Abstract:
Devices, arrangements, endoscopes, catheters and methods adapted to propagate at least one electro-magnetic radiation are provided. In particular, a waveguide apparatus specifically configured may be utilized to split the electro-magnetic radiation into a plurality of beams that are intended to illuminate a biological sample, and impart a unique associated characteristic unto each of the beams. The beams may be intended to illuminate a biological sample at distinct locations, and impart a unique associated characteristic unto each of the beams. In addition, a control apparatus may be provided which is configured to control at least one of the fibers and which can be input to the fibers so as to modify the unique associated characteristics of the beams being propagated along the fibers, and thereby modify the characteristics of the distinct locations on the sample.

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
       [0001]    This application is based upon and claims the benefit of priority from U.S. Patent Application Ser. No. 60/631,539, filed Nov. 29, 2004, the entire disclosure of which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to optical imaging, and more particularly devices and methods which are capable of performing optical imaging by simultaneously illuminating and detecting multiple points on a sample. 
       BACKGROUND OF THE INVENTION 
       [0003]    Endoscopic/catheter-based optical imaging techniques that utilize beam scanning to form an image such as optical coherence tomography and confocal microscopy, may be limited by an inability to rapidly scan a beam along one or two dimensions. The reason for this is that likely the only reliable methods for rapid optical scanning should be performed in free space. In addition, the size of these optical scanners may deter their use in small probes, such as in endoscopes or catheters. The capability to miniaturize the scanning mechanism would likely increase the number of medical applications of optical imaging techniques to include all surfaces of the body, gynecologic applications, probe based applications, and internal organ systems. 
         [0004]    U.S. Pat. No. 5,321,501 describes optical coherence tomography and U.S. Pat. No. 5,161,053 describes confocal microscopy, both of which utilize an optical fiber. However, the conventional methods described in these publications disclose the use of a single focused spot on the sample with an arrangement for scanning such spot. U.S. Pat. No. 5,659,642 describes the use of an optical fiber bundle to perform confocal microscopy. However, this publication also describes a switching arrangement for selectively illuminating individual channels. In the disclosure of this U.S. patent, a fiber bundle are used, with all points being illuminated and detected simultaneously, thereby eliminating the need for a switching mechanism for selectively illuminating certain channels. Endoscopic confocal microscopy technology has been proposed as a new diagnostic imaging technology capable of providing cellular resolution images in vivo. However, these proposed technology have not been easily realized using a single optical fiber due to the inability to develop a rapid beam scanning mechanism that can reside in a small diameter probe. Other approaches that have been used are selectively illuminating optical fibers in a fiber bundle by scanning a focused beam at the proximal end of a fiber bundle. These approaches have various difficulties due to a beam overlap between channels, thus causing two points to be illuminated simultaneously, which results in cross-talk and aberrations. It would be desirable to use a single fiber to perform endoscopic confocal imaging. If a fiber bundle is used, it may be preferable to illuminate multiple points simultaneously, so that each fiber is illuminated by a unique spot centered on the individual fiber cores. 
         [0005]    Optical coherence tomography (“OCT”) is an imaging modality that has been implemented in the internal organs of patients using optical fibers.  FIG. 1  shows an exemplary mechanical and associated optical elements that are common to particular OCT catheter designs. These catheter designs may include an inner core  120 , which can may contain a fiber optic element  115  that is coupled to the OCT system at the proximal end  110 ,  100 , and which can focus and redirect the light at the distal end  150 . The inner core  120  can rotate or translate to provide one-dimensional motion of the distal optics that serves to scan the beam on the sample. The inner core is enclosed in a transparent sheath  130 . 
         [0006]    The use of catheters in OCT that utilize motion transduction from a proximal actuator to the distal optics by an inner core is problematic due to artifacts that may occur when friction between the inner core and outer transparent sheath causes non-uniform rotation or linear motion  200 . This friction may cause linear artifacts that become more noticeable as the resolution of the imaging technology is increased. As a result, these non-uniform transduction artifacts may prevent the use of this type of catheter when ultra-high resolution OCT (e.g., 1 μm) becomes clinically available. Additional friction due to catheter bending or rotation during the procedure may further exacerbate the problem. 
       OBJECTS AND SUMMARY OF THE INVENTION 
       [0007]    One of the objects of the present invention is to overcome the above-described deficiencies and problems, and provide an exemplary embodiment of a device and arrangement for simultaneously illuminating multiple points on a sample that can be miniaturized and incorporated into a compact probe. Each point on the sample is encoded by frequency using an exemplary embodiment of a frequency encoding method according to the present invention. As a result, frequency analysis of the signal reflected or transmitted through the sample may allow a reconstruction of an image representing the interaction between the energy input and the sample. In addition, by allowing light delivery through a single optical fiber, this device may be also be incorporated into catheters or endoscopes. Other advantages of this exemplary embodiment of the device may include a lack of moving parts, heterodyne detection, and the potential for obtaining cross-sectional images. These properties promote this device for use in performing optical diagnostic imaging in all accessible surfaces of the body. As an example, two technologies that can use and/or incorporate this device are endoscopic confocal microscopy and optical coherence tomography. 
         [0008]    Using another exemplary embodiments of the device and method according to the present invention, multiple spots may be illuminated on the sample simultaneously, and can be detected simultaneously, thus possibly eliminating the need for scanning a single spot. 
         [0009]    Therefore, exemplary embodiments of devices, arrangements, catheters and methods adapted to propagate at least one electro-magnetic radiation are provided. In particular, a waveguide apparatus specifically configured may be utilized to separate or split the electro-magnetic radiation into a plurality of beams that are intended to illuminate a biological sample, and impart a unique associated characteristic unto each of the beams. The beams may be intended to illuminate a biological sample at distinct locations, and impart a unique associated characteristic unto each of the beams. In addition, a control apparatus may be provided which is configured to control at least one of the fibers and which can be input to the fibers so as to modify the unique associated characteristics of the beams being propagated along the fibers, and thereby modify the characteristics of the distinct locations on the sample. 
         [0010]    For example, the waveguide can be a multi-mode waveguide and/or a mirror tunnel. A first illumination arrangement may also be provided that receives the at least one electro-magnetic radiation, and produces a first radiation at least one of within and in a close proximity to the waveguide apparatus. A second illumination arrangement can also be provided that receives which produces a plurality of second radiations based on the first radiation. The second radiations may be approximations of the first radiation, and/or provided at distinct locations on a sample. The first illumination arrangement may include an optical fiber and/or a lens. 
         [0011]    According to another exemplary embodiment of the present invention, a further apparatus can be provided which is configured to control the waveguide apparatus so as to modify the unique associated characteristics of the beams. The unique associated characteristics may include path-lengths and/or phases of the respective beams. The further apparatus can control the waveguide apparatus by modifying structural characteristics of the waveguide apparatus. The modification of the structural characteristics of the waveguide apparatus may be asymmetric with respect to a cross-section of the waveguide apparatus. The further apparatus may control the waveguide apparatus by modifying optical characteristics of the waveguide apparatus. The optical characteristics can include a refractive index. 
         [0012]    Further, the second illumination arrangement can include a further illumination arrangement which is configured to arrange the second radiation in a predetermined pattern on the sample. The predetermined pattern may be approximately circular. The waveguide apparatus can include a plurality of fibers which are configured to transmit the beams. A control apparatus may further be provided that is configured to control the fibers and/or inputs to the fibers so as to modify the unique associated characteristics of the beams being propagated along the fibers, and thereby modify the characteristics of the distinct locations on the sample. Third radiations reflected from the sample may be transmitted back through the waveguide apparatus, and can be based on the second radiation. A reference arm section may be provided that is configured to propagate a portion of the electro-magnetic radiation which is intended to be forwarded to a reference. 
         [0013]    According to still another exemplary embodiment of the present invention, a combining apparatus may be provided which combines the third radiation and a fourth radiation returned from the reference arm to produce an interference radiation. A detection apparatus can be provided which is configured to detect the interference radiation. Further, a processing apparatus may be provided which is configured to generate data corresponding to the third radiations returning from the distinct locations on the sample based on the interference radiation. The processing apparatus may be further configured to generate an image of at least one portion of the sample based on the data. The electro-magnetic radiation can be generated by a narrowband light source that has a tunable center wavelength. The electro-magnetic radiation may be generated by a broadband light source, and the second radiation returned from the waveguide apparatus and a radiation returned from the reference arm section may be adapted to be received by a spectrometer apparatus. A probe (e.g., a catheter, endoscope and/or laparoscope) may be included which houses the waveguide apparatus. 
         [0014]    These and other objects, features and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the appended claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]    Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the invention, in which: 
           [0016]      FIG. 1  is a side cut-away view of a conventional OCT catheter; 
           [0017]      FIG. 2  is an OCT image using the conventional OCT catheter of  FIG. 1  that is acquired from a subject with Barrett&#39;s esophagus, which shows a non-uniform linear motion artifact; 
           [0018]      FIG. 3  is a schematic side view of a frequency encoded multiple beam OCT system according to one exemplary embodiment of the present invention; with the reference arm mirror potentially moving in a time domain (“TD”)-OCT or may remain fixed for a spectral domain (“SD”)-OCT or optical frequency domain imaging (“OFDI”) techniques; 
           [0019]      FIG. 4  is a schematic side view of a multiple beam optical imaging system according to another exemplary embodiment of the present invention, which includes a single mode fiber and multiple beam generating element at the distal end of a catheter; 
           [0020]      FIG. 5  is a schematic side view of a multiple beam optical imaging system according to still another exemplary embodiment of the present invention, which includes a fiber array and multiple beam generating element at a proximal end of the catheter; 
           [0021]      FIG. 6  is an enlarged schematic view of an exemplary embodiment of a multiple spot generating (“MSG”) device according to the present invention that includes two mirrors; 
           [0022]      FIG. 7  is an enlarged schematic view of another exemplary embodiment of the MSG device that can be used to generate a circumferential scan pattern; 
           [0023]      FIG. 8  is a side schematic view of an exemplary embodiment of a fiber optic arrangement according to the present invention which can be used for modulating purposes for each separate beamlet on the sample; and 
           [0024]      FIG. 9  is a side schematic view of another exemplary embodiment of the fiber optic arrangement for synthetic aperture beam scanning. 
       
    
    
       [0025]    Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the present invention will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments. 
       DETAILED DESCRIPTION 
       [0026]    The present invention provides exemplary variations of a catheter paradigm that generally does not scan the beam at the distal end of the catheter, thus eliminating the potential for non-uniform motion artifacts. In a conventional OCT system, one way for conducting OCT can be based on time domain OCT (TD-OCT) scanning. 
         [0027]    In thus exemplary procedure, the length of the reference arm in an interferometer  325  is rapidly scanned over a distance corresponding to the imaging depth range (as shown in  FIG. 3 ), producing an interference pattern when the path length of the reference arm matches the pathlength to a given scatterer in the sample arm to within the temporal coherence length of the source  310  light. For TD-OCT technique, broad bandwidth light  310  can be input into an interferometer, and separate or split into a reference arm  325  and a sample arm  345  arm. The optical path length of the reference arm is scanned by translating the reference arm mirror  320 . Light returned from the reference and sample arms  325 ,  345  combine at the splitter  330 . Interference fringes may be detected when the sample arm path length matches the reference arm path length to within the coherence length of the light. The detection of the fringe patterns may allow one axial scan (A-line) to be constructed that maps tissue reflectivity to a given axial or depth location. An image can be generated by repeating this process at successive transverse locations on the sample. 
         [0028]    In conventional OCT techniques, one single spot may be illuminated on the sample at one time. According to an exemplary embodiment of the present invention, instead, multiple beams  370  can be focused by the distal optics simultaneously illuminating one transverses dimension on the sample  360 . Each distinct beam or spot on the sample  360  can be encoded by frequency in a manner such that frequency analysis of the interferometric signal provides reconstruction of the entire OCT image. Another advantage of this exemplary OCT paradigm is that the reference arm path length scanning can be performed at a much slower rate, thus allowing conventional mechanical path length scanning techniques to produce OCT images at real time frame rates. 
       Exemplary System Overview 
       [0029]    A side schematic view of an exemplary embodiment of a system according to the present invention is shown in  FIGS. 4 and 5 . For example, each device can include an irradiation source  400 ,  500 , a sample path (impacting the sample  460 ,  560 ) and a reference path (impacting a reference  410 ,  510 ) and a detector  470 ,  570 . A catheter  430  of  FIG. 4  may contain a single optical fiber  435  with the multiple spot generating (“MSG”) device  440  at the distal end of the catheter. Alternatively, the MSG device  580  of  FIG. 5  may be placed at the proximal end of the catheter  530 , illuminating an optical fiber array  535 . Multiple points  450 ,  550  are thus illuminated on the sample  460 ,  560 . 
       Multiple Spot Generating (“MSG”) Device 
       [0030]    An enlarged view of a schematic diagram of one exemplary embodiment of the MSG device according to the present invention is shown in  FIG. 6 . A beam emitted from an optical fiber  600  diverges by focusing it to a spot by a lens  610  at the input to a mirror tunnel or optical waveguide  630 ,  640 . A lens at the opposite end  650  of the mirror tunnel images virtual sources or beamlets along a one-dimensional line. Light is reflected from the sample  660 , and returns along its conjugate path. The exemplary embodiment of the optical system according to the present invention provides a confocal rejection of out-of-focus light, due to the aperture of the fiber. 
         [0031]    Due to the geometry of this exemplary optical device, light that forms each beamlet (I n )  670  bounces off one of the mirrors n times. This same beamlet reflects off of the opposite mirror n−1 times. If one or both mirrors  630 ,  640  are moved using an electromechanical actuator, such as a piezoelectric transducer, each distinct beamlet can be imparted a phase shift, nv d , where v d  is the Doppler shift imparted by a double-passed reflection off one moving mirror: 
         [0000]    
       
         
           
             
               v 
               d 
             
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                   v 
                 
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         [0032]    Heterodyne detection of the signal returned from the probe can allow a simultaneous measurement of the Doppler shifted frequencies 0, v d , 2 v d  . . . nv d . The reflectivity from each point can be determined using a tapped bandpass filter or ramped frequency mixing demodulation. The bandwidth of the signal must be no greater than ½ v d  to avoid aliasing. 
       Brief Description of Components of Exemplary Device of FIG. 6 
       [0033]    Lens  610 : GRIN, cylindrical, plano-convex, convex-convex, drum, ball, asphere, multiple element. Asymmetric holographic diffuser. 
         [0034]    Mirrors  630  and/or  640 : Dielectric, omnidirectional mirrors, uncoated metal 
         [0035]    Mirror motion mechanism  635 : Piezoelectric transducer, cantilever. 
         [0036]    Lens  650 : GRIN (OCT), plano-convex, convex-convex, drum, ball, asphere, multiple element (confocal). 
       Conjugate Symmetry 
       [0037]    The exemplary two-mirror system described above with reference to  FIG. 6  has conjugate symmetry properties. Positive and negative beamlets of the same order may have the same Doppler shift if both mirrors are synchronous and have identical modulation frequencies. Discrimination of positive and negative orders may be accomplished by modulating the two mirrors  630 ,  640  with different phases and performing phase sensitive detection. Alternatively, each positive and negative order may be discriminated by frequency interleaving by modulating each mirror at a different frequency. 
       Alternative Mirror Configurations 
       [0038]    Two mirror (N=2) device can create a one-dimensional array of beamlets. 
         [0039]    Triangular mirror tunnel (N=3) can create a two-dimensional hexagonal array of beamlets. 
         [0040]    Rectangular array (N=4) can create a rectilinear array of beamlets. 
         [0041]    Higher orders (N=5,6) can create more complex two-dimensional patterns. 
         [0042]    Cylindrical waveguide may produce orders of rings on the sample. 
         [0043]    The use of N=2 mirrors may have the advantage that the aspect ratio can be maintained at 1:1. In addition, this exemplary configuration allows the illumination of a two-dimensional area, which is particularly well suited for endoscopic confocal microscopy. Disadvantages of two-dimensional illumination may include an increased complexity of the detection mechanism and an increased high reflectivity requirements for the mirror coatings. 
         [0000]    Exemplary Embodiment of Device (with N=2 Configuration) 
         [0044]    Using a mirror separation (d) of 10 a mirror length, L, of 2.0 mm, and a input divergence angle of 100°, a total of 520 points may be simultaneously illuminated and detected using the exemplary embodiment of the present invention. Assuming a mirror reflectivity of 0.997, the maximum double-pass accumulated loss at the edge of the scan would be 6.0 dB. Specifying dielectric coatings that provide maximal reflection at the higher angles may minimize this loss. 
       Endoscopic Confocal Applications 
       [0045]    For example, N=2 configurations may be used in conjunction with SECM for providing the slow scan axis of SECM. The exemplary MSG device (with N=2) can also be used to provide the fast scan axis for endoscopic confocal microscopy. One beneficial option can be the use of N&gt;2 configurations, which may provide the entire two-dimensional scan. 
       Cross Talk 
       [0046]    Cross talk can occur every (2M+1) pixels on the sample. Modulating M mirrors can allow interleaving of the cross-talk frequencies. Since cross talk exists between (2M++) illumination spots on the sample, increasing N and modulating all N=M mirrors allows increasing separation of the cross-talk channels with increasing N and M. For example, for N=M=2, cross talk occurs for spots that are 4 spot diameters from each other. If N=M is increased to 3, cross-talk occurs for spots that are 6 diameters from each other. Cross talk may also be reduced by increasing spot-spot separation or illuminating 1/N of the mirror tunnel and modulating only one mirror. 
       MSG Spot Symmetry 
       [0047]    When MSG illumination is in the center of the exemplary MSG device, identical frequency shifts and path length variations occur symmetrically around the center of the MSG. In order to avoid spot order ambiguity, these planes of symmetry must be broken. 
         [0048]    One way for breaking this symmetry is to illuminate the MSG device at a location slightly offset from the center. Another way of breaking this symmetry may be to utilize mirrors of slightly different lengths or angulation. 
       Electro-Optical Exemplary Embodiments of Device 
       [0049]    In the above descriptions, the use of a hollow, mirror-based waveguide has been described for generating multiple spots on the sample. An alternative exemplary embodiment of the present invention can use a silicon/glass/crystal waveguide, which would also produce the self-imaging effect. The waveguide may also contain an electro-optic material where a voltage applied to the crystal would change the extraordinary and ordinary refractive indices in such a manner as to modulate the phase of the different spot orders independently. This may have the same effect as physically modulating the mirror distances. 
       Optical Coherence Tomography Applications 
       [0050]    In standard axial (depth) priority scan OCT, the MSG device can be used to provide the slow scan axis within the OCT probe. This can allow for imaging at the distal end of the OCT probe, eliminating artifacts such as binding and non-uniform rotational defects (“NURD”) found using a cable to transduce motion from the proximal to distal ends of the catheter/endoscope probe. 
         [0051]    Since the MSG device is capable of rapid imaging, the priority of OCT can be modified from axial to transverse. This exemplary variant of the present invention can greatly diminish the requirements of the rapidly scanning optical delay line (“RSOD”), which could increase scan speeds of OCT systems significantly. 
       Exemplary OCT Circumferential Imaging Catheter Design 
       [0052]    An incorporation of a spatially varying directional grating  760  could allow circumferential OCT imaging with an elimination of non-uniform motion (as shown in the enlarged schematic view of the exemplary MSG device of  FIG. 7 ). This grating may take a line or two-dimensional array of Doppler encoded beamlets and maps this pattern into a circle  770 . The application of this exemplary technique may be desirable for OCT imaging of coronary arteries. Another exemplary embedment of the present invention that enables the circumferential imaging with the MSG device includes the insertion of a helical mirror in place of the custom grating  760  of  FIG. 7 . 
       Alternate Exemplary Embodiment of MSG Device 
       [0053]    Another exemplary embodiment of the MSG device according to the present invention, as shown in  FIG. 8 , can include a single fiber input  800  provided into a star coupler  810  or multiple fibers  820  arranged such that each fiber received a separate Doppler frequency. The Doppler frequencies may be applied using piezoelectric fiber stretchers, electro-optic or acustooptic modulators  830 . Each individual fiber can then be directed to focus a single spot on the sample  850  by distal optics  855 , each unique spot encoded by frequency. 
       Synthetic Aperture Beam Scanning for OCT and Confocal Microscopy 
       [0054]    Another exemplary embodiment for use with OCT or confocal imaging according to the present invention that excludes a transverse scanning mechanism may use a one- or two-dimensional fiber array  935  where the phase of light in each fiber could be controlled  930  or  960  (as shown in  FIG. 9 ). An arrangement for controlling the phase of light in each fiber can include mechanical manipulation of the individual fibers (e.g. piezoelectric transducers) or phase control of each fiber at the input of the array (e.g. via liquid crystal spatial light modulator). By controlling the phase of each individual channel, the output from each fiber can interfere with the outputs from other fibers in order to create a focus or multiple foci  950  on the sample, which can then be scanned. A circumferential scan can be conducted by insertion of a diffractive optic or helical mirror distal to the fiber bundle face at the end of the catheter/endoscope. 
       Detection 
       [0055]    A high sensitivity may be achieved through the use of heterodyne detection. If the reference arm  410  is modulated, the interference of light from the sample arm and the reference arm will also be modulated. High signal to noise ratios may be then achieved by lock-in detection on the reference arm modulation frequency. Frequency domain techniques such as SD-OCT and OFDI can also be utilized that would detect different spectral interference fringe frequencies for different spot orders, as a result of their different path length traveled through the MSG. 
         [0056]    The foregoing merely illustrates the principles of the invention. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention can be used with any OCT system, OFDI system or other imaging systems, and for example with those described in U.S. Provisional Patent Appn. No. 60/514,769 filed Oct. 27, 2003, and International Patent Application No. PCT/US03/02349 filed on Jan. 24, 2003, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. In addition, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly being incorporated herein in its entirety. All publications referenced herein above are incorporated herein by reference in their entireties.