Abstract:
An optical probe has multiple side-firing optical fibers which terminate in a linearly staggered fashion. A central fiber can be used as well. In diagnostic techniques, one fiber can be used as an emitter, while the others are used as receivers, or various fibers can be used as emitters and receivers at different times to form a map of the area. In therapeutic techniques, the treatment light can be emitted from the fibers in parallel or in sequence, and the fluence can be independently adjusted for each of the fibers. Therapy is readily combined with diagnosis and monitoring by directing the therapeutic light through the central fiber and using the side-firing fibers for reflectance and/or fluorescence spectroscopy before, during, and after therapy.

Description:
REFERENCE TO RELATED APPLICATIONS  
       [0001]     The present application claims the benefit of U.S. Provisional Application No. 60/790,540, filed Apr. 10, 2006. Related information is disclosed in WO 2006/025940 A2,A3. The disclosures of both of the above-cited applications are hereby incorporated by reference in their entireties into the present disclosure. 
     
    
     STATEMENT OF GOVERNMENT INTEREST  
       [0002]     The work leading to the present invention was funded by NIH Grants P01CA55719, R01CA68409, and T32HL66988. The government has certain rights in the invention. 
     
    
     FIELD OF THE INVENTION  
       [0003]     The present invention is directed to an optic array for tissue measurements and other optical inspection and more particularly to such an optic array in which side-firing optical fibers terminate in a linearly staggered fashion.  
       DESCRIPTION OF RELATED ART  
       [0004]     The accurate, real-time determination of measurable quantities that influence or report therapeutic dose delivered by photodynamic therapy (PDT) is an area of active research and clinical importance. Photosensitizer evolution, including photobleaching and photoproduct formation, and accumulation of endogenous porphyrins provide attractive implicit dose metrics, as these processes are mediated by similar photochemistry as dose deposition and report cellular damage, respectively. Reflectance spectroscopy can similarly report blood volume and hemoglobin oxygen saturation.  
         [0005]     Photodynamic therapy is a burgeoning cancer treatment modality in which a combination of light and drug is used to kill tumor cells with high selectivity. Leveraged with success in dermatology, opthalmology, and directly accessible tissues, PDT is being expanded into treatment of prostate cancer, lung cancer, liver cancer, nodular basal cell carcinoma, and other interstitial applications. In order to deliver and monitor effective dose in these new applications, however, it is important to understand the optical properties of the tissue, which are often heterogeneous between applications and can even change during therapy. It is therefore important to make measurements before and during a treatment to plan the therapy and assess its progress.  
       SUMMARY OF THE INVENTION  
       [0006]     It is therefore an object of the invention to measure the optical properties of tissue.  
         [0007]     It is another object of the invention to be able to do so over time.  
         [0008]     It is another object of the invention to provide a device for characterization and quantification of chromatophores and fluorophores within turbid media.  
         [0009]     It is another object of the invention to allow photodynamic therapy treatment source delivery and fluorescence and reflectance spectroscopies in needle- and catheter-accessible tissues.  
         [0010]     To achieve the above and other objects, the present invention is directed to an optical probe having multiple side-firing optical fibers which terminate in a linearly staggered fashion as well as to an instrument incorporating such a probe. A central fiber can be used as well, and the fibers can be disposed in a catheter or needle. The fibers can be used in various ways. For instance, in diagnostic techniques, one can be used as an emitter, while the others are used as receivers, or various fibers can be used as emitters and receivers at different times to form a map of the area. In therapeutic techniques, the treatment light can be emitted from the fibers in parallel or in sequence, and the fluence can be independently adjusted for each of the fibers. In a combined therapeutic and diagnostic/monitoring technique, treatment light may be delivered through the central diffuser fiber while the side-firing fibers monitor fluence. Or, the treatment light administered through the diffuser may be gated off for a brief interval while the side-firing fibers are used for reflectance and/or fluorescence spectroscopy of the tissue volume.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0011]     Preferred embodiments of the present invention will be set forth in detail with reference to the drawings, in which:  
         [0012]      FIGS. 1A and 1B  show the construction of the probe according to a first preferred embodiment;  
         [0013]      FIGS. 2A and 2B  show an instrument incorporating the probe of  FIGS. 1A and 1B  and its use;  
         [0014]      FIG. 3  shows a first use of the probe;  
         [0015]      FIGS. 4A-4D  show a second use of the probe;  
         [0016]      FIG. 5  shows a third use of the probe;  
         [0017]      FIG. 6  shows a fourth use of the probe;  
         [0018]      FIG. 7  shows a modification of the probe for a fifth use; and  
         [0019]      FIG. 8  shows a second preferred embodiment of the probe.  
         [0020]      FIGS. 9A and 9B  show a third preferred embodiment of the probe.  
         [0021]      FIGS. 10A and 10B  show a fourth preferred embodiment of the probe.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0022]     Preferred embodiments of the invention will bet set forth in detail with reference to the drawings, in which like reference numerals refer to like elements throughout.  
         [0023]     In a first preferred embodiment, as shown in  FIG. 1A , the probe  100  includes seven optical fibers in the known “six-around-one” fiber bundle geometry. That geometry, while generally known in the art, is novel in the context of the present invention. Six fibers  102  are helically wound and terminate in fiber ends  104 . A short segment of the central fiber  106  is coated with gold or another appropriate marker, allowing for x-ray guided positioning through a needle- or catheter-based delivery system, and is terminated with a cylindrical diffusing tip  108 . Coatings other than gold, which are well known in the field, can be used in addition to, or instead of gold to render the device detectable by other imaging modalities, such as magnetic resonance or ultrasound.  
         [0024]     The six outside fibers  102  are side-firing fibers, which are twisted around the central fiber  106  so that they form a linear array  110  along the long axis of the bundle. The ideal spacing along the axis, in the present embodiment, is 2 mm. By arranging the fibers in that manner, the probe is optimized for compactness, while providing a linear array of fiber ends. As shown in  FIG. 1B , the entire bundle can be encased in a transparent capillary  112  which can be inserted into tissue through a catheter or needle. Exemplary nominal diameters of the capillary are 0.033 inch for insertion into an 18-gauge needle and 0.047 inch for insertion into a 16-gauge needle.  
         [0025]     The probe can be inserted into any needle- or catheter-accessible tissue via standard methods and guided with x-ray or other imaging or guidance. The probe is useful in planning, delivering and monitoring PDT in accessible tissues. As shown in  FIGS. 2A and 2B , a probe assembly  200  is formed by inserting the above-described probe  100  into a needle or probe housing  202  having optical ports  204  corresponding to the ends  104  of the fibers  102  and a transparent cone  206  corresponding to the diffuser  106 . The probe assembly  200  is connected to a treatment laser  208  and a white-light source  210  through a switch  212  and a treatment fiber  214  and to spectrometers  216  through collection fibers  218 . A computing device  220  analyzes the outputs of the spectrometers  216 . The probe assembly is shown as being inserted into tissue T.  
         [0026]     Before treatment, for example, white light reflectance spectroscopy can be used to assess the optical properties of the tissue in which the probe is located. This can be used to determine the scattering and absorption coefficients of the tissue, which can be used to determine the amount and distribution of photosensitizer present and the volume and oxygenation of hemoglobin. Those parameters are useful for planning a PDT treatment. White light spectroscopy can nominally be performed by using one of the fibers in the linear array as a source by directing broadband light through that fiber. Spectra can then be collected from the other fibers, and a fitting algorithm can be used with the data to determine the optical properties of the tissue.  
         [0027]     During treatment, either one of the side-firing fibers or the cylindrical diffusion fiber can act as a source, while the other fibers collect fluorescent spectra concurrently. That provides information on dose metrics such as fluorescence photobleaching and photoproduct accumulation. Additionally, brief treatment interruptions can be used to interrogate the tissue with white light in order to monitor changes in blood volume and blood oxygenation.  
         [0028]     The optical probe could be integrated into a portable PDT system straightforwardly. For example, its design is compatible with the instrument disclosed and claimed in the above-cited PCT publication.  
         [0029]     The probe described above can be used in many ways, including the following.  
         [0030]     Single treatment/interrogation beam with many simultaneous data collection fibers, constituting a linear detection array: This functionality is described above and is likely the most immediate use for the probe. As shown in  FIG. 3 , a single side-firing fiber  102  functions as the source fiber  302 , while the remaining side-firing fibers  102  function as detection fibers  304 .  
         [0031]     Multiple interrogation beams with multiple detectors: Several fibers can be used to perform optical interrogation using fluorescence or reflectance spectroscopy. For example, as shown in  FIG. 4A , a first fiber can be used as a white light source  404 , and a second adjacent fiber  402  can be used for detection, creating a detection region  406 . Then, as shown in  FIG. 4B , the second fiber can be used as a source  410 , and a third fiber can be used as a detector  408 , creating a detection region  412 . As shown in  FIG. 4C , the same source  410  can be used with a different detector  414  to create a detection region  416 . As shown in  FIG. 4D , the same detector  408  as in  FIG. 4B  can be used with a source  420  to create a detection region  422 . Different source/detector fiber combinations with appropriate optical switching can be used to map out local volumes within the tissue along the axis of the probe.  
         [0032]     Multiple treatment beams with independently adjustable fluorescence rates: As shown in  FIG. 5 , each optical fiber  102  can be used to deliver the PDT treatment beam to a treatment region TR in the tissue T. Delivery of PDT could be done serially (cycling through the fibers) or in parallel (all fibers being used concurrently). The fluence rate of light delivered through each fiber can be optimized independently so that an optimal light distribution in the tissue can be obtained. That method could make use of the multiple interrogation method described above and use the map of local regions to determined an optimal fluence rate for each delivery fiber.  
         [0033]     Multiple treatment beams with multiple simultaneous detection: As shown in  FIG. 6 , first plurality of fibers  602  is used to deliver the PDT treatment beam, and a second plurality of fibers  604  is used for detection. The fluence rate of light delivered through each fiber can be optimized independently, so that an optimal light distribution in the tissue can be obtained. That method could make use of detector feedback to determine an optimum fluence rate for each delivery fiber.  
         [0034]     Multiple treatment beams with fluorescence detection/feedback: Each optical fiber can be used to deliver the PDT treatment beam. Fluorescence spectra are collected during PDT delivery through either adjacent dedicated detection fibers or backwards through the delivery fiber. Detected signals can be used as feedback to control therapy delivery.  FIG. 7  shows a treatment/detection fiber  702  and a dichroic beamsplitter  704  used at the distal (non-probe) end of the fiber.  
         [0035]     Variations of the probe geometry described above can also be realized. For example, as shown in  FIG. 8 , pairs  802 ,  804  of fibers can be used, in which one fiber  806 ,  810  serves as a source and the other fiber  808 ,  812 , as a detector. Tissue optical properties and/or treatment can be made around the probe.  
         [0036]     Another geometry uses fibers which are staggered in axial position and direction so that they form a “spiral staircase” structure as shown in  FIG. 9A . In this embodiment, cylindrical diffuser  108  is surrounded by side-firing fiber array  901 . Each fiber in the array is offset linearly from the adjacent fibers along the axis of the probe. Axial view  FIG. 9B  illustrates the 6-around-1 probe geometry and the acceptance/delivery cone  902  for the light entering/exiting one fiber.  
         [0037]     Yet another geometry uses fibers pairs in which one fiber in the pair is offset in axial position, and both fibers face the same direction as shown in  FIG. 10 . In this embodiment, cylindrical diffuser  108  is surrounded by side-firing fiber array  1001 . Three fiber pairs are arranged in the probe such that each pair has one fiber substantially at the same first location along the axis of the probe and a second fiber substantially at the same second location along the axis of the probe, as shown in  FIG. 10A . Axial view  FIG. 10B  illustrates the 6-around-1 probe geometry and the acceptance/delivery cones  1002   a  and  1002   b  for the light entering/exiting the fiber in one fiber pair.  
         [0038]     While preferred embodiments of the invention have been set forth above, those skilled in the art who have reviewed the present disclosure will readily appreciate that other embodiments can be realized within the scope of the invention. For example, numerical values are illustrative rather than limiting. Therefore, the invention should be construed as limited only by the appended claims.