Abstract:
A needle biopsy includes the step of inserting an optical spectroscopy probe in the needle and gathering optical information through a window formed in the side of the needle at its distal end. The optical probe includes an illumination optical fiber which conveys light to the tissues adjacent the side window and a detection optical fiber which collects light from the same tissues and conveys it to an optical spectroscopy instrument. Based on the results of the optical spectroscopy measurement, the optical probe may be withdrawn from the needle and a cutter advanced to acquire a sample of the tissues adjacent the side window.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims the benefit of U.S. Provisional patent application Ser. No. 60/547,262 filed on Feb. 24, 2004 and entitled “SIDE-FIRING OPTICAL PROBE FOR CORE NEEDLE BIOPSY”; U.S. Provisional patent application Ser. No. 60/553,825 filed on Mar. 17, 2004 and entitled “ENDOSCOPICALLY COMPATIBLE NEAR INFRARED PHOTON”; and U.S. Provisional patent application Ser. No. 60/615,671 filed on Oct. 4, 2004 and entitled “OPTICAL SENSOR FOR BREAST CANCER DETECTION DURING BIOPSY”. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH  
       [0002]     This invention was made with government support under Grant No. NIH EB00184 awarded by the National Institute of Health. The United States Government has certain rights in this invention. 
     
    
     BACKGROUND OF THE INVENTION  
       [0003]     The field of the invention is optical spectroscopy, and particularly, the use of optical spectroscopy during the performance of core needle biopsy procedures.  
         [0004]     Percutaneous, image-guided core needle biopsy is being increasingly used to diagnose breast lesions. Compared to surgical biopsy, this procedure is less invasive, less expensive, faster, minimizes deformity, leaves little or no scarring and requires a shorter time for recovery. Needle biopsy can obviate the need for surgery in women with benign lesions and reduce the number of surgical procedures performed in women with breast cancer. However, the caveat is that needle biopsy has a limited sampling accuracy because only a few small pieces of tissue are extracted from random locations in the suspicious mass. In some cases, sampling of the suspicious mass may be missed altogether. Consequences include a false-negative rate of up to 7% (when verified with follow up mammography) and repeat biopsies (percutaneous or surgical) in up to 18% of patients (due to discordance between histological findings and mammography). The sampling accuracy of core needle biopsy is highly dependent on operator skills and on the equipment used.  
         [0005]     Optical spectroscopy may be used to characterize tissues. These methods include ultraviolet-visible (UV-VIS) reflectance and fluorescence spectroscopy and Near infrared (NIR) optical spectroscopy.  
         [0006]     Near infrared (NIR) optical spectroscopy is a technique in which a light source is placed on the tissue surface launches photon density waves into the tissue having a wavelength in the range of 600 nm to 1000 nm. A fraction of these photons, which propagate through the tissue, reach a collector some distance (0.5 cm to 8 cm) from the light source. The collected photons, on average, have traversed a banana shaped path within the tissues which extends into the tissue a distance equal to approximately half the separation between the source and the collector. The absorption and scattering properties of the tissue can be retrieved from the amplitude and phase shift of the collected light using a light transport algorithm based on the Diffusion equation. The concentrations of absorbers can be derived from the absorption coefficient using Beer&#39;s law. Endogenous absorbers in breast tissue at NIR wavelengths include oxy and deoxy hemoglobin, water and lipids. The scattering is associated with microscopic variations in the size, shape and refractive indices of both intracellular and extra cellular components.  
         [0007]     Tissue vascularity, hemoglobin concentration and saturation have all been identified as diagnostic markers of breast cancer using a variety of different techniques including immunohistochemistry, needle oxygen electrodes and magnetic resonance spectroscopy. Breast cancers are more vascularized and are hypoxic compared to normal breast tissues. A number of groups have demonstrated that these sources of contrast can be exploited for the non-invasive detection of breast cancer in the intact breast using NIR diffuse optical imaging. For example, Ntziachristos et al developed and tested a novel hybrid system that combines magnetic resonance imaging and NIR diffuse optical imaging for non-invasive detection of breast cancer. Using this technique, they quantified oxygenated hemoglobin (HbO 2 ) and deoxygenated hemoglobin (Hb) concentrations of five malignant and nine benign breast lesions in vivo. The average total hemoglobin concentration for the cancers, fibroadenomas and normal tissues were 0.130±0.100 mM, 0.060±0.010 mM and 0.018±0.005 mM, respectively. This representative study demonstrates that NIR diffuse optical methods can discriminate malignant from benign lesions based on tissue vascularity.  
         [0008]     Ultraviolet-visible (UV-VIS) reflectance and fluorescence spectroscopy (RFS) is a combination of two techniques. Reflectance spectroscopy is a technique in which broad spectrum light containing wavelengths from 350 nm to 600 nm illuminates the tissue. The reflected light is collected, separated into its component wavelengths and measured. This enables us to examine several chemicals which absorb light including oxy and deoxy hemoglobin, and beta-carotene. Fluorescence spectroscopy is a technique where a single wavelength is used to illuminate the tissue. The illumination light is absorbed by endogenous and/or exogenous chemicals in the body, then re-emitted as fluorescence light at a different wavelength. This re-emitted light is collected and measured. This is done for a series of illumination wavelengths of light in the range of 300 to 460 nm. Fluorescence spectroscopy allows us to characterize several tissue components such as FAD, NADH, collagen and Tryptophan. These two techniques can be done in rapid succession, with a single instrument.  
         [0009]     All of the optical spectroscopy techniques require that the light source and light detector be positioned close to the tissues to be examined. In both methods the measured properties are averages of all the tissues where the light has traversed. In the former method, small areas inside large tissues can be difficult to distinguish without complex imaging techniques. The UV-VIS light used in the latter method does not penetrate deeply into human tissue and this is typically used to examine the surface of tissues. The light may also be delivered to a tissue through an optical fiber that extends through an endoscope such as that described in U.S. Pat. No. 5,131,398 to examine the surface of an internal organ.  
       SUMMARY OF THE INVENTION  
       [0010]     The present invention is a method and optical probe for making optical spectroscopy measurements during the performance of a core needle biopsy. The optical probe is inserted into the biopsy needle after the needle has been inserted into the candidate tissue to be biopsied; light is applied to the probe and is emitted into tissue surrounding the tip of the biopsy needle; and light from these tissues is collected by the probe and conveyed to a spectroscopy instrument for analysis. When target tissue is detected, the probe is removed from the biopsy needle and a tissue sample is acquired by advancing a cutting tool.  
         [0011]     The optical probe includes: an end cap which is sized and shaped to fit into the central opening of a biopsy needle; one or more illumination fibers having a distal end retained to the probe end cap and a proximal end which connects to a source of light; one or more detector fibers having a distal end retained to the probe end cap and a proximal end connected to a spectroscopic instrument; and wherein the probe end cap may be positioned near the distal end of the needle to emit light from the distal end of the illumination fiber through a window formed in the side of the biopsy needle and receive light from tissues through the window and convey it through the detector fiber to the spectroscopic instrument.  
         [0012]     By inserting the optical probe in the biopsy needle and examining the tissue surrounding the tip of the needle, the candidate tissue can be evaluated prior to the biopsy. This enables different and larger regions to be examined before the biopsy is taken, thus increasing the probability that the correct tissue is biopsied and that another biopsy will not be required. This method has the potential to improve the lives of thousands of women by eliminating the need for 90,000 to 180,000 repeat biopsies per year and improving the accuracy of diagnosis for thousands more. This will significantly alleviate the physical and emotional costs to thousands of women undergoing this procedure.  
         [0013]     A general object of the invention is to provide an optical spectroscopy system which improves the sampling accuracy of an image guided core needle biopsy. The system includes optical fibers that are inserted into the bore of a biopsy needle to illuminate and acquire light from surrounding tissues, and a spectrometer which receives this light and provides a measure of tissue physiological parameters. Parameters such as tissue vascularity and fluorescent spectra distinguish malignant from non-malignant breast tissue. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]      FIG. 1  is a pictorial view of an optical spectrometer, side firing probe and needle which employs the present invention;  
         [0015]      FIG. 2  is a schematic representation of an optical probe in a biopsy needle according to the present invention;  
         [0016]      FIG. 3  is a pictorial view of a preferred embodiment of a NIR optical probe in a biopsy needle;  
         [0017]      FIG. 4  is a pictorial view of the probe and needle of  FIG. 3  in cross-section;  
         [0018]      FIG. 5  is a schematic diagram of a NIR optical spectroscopy instrument used with the optical probe of  FIG. 3 ;  
         [0019]      FIG. 6  is a pictorial view of a preferred embodiment of a UV-VIS spectroscopy optical probe in a biopsy needle;  
         [0020]      FIG. 7  is an alternative embodiment of an optical spectroscopy probe; and  
         [0021]      FIG. 8  is a view in cross-section of the needle with a cutter deployed in place of the optical probe.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0022]     Referring particularly to  FIG. 1 , an optical spectroscopy system which employs the present invention includes a light source  10  that connects to the proximal end of an illumination optical fiber  12  and is operated by a controller  14  to produce light of the proper wavelength at a probe  16 . The controller  14  also operates an optical spectrometer instrument  18  which receives light through a detector optical fiber  20  which has a distal end fastened to the probe  16 . The diameter of the probe  16  is sufficiently small that it can be inserted into a central channel formed in a biopsy needle shank  22 . A breast biopsy needle such as that disclosed in U.S. Pat. No. 6,638,235 and manufactured by Suros Surgical Systems, Inc. is employed in a preferred embodiment. The needle shank  22  extends completely through a handle  24  that contains a mechanism for extracting a tissue sample through the needle  22 . For a 9-gauge needle, the shank  22  has a length of 12 cm and a 3.7 mm outside diameter. A sample holder  21  attached to a connector  23  on the proximal end of the handle  24  is removed during the optical data acquisition portion of the procedure to provide access to the proximal end of the needle shank  22  for optical probe  16 . When this step of the procedure is completed, the optical probe  16  is withdrawn and the sample holder  21  is reattached.  
         [0023]     As shown in  FIG. 2 , when the optical probe  16  is properly positioned at the distal end  26  of the needle shank  22  the distal ends of both optical fibers  12  and  20  are aligned axially along a longitudinal axis  25  with a window  27  formed by an opening  28  in the shank  22  of the needle near its distal end  26 . This window is 20 mm long and 3.7 mm wide in the preferred needle and is used during the biopsy procedure for tissue collection. The distal end of illumination optical fiber  12  is cut at a 43° angle such that light emanating from light source  10  and traveling through the fiber  12  is reflected radially outward through the window  27  into surrounding tissue. That is, the illumination light travels axially along the length of the biopsy needle shank  22  and is redirected by the bevelled distal end to make a substantially right angle turn as indicated by arrow  30 .  
         [0024]     The distal end of the detection optical fiber  20  is similarly beveled at a 43° angle. As a result, light entering through the window  27  in a substantially radially inward direction is reflected off the beveled end and is redirected axially along the optical fiber  20  as indicated by arrow  32 . Illumination of tissues located in the region outside the window  27  is thus performed by conveying the desired light along fiber  12  and collecting the resulting light produced in these tissues with the optical fiber  20 . The collected light is conveyed back to the optical spectrometer  18  by the detector optical fiber  20 . Tissues surrounding the distal tip  26  of the biopsy needle  22  can thus be spectroscopically examined by rotating the needle  22  about the longitudinal axis  25  to “aim” the window  27  in a succession of radial directions.  
         [0025]     As will now be described in more detail, the number and size of the optical fibers as well as their positioning in the optical probe  16  will depend upon the particular spectroscopic measurement being made. It is contemplated that a number of different probes  16  may be used in any single biopsy procedure in order to gather enough information to make a clinical decision. The biopsy needle  22  is inserted in the patient and its distal end  26  is guided to the candidate tissues using an imaging modality such as ultrasound or MRI. An optical probe  16  may then be inserted into the needle  22  and oriented as described above to acquire optical information for the spectrometer  18 . This may be repeated using the same or a different probe  16  until a decision is made to biopsy. The optical probe  16  is then withdrawn from the needle shank  22 . A gentle vacuum is applied to the needle, pulling a small amount of tissue in the window  27 . A cutter  29  is then advanced, as shown in  FIG. 8 , slicing this tissue where it enters the needle. The vacuum then pulls this sample of tissue down the needle&#39;s length and into a collection chamber. It can be appreciated that by performing optical spectroscopy through window  27  on the very same tissue that is removed by the biopsy step, highly reliable clinical information is acquired.  
         [0026]     Referring particularly to  FIGS. 3 and 4 , the first preferred embodiment of the invention is a photon migration spectroscopy technique in which near infrared (NIR) photon density waves are launched into the tissue using two illumination optical fibers  36  and  38  and reflected light is gathered from the tissue using a single detection optical fiber  40 . The distal ends of these optical fibers  36 ,  38  and  40  are encased in a rigid, optically transparent quartz end cap  42  to form the optical probe  16 . Flexible tubing  44  such as that sold under the trademark “TYGON” fastens to the cap  42  and extends along the length of the optical fibers to hold them together and provide a limited amount of protection. At the proximal end of this Tygon tubing there is an aluminum junction (not shown), which bifurcates into three parts, one for each fiber. Each of these parts is sheathed in polyvinyl chloride (PVC). After the junction all of the fibers are reinforced with Kevlar fibers and each fiber is terminated in a “Fiber Connector”, which connects the sensor to the NIR instrument described below.  
         [0027]     The optical fiber diameters and the spacing between their distal ends are selected to optimize the signal level and the depth of the tissue that can be measured outside the window  27 . In the resulting optical probe  16  the two illumination optical fibers  36  and  38  have a diameter of 200 μm and a numerical aperture of 0.22; the detection optical fiber  40  has a core diameter of 600 μm and a numerical aperture of 0.22; and quartz end cap  42  has a length of 25 mm and an outer diameter of 2.4 mm. All optical fiber distal ends are polished at an angle of 43° and radially oriented such that the light from each fiber is normal to the cylindrical surface of the quartz end cap  42 . This radial orientation minimizes specular reflection into the collection fiber  40 .  
         [0028]     The relative placement and orientation of the fiber tips is fixed by gluing the fibers  36 ,  38  and  40  together. Epoxy at the junction of the end cap  42  and the flexible tube  44  fixes the fibers inside the quartz end cap  42 . The outer diameter of the cap  42  is stepped down at its proximal end so it fits inside the distal end of flexible tube  44 . This provides strength at the junction and makes the junction smooth for easy insertion and removal of the probe  16  from the biopsy needle  22 . The distal end of illumination fiber  36  is spaced 10 mm from the distal end of detector fiber  40  to provide deeper penetration and probe deeper into the tissues as indicated by dashed line  46 . The tip of the other illumination fiber  38  is spaced only 5 mm from the detector fiber tip to probe at a much shallower depth as indicate by dashed line  48 . This latter depth approximates the depth of tissue acquired by the subsequent biopsy. The preferred probe  16  thus enables two measurements to be made at different spacings. This enables automatic correction for instrument response and collection fiber bending loss, thus obviating the need for the use of calibration phantoms.  
         [0029]     Referring particularly to  FIG. 5 , the instrument to which this NIR probe is coupled, is a frequency domain system similar to that described by T H Pham, P Coquoz, J B Fishkin, E Anderson, B J Troberg, in a publication entitled “Broad Bandwidth Frequency Domain Instrument For Quantitative Tissue Optical Spectroscopy,”  Review Of Scientific Instruments  71, 2500-2513 (2000). It consists of a laser diode driver  50  (ILX lightwave LDC-3908) and a network analyzer  52  (Agilent 9712ET), which amplitude modulates 811 nm and 850 nm laser diodes  54  (JDS Uniphase SDL5421-H1-810, JDS Uniphase SDL 5401-G1-852). Associated with each laser diode  54  is a bias-tee  55  for combining direct current bias and rf power. The output of the laser  54  is connected to the illumination optical fibers  36  and  38  through an optical switch  56  (Dicon GP700). The two laser diode wavelengths lie within the absorption bands of HB and H 2 0. The average power delivered by lasers  54  at the probe tip is approximately 6 mW.  
         [0030]     The probe&#39;s collection fiber  40  is connected to an avalanche photo diode  58  (Hamamatsu C5658), and a 19 dB amplifier  60  (Mini Circuits ZFC-500HLN). For each measurement,  101  data points are collected over the frequency range of 50-150 MHz. At a bandwidth of 15 Hz (resulting in a measurement sweep time of 8 seconds), the signal to noise ratio of the instrument and probe is greater than 300:1 over the 50 to 150 MHz range in a liquid phantom with an absorption coefficient of 0.2 cm −1  and reduced scattering coefficient of 10 cm −1 . This instrument records phase and amplitude data. This data is fit to an infinite solution of the diffusion equation, which is appropriate for the interstitial geometry used in the breast needle biopsy application.  
         [0031]     The present invention may also be used to perform ultraviolet-visible reflectance and fluorescence spectroscopy. Because light at these wavelengths does not penetrate deeply into human tissue, the distal ends of the illumination fiber and the detection fiber must be spaced much closer together than the 5 mm to 10 mm range used in the NIR embodiment described above.  
         [0032]     Referring particularly to  FIG. 6 , a preferred embodiment of an optical probe  16  for use at ultraviolet and visible wavelengths is substantially the same as that described above for NIR applications. In this case, however, the larger 600 μm optical fiber  40 ′ is employed to illuminate tissue and the smaller 200 μm optical fibers  36 ′ and  38 ′ are employed to detect light received from the tissue. The optical fibers  36 ′,  38 ′ and  40 ′ are bonded together and sealed inside the quartz end cap  42  as described above, however, the spacing between their distal ends is significantly smaller. The distal ends of collection fibers  36 ′ and  38 ′ are positioned near the distal end of illumination fiber  40 ′, but they are disposed on opposite sides of the illumination fiber  40 ′ and their bevelled tips are oriented at an angle such that their collection regions are disposed circumferentially around the quartz end cap  42 , but do not overlap each other. The use of two collection fibers thus increases the field of view of the probe.  
         [0033]     The instrument to which this optical probe is connected is significantly different than the NIR instrument described above. In this embodiment the light source  10  is a broad band light source with a monochromator coupled to its output to select a single wavelength of light for application to the illumination fiber  40 ′. The light collected by detector fibers  36 ′ and  38 ′ is coupled to a grating to separate the light into its component colors. The separated light is applied to a CCD device which measures the amplitude of each component color.  
         [0034]     In some clinical applications it is desirable to reduce the “leakage” of light that can occur between the illumination and detector optical fibers. An alternative embodiment of the invention which minimizes such leakage is shown in  FIG. 7 . This is a variation of the embodiment described above with respect to  FIG. 2  in which like elements are indicated with the same reference numbers. The difference in this alternative embodiment is that an opaque sheath  60  is disposed around the detection optical fiber  20  to block any leakage of light into the optical fiber  20  along its length. The selection of material will depend on the wavelength of light to be blocked. In addition, a light baffle  62  is disposed between the distal end of the illuminating optical fiber  12  and the distal end of the detector optical fiber  20 . Baffle  62  is formed from an opaque material for the wavelengths used and it extends radially outward from the surface of the opaque sheath  60  as far as possible without interference with the quartz end cap  42 . It extends circumferentially around the opaque sheath  60  a sufficient distance to serve as a light barrier between the optical fiber tips. In this embodiment a higher percentage of the light produced by illuminating optical fiber  12  passes through the subject tissues before being captured by the detection optical fiber  20 .  
         [0035]     It should be apparent that variations from the preferred embodiment described above are possible without departing from the spirit of the present invention. Cutting the ends of the optical fibers at a 43° angle with respect to longitudinal axis  25  reflects the light at approximately 90°. Depending on the size of the window  27  and the location of the distal end of an optical fiber, other angles are possible. Also, mirror like structures such as gold can be added as a coating to the bevelled tips of the optical fibers to increase the percentage of light that is reflected to and from the tissues.