response to the pressure excitation. 
     It can be seen in the tympanic membrane shown as  1115  in  FIGS. 11 and 13, and 1650  in  FIGS. 16 and 17 , that the tympanic membrane has a conical shape with a distant vertex ( 1119  of  FIGS. 11 and 13, 1651  of  FIGS. 16 and 17 ), which is known in otolaryngology as the “cone of light”, as it is the only region of the tympanic membrane during a clinical examination which provides a normal surface to the incident optical energy. Similarly, when using an ultrasonic source of prior art systems, the cone of light region is the only part of the tympanic membrane which provides significant reflected signal energy. The optical system of the present invention is operative on the reflected optical energy from the surface, which need not be normal to the incident beam for scattered optical energy, thereby providing another advantage over an ultrasound system. 
       FIG. 18A  shows an example sinusoidal pressure excitation from excitation generator  1704  applied to a tympanic membrane, such as a sinusoidal waveform  1821  applied using a voice coil diaphragm actuator displacing a volume sufficient to modulate a localized region of the tympanic membrane or surface pressure by 100 daPa (dekapascals) p-p. Sub-sonic (below 20 Hz) frequencies may require sealing the localized region around the excitation surface, whereas audio frequencies (in the range 20 Hz to 20 kHz) and super-audio frequencies (above 20 kHz) may be sufficiently propagated as audio waves from generator  1704  without sealing the ear canal leading to the tympanic membrane to be characterized. The sinusoidal pressure excitation  1821  results in a modulation of the surface, which is shown as plot  1832 , as the modulation in surface position corresponds to a change in the associated Lref path length by the same amount. Each discrete circle of waveform  1832  represents a sample point from the OCT measurement system  1700 , corresponding to the Lref path length and change in tympanic membrane position, with each point  1332  representing one such sample. In one example embodiment of the invention, a series of sinusoidal modulation excitation  1821  frequencies are applied, each with a different period  1822 , and the delay in response  1830  and peak change in Lref are used in combination to estimate the ductility or elasticity of the tympanic membrane, fluid viscosity, or other tympanic membrane or fluid property. In the present examples, there is a 1:1 relationship between the displacement of the tympanic membrane and associated change in path length of the reference path which results in the peak response. For example, if the scale of  FIG. 15B  is a sequence of 0, −0.5 mm, −1 mm, −0.5 mm, 0 mm, 0.5 mm, etc, then this represents a corresponding displacement in the tympanic membrane by these same distances. By applying a series of audio and sub-audio tones with various cycle times  1822  and measuring the change in Lref as shown in plot  1832 , it is possible to estimate the displacement of the tympanic membrane and extract frequency dependent characteristics such as viscosity or elasticity of the fluid behind the tympanic membrane. For example, an exemplar elasticity metric measurement associated with the changed density or viscosity of the fluid could be an associated change in surface or membrane response time  1874  for a step change, or phase delay  1830  for a sinusoidal frequency. In this manner, a frequency domain response of the surface may be made using a series of excitations  1821  and measuring a series of surface responses  1832 . The reference path modulator  1614  of  FIGS. 16 and 17 , or mirror  1114  of  FIG. 13 , may include a first path length modulator which centers the reference path length to include the tympanic membrane, and a second path length modulator which rapidly varies the reference path length to provide adequate sampling of the axial movement of the tympanic membrane. 
     Whereas  FIG. 18A  shows a sinusoidal excitation which may be provided in a series of such excitations to generate a phase vs. frequency response plot of the surface displacement from the series of measurements,  FIG. 18B  shows a time domain step response equivalent of  FIG. 18A , where a surface step pressure excitation  862  of 50 daPa peak is applied to the tympanic membrane, which generates the measured tympanic membrane displacement sequence  1872 . It is similarly possible to characterize the surface response based on a time delay  1874  and amplitude response (shown as 0.5 mm) for displacement response plot  1872 . 
     In one example of the invention, a separate low-coherence optical source  1102  or  1602  such as an infrared range source is used for increased penetration depth, and a separate visible source (not shown) is used co-axially to indicate the region of the tympanic membrane being characterized while pointing the measurement optical path onto the tympanic membrane. The optical source  1102  or  1602  may be an infrared sources to reduce scattering, thereby providing additional depth of penetration. In another example of the invention, the low-coherence optical source  1102  or  1602  is a visible optical source, thereby providing both illumination of the tympanic membrane region of interest, and also measurement of displacement of the tympanic membrane, as previously described. 
     The present examples are provided for understanding the invention, it is understood that the invention may be practiced in a variety of different ways and using different types of waveguides for propagating optical energy, as well as different optical sources, optical detectors, and methods of modulating the reference path length Lref. The scope of the invention is described by the claims which follow. 
     The foregoing is a description of preferred embodiments of the invention. It is understood that various substitutions can be made without limitation to the scope of the invention. For example, other wavelengths may be preferable for bacterial absorption or water absorption than those specified.