Patent Application: US-61595009-A

Abstract:
appropriate assessment of wound oxygenation is critical to establish a diagnosis , to monitor the effect of the treatment , to guide the therapeutic process , to identify the presence of infection , and to predict the treatment outcome . embodied systems and methods represent an enabling technology for noninvasive and objective assessment of wound tissue oxygenation . in addition to wound healing , disclosed embodiments offer low cost and portable avenues for noninvasive assessment of multiple clinical parameters for the detection and intervention of various malignancies in multiple soft tissue systems .

Description:
unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains . although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the exemplary embodiments , suitable methods and materials are described below . all publications , patent applications , patents , and other references mentioned herein are incorporated by reference in their entirety . in case of conflict , the present specification , including definitions , will control . in addition , the materials , methods , and examples are illustrative only and not intended to be limiting . as used herein , the phrase “ operably connected ” is intended to mean coupled or connected , either directly or indirectly , such that the connected structures are operable to perform a desired function . fig1 shows an exemplary embodiment of the wound goggle system 10 for quantitative assessment and / or visualization of wound tissue oxygenation of a subject tissue . the wearable goggle system 10 comprises an eyewear unit 50 , an illumination unit 65 , and a control unit 200 . the eyewear unit 50 of an exemplary embodiment comprises one or more imaging units 85 , 86 . preferably , imaging units 85 , 86 comprises automated zoom lenses for receiving emitted and / or reflected light from at least a portion of a subject tissue . to display the generated image , the eyewear unit 50 further comprises a head mounted image display ( hmd ) unit 207 , for example , a personal cinema system by head play inc . ( los angeles , calif .). the control unit 200 may comprise a light processing module 109 and a computer 310 . the control unit 200 may be operably connected to the eyewear unit 50 and the illumination unit 65 via a cable 37 . alternatively , the control unit 200 may be wirelessly connected to the eyewear unit 50 and / or the illumination unit 65 . in various exemplary embodiments , the illumination unit 65 , imaging units 85 , 86 , hmd 207 , and the light processing module 109 are connected to the computer 310 . the computer 310 may comprise a commercial vision system , for example , a compact vision system ( cvs ) from national instrument ( austin , tex . ), with embedded programs for real time control and synchronization of illumination , automatic focus , image acquisition , processing , and image display . in at least one embodiment , at least a portion of the control unit 200 may be specifically designed as a portable backpack unit 110 . such a backpack unit 110 would comprise a compact image acquisition and processing module that would allow unlimited and unrestricted mobility to the clinician . in operation , excitation light from a spectrally tunable illumination unit 65 may be modulated and collimated for pulsed illumination on the surgical site . diffuse reflectance is collected by automated zoom lenses within the imaging unit 85 , 86 and delivered through high resolution imaging fiber guides 44 to the control unit 200 . the control unit 200 may house the image acquisition and processing module components of the system . fig2 shows an exemplary embodiment of the eyewear unit 50 . in this embodiment , two imaging units 85 , 86 may be positioned parallel to the axis of the image display 207 of eyewear unit 50 . imaging units 85 , 86 include motorized zoom lenses . high resolution imaging fiber guides 44 connect the imaging units 85 , 86 with the control unit ( not shown in fig2 ). collected images are transferred to the control unit 200 for multi - spectral processing . eyewear unit 50 includes a head mounted image display unit 207 adapted to display a generated image . eyewear unit 50 also includes a spectrally tunable excitation illumination unit 65 . the illumination unit 65 is adapted to illuminate at least a portion of the subject tissue . the illumination unit 65 is connected to the control unit ( not shown ) via cable 37 . referring to fig3 , the control unit 200 includes a light processing module 109 . direct incident light or light delivered from imaging fibers 44 is received into the light processing module 109 . preferably , the light processing module 109 comprises a ccd camera 300 equipped with a liquid crystal tunable filter 442 and an optical adaptor 452 . the ccd camera 300 may comprise view separation optics similar to that used with color photography that allow simultaneous acquisition of background and fluorescence images from if two or more fiber bundles 44 are used as shown . the light processing module 109 may further comprise a polarizer / analyzer 463 , which may be used to reduce specular reflection and to study tissue polarization characteristics . the control unit 200 further comprises a computer 310 programmed with an imaging acquisition module . in an exemplary embodiment , the computer 310 is programmed to synchronize tissue illumination , filter configuration , lens control , data acquisition , and image display . the control unit 200 also synchronizes the controls and synchronizes the light processing module 109 . high resolution imaging fiber guides 44 transport emitted light received by the zoom lenses ( not shown ) to a light processing module 109 . in an alternative embodiment , a miniature monochrome ccd camera may be positioned on the eyewear unit , eliminating the need for fiber guides 44 . an exemplary embodiment may comprise an image processing toolkit for near real - time co - registration , segmentation and visualization of the oxygen map and hypoxic margins . in at least one embodiment , image analysis may be performed using insight segmentation and registration toolkit ( itk ) ( national library of medicine &# 39 ; s office of high performance computing and communication ( hpcc )). itk is a c ++ library and has a wide range of functionalities for registration and segmentation and provides viable interfaces for other tasks such as reconstruction and visualization . to provide an immersive visual environment with minimal interference to the surgical procedure , an exemplary embodiment may integrate basic functions of itk into the labview real - time environment ( national instrument ) through dlls . referring to fig4 , the illumination unit 65 may be connected to control unit 200 via cable 37 . alternatively , illumination unit 65 may be connected to control unit 200 via a wireless connection ( not shown ). the illumination unit 65 may comprise a tunable light source 650 , a polarizer 655 , a beam splitter 670 , an optical chopper 675 , and a shutter 680 . in an exemplary embodiment , visible light from a digital light processing ( dlp ) based tunable light source 650 and will be polarized . the exiting light may be split if a beam splitter 670 is included . before exiting through iris shutter 680 , the light may be modulated with an optical chopper 675 . embodiments may operate in the various illumination modes : ( 1 ) hyperspectral or multispectral imaging mode with full - field broadband illumination , ( 2 ) point - to - point scanning mode without full - field background illumination , ( 3 ) combination of full - field illumination and point - to - point scanning within a specific region of interest . in various embodiments , the illumination unit 65 may generate light at multiple wavelengths in sequence . the tunable light source 650 may be positioned on the eyewear , or alternatively , may be located on the control unit . if the tunable light source 650 is located on the control unit it may be directed to by fiber optic cables to illuminate the desired area of interest . referring to fig5 a , in embodiments where illumination unit 65 provides full field illumination , multi - wavelength light is emitted from a tunable light source 650 ( e . g ., light emitting diodes ( leds ), laser diodes ( lds ), optical fibers , etc .). the emitted light may be directed through a lens assembly 693 before illuminating the desired field . in this way , the entire wound or a portion thereof may be evenly illuminated if desired , such that the diffuse reflectance image may be captured at the same time . however , the illumination mode depicted in fig5 a may not be appropriate for particular wound imaging applications because of the following reasons . first , since light is multi - scattered in biologic tissue , simultaneous illumination of multiple heterogeneous regions will introduce crosstalk and eventually degrade the accuracy and the sensitivity of regional tissue oxygen measurements . second , simultaneous illumination of multiple regions will significantly increase the background signal intensity and put heavy load to the camera system . in the case of imaging the wound tissue with large absorption contrast ( for example , necrosis surrounded by normal tissue ), an appropriate illumination condition may not be achievable because of the difficult to balance between the over - exposure of the surrounding tissue and the under - exposure of the necrosis . over - exposure will saturate the camera while under - exposure will force the camera to work at the low end of dynamic range . referring to fig5 b , various embodiments overcome these limitations using a point - to - point scanning light source . in embodiments where illumination unit 65 provides point - to - point scanning , multi - wavelength light from a tunable light source 650 ( e . g ., light emitting diodes ( leds ), laser diodes ( lds ), optical fibers , etc .) may be modulated using an optical chopper ( not shown ) and steered using a mirror galvanometer 733 to rapidly scan the region of interest , preferably following a programmed pattern . in these embodiments , the illumination intensity and the camera exposure can be optimized at the area of interest . a polarizer / analyzer positioned on the light processing unit 65 may reduce specular reflection and to study tissue polarization characteristics . reflected light from the superficial tissue layers will pass a liquid crystal tunable filter ( lctf ) and collected by a ccd camera . depending on the specific clinical application , these operational modes may be used interchangeably . for example , to image the dark necrotic region surrounded by tissue of less absorption , the combinational imaging mode may be used . in this example , the necrotic region will be scanned point - by - point to increase the measurement sensitivity while the full - field illumination may provide the oxygen map of the surrounding tissue . in an exemplary embodiment , a programmable galvanometer is used to facilitate custom design of the scanning pattern for maximal imaging quality within the region . the programmable galvanometer permits custom design of the scanning pattern for maximal imaging quality within the region of interest . in addition , the system can also be used for other applications such as fluorescence imaging . since the scanning speed of the galvanometer is greater than 500 μs / line and the diffuse reflectance patterns at multiple scanning points of light can be captured by a single snap shot of the ccd camera with the designated exposure time , the expected sampling rate for this proposed imaging system will be comparable with that of existing wound imaging systems . exemplary embodiments may utilize optical scanning mechanisms similar to those which have been successfully implemented in many commercial products such as bar code readers . current technical advances in optical scanning and camera systems allow for near real - time image acquisition rate in these point - to - point systems . exemplary embodiments may employ quantitative methods for diffuse optical measurements of tissue oxygenation ( sto2 ) and hemoglobin concentration ( hbt ) which have been previously described ( see e . g ., 20 - 23 , incorporated by reference herein ). additionally , tissue oximeter prototypes have been previously validated through benchtop tests , animal studies , and clinical trials ( 24 - 27 ). the quantitative methods for tissue oxygen measurement have been tested in multiple clinical applications , including breast cancer detection and peripheral vascular disease ( pvd ) diagnosis ( 15 , 25 , 28 ). furthermore , tissue sto2 measurements were integrated with oxygen tension ( po2 ) and blood flow measurements for quantitative evaluation of tumor tissue oxygen metabolism . an exemplary embodiment may utilize an integrated system consisting of a near infrared tissue oximeter for sto2 and hbt measurements , a laser doppler for blood flow ( bf ) measurement , and an electron paramagnetic resonance spectroscope ( eprs ) for oxygen tension ( po2 ) measurement . the strategy of simultaneous quantitative measurement of multiple tissue parameters permits detection and analysis of oxygen transport deficiencies in wound tissue which will facilitate accurate diagnosis and efficient treatment . to determine a resection boundary , an exemplary embodiment may utilize various image segmentation techniques including both color and texture segmentation to classify the pixels into different structures . the initial boundary of the region of interests or structures may be obtained from a color segmentation algorithm followed by morphological operations . the boundaries will be further refined and smoothed using elastic deformable techniques ( i . e ., active contour , available in itk ). a closed elastic curve is then fitted and grown by suitable deformations so that the curve encloses homogenous regions . given the dynamic nature of the acquisition , the fitted region is obtained for one of the first acquired images . for consecutively acquired images , the resection boundaries may be determined based on the active contour model with the input of previously fitted region to minimize the computational cost ( 30 - 32 ). in addition , in order to avoid effects of changes in illumination and view angles , temporal filtering among multiple consecutive frames and periodic re - initialization may be carried out . various image analysis systems and algorithms previously developed for processing large image sets with terabytes of data have been previously described . specific embodiments leverage and extend the systems above to achieve near real - time image analysis and display . specifically , fast color segmentation algorithms may be used to initialize the boundary detection . subsequently , the c ++ implementations of the active contour algorithm in itk may be used to achieve efficient boundary tracking . for image co - registration , two approaches may be used . first , extrinsic calibration may be carried out for the cameras for different modalities . this will provide an initial estimate of the transformation between the images . next , color - based fast segmentation of landmarks may be used on the tissue to enable quick feature matching for fine tuning of the affine transformation between different images . referring to the exemplary embodiment shown in fig6 , the goggle system may be adapted to include 3d multi - view , multi - spectral imaging capability by positioning a cylindrical mirror 833 between the proposed multi - spectral imaging system and the in vivo tissue of interest , as shown in fig6 a . referring to fig6 b , a typical snapshot of the ccd camera includes a top view image of the tissue at the center , surrounded by image segments from multiple view points . as represented in fig6 b , the multiple view points are due to the reflection of light by the inner surface of the cylindrical mirror . the mapping between the sample space and the cylindrical mirror space will be calibrated in advance . the field of view is defined as φ = tan − 1 [ 2 cos θ sin 2 θ /( sin θ + 2 sin θ cos 2 θ )], where θ is the half field of view . the tangential resolution is defined as the ratio between a circle of pixels of radius ρ i on the image plane and a circle of radius ρ s on the scene plane : ρ i / ρ s = p i sin θ /( 2 sin θ − wρ i sin θ ), where r is the radius of the cylindrical mirror and w is the depth of the scene . the above radical imaging system can be used to estimate the diffusion and reflection parameters of an analytic bidirectional reflectance distribution function ( brdf ) model . the 3d multi - view , multi - spectral radical imaging system of an exemplary embodiment facilitates several techniques for quantitative wound margin assessment : ( 1 ) 3d images acquired at multiple wavelengths to reconstruct and document wound oxygen distribution in 3d ; ( 2 ) by moving the cylindrical mirror in the axial direction , it is possible to obtain a large number of multi - view images for improved spatial ( especially depth ) resolution of the reconstructed wound images ; ( 3 ) when the sample is illuminated by an obliquely incident light beam , the multi - view , multi - spectral radical imaging system can capture the diffuse reflectance profiles from all the view angles , allowing for accurate reconstruction of regional tissue absorption and scattering properties . continuous scanning of the light beam at different wavelengths will generate a 3d map of tissue optical properties and oxygenation distribution . referring to fig7 , exemplary embodiments include methods for intra - operative visual wound assessment . an exemplary method includes the steps of : providing a wearable goggle system comprising an eyewear unit , a spectrally tunable light source , and a control unit ; illuminating a subject tissue with excitation light of multiple wavelengths ; receiving diffuse reflected light emitted from the subject tissue ; processing the emitted light to generate a processed image 96 comprising reflectance spectra data for oxy and deoxy hemoglobin ; and displaying the processed image 96 in near real time onto a head mounted image display 207 in the eyewear unit 50 . the following references and others cited herein but not listed here , to the extent that they provide exemplary procedural and other details supplementary to those set forth herein , are specifically incorporated herein by reference . 1 . a . j . singer , r . a . clark , n engl j med 341 , 738 ( sep . 2 , 1999 ). 2 . h . brem et al ., mol med 13 , 30 ( january - 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