Abstract:
A handheld optical coherence tomography imaging and tissue sampling system and method of imaging and sampling a tissue is disclosed. The method includes inserting a catheter probe into a biopsy needle. The biopsy needle can be attached to a hand-held scanning and sampling device. The biopsy needle is maneuvered to an investigation site. A three-dimensional image of the tissue at the investigation site is captured with the catheter probe.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of and priority to U.S. Provisional Application No. 62/022,497, filed Jul. 9, 2014, which is owned by the assignee of the instant application and the disclosure of which is hereby incorporated herein by reference in its entirety. 
     
    
     STATEMENT OF GOVERNMENT INTEREST 
       [0002]    The subject matter described herein was developed in connection with funding provided by the National Institute of Health (NIH) under Grant No. 5R44CA117218-04 and NIH contract No. HHSN26120140006C. The Federal government has rights in the technology. 
     
    
     FIELD OF THE INVENTION 
       [0003]    The invention relates generally to an apparatus and method for optical coherence tomography (“OCT”) imaging for assessment of interstitial tissue. More particularly, OCT images of the interstitial tissue are taken as a needle including an optical probe is moved within the tissue. 
       BACKGROUND 
       [0004]    Optical coherence tomography (OCT) can be viewed as an optical analog to ultrasound for capturing micrometer-resolution, three-dimensional images from within optical scattering media (e.g., biological tissue). OCT is an interferometric technique that typically employs near-infrared light. OCT typically uses relatively long wavelength light that allows the light to penetrate into a scattering medium. OCT is based on low coherence interferometry. 
         [0005]    During OCT imaging, light from a broad band light source (e.g., superluminescent diode) can split between two arms of an interferometer, a sample arm that contains an item of interest and a reference arm (e.g., a mirror). The combination of reflected light from the sample arm and reference light from the reference arm can yield an interference pattern when the interferometer arms are substantially matched within the coherence length of the light source. 
         [0006]    OCT imaging can be used to noninvasively or minimally invasively visualize sample morphology on the micron scale. OCT imaging at the micron scale level typically requires the use of a high fidelity scan, where the sample arm light beam of an interferometer is scanned with high linearity (e.g., over 99%) across the sample. However, when the imaging has to be done with a needle size probe that passes through several mm to several cm of an interstitial sample (e.g., tissue), the generation of high linearity scan can require the use of rotary or axial movement of the probe within the tissue, which becomes problematic due to tissue friction. 
         [0007]    High-resolution OCT imaging of non-interstitial tissue can require the use of a closed-loop linear scanning engine to scan an optical beam across the tissue and generate a two-dimensional map (e.g., a cross sectional image in the OCT mode and a single dimension map in the spectroscopy mode). Minimally invasive high-resolution OCT imaging of epithelial tissue usually requires the use of a high-speed axial or rotary scanning engine to which the minimally invasive OCT probe is attached. Each of these techniques can prove difficult when imaging interstitial tissue. High-speed and/or rotational movement of an imaging probe in interstitial tissue can cause tissue morbidity by, for example, catching and/or dislocating the tissue, and thus also degrading the linearity of the scan. More recently, scanning mechanisms are being used at the tip of the catheter. However, the size of the scan is limited to a few mm or less, and therefore is not practical for imaging large size areas within the tissue. In addition, the diameter of the catheter is on the order of at least 1 mm and the scanning mechanism cannot be in direct contact with the tissue. 
         [0008]    One possible solution to address tissue morbidity and scanning linearity is to place a protective tube over the imaging probe and move the probe inside of it. However, a protective tube typically cannot be pushed to penetrate the tissue. In addition, it increases the overall diameter of a probe, and thus cannot be passed through be 19 gauge or smaller diameter biopsy guidance needles. 
         [0009]    A possible solution to minimize tissue disruption and reduce morbidity is to use a manually controlled OCT imaging probe with a sharp tip, similar to a biopsy needle. In this way an operator can maneuver the probe slowly through the tissue in a manner that is less disturbing to the tissue. Scanning linearity however still remains a serious issue. Hand-held OCT imaging devices can suffer from inaccurate imaging due to high nonlinearity of the manual scan. One approach to correct the distortion of the OCT image is to use a computational algorithm (e.g., a speckle model to the OCT decorrelation function to explicitly correlate a cross-correlation coefficient (XCC) to a lateral displacement between OCT A-scans). However, this approach is computationally intensive and is not realistic for real-time correction of images. 
         [0010]    Thus, it is desirable for high-resolution OCT imaging of interstitial tissue that both scans nonlinearity and accounts for tissue morbidity. 
       SUMMARY OF THE INVENTION 
       [0011]    One advantage of the invention is that is allows for high-resolution OCT imaging of interstitial tissue by correcting for the nonlinearity of the manual scans and for the distortion of the image caused by tissue noncompliance when the probe is passed through it. Another advantage of the invention is that it provides minimally invasive OCT imaging a minimal tissue disruption due to the operator controlling the position of an optical probe within the interstitial tissue. 
         [0012]    Another advantage of the invention is that it does not require probes that are rotated at a high speed and/or moved axially at a high speed to generate high fidelity OCT images. Another advantage is that the low speed scanning enables the recording of high yield co-registered OCT/spectroscopy images. The reasonable integration times (e.g., tens to hundreds of ms) can be used for each imaging voxel, and thus to collect sufficient photons and generate such images. The elimination of the high speed rotation/movement requirements can also allow the use low cost disposable probes. 
         [0013]    Another advantage of the invention is that is allows for tissue mapping over relatively long distances (e.g., up to several centimeters), due to the fact that a scanning engine is no longer needed. The interventional radiologist passes the probe through the investigated tissue mass, and the OCT image of the entire trajectory of the probe can be recorded in real-time and conveyed to the operator. Another advantage of the invention is that it can capture a high-resolution OCT image independent of scanning speed. Another advantage of the invention is ease of repeating a procedure because manual positioning of the probe allows for the procedure to be repeated several times without removing the probe from the tissue. 
         [0014]    Another advantage of the invention is that it allows for fluorescence imaging or spectroscopy imaging synchronously with OCT imaging due to the elimination of the need for high speed movement to capture an OCT image. 
         [0015]    In one aspect, the invention involves a method of imaging a sample. The method involves inserting a guidance needle and an optical probe into an investigation site of the sample, the optical probe being positioned within the guidance needle. The method also involves establishing, using a position sensor, a reference location of the optical probe at a first spatial position at the investigation site relative to the guidance needle. The method also involves capturing a first optical coherence tomography (OCT) A-line with the optical probe at the first spatial position when the optical probe is moved relative to the reference location. The method also involves detecting, using the position sensor, a spatial location of the optical probe relative to the reference location during movement of the optical probe within the sample. The method also involves capturing an OCT A-line with the optical probe at a second spatial position if the reference location and the spatial location are separated by greater than a predetermined threshold value. The method also involves if the second OCT A-line is captured, determining whether the second OCT A-line is identical to the first OCT A-line and discarding the second OCT A-line if it is identical to the first OCT A-line and storing the second OCT A-line and the first OCT A-line if the second OCT A-line and the first OCT A-line are not identical. 
         [0016]    In some embodiments, the method involves detecting, using the position sensor, a second spatial location of the optical probe relative to the reference location when the optical probe is moved relative to the reference location. The method also involves capturing an OCT A-line with the optical probe in a third spatial position if the second spatial location and the first spatial location are separated by greater than the predetermined threshold value. If the third OCT A-line is captured, determining whether the third OCT A-line is identical to the second OCT A-line then discarding the third OCT A-line if it is identical to the second OCT A-line, and storing the second OCT A-line and the first OCT A-line if the second OCT A-line and the first OCT A-line are not identical. 
         [0017]    In some embodiments, the method involves generating an aggregate OCT image comprising the first OCT A-line and each OCT A-line of the second OCT A-line, the third OCT and any subsequent A-lines for subsequent spatial position OCT A-line that are not a repeat. In some embodiments, maneuvering the optical probe further comprises control by a person, a robot, or any combination thereof. In some embodiments, the second OCT A-line is a repeat of the first OCT image if each A-scan line is substantially similar. 
         [0018]    In some embodiments, the aggregate OCT image is a cross-sectional OCT image. In some embodiments, the method involves emitting light from the optical probe that has a wavelength of approximately 1310 nanometers or approximately 1060 nanometers with a bandwidth of between 10 nanometers and 100 nanometers. In some embodiments, a fluorescence image or a spectroscopy data set is spatially co-registered with the OCT image. 
         [0019]    In another aspect, the invention includes a hand-held optical coherence tomography (OCT) sample imaging system. The system also includes an optical probe positioned and movable within a guidance needle, the optical probe capable of capturing OCT A-lines of the sample. The system also includes an optical scale coupled to the optical probe. The system also includes a position sensor spatially positioned relative to the optical scale, the position sensor configured to detect a location of the optical probe relative to the guidance needle for each OCT A-line taken during imaging, the detection is based on the location of the optical scale. The system also includes a processing unit in communication with the optical probe is configured to record and display cross-sectional OCT images of the sample. 
         [0020]    In some embodiments, the system also includes a fluorescence or spectroscopy unit coupled to the optical probe configured to record a spatially co-registered fluorescence image or spectroscopy data set with the OCT image. In some embodiments, the processing unit is configured to determine whether a first OCT A-line taken at a first spatial location is a repeat of a second OCT A-line taken at a second spatial location, and generate an aggregate OCT image comprising the first OCT A-line and the second OCT image if the second OCT A-line and subsequent OCT A-lines are not a repeat. 
         [0021]    In some embodiments, the reference point is the handle or the guidance needle. In some embodiments, the system also includes a person, a robot or any combination thereof, maneuvers the optical probe by manipulating the hand-held unit. In some embodiments, the system also includes the second OCT A-line is a repeat of the first OCT A-line if each A-line is substantially identical. 
         [0022]    In some embodiments, the system also includes the optical probe emits light that has a wavelength of approximately 1310 nanometers or approximately 1060 nanometers with a bandwidth of between 10 nanometers and 100 nanometers. In some embodiments, the system also includes the aggregate OCT image is a cross-sectional OCT image. In some embodiments, the system also includes an optical scale coupled to the optical probe. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0023]    The advantages of the invention described above, together with further advantages, may be better understood by referring to the following description taken in conjunction with the accompanying drawings, in which like reference characters refer to the same elements throughout the different views. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. 
           [0024]      FIG. 1  is a diagram of a hand-held optical imaging probe, according to an illustrative embodiment of the invention. 
           [0025]      FIG. 2  is a diagram of a hand-held optical probe, according to an illustrative embodiment of the invention. 
           [0026]      FIG. 3  is a flow chart of a method for interstitial tissue OCT imaging and biopsy guidance, according to an illustrative embodiment of the invention. 
           [0027]      FIG. 4  is a schematic of a system combined OCT/spectroscopy or OCT/Fluorescence imaging that includes the connection to a hand-held optical imaging device, according to an illustrative embodiment of the invention. 
           [0028]      FIG. 5  is a graph showing a comparison of OCT images of interstitial tissue with and without encoder correction, according to an illustrative embodiment of the invention. 
           [0029]      FIG. 6  is a graph showing a comparison of OCT images of interstitial tissue with and without corrections, according to an illustrative embodiment of the invention. 
       
    
    
     DESCRIPTION OF THE INVENTION 
       [0030]    Generally, an apparatus including an optical probe capable of taking an OCT image is inserted into interstitial tissue. The optical probe is manually moved (e.g., by a technician or a robot). When the optical probe is moved more than approximately 5 microns from a reference point (e.g., a guidance needle or a handle), an OCT reflectivity profile or A-line is taken. Each OCT A-line is analyzed by a data processor to determine whether or not it is a repeat of the previous A-line. Repeated A-lines are discarded. The data process presents an aggregate OCT image of the interstitial tissue based on each non-discarded OCT A-line. 
         [0031]      FIG. 1  is a diagram of a hand-held optical imaging device  100 , according to an illustrative embodiment of the invention. The hand-held optical imaging device  100  includes an optical fiber  105 , an optical scale  110 , a position sensor  115  (e.g., optical encoder), a connector  120  (e.g., male luerlock connector), a guidance needle  125 , and an optical probe  130  encapsulated into a hypodermic tube with a sharp tip. When in use, the hand-held OCT imaging device  100  emits a light beam  140 . 
         [0032]    The connector  120  is coupled to the guidance needle  125 . The guidance needle  125  has the optical probe  130  disposed therein. The optical probe  130  passes through the connector  120  and has attached or engraved an optical scale  110 . The optical encoder  115  is coupled to the connector  120  at a location that allows the optical encoder  115  to detect a change in position of the optical scale  110 . 
         [0033]    The optical fiber  105  is coupled to the optical probe and connects it to an optical imaging instrument (not shown). 
         [0034]    In some embodiments, the optical probe  130  is a single mode (SM) OCT fiber probe that is terminated with a side looking micro-objective lens. In various embodiments, the optical probe  130  is a combined OCT/fluorescence or absorption/Raman spectroscopy probe, which utilizes either a double clad fiber to collect the fluorescence or absorption/Raman spectroscopy signal, or a separate fiber adjacent to the OCT fiber. In some embodiments, the guidance needle  125  is a transcutaneous biopsy needle. In some embodiments, the guidance needle  125  is up to several inches in length (e.g., 3 to 15 inches). In some embodiments, the guidance needle  125  is a long biopsy needle (e.g., 4 to 6 feet in length), used in conjunction with GI endoscopes, being delivered inside the body through the instrument channel of such endoscopes. 
         [0035]    During operation, the guidance needle  125  is first inserted into the interstitial sample (e.g., kidney, heart, lungs, liver, etc., of a patient) by an operator. Ultrasound or CT guidance can be used for correct placement of the transcutaneous biopsy needles within the tissue location to be examined, while endoscopy guidance is used for proper placement of long needles. 
         [0036]    The operator inserts the optical probe  130  through the guidance needle  125  until the tip of the optical probe  130  outreaches the tip of the guidance needle  130  to a position sufficient to send the imaging beam to the interstitial tissue (e.g., 2-5 mm). Once in a desired position, the operator can maneuver only the optical probe  130  to extend further into the interstitial tissue, while the guidance needle  125  remains substantially unmoved. 
         [0037]    The optical encoder  115  detects any incremental movement of the optical scale  110 . When the optical encoder  115  detects that the location of the optical probe  130  moves more than a predetermined threshold (e.g., 5 microns or more), the optical encoder  115  generates a trigger signal that is transmitted to an OCT spectrometer camera (not shown). In some embodiments, the predetermined threshold is a function of the resolution of the encoder/scale assembly. 
         [0038]    The trigger signal instructs the OCT spectrometer camera to take a signal (e.g., record an OCT reflectivity profile or A-line). An operator maneuvering the optical probe  130  can move as quickly or as slowly as is needed (e.g., for comfort of the patient) because the triggering event for taking an OCT image can be based on location and not time. 
         [0039]    For each OCT A-line taken, the data processor compares the image with a previous OCT A-line taken. If the A-lines are substantially the same, then the data processor discards the repeated A-lines. An aggregate OCT image (e.g., a tomographic OCT image or cross-sectional) is compiled based on all non-repeat A-lines. In this manner, if the optical probe  130  is stuck within the interstitial tissue such that the interstitial tissue moves with the optical probe  130 , a correction is made to discard the repeat voxels from the image. The aggregate OCT image can be displayed in real-time. 
         [0040]    In some embodiments, the predetermined threshold is based on desired imaging resolution, usually 5 to 25 microns. In some embodiments, the optical scale  110  is an engraved optical scale. In some other embodiments, the optical scale  110  is an attached scale. An attached scale can allow the optical probe to be disposable with a low cost. 
         [0041]    In some embodiments, the optical probe  130  is between 300 and 2000 microns in diameter. In some embodiments, the optical probe  130  diameter depends on the size and the length of the biopsy guidance needle. In some embodiments, the optical probe  130  is a regular single mode (SM) fiber that is optic-based. In some embodiments, the optical probe  130  is a combination of a SM fiber and a multimode (MM) fiber, the SM being used for OCT imaging and the MM used for fluorescence or spectroscope. In some embodiments, the optical probe  130  is a dual clad fiber where the core is used for OCT and spectroscopy or fluorescence illumination, and the 2 nd  clad for collecting the fluorescence or spectroscopy photons. 
         [0042]      FIG. 2  is a diagram of a hand-held OCT imaging device  200 , according to an illustrative embodiment of the invention. The hand-held OCT imaging device  200  includes an optical probe  210 , a biopsy needle  220 , a jacket  230 , an optical scale  240 , an encoder  250 , a holder  260  and a handle  270 . 
         [0043]    The optical probe  210  is positioned within the biopsy needle  220 . The biopsy needle is positioned within a jacket  230 . The jacket  230  is coupled to the holder  260 . The holder  260  is coupled to the optical scale  240 . The holder  260  is coupled to the handle  270 . The handle  270  is coupled to the encoder  250 . 
         [0044]    During operation, the biopsy needle  220  with a stilet disposed therein (not shown) is placed within the interstitial tissue of interest under endoscopic guidance. The stilet is removed and the optical probe  210  is inserted into the biopsy needle  220  until it reaches the interstitial tissue (e.g., a pancreas, stomach, or other organ of interest). The optical probe  210  is locked to the biopsy needle  220 , so that the optical probe  210  and the biopsy needle  220  can move together when the handle  270  is moved. The biopsy needle  220  is maneuvered by a person (or a robot) manipulating the handle  270 . 
         [0045]    When the handle  270  is moved forward, the biopsy needle  220  and the optical probe  210  are moved forward. The encoder  250  attached to the handle  270  moves relative to the optical scale  240 , which is attached to the holder  260 . Therefore, any movement of the optical probe  210  inside the tissue is monitored by the encoder  250 , which generates trigger pulses and starts the acquisition of the OCT A-lines. 
         [0046]      FIG. 3  is a flow chart of a method  300  for sample OCT imaging and biopsy guidance, according to an illustrative embodiment of the invention. The method involves inserting a guidance needle (e.g., guidance needle  125  as shown above in  FIG. 1 ) and an optical probe (e.g. interstitial sample (Step  310 ), the optical probe being positioned within the guidance needle. In some embodiments, the guidance needle is inserted into the sample with a stilet, the stilet is removed and then the optical probe is inserted. In some embodiments, the guidance needle and the optical probe are coupled prior to insertion. 
         [0047]    The sample can be any tissue of a mammal that needs to be investigated or any biological/non-biological specimen. The investigation site, in a mammal, can be a site of interest having some shape and size defined by previous radiological or ultrasound imaging, or by real-time radiological or ultrasound imaging. For example, for a patient that previously had cancer (e.g., breast cancer), the investigation site can be well defined area having a different radiological appearance than the surrounding tissue. In some embodiments, the investigation site is based on the images (e.g., Ct or ultrasound) taken during the investigation (e.g., biopsy procedure). The optical probe can be an OCT imaging probe. 
         [0048]    The method also involves establishing, using a position sensor, a reference location of the optical probe at a first spatial position at the investigation site relative to the guidance needle (Step  320 ). 
         [0049]    The method also involves capturing a first optical coherence tomography (OCT) A-line with the optical probe at the first spatial position when the optical probe is moved relative to the reference location (Step  330 ). 
         [0050]    The method also involves detecting, using the position sensor, a spatial location of the optical probe relative to the reference location during movement of the optical probe within the sample (Step  340 ). The position sensor can be an optical encoder, a magnetic position sensor, or any position sensor as is known in the art. 
         [0051]    The method also involves capturing an OCT A-line with the optical probe at a second spatial position if the reference location and the spatial location are separated by greater than a predetermined threshold value (Step  350 ). In some embodiments, the predefined threshold value is 5 microns. In various embodiments, the predefined threshold value is between 1 and 25 microns. 
         [0052]    The method also involves determining whether the second OCT A-line is identical to the first OCT A-line (Step  360 ). In some embodiments, the determination as to whether the first and second OCT A-lines are the same is based on the following: 
         [0000]      If  I   Axi+1   −I   Axi   &gt;k , then  A   xi+1 =0   (EQN. 1)
 
         [0000]    Where I Ax  is intensity of each pixel from successive A line of the first OCT image, I Axi+1  is intensity of each pixel from successive A line of the second OCT image, and k is a threshold constant. In various embodiments, k is an experimentally established threshold based on image intensity, or is automatically determined by the OCT processor. 
         [0053]    If the first OCT A-line and the second OCT A-line are identical then the second OCT A-line is discarded (Step  370 ). If the first OCT A-line and the second OCT A-line are not identical the first OCT A-line and the second OCT A-line are stored (Step  380 ). The first OCT A-line and the second OCT A-line can be stored in an array. 
         [0054]    In this manner, at periodic intervals, an OCT A-line image is taken each time the optical probe moves beyond the predetermined threshold. For each A-line image that is taken, if it is not identical to the previous A-line image, then it is stored in the array. The array can be used by the processor to append all of the non-discarded A-lines into one cohesive OCT image. 
         [0055]    In some embodiments, the imaging probe is a combined OCT/fluorescence or OCT/Spectroscopy image. The Fluorescence or spectroscopy data can be used in conjunction with the OCT data to provide enhanced differentiation of tissue nature (e.g., normal, solid tumor, heterogeneous tissue, necrotic tissue). Either the operator or an automated tissue differentiation algorithm can be used to determine tissue nature in real time. 
         [0056]    In some embodiments, the probe is reoriented into a different spatial location of the tissue, e.g., if the investigated location by OCT or combined OCT/fluorescence/spectroscopy does not show a correlation with the radiological finding. In these embodiments, the optical probe can be manually retracted until it reaches the tip of the biopsy guidance needle and the needle optical probe assembly can be reoriented to a different position or angle to reach a different area of the investigated tissue ( 350 ) to collect a new data set. 
         [0057]    If used for biopsy guidance, the procedure can be repeated several times until the operator determines, based on the collected data, that a specific location within the tissue specimen is the right one to collect a tissue specimen. Then, the optical probe is retracted and the biopsy cutting needle is inserted through the guidance needle to collect a tissue specimen (biopsy core or an assembly of cells and fluid (for aspiration biopsies). 
         [0058]      FIG. 4  is a schematic of a system  400  for OCT imaging includes a hand-held OCT imaging device, according to an illustrative embodiment of the invention. 
         [0059]    The system  400  includes a spectroscopy/fluorescence imaging unit  410 , an OCT unit  420 , a system control and data processing unit  430 , a signal conditioner  440 , an OCT imaging probe  450  that includes a position sensor  455  and a division multiplexing fiber component  460 . 
         [0060]    The spectroscopy/fluorescent imaging unit  410  and the OCT unit  420  are in communication with the OCT imaging probe  450  through the division multiplexing fiber component  460 . The spectroscopy/fluorescent imaging unit  410  and the OCT unit  420  are also in communication with the system control and data processing unit  430 . The system control and data processing unit  430  is also in communication with the OCT imaging probe  450  via the signal conditioning unit  440 . 
         [0061]    During operation, the OCT imaging probe  450  is inserted into interstitial tissue. The position sensor  455  detects the position of the probe in the interstitial tissue during imaging. The signal conditioning unit  440  receives the imaging data and minimizes noise on the received data and/or instructs the system control and data processing unit  430  to start acquisition of the signals. The system control and data processing unit uses the position data from the position sensor  455  to append the consecutive signals to an array and form a cross-sectional OCT image. It also determines whether consecutive A-lines are repeats or new A-lines of an investigation site of the interstitial tissue (e.g., for example, by using method  300 ). 
         [0062]    The spectroscopy/fluorescence imaging unit  410  transmits/receives signals from the imaging probe that can be used in correlation with the OCT image to improve tissue discrimination. The wavelength can be between 400 and 800 nanometers. 
         [0063]      FIG. 5  is a graph  500  showing a comparison of OCT images of interstitial tissue with and without correction, according to an illustrative embodiment of the invention. The image with encoder feedback represents a distorted image of the tissue true morphology, while the one with encoder feedback represents the true morphology of the tissue. 
         [0064]      FIG. 6  is a graph  600  showing a comparison of OCT images of interstitial tissue, according to an illustrative embodiment of the invention. As observed the repeated voxels from the uncorrected image are eliminated from the corrected image, which is physically shorter and represents the true morphology of the tissue 
         [0065]    Although various aspects of the disclosed methods, devices and systems have been shown and described, modifications may occur to those skilled in the art upon reading the specification. The present application includes such modifications and is limited only by the scope of the claims.