Abstract:
An OCT apparatus and method for characterization of a fluid adjacent to a tympanic membrane has a low coherence source which is coupled to a splitter which has a measurement path and a reference path. The reference path is temporally modulated for length, and the combined signals from the reference path and the measurement path are applied to a detector. The detector examines the width of the response and the time variation when an optional excitation source is applied to the tympanic membrane, the width of the response and the time variation forming a metric indicating the viscosity of a fluid adjacent to the tympanic membrane being measured.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates optical coherence tomography (OCT). In particular, the device relates to OCT for use in the diagnosis of otitis media (OM). 
       BACKGROUND OF THE INVENTION 
       [0002]    Otitis Media is a common disease of the inner ear, involving tissue inflammation and fluidic pressure which impinges on the tympanic membrane. Otitis Media may be caused by a viral infection, which generally resolves without treatment, or 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. 
         [0003]    The definitive diagnostic tool for inner ear infections is myringotomy, an invasive procedure which involves incisions into the tympanic membrane, withdrawal of fluid, and examining 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 result, as treatment of viral infectious agents with antibiotics is ineffective. An improved diagnostic tool for the diagnosis of otitis media is desired. 
       OBJECTS OF THE INVENTION 
       [0004]    A first object of the invention is a non-invasive medical device for the identification of fluid type adjacent to a tympanic membrane. 
         [0005]    A second object of the invention is a method for identification of a fluid adjacent to a tympanic membrane. 
         [0006]    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. 
         [0007]    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. 
         [0008]    A 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. 
         [0009]    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. 
       SUMMARY OF THE INVENTION 
       [0010]    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. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]      FIG. 1  shows a block diagram of an optical coherence tomography characterization system. 
           [0012]      FIG. 2A  shows a plot of mechanical actuator displacement vs actuator voltage. 
           [0013]      FIG. 2B  shows a plot of reference path length over time, as controlled by actuator voltage or current. 
           [0014]      FIG. 3  shows a block diagram for an optical coherence tomography characterization system for use examining a tympanic membrane. 
           [0015]      FIG. 4  shows a polychromatic detector. 
           [0016]      FIG. 5A  shows a plot of an example excitation waveform for modulation of a reference length 
           [0017]      FIG. 5B  shows a detector signal for a tympanic membrane adjacent to fluid such as from OME and a detector signal for a normal tympanic membrane. 
           [0018]      FIG. 6  shows an optical waveguide system for measurement of a tympanic membrane. 
           [0019]      FIG. 7  shows an optical waveguide system for measurement of a tympanic membrane with an excitation source. 
           [0020]      FIG. 8A  shows a plot for a sinusoidal excitation applied to deformable surface or membrane with a reflected response signal. 
           [0021]      FIG. 8B  shows a plot for a step excitation applied to a deformable surface or membrane, and a response to the step excitation. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0022]      FIG. 1  shows a block diagram for an optical coherence tomography (OCT) device 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  102  such as a broadband light emitting diode (LED) with a collimated output generates optical energy along path  104  to first optical splitter  106 , and optical energy continues to second optical splitter  108 , where the optical energy divides into a measurement optical path  118  and a reference optical path  112 , which include the segment from second splitter  108  to mirror  110  to path length modulator  114 . The optical energy in the measurement optical path  118  interacts with the tympanic membrane  120 , and reflected optical energy counter-propagates to the detector via path  118 , where it is joined by optical energy from reference optical path  112  reflected from mirror  110  and splitter  108 , and the combined reflected optical energy propagates to first splitter  106 , thereafter to mirror  105 , and to detector  124  via path  122 . Detector  124  generates an electrical signal corresponding to the intensity of detected optical energy on path  122 , 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  114  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. 
         [0023]    In one example of the present invention, the path length modulator  114  varies the reference path length by a distance corresponding to the measurement path length from  126   a  to  126   d  of  FIG. 1 , corresponding to a region of movement of a tympanic membrane  115  to be characterized. As modulator  114  increases the reference path length, the signal delivered to the detector is closer to region  126   d  and when modulator  114  decreases the distance of the reference path length, the region signal delivered to the detector is in region  126   a.    
         [0024]      FIG. 2A  shows an example relationship between actuator voltage or current and axial displacement of path length modulator  114 , which is driven by a mechanical driver circuit  116 , which may be a voice coil driver for a voice coil actuator coupled to mirror  114 , modulating the mirror about the optical axis of  112 . The type of driver and path length modulator  114  is dependent on the highest frequency of displacement modulation, since the energy to displace path length modulator  114  is related to the mass of the path length modulator  114 , 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. 
         [0025]      FIG. 2B  shows the controller  117  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  202   a , corresponding to the displacement position  126   a  of  FIG. 1 , and the other voltages  202   b ,  202   c , and  202   d  may correspond to positions adjacent to the tympanic membrane of  126   b ,  126   c , and  126   d , respectively. 
         [0026]      FIG. 3  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. 1 and 3  are partially reflective mirrors. The principal elements show in  FIG. 3  correspond to the same functional elements of  FIG. 1 . By rearrangement of the reference optical path, the elements of the system may be enclosed, as shown. 
         [0027]    In one example of the invention, detector  124  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  124  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. 4  shows collimated optical energy  122  entering chromatic detector  124 A, where it is split into different wavelengths by refractive prism  124 B, which separates the wavelengths λ 1 , λ 2 , λ 3 , λ 4  onto a linear or 2D detector  124 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. 
         [0028]    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. 
         [0029]      FIGS. 5A and 5B  show an example of the invention for use in detecting position of a tympanic membrane over time. The controller  117  generates a triangle waveform  502  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. 5B  are examined by controller  117  of  FIG. 3 . A first set of waveforms  509  shows a time domain response which includes an initial peak  507  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  508 . The presence of pedestal  508  indicates the presence of fluid behind the tympanic membrane. This may be contrasted with the second set of responses  511  for a normal tympanic membrane, such as the peak of waveform  522 , which is comparatively narrow and of shortened duration  520 , as reflective fluid is not present behind the tympanic membrane. 
         [0030]    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  114 , 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. 
         [0031]      FIG. 6  shows a fiber-optic example of an optical coherence tomography system  600 . Controller  618  coordinates the various subsystems, including enabling low coherence source  602 , which couples optical energy to an optical fiber  604 , which delivers this optical energy thereafter to a first splitter  606 , thereafter to optical fiber  608  and to second splitter  610 . Optical energy from second splitter  610  is directed down two paths, one a measurement path  612  with length Lmeas  615  to a tympanic membrane, and the other to reference optical path  617  with length Lref and terminating into an open reflective fiber end  619 , which may alternatively be a mirrored polished end or optical reflective termination, with the optical path  617  including an optical fiber wrapped around a PZT modulator  614 , which changes dimensional shape and diameter when an excitation voltage is applied to the PZT. When the PZT modulator  614  is fed with a sine wave or square wave excitation, the PZT modulator  614  increases and decreases in diameter, thereby providing a variable length Lref. The PZT modulator  614  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  614  shown for reference only. The combined optical energy from the Lmeas path and Lref path reach the second splitter  610  and return on fiber  608 , comprising the sum of optical energy reflected from PZT modulator  614  and reflected from the tympanic membrane  650 . The combined optical energy travels down path  608  to first splitter  606 , through fiber  620 , and to detector  622 , where the coherent optical energy superimposes and subtracts, forming a detector  622  output accordingly, which is fed to the controller  618  for analysis. The controller  618  also generates the PZT modulator excitation voltage  616 , such as the voltage or current waveform  502  of  FIG. 5A , and may also generate a signal to enable the low coherence source  602 , and perform analysis of the detector  622  response, which may be a single intensity value over the wavelength response of the detector  622 , or the individual wavelength output provided by the sensor of  FIG. 4 . 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. 
         [0032]      FIG. 7  shows an extension of  FIG. 6  with an external tympanic membrane excitation generator  704  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  614  is at a rate which exceeds the highest frequency content of the excitation generator  704  by at least a factor of 2 to satisfy the Nyquist sampling requirement. 
         [0033]    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. 
         [0034]    It can be seen in the tympanic membrane shown as  115  in  FIGS. 1 and 3, and 650  in  FIGS. 6 and 7 , that the tympanic membrane has a conical shape with a distant vertex ( 119  of  FIGS. 1 and 3, 651  of  FIGS. 6 and 7 ), 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. 
         [0035]      FIG. 8A  shows an example sinusoidal pressure excitation from excitation generator  704  applied to a tympanic membrane, such as a sinusoidal waveform  821  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  704  without sealing the ear canal leading to the tympanic membrane to be characterized. The sinusoidal pressure excitation  821  results in a modulation of the surface, which is shown as plot  832 , 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  832  represents a sample point from the OCT measurement system  700 , corresponding to the Lref path length and change in tympanic membrane position, with each point  332  representing one such sample. In one example embodiment of the invention, a series of sinusoidal modulation excitation  821  frequencies are applied, each with a different period  822 , and the delay in response  830  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. 5B  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  822  and measuring the change in Lref as shown in plot  832 , 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  874  for a step change, or phase delay  830  for a sinusoidal frequency. In this manner, a frequency domain response of the surface may be made using a series of excitations  821  and measuring a series of surface responses  832 . The reference path modulator  614  of  FIGS. 6 and 7 , or mirror  114  of  FIG. 3 , 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. 
         [0036]    Whereas  FIG. 8A  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. 8B  shows a time domain step response equivalent of  FIG. 8A , 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  872 . It is similarly possible to characterize the surface response based on a time delay  874  and amplitude response (shown as 0.5 mm) for displacement response plot  872 . 
         [0037]    In one example of the invention, a separate low-coherence optical source  102  or  602  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  102  or  602  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  102  or  602  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. 
         [0038]    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.