JP2010501246A - Fiber optic scope with non-resonant illumination and resonant focusing / imaging capabilities for multi-mode operation - Google Patents

Abstract

  A scanning fiber endoscope system that selectively operates in a plurality of different modes is provided. One or more illumination optical fibers carry different types of light to the internal location. A scanner driven resonantly in the desired pattern collects light from the internal location. The scanner can be the end of the scanning optical fiber or the cantilever of the scanning mirror. The illumination optical fiber can be moved non-resonantly to change the direction in which the light is emitted. In the treatment mode, relatively high power light can be incident on the location, while in the monitoring mode, the scanner can be used to image tissue at the internal location after or during treatment. . An exemplary SFE probe is disclosed to measure scattering angle (absorption of large cancer cell nucleus-to-cytoplasm ratio), absorption depth, distance along the axis to the tissue, and other conditions at the internal location. Is done.

Description

  The present invention relates to a fiber optic scope having non-resonant illumination and resonant focusing / imaging capabilities for multi-mode operation.

  In less invasive medical procedures, such as those performed with an endoscope, optical therapy is generally performed by a laser connected to a multimode optical fiber having a single large core. The end of the multimode optical fiber is introduced into the body using a human hand and advanced so that its tip is in physical contact with the tissue of interest at the internal location. Alternatively, the light beam emanating from the distal tip of the optical fiber can be scanned over the tissue using a human hand, or can be applied to the target tissue using a light diffuser attached to the distal end of the optical fiber. Spread the radiation dose over the entire area. Imaging the tissue of a subject before and after treatment (and monitoring the effectiveness or extent of treatment) generally involves a flexible or rigid endoscope that carries the monitoring optical fiber to the region of interest within the body. This is done using a mirror. For cardiovascular applications, the optical fiber is generally introduced along with a non-imaging catheter, and the imaging of the treatment site is performed outside of the patient's body by conventional imaging methods such as fluoroscopy. Etc.

  In recent years, new very thin and flexible forms of scanning fiber endoscope (SFE) or catheter scope technology have been developed, as well as those introduced via catheters, flexible endoscopes, rigid laparoscopes, bronchoscopes, And allows for the introduction of light radiation into the body in devices used for less invasive medical procedures, such as rigid or soft scopes. The light radiation can be delivered to the tissue using one of several methods, such as, for example, a method that couples directly to the core and / or cladding of a resonant fiber scanner, or a single, or Can be supplied using two or multiple clad optical fibers, or more traditionally, but can be supplied via an optical fiber simultaneously with another resonant optical fiber scanner .

“All-Optical Histology Ultrashort Laser Pulses”, Filbert S., et al. T. Tsai, et al. Neuron, 39, pp. 27-41 (July 3, 2003) “Quantitative reflectance spectrophotometric for the non-invasive measurement of photosensitizer concentration of photosensitizer in tissue during photodynamic treatment”. Quantitative reflectance spectrophotometric for the non-invasive measurement of photosensitizer concentration M.M. S. Patterson, E.C. Schwartz, and B.C. C. Wilson, photodynamic therapy: Photodynamic Therapy (Mechanisms), Proceeding SPIE, 1065, p. 115-122, (1989). “Optical reflectivity and transmission of tissues: principals and applications”, B.C. C. Wilson and S.W. L. Jacques, IEEE Journal of Quantum Electronics, Vol. 26, No. 12, page 2186-2199 (December 1990) “Application of time-resolved light scattering measurement to photodynamic therapy dosimetry”, M. et al. S. Patterson, J.M. D. Multon, B.M. C. Wilson, and B.W. Chance, photodynamic therapy: Mechanism (Photodynamic Therapy: Mechanisms), Proceeding SPIE, 1203, pages 62-75, (1990) “A full color scanning fiber endoscope”, optical fibers and sensors for medical diagnostic and therapeutic applications VI (Optical Fibers and Sensors for Medical Diagnostics. J. Seibel, R.A. S. Johnston, and C.I. D. Melville, Proceeding SPIE, Volume 6083, ID # 608303 (2006) "Fourier-Domain Angle-Resolved Low Coherence Interferometric Through the Endotropic Fiber Bundled Fiber Strain for Light Scattering Spectroscopy" John W. Pyhtila, Jeffery D. Boyrey D. Boyer, Kevin J. Kevin J. Charut and Adam Wax, OPTICS LETTERS, Vol. 31, No. 6, March 15, 2006 “Determining Nuclear Morphology Using an Improved Angle-Resolved Low Coherence Interferometry System”, John W. John W. Pyhtila, Robert N. Graph (Robert N. Graf) and Adam Wax, Optics Express, Page 3473, Volume 11, Issue 25, December 15, 2003

  Previously developed SFE technology uses a resonant fiber optic scanner to deliver light to the site, where the spot of light is constantly moving on the illumination surface. If a high therapeutic light dose is required, an extremely high power laser is instantaneously generated when the required illumination pixel and the scanning fiber tip corresponding to the area of interest to be treated are aligned. Must be turned on and off. The direct integration of optical therapy using previously proposed SFE imaging is therefore limited by the level of light output that can be delivered during this short period of time. Overcoming this limitation is expensive.

  Without limiting the treatment (or other procedure) time to the alignment time of the scanning optical fiber, monitoring the internal position in real time while the therapy is delivered (or while other procedures are performed) Obviously it would be desirable. For example, it may be desirable to be able to monitor the progress of optical therapy either thermally or with fluorescence, and these wavelengths will be used to display site images to medical practitioners in real time.

  Various embodiments of scanning probes have been developed for use in performing many different functions within a patient's body by selectively operating in a plurality of different modes using a plurality of different types of light. It was. In particular, certain embodiments of the probe are useful for implementing at least two different modes. For example, different modes may be used to image a site using visible light, to diagnose the medical condition of the site using light useful for measuring the tissue condition of the site, and to select the appropriate wavelength. Treating the site with a relatively high power of light in the band and monitoring the site, for example, in real time to determine the outcome of the treatment performed. In connection with the diagnosis of medical conditions, one embodiment of an SFE probe has been developed that uses a resonant scanner to image an internal location or collect light from the site. The SFE probe can determine the scattering angle of light from the site, and this information can be based on the measured scattering angle and the size of the cell nucleus determined as a function of light frequency or wavelength, for example, cancer Can be used for diagnosis. Absorption is proportional to optical distance, which can be varied by the point of illumination or the radius of the helical scan provided by the scanner in the SFE probe from the beam, so that the light (at the desired wavelength) The absorption of light by the tissue can be determined relative to the penetration depth. Further, the axial length between the probe and the tissue surface can be determined using a scanner in an exemplary SFE probe to collect light reflected from the illuminated tissue. A variety of exemplary new SFE probes that implement at least two of these different modes using a stationary or non-resonantly movable illumination optical fiber and a resonant scanner for imaging or collection These functions and applications of such embodiments are described in detail below.

  In particular, an exemplary fiber optic system for illuminating an internal location of a patient's body with different types of light in different modes and responding to light received from the internal location is described below. The system includes a plurality of light sources that generate different types of light. An illumination optical fiber having a distal end carries light for the current mode to the distal end of the illumination optical fiber and is selectively coupled to a plurality of light sources for illuminating an internal location. A scanning driver or actuator adapted to be excited by the drive signal is included and connected to the scanning optical fiber proximate to the end. The scan driver or actuator is configured to drive the scanner to scan at least a portion of the internal location in a desired pattern. Light received from at least a portion of the internal location illuminated by light from the illuminating optical fiber in the current mode enters the end of the scanner optical fiber and is carried toward the near end by the scanner optical fiber. An optical sensor or detector couples to the scanner optical fiber and receives the carried light. In response, the photosensor generates an output signal indicative of at least one parameter of light received from the internal location.

  Another aspect of the method relates to a method for scanning an internal position of a patient's body in a plurality of different modes. For each of at least two modes of the plurality of different modes implemented, the method is for illuminating one of a plurality of different types of light from a light source selected for use in the current mode of the at least two modes. Carrying to the end of the optical fiber. Light emitted from the end of the illumination optical fiber is directed onto the internal location. The distal end of the illumination optical fiber can move relatively slowly with static or non-resonant motion. At least one portion of the internal location is scanned to collect the received light. Light received from at least that portion of the internal location is carried through the scanner optical fiber to the near end of the scanner optical fiber. The received light is detected and an output signal is generated in response. At least one parameter of at least a portion of the internal location is determined using the output signal for the current mode currently implemented.

  Yet another aspect is a fiber optic scope for illuminating an internal location within a patient's body with multiple different types of light during operation in multiple different modes and responding to light received from the internal location. Directed. In one exemplary configuration, the fiber optic scope includes a plurality of different light sources that generate different types of light for illuminating an internal location. A long extending housing is placed at the end of the fiber optic scope. The scanner is then arranged approximately at the center of the end of the fiber optic scope. The scanner is driven to move near the resonant frequency in the desired pattern, and light received from at least the desired portion of the internal location is collected by the scanner and passes through the scanner optical fiber through the scanner optical fiber. Configured to be carried to the near end. A plurality of illuminating optical fibers having ends are separated and placed around the scanner in an elongated housing. The plurality of illumination optical fibers carry a selected light of a plurality of different light sources to the end of the illumination optical fiber operating in the current mode. The light emitted from the end of the illumination optical fiber is then directed to the internal location. The sensor is coupled to the scanner optical fiber and is responsive to received light carried through the scanner optical fiber. The sensor generates an output signal that can be processed to provide data about the tissue at an internal location for the current mode being implemented by the fiber optic scope.

  Means for solving this problem have been provided to introduce in a simple way a few concepts which will be explained in more detail in the following description. However, the means for solving this problem are not intended to define important or essential features of the claimed subject matter, but are used as auxiliary means for determining the scope of the claimed subject matter. It's not something to try.

  The various aspects and attendant advantages of one or more embodiments and variations thereof will be more readily understood as the same is better understood by reference to the following detailed description when considered in conjunction with the accompanying drawings. It will be.

Schematic elevation view of the distal end of an exemplary probe having a non-resonant illumination optical fiber and a resonant scanning optical fiber that collects and / or images light from an internal location of the patient's body It is. Schematic elevation of the distal end of another exemplary probe with a non-resonant illumination fiber and a resonant scanning mirror that collects and / or images light from an internal location of the patient's body FIG. Relatively high power laser treatment using ultrafast laser pulses and site monitoring by imaging using non-confocal or quasi-confocal multiphoton scanning of internal positions using a resonant fiber optic scanner. FIG. 6 is a schematic elevational view of the end of yet another exemplary probe adapted to perform. Some examples of different resonant scan patterns that can be used are a spiral scan pattern, a linear scan pattern around the central axis, a raster scan pattern, a propeller scan pattern around the central axis, and a Lissajous scan pattern. is there. Some examples of different resonant scan patterns that can be used are a spiral scan pattern, a linear scan pattern around the central axis, a raster scan pattern, a propeller scan pattern around the central axis, and a Lissajous scan pattern. is there. Some examples of different resonant scan patterns that can be used are a spiral scan pattern, a linear scan pattern around the central axis, a raster scan pattern, a propeller scan pattern around the central axis, and a Lissajous scan pattern. is there. Some examples of different resonant scan patterns that can be used are a spiral scan pattern, a linear scan pattern around the central axis, a raster scan pattern, a propeller scan pattern around the central axis, and a Lissajous scan pattern. is there. Some examples of different resonant scan patterns that can be used are a spiral scan pattern, a linear scan pattern around the central axis, a raster scan pattern, a propeller scan pattern around the central axis, and a Lissajous scan pattern. is there. FIG. 6 schematically illustrates the ends of an exemplary probe showing a plurality of optical fibers used for different purposes, grouped around a resonant scanner. FIG. 10 schematically illustrates another embodiment of a probe having a non-resonant illumination optical fiber on opposite sides of a scanning optical fiber and using a plurality of lenses for focusing on an internal location. 1 is a schematic block diagram of a scanning system using a probe according to one embodiment. FIG. It is the schematic which shows the relationship between the specular reflection light from a tissue surface, and a diffuse reflection light. For example, a diagram of a controller of a scanning system that can be used to determine the distance between the distal portion of the probe and the surface. It is the schematic which shows the functional relationship between the optical fiber for irradiation with respect to the surface of an internal position, and a scanner. FIG. 3 shows three different specular reflection patterns at different distances between the probe end and the surface of the internal tissue. FIG. 3 shows three different specular reflection patterns at different distances between the probe end and the surface of the internal tissue. FIG. 3 shows three different specular reflection patterns at different distances between the probe end and the surface of the internal tissue. Shows two different illumination patterns at the same distance between the distal end of the probe and the internal tissue surface when the probe is rotated during illumination and when the illumination is radially displaced while the probe is rotating FIG. Shows two different illumination patterns at the same distance between the distal end of the probe and the internal tissue surface when the probe is rotated during illumination and when the illumination is radially displaced while the probe is rotating FIG. Driven to scan a region with any of a plurality of different scanning patterns, including a variable radius circle or a spiral scanning mode, when the region is imaged, it is placed around the collective lens at the end of the scanning device FIG. 2 illustrates an exemplary scanning device having a resonant scanning optical fiber that collects light from a region illuminated by light from a plurality of illuminated illumination optical fibers. Schematic cross-section of one embodiment of using a balloon filled with fluid to move the fiber (non-resonantly) to selectively change the location where light emitted from the illumination optical fiber is incident on the internal surface It is. FIG. 6 is a schematic cross-sectional view of one aspect of another embodiment in which a fiber is moved using a bimorph displacement device to selectively change the location where light emitted from an illumination optical fiber is incident on an internal surface. FIG. 14 is a schematic cross-sectional isometric view of an end portion of an embodiment similar to that shown in FIG. 13 (one of the four illuminating optical fibers has been removed to simplify the drawing) FIG. 5 is a diagram illustrating the position of the illumination optical fiber when it is not generally inflated and another position of the illumination optical fiber after the pressurized fluid has at least partially inflated the balloon. FIG. 14 is a schematic cross-sectional isometric view of an end portion of an embodiment similar to that shown in FIG. 13 (one of the four illuminating optical fibers has been removed to simplify the drawing) FIG. 5 is a diagram illustrating the position of the illumination optical fiber when it is not generally inflated and another position of the illumination optical fiber after the pressurized fluid has at least partially inflated the balloon. 15A and 15B are schematic isometric views of the distal portion of the embodiment of FIGS. 15A and 15B, respectively, where the position of the illumination fiber when the balloon is generally not inflated, and the fluid at least partially inflate the balloon. It is a figure which shows another position of the optical fiber for illumination when it is used for. 15A and 15B are schematic isometric views of the distal portion of the embodiment of FIGS. 15A and 15B, respectively, where the position of the illumination fiber when the balloon is generally not inflated, and the fluid at least partially inflate the balloon. It is a figure which shows another position of the optical fiber for illumination when it is used for. An exemplary SFE is used to move a fiber or a cable or line extending closely through the lumen to selectively change the location where light emitted from the illumination optical fiber is incident on the internal surface. FIG. 6 is a schematic cross-sectional view of one side of a distal portion of still another embodiment of the probe. FIG. 2 is a schematic cross-sectional view of an exemplary SFE probe in which a Fourier transform lens is used to determine light scattering and the size of cellular components or particles that scatter light. FIG. 6 is a cross-sectional view of yet another embodiment of a probe capable of both high-definition imaging and capture of different scattering angles using a Fourier transform lens and a longitudinally movable resonant fiber optic scanner. For example, measuring / mapping local diffuse reflection collected within the inner cladding of a scanning optical fiber, as well as using a single mode core of the scanning optical fiber to couple different light sources for high definition imaging It is sectional drawing of the probe containing the optical fiber for irradiation to perform. Of an example SFE probe embodiment that includes two illumination optical fibers of FIG. 19 and 12 other multimode optical fibers (not visible but with a scanner) that can be used for various functions. FIG. FIG. 4 is a schematic axial view of an internal position illuminated with light from two illumination optical fibers, showing a vector for light emitted from each different illumination optical fiber having different characteristics. For example, in a system that uses an SFE probe as described herein to perform any one or more of imaging, monitoring, diagnosing, and treating an internal location of a patient's body. It is an example functional block diagram which shows the flow of a functional component and a signal.

The drawings and the disclosed embodiments are not limited. Examples are illustrated in the referenced drawings. The embodiments and figures disclosed herein are intended to be considered illustrative rather than restrictive. No limitations with respect to the present technology and the following claims are inferred by the examples shown in the drawings and described herein.

Resonant Scanner Embodiments Each of the embodiments disclosed herein can be used in a system for selectively implementing at least two different modes using different types of light. For example, the different modes include (1) a diagnostic mode that is used to determine the condition of the tissue at an internal location by responding to light received from the tissue, and that determines a parameter that indicates the condition of the tissue; 2) an imaging mode used to generate an image of the internal location using an imaging technique (eg, using visible light monochromatic light or light having red, green, and blue (RGB) components); (3) a treatment mode for treating a tissue at an internal position using a relatively high-power treatment light; and (4) an image of a site before, during and / or during the execution of the treatment at the internal position. And a monitoring mode used to evaluate the condition of the tissue at the internal position. The modes implemented by each of the embodiments described below are not necessarily specifically shown, but will be apparent to those skilled in the art based on the present disclosure.

  In some examples, such as the embodiments of FIGS. 1, 2, and 10, illustrated and described below, the objective lens system is not shown. However, for probes used in endoscopic applications of this technology, one of many possible different combinations of objective lens systems uses high numerical aperture optics to achieve high magnification focus (and imaging). It is considered that it can be included in the use for both realizing and ensuring high light collection efficiency. Exemplary objective lens systems that may be included are shown in FIGS. 3, 6, 12, 13, and 17-19. For the exemplary probe endoscopic application described, such an imaging lens system was illuminated with a resonant scanner to collect with greater efficiency using a large numerical aperture optics. You may arrange | position between tissues. In addition, the objective lens system can be designed to contact tissue and / or be immersed in water at its distal (ie, tip) surface.

  A first embodiment of a probe 30 suitable for collecting or imaging from an internal location 44 within a patient's body (not shown) using a resonant scanner is illustrated in FIG. The probe 30 includes a housing 32, only the distal portion of which is shown schematically. A plurality of irradiation optical fibers 34 are disposed in the housing 32. Although only two of such illumination optical fibers are illustrated in this figure, as will become apparent from the following description, the SFE probe can include only a single illumination optical fiber, as well It is believed that more than two can be included. As an option, each of the illuminating optical fibers 34 includes a displacer 36, which is simply illustrated as a schematic block in this figure, and the illuminating optical fiber for changing the direction in which the illumination light is emitted is non-illuminated. It is intended to represent a mechanism that resonates and thus selectively changes the location where the illumination light is incident on the internal location 44. As a further option, each illuminating optical fiber may be a rod lens 38 and, for example, a graded refractive index (GRIN) for collecting light emitted from the illuminating optical fiber more efficiently onto an internal location. ) A lens can be included.

  In the example shown, the illumination light 40 emitted through the rod lens 38 is incident on the internal location and collected at point 42. The illuminating optical fiber can have a relatively large multimode core, and therefore can carry a relatively strong intensity of light at a suitably selected wavelength, as described in detail below. Achieve different functions. In some embodiments, the one or more illumination optical fibers can comprise single mode optical fibers.

  The probe 30 can be used in a variety of different applications. In imaging applications, the illumination light carried through the illumination optical fiber 34 and directed to the interior location 44 is simple white light (having red, green, and blue components) suitable for illuminating the interior surface. Or monochromatic light. When used to deliver treatment to an internal location, therapeutic light radiation typically damages the irradiating optical fiber 34 through the irradiating optical fiber 34 with sufficiently high power and sufficient pulse width or duration. It can be carried without giving the desired therapeutic effect. Further, if a displacer 36 is included, instead of illuminating the internal location 44 with a fixed spot 42, the illumination light 40 may be directed to other spots or to a single spot, eg, spot 46 Can increase the effective power supplied to the internal location and reduce all coherence effects.

  Also included is a scanning optical fiber 50 that is moved in a desired pattern, at or near the resonant frequency, by a piezoceramic tube actuator 52, or other suitable scanning driver. To be driven. The scanning optical fiber can be selectively driven with linear, resonant or near-resonant motion, as indicated by the dashed position of the optical fiber 50 ', or with respect to two orthogonal axes. With the applied driving force, it can be driven in a more complex two-dimensional motion. Some examples of scanning patterns that can be realized by the scanning optical fiber 50 are shown and described in the drawings below. The scanning optical fiber 50 comprises a distal end of a single mode (or multimode) optical fiber 54 that extends to the proximal end (not shown) where light entering the scanning optical fiber is sensor or It can be detected by a detector or can be used to generate an image on a display device, as will be described in more detail below. As an option, one or more objective lenses can be placed between the optical fiber 54 and the internal location 44, and as shown in other embodiments described below, a high numerical aperture The optical system is used to provide high power magnification and greater light collection efficiency. In various applications and embodiments described herein, alternatively, the scanning optical fiber can also comprise a multilayer clad optical fiber or a combination of multimode optical fiber and single mode optical fiber.

  The SFE probe 30 can be used for flexible scopes, rigid laparoscopes, Rocco scopes, and other rigid or flexible scopes, as well as scopes associated with catheters used for less invasive medical procedures. Such a variety of different devices can be easily introduced into a patient's body and have a size. Since the scanning optical fiber 50 can image the internal location 44 independently of the illumination light 40 used for treatment, the scanning optical fiber monitors the internal location 44 in real time and treats the internal location. Can be used to determine the progress of the process and its effects. The illumination optical fiber 34 that supplies illumination light and is used to perform therapy is used to collect infrared (IR) light that is received from an internal location and that monitors the heat generated during the therapy. You can also. At the near end of the irradiating optical fiber, an illuminating laser that is used for therapy and generates light of near IR wavelength is, for example, a long wavelength pass filter arranged at an angle of 45 ° (not shown). ), Can be separated from concentrated heat removal and longer wavelength IR using a dichroic beam splitter. The therapeutic light radiation emitted from the irradiating optical fiber 34 can be collected by a rod lens 38 specially designed for the wavelength of the therapeutic light.

  For example, techniques have been developed for registering illumination / treatment surfaces along with scanning imaging surfaces for SFE, such as probe 30. By using a computer to control the SFE (see FIG. 22 and related descriptions), it is possible to register two image planes accurately. For example, a low-power near-IR light source can be selectively coupled to the near end of the illumination optical fiber 34 that is typically used to provide higher-power light than is used for therapy. The same sensor or photodetector coupled to the near end of a single mode (or multimode) optical fiber 54, typically used to image the internal location or monitor the outcome or progress of an ongoing treatment, It is then used to map pixel locations within the red, green, and blue (RGB) images of the low power IR light spot. The measured position, size, and shape spots can be recorded by a computer system that controls the scanning optical fiber. As desired by the user, a colored circle is drawn and displayed around each spot with the full width at half maximum of the light output distribution measured during the initialization process for the user. By selectively controlling the SFE probe with a computer system, the SFE probe can be skillfully moved so that the full high power therapeutic light irradiation is imaged of the subject before it is performed through the irradiating optical fiber. The region is circled by one or more colored circles to ensure that the treatment is delivered to the desired portion or region of the internal location registered in the image of the region provided by the scanning optical fiber. To do.

  Depending on the application applied, the SFE probe can be used to scan the internal location 44 by combining multiple illumination light beams used for optical therapy into a single spot within the imaging field of the scanning optical fiber 50. Can be designed and configured to increase the total intensity of therapeutic light that can be delivered to a desired area within the surface. Thus, when the treatment light emitted from the four irradiation optical fibers is collected on a single spot in the imaging field, the total output supplied to the spot is one of the irradiation optical fibers. It will be about 4 times the power of the therapeutic light delivered alone. Alternatively, multiple irradiating optical fibers are configured such that the treatment light they emit forms a square, rectangle, circle, or other shape that is approximately four times the area of a single spot. Can be done. If a larger area is desired, the SFE probe can be moved manually, eg, by sweeping or rotating the end back and forth so that the optical treatment light spans the area of interest at the internal location 44. Can be swept. For example, a pseudo-color (not shown in FIG. 1 but described in detail below) user interface or display device may provide a tissue surface as real-time feedback of tissue conditions while optical therapy is being performed. Can provide temperature indication. As a further example, the scanning optical fiber can detect infrared light from the site where the optical treatment is being performed and provides an indication of the progress of the optical treatment or the tissue response to the treatment. If heat is not a measure of the progress of optical therapy, the scanning optical fiber 50 will instead have phosphorescence, autofluorescence ratio (wavelength or deflection), or extrinsic fluorescence intensity or (treatment is photodynamic therapy (PDT) It can be configured to image the internal location to respond to the emission lifetime (which is particularly useful in some cases).

  As an alternative to using the scanning optical fiber 50 shown in FIG. 1, the SFE probe 30 ′ shown in FIG. A mirror scanner 56 having one or more (not shown) reflective surfaces driven near the frequency is included. The mirror scanner 56 can include one or more movable microelectromechanical system (MEMS) reflective surfaces, or, for example, in the x-direction with one reflective surface and other reflective It may include one or more piezoelectric or galvanometer drivers coupled to a reflective surface driven in an orthogonal direction for resonant scanning in the y direction with the surface. The SFE probe 30 ′ includes components that are otherwise substantially identical to the probe 30, so that the illumination light 40 emitted from the end of the illumination optical fiber 34 illuminates the internal location 44 at the point 42. Or as otherwise desired. By appropriately configuring the illumination fiber to be selectively moved by the displacer 36, the illumination optical fiber can direct the emitted illumination light to a desired area or point on the internal location 44. As an option, one or more objective scanning lenses can be arranged between the mirror scanner 56 and the internal position to collect the illumination light and to collect the optical signal. It provides both a large numerical aperture and a large optical magnification.

Example of non-confocal SFE using high power laser pulses In order to achieve both high power laser illumination and to remove (optically remove) material at internal locations, the amplified ultrashort laser pulses are Focused on the surface of the tissue. In general, these laser amplifiers operate in the near infrared (NIR) region of the optical spectrum and have pulse durations in the femtosecond (fs) to picosecond (ps) range, but other optical frequencies. A nanosecond (ns) to millisecond (ms) pulse is sufficient. High pulse repetition rates are avoided in order to remove material or remove only the focal tissue and minimize collateral defects that cause other tissues. In general, the light source can comprise an amplified fs pulsed laser system having an output with a wavelength of about 800 nm. Laser sources with this requirement are now available from major US manufacturers such as Spectra-Physics, Newport Corporation, and Coherent Inc. It is. In order to remove tissue at this optical frequency of NlR, pulses with a power level in the tissue of approximately 1 μJ or more are generally required. Specially designed and manufactured hollow cores and / or large area core diameter photonic crystal optical fibers have been developed to transmit ultrafast NIR pulses to internal locations, for example, Danish Crystal Fiber Company (Crystal). Available from Fiber, Denmark). Single mode photonic crystal fibers and optional rod, GRIN, or objective lens systems can be used to focus high power laser illumination light onto an internal location. By this non-resonant scanning of the illumination light, single or multiple high power ultrafast pulses can be irradiated onto the surface of the tissue using a low repetition rate amplifier. At the same time, fast scanning of the internal position with the resonant fiber (or mirror) is used to collect the optical signal from the illuminated internal position, monitoring the laser cutting process in real time. The ideal monitoring fiber is a double-clad optical fiber that allows high-resolution surface imaging from a single-mode core in addition to multimode collection in the inner cladding to monitor treatment. May be. As an alternative, double-clad photonic crystal optical fibers are now commercially available from Danish Crystal Fiber (Denmark). Standard single mode or multimode optical fibers can be used, as well as optical fibers having a hollow core and a band gap. Monitoring methods may include direct endoscopic imaging methods by collecting backscattered light from an internal location using a scanning beam of visible wavelengths (eg, red, green, and blue visible light). it can. Further methods for monitoring laser therapy include mapping by imaging tissue at wavelengths of light outside the visible spectrum of fluorescence, thermal radiation, and the visible spectrum. Also, the optical properties of the tissue can be monitored during treatment or to treat the disease state of the remaining tissue using both non-resonantly scanned illumination light and detection by resonant scanning. Can be evaluated simultaneously. Furthermore, the pattern of the removal process or other laser treatment non-resonant scan can be monitored by a resonant scan to ensure that the desired pattern of illumination is followed.

  An exemplary desirable method for monitoring the depth of a laser ablation process and a diseased fluorescent marker in tissue is multiphoton fluorescence imaging using a relatively low power laser illumination at an ultrashort NlR optical frequency. It is. The advantages of using a non-confocal design for a two-photon scanning fiber endoscope are described below. NIR light penetrates tissue with an optical loss that is less than the optical loss due to scattering and absorption that occurs when using ultraviolet or visible wavelengths. Thus, although the wavelength of NIR is longer than ultraviolet or visible light, NIR light creates a sharp focus with minimal loss in the tissue. There is sufficient light output at the focus only to create a measurable two-photon absorption. Thus, all fluorescent photons transmitted from the tissue can be added to the signal for measuring fluorescence. By scanning the tissue in two dimensions, a 2-D fluorescence image can be generated. In general, the original 2-D image is repeated for different axial depths (slices) to generate a 3-D fluorescent image. Since the two-photon fluorescence imaging technique is most often used to generate 3-D images, the fluorescence signal generated from below the tissue surface has a very high probability of being scattered before leaving the tissue surface. Is done. Scattering redirects the effective light source point from the point that emits fluorescence within the illuminated volume to the last scattering point before exiting the tissue, so confocal optics to collect the fluorescence signal The design can remove most of the signal. Only a small percentage of fluorescent photons that are not scattered from the illuminated volume can be detected with a confocal optical design. Due to the fact that in non-confocal designs, the area of light detection can be several orders of magnitude larger, with respect to pseudo and non-confocal optical designs, the collection efficiency of the fluorescence signal is also higher than with confocal designs. A few orders of magnitude increase. The large signal intensity achieved without increasing the illumination light output is an important advantage of a non-confocal design SFE probe for two-photon imaging of fluorescence from a point below the surface of the tissue.

  Prior to performing two-photon imaging, the SFE probe needs to be moved to a position within the patient's body. One way to do this is to guide the probe to its location using an image made from backscattering of illumination light from the tissue surface. In order to provide illumination light for imaging, it is necessary to add white light containing red, green and blue components to NIR light used for two-photon excitation of visible fluorescence. By looking at the image formed with visible backscattered light, the operator can determine the specific position of the SFE probe and determine where to implement two-photon imaging. In this case, the two-photon SFE probe system will have at least two imaging modes. The two-photon imaging mode will use a single visible channel matched to the emission of fluorescence, while the visible light imaging mode will detect red, green, and blue light sources and the corresponding visible light Will use a vessel. In addition, visible imaging can be a full color using, for example, three lasers or other red, green, and blue light sources such as light emitting diodes or filtered arc lamps, or a single laser or a single visible light source. It will be apparent that the image is monochrome with other light sources that emit color. In addition, the probe system is collected via two-photon imaging combined with other parts collected on a frame-by-frame basis, image-by-image, or as a standard visible image based on operator demand. For each part of a single image, it should be possible to switch between two-photon imaging and standard visual imaging using a separate display device. Also, one of the red, green, or blue visible light detectors can be used for the detection of two-photon fluorescence, or another photodetector can respond to the two-photon light and display the fluorescence image It can also be used to generate. This type of SFE probe may have a function of superimposing a two-photon fluorescence signal with a standard visible endoscopic image signal on a visible display device.

  FIG. 3 illustrates a two-photon SFE probe 60 that includes two or more illumination optical fibers 62 having near ends connected to a relatively high intensity NIR laser source. As an option, the rod lens 64 is placed on the distal end of the illumination optical fiber 62, which includes, for example, a GRIN lens that corrects for any large color shift between the illumination light and the collected optical signal. . It should be noted that in this configuration, the rod lens collects NIR light 74 into the illumination field 76 in cooperation with the lenses 70 and 72. By rotating the probe, the annular illumination field 76 can be created by the movement of individual illumination spots on the internal location. Objective lenses 70 and 72 also focus the two-photon light received from the tissue at the internal location onto the distal end of the scanning optical fiber 66. A scanning region within the illumination field 76 is incident on a scanning optical fiber 66 that is driven to scan in a desired scanning pattern by a piezoelectric biaxial driver 68 at or near the resonance of the scanning optical fiber. Photon light 78 is emitted. The two-photon light is carried back to a suitable optical sensor and removes excitation light (not shown) located at the near end of the scanning optical fiber through a filter. Additional light can be added by using a double clad optical fiber for illumination and collection, or simply by adding an additional collection optical fiber that surrounds a centered resonant scanner. Can be condensed. Ideally, the illumination field 76 is placed very close to or in contact with the end of the SFE probe 60, for example, held or moved by an inhalation tube or mechanical means (not shown). be able to. Contact by water immersion or tissue contact (oil immersion) on the front surface of the objective lens achieves the high-resolution imaging used to perform laser therapy and the image stability required for high-power optics. Can do.

  An exemplary application of the SFE probe 60 is to implement the technique described in NPL 1. This document describes the technique used to automate the three-dimensional histological analysis of brain tissue, and femtosecond laser pulses to repeatedly cut and image fixed and fresh brain tissue. Has demonstrated the use of. Obviously, the probes 60 and methods disclosed herein can be effectively used to perform such studies and for many other applications.

Exemplary Scan Patterns FIGS. 4A-E illustrate a number of different scan patterns that can be implemented by the scanning apparatus described herein in connection with various embodiments of SFE probes. FIG. 4A is realized, for example, by driving an optical scanning fiber with a sine wave modulated with a triangle along a first axis and with a cosine wave modulated with a triangle along a second orthogonal axis. The spiral scanning pattern 90 is illustrated. FIG. 4B illustrates a linear scan pattern 92 that rotates about a central axis. FIG. 4C shows an exemplary raster scan pattern 94. FIG. 4D shows an exemplary propeller scan pattern 96 that rotates about a central axis. FIG. 4E shows an exemplary Lissajous scan pattern 98. Many other scanning patterns can be realized by driving the actuator of the scanning device with one or more suitable drive signals.

Embodiments with Additional Optical Fibers All the embodiments related to the SFE probe described above include one or more illumination optical fibers to carry light to the tissue at the internal location being scanned. FIG. 5 illustrates an exemplary SFE that includes four illumination optical fibers 102, 104, 106, and 108 disposed around a central region 116 in which a scanning device used for imaging and / or optical diagnostics is disposed. The end of the probe 100 is shown. In addition, the SFE probe 100 includes concentrating fibers 110, 112, and 114 disposed between adjacent pairs of optical illumination fibers. These focusing fibers are stationary and operate to collect red, green, and blue light or other wavelengths of light that are received from tissue at an internal location. Alternatively, the collecting fiber is replaced with a photodetector or sensor located near the end of the SFE probe. During or after optical therapy is applied through the irradiating optical fiber, it is collected by the collecting fiber (or by an alternative photodetector or sensor) as part of the task of diagnosing or monitoring the tissue. The emitted light can be used to image or determine the condition of the tissue at the internal location. Alternatively, larger lumens or conduits 118 disposed between these light-illuminating fibers can be used, for example, for washing, washing processes, optical labeling, tissue staining, or removal of cells or secretions. For such purposes, it can be used to introduce fluid to and remove fluid from the internal location by varying the applied pressure. The lumen or conduit can be of sufficient size to allow a biopsy tool, needle, or brush to pass through.

  As shown in the embodiment of the SFE probe 120 of FIG. 6, each of the illumination optical fibers 122 is provided with a separate lens 124, while the lens 132 is resonantly driven by an actuator 128 with light from an internal location. Then, the light is condensed into the end of the scanning optical fiber 130. Light entering the scanning optical fiber is then carried through optical fiber 126 to a suitable detector or sensor (not shown).

Exemplary System for Determining the Distance Between the Scanner and the Tissue Surface FIG. 7 is a simplified block diagram illustrating an exemplary external control system 134 coupled to the SFE probe 131 through an interface and connector member 133. is there. The SFE probe 131 and the external control system 134 are generally used as described below to determine the distance between the probe and the tissue at the internal location 140 as a function of specular reflection from the surface of the tissue. Composed. The SFE probe 131 generally includes one or more illumination optical fibers 138 that carry the illumination light to the internal location 140 as described above. The illumination light reflected from the surface of the internal position 140 has two main components including a diffuse reflection component and a specular reflection component. The diffuse reflection component spreads over a wider angle with respect to the direction in which the illumination light is incident on the tissue surface at the internal location, and this angle is commonly referred to as the Lambertian angle. In contrast, the specular component is reflected from the tissue surface at the same angle as it is incident on the surface. The proportion of light absorbed, diffusely reflected, or specularly reflected by the tissue depends on the material properties of the tissue surface and the wavelength of incident illumination light. A bright or wet tissue surface generally has a higher specular component than a dull surface.

  Reflected light from the surface of the tissue at the internal location 140 enters a scanner 142, which depends on the end of the scanning optical fiber or scanning mirror, as described above, depending on the embodiment used. can do. This light thus collected by the scanner is carried through an optical scanner waveguide 144, eg, an optical fiber, to an interface and connector member 133 that couples the light to the external control system 134. The scanner 142 is driven by a scanner driver or actuator 150 in response to signals received from the external control system via the interface and connector member 133.

  The external control system 134 generally includes one or more laser light sources that generate one or more wavelengths of coherent light associated with the input to the near end of the illumination optical fiber 138 that is carried through the interface and connector member 133. A light source 136 provided. As an option, light source 136 may also include any one or more red, green, and blue light sources, IR light sources, and ultraviolet light sources. The light source depends on the application or if the light source is used, for example for imaging in one frame in a series of frames, for treating in another frame, and still others. In this frame, the continuous mode may be switched to the pulse mode for another purpose. Where multiple different wavelengths of light are generated by the light source 136, a coupler may be used to combine the different wavelengths, or the different wavelengths of light are carried separately through different illumination optical fibers 138. May be.

  The external control system also includes a controller 152 that includes, for example, one or more microprocessors, application specific integrated circuits (ASICs), gate arrays, logic devices, or other forms of computing devices. Can be included. The controller 152 is used to control the scanner driver 150 by providing one or more appropriate drive signals, and by driving the scanner 142 at or near the resonance frequency, the desired value can be obtained. A scanning pattern is realized. The controller 152 can be coupled to a memory 154 having machine language instructions stored to control a central processing unit (CPU) or other computing device comprising the controller 152 and is disclosed herein. The functions of the external control system are executed. A display device 146 is typically included to validate an image of the internal location 140 created in response to light received from the internal location by a scanner viewed by an operator. As an option, the image storage device 148 is provided for storing data corresponding to the image of the internal location derived from the light carried from the scanner 142 for the purpose of further processing, display or storage. be able to. A user interface 156 is provided to allow the user to enter control parameters or to perform various desired functions with the SFE probe 131 and to control the SFE probe as desired by the user. The user interface may include a keyboard, keypad, pointing device, or other suitable mechanism for entering user control actions, selections, and values. A power supply 158 provides the appropriate voltage and current levels for operating each of the electronic components included in the external controller 134. Many other components and configurations that can be used to couple and control an SFE probe as disclosed herein can be used with equal convenience, so that of the external control system 134 Those skilled in the art will appreciate that this example is not intended to be limiting.

  Further functional details of the external control system 134 are shown in FIG. In order to allow both imaging and distance measurement using the external control system 134, the controller 152 is used to separate the specular portion of the light received by the scanner from the diffusive portion. A specular / dispersed light separator 166 is included. In response to the diffusive part of the light, a signal is generated and input to the image processor 162. A signal generated in response to the specular portion of light is conveyed to the surface geometry processor 164. Image data from the image processor 162 is output from the controller 152 and used to drive the display device 146 so that the operator can view the image at the internal location. However, the surface geometry processor 164 can also communicate data to the display device 146, a portion of which is provided to the geometric data output 168. Alternatively, the geometric information is superimposed on or separated from a conventional image of the internal location provided on the display device 146 and shown on a different display device or at a different time than the image of the internal location.

  It should be understood that although the image processor 162 primarily uses a dispersive portion of light received from the tissue surface at an internal location, the image processor can also use specularly reflected light. In addition, the surface geometry processor 164 may utilize some of the optical signal dispersed from the specular / dispersed light separator 166. Further, the specular / dispersed light separator 166, the image processor 162, and the surface geometry processor 164 may comprise modules including hardware and / or software. For example, a machine language program for performing functions such as specular reflection light measurement may be provided in the controller 152 from the storage medium 170. The storage medium 170 may comprise, for example, an optical disc such as a compact disc read only memory (CD-ROM) or a digital multipurpose disc (DVD) read by the media drive 172. Other alternatives for entering these program instructions and / or data are, for example, floppy (registered trademark), as well as remote data sources coupled to the controller via a network, wireless connection, or the Internet. ) Including magnetic recording media such as disks or removable hard disks.

  A schematic representation illustrating the relationship between the illumination light 180 incident on the tissue surface 182, the specular reflection 184, and the diffusive reflection 188 is shown in FIG. The angle of the specular reflection 184 relative to the surface normal 186 is equal to the angle between the illumination light 180 and the surface normal. In contrast, diffusive reflections 188 are distributed at various other angles with respect to the surface normal. Some of the illumination light 180 that strikes the tissue surface 182 is absorbed by the tissue and not reflected.

  An important reason for measuring the specular reflection from the tissue surface 182 is that the distance between the end of the SFE probe and the tissue surface can easily be determined as a function of the specular reflection. FIG. 10 schematically illustrates the geometric relationship between the distal end of the SFE probe 137 and the tissue surface 182 in connection with the illumination light 180 emitted from the illumination optical fiber 138. As shown in this figure, the specular light 184 enters the scanner 142 and is carried through the scanner optical fiber 144 to the near end. 7 and 9, the distance d is easily determined by the controller 152 as a function of the scanner position relative to the illumination light 180. At one position of the scanner, mainly diffusely reflected light is received by the scanner, while when the scanner is in a different second position, mainly specularly reflected light is received and input to the scanner. Is done. The specular reflection portion of the light input to the scanner has substantially higher energy than the diffuse reflection portion, and therefore receives specular reflection light compared to receiving diffuse reflection light from the internal position. Sometimes the signal response of the scanner is much larger. The specular / dispersed light separator 166 in the controller 152 (FIG. 9) may include a threshold for separating the diffuse reflection portion from the specular reflection portion. Known image processing techniques can be readily used to identify the perimeter, area, cross-sectional size, center of gravity, etc. of the specular reflection portion of light.

  FIG. 11A illustrates an image 200 that is created when the SFE probe 137 is used for imaging the surface of a tissue that is perpendicular to the axis of the SFE probe. In the image shown in FIG. 11A, when the illumination optical fiber is positioned symmetrically around the scanning center of the scanner, the eight bright spots 202a define a specular reflection pattern at the center of the image. Since the high intensity of specular reflection tends to spoil or distort the desired image formation as compared to the diffusely reflective portion (based primarily on image formation), the specular reflection pattern is the SFE probe 137. There is a problem during image formation using. To reduce the effect of specular reflection in the displayed image of the tissue surface, specular reflection separation, specular pattern identification, filtering, and / or other image processing steps can be employed.

  The size of the specular pattern is determined, at least in part, by the magnitude of the scan by the SFE probe 137 during imaging, which can be expressed as an angle field of view (FOV), and by the distance between the scanner and the tissue surface 182. Determined. During scanning with a constant FOV, the specular pattern is scanned as shown by comparing the specular pattern with spots 202b and 202c in the images 200 of FIGS. 11B and 11C with the specular pattern of FIG. 11A. Larger when the vessel is closer to the surface, smaller as it moves away from the surface. Thus, the size of the specular reflection pattern can be used to determine the distance between the end of the SFE probe and the surface of the tissue.

  In the simple case discussed above, it is assumed that the surface of the tissue is perpendicular to the scan direction. Certain parameters for the SFE probe 137 are known. For example, r is a known distance between the center of the scanning optical fiber and the irradiation optical fiber 138.

Is the known maximum field of view of the scanner,

Is the known number of scanning spirals that form the image (assuming a spiral scanning pattern is used). Using these known parameters, the distance d between the end of the probe and the surface of the tissue can be calculated by capturing the image and performing a binary threshold on the image data to receive the specular reflection. Pixels in the image are assigned binary 0. At least one tied image object corresponding to the end of the scanner should be identified in the tied image. The center of the connected object, or the pixel closest to it, is then determined and the remapping is performed at the center or center of gravity of the object connected with the center of the image scan.

Is used to determine the scan angle between. The scan angle can be stored in the remapping of the lookup table for each pixel.

  The distance d from the end of the probe to the surface of the tissue is calculated as follows.

  If the image contains one or more combined objects that result from the use of multiple irradiating optical fibers, the distance from the end of the SFE probe to the tissue surface is calculated for each of the combined objects. And averaged to give more accurate values. If the tissue surface normal is not aligned with the longitudinal axis of the SFE probe, the calculation is a bit complicated. However, the use of multiple illumination optical fibers allows the distance to the central scanner to be easily calculated.

A further reason for measuring the specular light reflection from the tissue surface 182 is that at a fixed distance d, the illumination pattern can be monitored because it is deformed by non-resonant scanning. . As shown in the image 200 of FIG. 11D, as the illumination beam rotates relative to the tissue orientation, the individual spots of FIGS. 11A-11C create annulus illumination 204. If the entire SFE probe 60 rotates relative to the internal position, the corresponding illumination field 76 is also shown in FIG. As shown in the image 200 of FIG. 11E, simultaneously with the rotation with respect to the tissue, the individual spots of FIGS. 11A-11C meet and the spiral trajectory 208 is timed as the illumination beam points inward toward the central optical axis. The illumination 206 of the area filling pattern to be traced over is created. The purpose of monitoring the changing non-resonant illumination scan pattern is to provide therapeutic illumination over the entire area of the subject, with the recognition that no illumination gap has occurred.
Exemplary SFE probe with fixed illumination optical fiber

  FIG. 12 illustrates an exemplary scanning optical fiber 222 that is driven to scan at or near a resonant frequency in a desired scanning pattern, as shown at phantom reference number 222 ′. An SFE probe 220 is shown. The collective lens 224 is provided at the end of the SFE probe 220 and is used to collect light received by the scanning optical fiber 222. Two or more illumination optical fibers 226 are disposed around the scanning optical fiber 222 and are used to carry illumination light or treatment light to a desired internal location in the patient's body (not shown). . In this embodiment, the illuminating optical fiber 226 is fixed in place, but each has an optional distal end disposed to collect light emitted from the illuminating optical fiber more efficiently. A rod lens 238 may be included. Scanning optical fiber 222 is a piezoelectric tube associated with two orthogonal axes in a desired pattern in response to drive signals supplied to electrodes 232 and 234 through electrical leads 236 extending proximally from SFE probe 220. It is driven by the actuator 230. A single axis (linear) scan pattern can be generated, for example, by applying a voltage to one or two of the opposing electrodes 232 of the piezoelectric tube actuator 230. By applying an oscillating periodic voltage (e.g., a sine wave) having a frequency at or near the mechanical resonance frequency of the scanning fiber cantilever excited at the bottom to the actuator through electrical lead 236, the amplitude of the tip motion Can be mechanically amplified by the mechanical resonance of the scanning optical fiber cantilever. Further, for example, by simultaneously applying a second periodic voltage (cosine wave) of the same or slightly different resonance frequency to the electrode 234 (perpendicular to the electrode 232) on the actuator, the resonating fiber tip is in an elliptical scanning pattern. Can move.

  Signals useful for creating an image are generated by the fiber optic scanner shown in FIG. 12 by directing light from illumination fiber 226 onto the region of the internal location. Light received by the scanning optical fiber cantilever from this region is focused using the imaging lens 224. In general, the imaging lens focuses the scanned portion of the internal location by resonatingly scanning the site in a linear (one-dimensional) pattern or in a spiral or elliptical (two-dimensional) pattern. Then enlarge. By changing the amplitude of the voltage applied to the actuator during elliptical scanning, a two-dimensional (2-D) space-compensated scanning pattern is formed. An irradiating optical fiber 226 surrounding the fiber optic scanner is used to provide illumination light reflected from tissue at an internal location to generate a 2-D image or evaluate other parameters of the tissue. The light used for the purpose is condensed. In general, the illumination optical fiber 226 is a large core multimode optical fiber having a large numerical aperture (NA) with excellent light transmission efficiency. Alternatively, a new large core, but single mode photonic crystal optical fiber may be used to provide a light output of 0.5 Watt or higher. In contrast, the fiber optic cantilever 222 used to collect the scanned light or for imaging is a multi-clad optical fiber with a large NA multimode inner cladding to add functionality. As part, for example, a single mode core with a small diameter can be provided.

  In many applications, there is no inconvenience to using a fixed illumination optical fiber, as it is not necessary to change the fiber orientation or focus so that the illumination optical fiber emits light that is directed to an internal location. However, in other applications, light is emitted from the illumination optical fiber, for example, by changing the angular orientation of the illumination optical fiber, and in some cases, changing the focus of the illumination optical fiber. It may be necessary to selectively change the direction.

  For example, in one exemplary application of the SFE probe, the optical properties of the tissue can be measured by illuminating the surface of the tissue with a point light source or a focused beam of light, followed by tissue reflection. The rate is measured as a function of wavelength and spatial distance from the point source. By measuring the total and relative spatial distribution of steady-state diffusive reflectance from the tissue surface, the local tissue propagation scattering and absorption coefficient optical properties can be calculated. The diffusion theory of light propagation in tissue is a theoretical framework for modeling light-tissue interactions in the optical window of light frequencies from red to IR, ie in the wavelength range of 600 nm to 1300 nm. The optical properties of the absorption and scattering coefficients in this optical window indicate how much laser light reaches different depths in the tissue for laser therapy such as photodynamic therapy, laser heating and laser removal. And which fraction of this light is absorbed is useful. By illuminating the tissue with a plurality of different wavelengths of light in this optical window, and by using a circular or spiral scan pattern or other scan pattern with a known size radius, More accurate measurement of penetration depth and spatial distribution of light irradiation, calculation of absorption and concentration of light absorber in tissue, and therapeutic power in tissue properties with less invasion to surrounding tissue It is possible to monitor changes.

  Point illumination can be provided using one or more optical fibers, while the spatial distribution of diffusive reflectance is the scanned optical fiber shown in FIG. 1 or the optical fiber shown in FIG. It can be detected using a mirror scanning system. An optical lens system may be used between the illumination optical fiber and the tissue surface to focus the illumination light and illuminate a smaller area on the tissue surface, as shown in FIGS. it can. The illumination light from each optical fiber can be focused on the surface of the tissue as an individual point source, or the light can be combined to illuminate a single central point as shown in FIG. Ideally, if single-center light illumination is used, then use a resonant fiber scanner or mirror scanner as discussed above, with a slowly expanding helix, or this It is desirable to use a detection method that is simply scanned using a circular pattern at a desired radial distance from the central illumination point source. Since each scan cycle in the circular pattern is a constant radial direction from the central point source, all light detected from this circular pattern can be averaged (to reduce noise during measurement) and this particular Gives an accurate determination result of the diffuse reflectance R (ρ) at a radial distance of. The radial distance (ρ) can be varied over a wide range simply by changing the scanning angle of the resonant scanner. By measuring the light output in an optical fiber used for illumination, the relative spatial distribution of light reflectance can be measured over a wide range of radial distances. Finally, the absolute measurement of reflectivity from a single point source is made uniform by integrating these space measurements over this limited range of measured radii, and thereafter This value can be estimated by scaling this value to determine an estimate of the reflectance distribution when all radii are measured assuming a semi-infinite tissue characteristic.

  The relationship between the measured optical properties of the tissue and these measurements of the absolute and relative spatial distribution of the tissue surface reflectance from a point light source is the relationship between the tissue when applying diffusion theory. Even when simplification assumptions are made, it provides a good correlation with in vitro measurements. One skilled in the art will readily understand how these measurements are performed and how to apply the optical properties of the tissue, so no further details need to be provided. For the purpose of demonstrating the knowledge of those skilled in the art, these mathematical and experimental relationships and measurement techniques are discussed in Non-Patent Document 2, and Non-Patent Document 3, which details the extension of the study. However, conventional implementations of measuring tissue optical properties disclosed in two references have limitations when applied to medical practice. A major challenge for less invasive medical devices is the need for small size and high precision optical measurements. As noted in non-patent document 4, which is an invited paper, even the authors of the techniques disclosed in these references recognize two practical limitations of their methodology. Two limitations of the technique described therein are that diffuse reflectance measurements must be made at many different locations on the tissue surface, and these measurements are quantitatively related to the incident dose. It must be attached. The methods disclosed in these references used an integrating sphere to measure R and a moving stage to measure R (ρ), while a camera detector array is a future embodiment. It has only been proposed. However, with the new method disclosed herein, it is believed that R (ρ) can be measured using a resonant scanning system after being illuminated by one or more optical fibers. Each optical fiber can be measured to quantitatively relate this incident illumination to the measured R (ρ). Particular embodiments use illumination with a single and central point source and use a circular or spiral to average the diffuse reflectance R detected at a slowly varying distance (ρ) from the central point source. R (ρ) is detected using the scan pattern. Resonant scan detection systems can make the range of R (ρ) measured wide and variable by simply adjusting the drive signal to the scanner to make the scan range larger or smaller. it can. As reported in Non-Patent Document 5, for the same small size with a diameter less than 2 mm, the resonant fiber scanner has a standard coherent fiber bundle or micro camera for flexible endoscopes It has been demonstrated to achieve a resolution greater than twice the image resolution of the chip. Therefore, R (ρ) measurement uses a small and accurate resonant fiber scanning device that has overcome technical challenges that have not previously made local measurement of optical properties practical. It can be made at many locations on the surface of deep tissue.

Embodiment with Non-Resonantly Moving Illumination Optical Fiber FIG. 13 shows that the illumination optical fiber 252 can selectively move (ie, gradually, not at the resonant speed), and the illumination light 256 is an option. FIG. 6 illustrates the end of an SFE probe 240 that includes a first embodiment in which the direction emitted from the rod lens 254 can be changed as desired. The SFE probe 240 has a housing 242 in which the scanning optical fiber 244 is driven by a driver (not shown in this figure) to move at or near the resonance frequency and in a desired operating pattern. . Light 260 from the internal location 258 passes through a transparent cover 268 located at the end of the SFE probe, and then is received by the scanning optical fiber 244 after passing through lenses 250, 248, and 246. The distal end of illumination optical fiber 252 (including rod lens 254, if provided) extends into one or more lumens extending from a pressurized source located near the proximal end of the SFE probe. By inflating balloon 264 with fluid carried through 262, it is selectively moved radially inward relative to the longitudinal center of SFE probe 240. The pressurized fluid in the balloon 264 inflates the balloon, and the balloon applies a force radially inward against the end of the illumination optical fiber 252.

  The natural stiffness of the illuminating optical fiber tends to resist the deflection force applied by the balloon 264 when inflated. Alternatively, a spring or other mechanism that exerts an outwardly directed force (eg, a helical spring or flat spring extending along the longitudinal axis of the illumination optical fiber) may be provided and applied by the balloon The end of the illumination optical fiber is offset outward in the radius so as to resist the force. When the balloon is deflated, the end of the illumination optical fiber is moved radially outward by this biasing force. The ring (or one or more knobs) 266 can serve as a stopper that inhibits outward radial movement beyond the desired limits of the illumination fiber / rod lens.

  FIG. 15A shows that the balloon 272 (placed between the illumination optical fiber and the outer surface of the scanner lens housing 274) is generally deflated, placed radially in position and angled. FIG. 5 is a cutaway view of the distal end of an alternative SFE probe 270 illustrating an example of an illumination optical fiber 252 and a rod lens 254. As shown in FIG. 15B, the illumination optical fiber and rod lens are responsive to a balloon 272 that is selectively inflated with pressurized fluid supplied from a source (not shown) located at the proximal end of the SFE probe. Angled more outward in the radial direction. 15C and 15D are isometric views of the SFE probe 270 corresponding to FIGS. 15A and 15B, respectively, showing a cover 276 of elastic material.

  FIG. 14 includes one or more illumination optical fibers 252 with optional rod lenses 254. A partial cutaway view of an exemplary SFE probe 280 is shown. The SFE probe 280 does not include a balloon for moving one or more illumination optical fibers to different angular orientations. Instead, it uses an electromechanical actuator or piezoelectric bimorph bender 284 held in place by securing a screw / support 286 that extends near the stop 288. The stop 288 prevents radial outward movement beyond the desired limits of the illumination optical fiber. Electrical lead 292 extends through lumen 282 from a power source (not shown) located at the proximal end of the SFE probe. The current in electrical lead 288 is very low and the voltage is relatively low. One or both of these parameters can be selectively controlled to move the illumination optical fiber to a desired angular orientation using an electromechanical actuator or a piezoelectric bimorph bender 284. A low friction and non-conductive tip 290 is provided at the end of the electromechanical actuator or piezoelectric bimorph bender where it connects to the illumination optical fiber. A longitudinally extending spring (not shown) along the irradiating optical fiber or a radially extending spiral spring (also not shown) is connected to the electromechanical actuator or piezoelectric bimorph. It can be used as an option to provide a radially outward biasing force that opposes the radially inward force provided by the bender 284.

  A partial cut-away view of the distal end of yet another embodiment of an SFE probe 300 having means for moving the illumination optical fiber is illustrated in FIG. Specifically, the SFE probe 300 includes a cable or wire 302 coupled around an irradiating optical fiber 252 via a loop 306 (or around a rod lens 254) and through the lumen 304 to the proximal end. It has extended to. The stop 288 prevents radial outward movement beyond the desired limits of the illumination optical fiber or rod lens. The helical spring 308 is coupled to the tip 310 on the inner surface of the housing 242 and is used to generate a radially inward biasing force relative to the illumination optical fiber 252 (or rod lens 254). . As the cable or wire 302 is pulled, the force applied to the illumination optical fiber or rod lens compresses the helical spring 308, moving the illumination optical fiber radially outward, from its angular orientation and from the illumination optical fiber. Change the direction in which the emitted light travels toward the internal location. When the tension of the cable or wire is relaxed, the spiral spring moves the irradiation optical fiber 252 and the rod lens 254 radially inward.

Example for Capturing Different Scattering Angles Ends of an exemplary SFE probe 320 designed to measure scattering angles endoscopically in a Fourier transform plane using one or more illumination optical fibers 324 Is illustrated in FIG. The distal end of each irradiation optical fiber is provided with a rod lens 326 in order to realize effective point light source illumination. Also included in the SFE probe is a resonant scanning optical fiber 338. The SFE probe 320 is disposed in a housing 322 that supports a Fourier transform lens 330 having a focal length f. Light 328 carried through the irradiating optical fiber is collimated or quasi-collimated by the rod lens 326 and directed by the Fourier transform lens 330 to a local region 334 on the internal position like the light 332. The rod lens can be configured to adjust the position and parallelism of the effective point source of the illumination light. Light 336 scattered from particles in region 334 enters Fourier transform lens 330, which creates light 337 that is quasi-parallel, which is collected by scanning optical fiber 338. The signal generated by a detector (not shown in this figure) coupled to the near end of the scanning optical fiber is used to determine the scattering angle of the collected light. This scattering angle indicates the relative size of the particles that caused the scattering.

  Measurement of the scattering angle is very useful for diagnosing the condition of the tissue at the internal location. For example, cancer cells are known to tend to have a much greater nucleus-to-cytoplasm ratio (the value of nucleus diameter divided by cell diameter) than normal cells. Thus, measuring the normalized scattering of light from the internal location allows for sharper peaks for larger cancer cell nuclei compared to that of normal cell nuclei.

  Techniques that can be used to determine the scattering angle are well known to those skilled in the art, and no further details need to be provided in this disclosure document. For example, exemplary techniques are disclosed in Non-Patent Document 6 and Non-Patent Document 7. The conventional methods disclosed in these two papers use a minimally stationary single mode optical fiber placed behind the optical fiber bundle and the objective sphere lens, and the ability to image with SFE is I don't have it. However, the paper notes the ability to select the depth of light scattering in tissue using the coherence effect, but instead, standard polarizing filter techniques can be used for this purpose. It is considered possible. Furthermore, unlike the prior art disclosed in the article, the method is more efficient using scanned light to measure and map the optical properties of the tissue.

  An exemplary range of scattering angles of cellular components, such as cell nuclei, that can be measured with the system shown in FIG. 17, is from about 5 ° to about 30 °. The minimum scattering angle is limited by the focal length of the Fourier transform lens, which is about 3 mm in this example. On the other hand, the maximum scattering angle is limited by the radius r of the helical scanning pattern made with the scanning optical fiber 338, which is about 1 mm for a maximum scattering angle of 30 °. To achieve this radius for the helical scan pattern, scan with other SFE probes compared to the scan optical fiber described above (assuming that the scan optical fiber diameter is maintained at a nominal value of about l25 μm). It is necessary to increase the length of the optical fiber and / or increase the magnitude of the drive signal applied to the scanning optical fiber actuator to a value exceeding 20 volts.

  In one embodiment, the scanning optical fiber comprises a double-clad single-mode optical fiber that allows high resolution imaging of the internal location and has a collection efficiency for sampling scattering at various angles. Ensure that it is increased. For example, in successive frames, the scattering angle can be measured, and then the internal position is imaged using a scanning optical fiber. Alternatively, while one or more additional optical fibers (eg, optical fibers that are not used to provide illumination light) can respond to the backscattered light to measure the scattering angle Thus, a collimating microlens (eg, a spherical lens) can be provided at the distal tip of the scanning optical fiber 338, and the scanning optical fiber can be used more efficiently to image the internal location. Yet another alternative embodiment for both internal location imaging and capture of different scattering angles for particles at the internal location is shown in FIG. 18 and discussed below.

  By using multiple irradiating optical fibers, two or more substantiations are possible to allow different penetration depths within the tissue at the internal location and to change the relative scattering angle for tissue structures at different depths. Illuminating light having different wavelengths can be used. In addition, using a plurality of irradiation optical fibers 324 can facilitate the supply of illumination light having different polarizations, and can reduce noise from speckle of a laser or other light source. Polarization filter technology can be used to identify light scattering from the surface area of the tissue (eg, the epithelial layer) and not from deeper areas of the tissue. Linearly polarized illumination light can be used to implement this technique of filtering multiple scattered photons from single scattered photons or photons that have only undergone only a few scatterings. In this case, the illumination fiber 324 may be a polarization maintaining optical fiber. A wire grating polarization filter may optionally be placed at the distal tip 339 of the probe that has properties that match the polarization of the illumination light, and will attenuate any polarization shift due to multiple scattering events. .

  Referring to FIG. 18, an example of an SFE probe 340 designed for both imaging the internal location 346 and capturing different scattering angles for particles in the tissue at the internal location is illustrated. In this embodiment, the illuminating optical fiber 342 carries light from one or more different light sources through the rod lens 344, which at least partially collimates the light into an internal position as light 348. Turn to. Piezoelectric tubular actuator 350 includes a slide including an annular groove 358 that restricts the longitudinal movement of the piezoelectric tubular actuator and scanning optical fiber 352 to a total distance equal to Δz corresponding to the distance between the image plane and the transform plane. It is mounted on the type joint ring 354. The illumination optical fiber 342 includes a groove 358 and an engaging stop 356. Alternatively, in one embodiment, similar sliding devices can be used to move the illumination supply system and the objective lens system, including lenses 360 and 362.

  When collecting the light scattered from the internal position to determine the scattering angle, the end of the scanning optical fiber 352 is located on the conversion surface, while when imaging the internal position, the piezoelectric tubular actuator and the scanning The optical fiber moves longitudinally and the end of the scanning optical fiber is placed on the image plane. Instead, a similar movement over the distance Δz can be applied to the objective lens system, depending on whether the scattering angle is measured or the object plane at the internal position is imaged, the end of the scanning optical fiber. The objective lens system is positioned to change so that is in either the conversion plane or the image plane.

Example for Measuring / Mapping Local Diffuse Reflectance The exemplary SFE probe 364 illustrated in FIG. 19 is configured for both high resolution imaging and higher reflected light collection, Useful when measuring and / or mapping local diffusive reflections from tissue surfaces at internal locations. Within the housing 366, the first illumination optical fiber 368a carries the illumination light 372a through the optional rod lens 370a and the light is focused on the internal location. Similarly, the second illumination optical fiber 368b carries the illumination light 372b through the rod lens 370b, which focuses the light onto the internal position. Light 374a and light 374b corresponding to each illumination light 372a and 372b is located near the transparent window 377 from the internal position and is directed to lenses 376a, 376b, and 376c that focus the reflected light to the end of the scanning optical fiber 378. Reflected towards.

  In this embodiment, the scanning optical fiber 378 is a double clad single mode core optical fiber. To image the internal location, the single mode core carries the reflected light to a detector located at the near end of the scanning optical fiber. Selective spatial filtering is used for confocal placement to collect light and illumination through the same single-mode double-clad fiber optic core to selectively collect light from the desired axial depth. May be. However, the multimode cladding layer inside the scanning optical fiber, which has a much larger numerical aperture (NA) than the single mode core, is more likely to concentrate reflected light (ie, more reflected light from the internal location) High concentration of reflected light is useful in detecting certain properties of the collected light, and thus assessing the condition of the tissue where the light is collected To do. As one example of how this SFE probe can be utilized, the illumination optical fiber 368a can illuminate monochromatic light or red, green, and blue light for internal location for imaging or other purposes. While the illumination optical fiber 368b can carry polarized light or light of a specific wavelength intended for diagnostic purposes. The scanning optical fiber can then image the internal location using a single mode core, and then use the internal cladding layer to collect the light used for diagnostic or other purposes. it can. Sequential imaging and collection can be alternated from frame to frame or can be performed in some other desired connection.

  It should also be understood that the SFE probe can include other optical fibers in addition to one or more illumination optical fibers and scanning optical fibers. FIG. 20 shows a first irradiating optical fiber 384, grouped around a central scanning aperture, with a scanning optical fiber behind (not specifically shown in this figure). Second illumination optical fiber 386, six multimode optical fibers 388 (designated individually as "A"-"F"), and 6 (designated individually as "G"-"L") 8 illustrates an end face of an exemplary SFE probe 380 that includes a housing 382 having a multi-mode optical fiber 390. Polarization filtering can be used to completely separate the diffuse light reflected from the tissue from the surface reflection and the light scattered from the top surface. Cross-polarization filtering can be used to select light that is backscattered from deep regions of the internal location. In order to implement this method, the illumination fiber will be a polarization-maintaining optical fiber of a specific orientation. However, in contrast to FIG. 17, the polarizing filter used in FIG. 19 is centered, the filtered photons hit only the resonantly scanned optical fiber, and the polarizing filter is orthogonal or with respect to the polarization axis of the illumination light. Axis crosses. One or more multimode optical fibers 388 and 390 are high resolution SFE images (collecting red, green, and blue backscatter from illumination from the single mode core of double clad scanning optical fiber 378). Or can be used to carry additional illumination light, to provide optical therapy, or to collect light useful for diagnostic and other purposes. From this example, many other combinations of one or more illumination optical fibers, scanning optical fibers, and one or more other multimode optical fibers are fixed one or more individually, or Nearly all of the SFE probes described herein can be equipped to achieve the benefits of using a scanning device (eg, scanning optical fiber or scanning mirror) with a non-resonantly movable illumination optical fiber. It will be clear that you can.

  FIG. 21 shows that light from an internal location 394 is coupled to two or more illumination sources having different characteristics when received using a scanning optical fiber in an SFE probe as discussed above. Illustrates how two or more illumination optical fibers can be used to achieve different results. In this figure, an axial view of the internal position (that is, a view perpendicular to the longitudinal axis of the SFE probe not shown) is shown. An illumination light spot 396 is created by one or more illumination optical fibers of the SFE probe using the first illumination light source on the internal location 394. Similarly, the illumination light spot 398 is created by one or more other illumination optical fibers on the SFE probe. The circle shown in this figure represents the FOV of the scanning optical fiber. It should be understood that the light spots 396 and 398 are within or near the collection area represented by this FOV, and there is only one light spot or more than two light spots. Further, the plurality of light spots can each have different characteristics, or can have the same characteristics, or a combination of light spots can have different characteristics than other combinations of light spots. . Illumination light sources used to create different illumination light spots, for example, generate illumination light having different wavelengths, polarization, coherence, or modulation characteristics. The two vectors shown in the FOV of FIG. 21 indicate that the light used to generate the light spot 396 has different characteristics than that used to generate the light spot 398. If an illuminating optical fiber deflector is used, then the two light spots shown around the imaging field will become one at a single point in the field, ideally the center A point light source illumination can be formed. Diffuse reflectance R (ρ) from the tissue surface can be measured using a resonant helix or a slowly changing circular scanning pattern, allowing a very accurate measurement of the local optical properties of the illuminated tissue To.

Exemplary Scanning System FIG. 22 illustrates a method in which signals generated by an SFE probe inside a patient's body are processed by external equipment and used to control the SFE probe system and within a scan frame. FIG. 6 illustrates a system 450 illustrating a method in which signals that change scanning parameters are input to an SFE probe located within a patient's body. To achieve imaging and other functional integration, the system 450 can thus be used for components external to the patient's body and those used internally (ie, components on the SFE probe within the dashed line 452, Some of them are optional). Block 454 lists the functional components located at the end of the SFE system. As shown herein, these exemplary components include illumination optics, one or more electromechanical scanning actuators that can drive a scanning optical fiber or scanning mirror, one or more illumination fiber optic actuators, It can include a selective photon detector for imaging the internal location, and optionally a further photon detector or multimode optical fiber for diagnostic and therapeutic and / or monitoring purposes. The photon concentrator for imaging can be a discrete sensor mounted on the SFE probe, or another multimode optical fiber as shown in FIG. 20 and discussed above. Can do. It should be noted that with respect to system 450, only functional components that are actually needed for a particular application of the SFE system are included. Also, further functions other than imaging can be diagnosis, treatment, or any combination thereof.

  As indicated by block 456, externally the illumination optics and scanner are supplied with light from the imaging light source and modulator. Further details regarding some preferred embodiments of an external light source system 458 for generating RGB, UV, IR and high intensity light carried to the end of the fiber optic system will be apparent to those skilled in the art. I will. The (optional) scanner sensor can be used to generate a feedback signal that controls the scanner actuator, illumination source, and modulator, and implements scan control after signal processing in block 460. To do.

  At block 460, image signal filtering, buffering, scan conversion, amplification, and other processing functions may be used for imaging photon detectors and any other photon detectors used for diagnostic / therapeutic and monitoring purposes. Is implemented using electronic signals generated by. Blocks 456, 458, and 460 are interconnected bi-directionally to carry signals that enable the functions performed in each individual block. Similarly, each of these blocks is a signal supplied to a computer workstation user interface or other computing device that can be used for image acquisition, processing, executing related programs, and other functions. To communicate with block 462, which is provided with analog-to-digital (A / D) and digital-to-analog (D / A) converters. Control signals from the computer workstation are fed back to block 462 and converted to analog signals, where appropriate, to control or enable each of the functions provided in blocks 456, 458, and 460. The A / D and D / A converters in block 462 are also bi-directionally coupled to block 464 and block 466 that comprise data storage. Block 466 represents a user interface for manipulation, positioning, and stabilization of the SFE probe within the patient's body.

  In block 464, the data storage device stores image data produced by the detector in the patient's body and other data related to the functions implemented by the imaging and SFE probes. Used for. Block 464 is also bi-directionally coupled to the computer workstation 468 and the interactive display monitor in block 470. Block 470 receives an input signal from block 460 and allows an image of the internal location to be interactively displayed. Further, as shown in block 472, one or more passive video display monitors may be included in the system. For example, other types of display devices 474 such as a display device (HMD) system mounted on the head can be provided, allowing the physician to view the internal location as a pseudo-stereo image.

  While the concepts disclosed herein have been described in connection with preferred forms of implementation and variations thereof, those skilled in the art will recognize many other variations that are within the scope of the following claims. Will do. Accordingly, the scope of the concept is in no way intended to be limited by the above description, but rather is determined entirely by reference to the following claims.

Claims (59)

Illuminating an internal location within a patient's body with a different type of light for each of at least two different modes, selectively operable in a plurality of different modes, and in the at least one mode of the plurality of different modes, the internal In an optical fiber system that responds to light received from a location,
(A) a plurality of light sources for generating the different types of light, wherein at least one light source can be selectively excited during operation of the fiber optic system in a current mode;
(B) an illumination optical fiber having a distal end, selectively coupled to a different one of the plurality of light sources, for emitting the type of light thereby emitted in operation in the current mode; An irradiating optical fiber carried to the end of the optical fiber and illuminating the internal position with one of the plurality of different types of light;
(C) a scan driver adapted to be excited by a drive signal;
(D) a scanner optical fiber having a near end and a distal end coupled to the scan driver, wherein the scan driver scans at least one portion of the internal position in a desired pattern, The light received by the scanner optical fiber is configured to receive light from at least the portion of the internal position illuminated by the light from the irradiation optical fiber in the mode of the scanning light. A scanner optical fiber incident on the distal end of the fiber and carried to the proximal end thereof by the scanner optical fiber;
(E) coupling to the scanner optical fiber, receiving the light carried by the scanner optical fiber, and wherein the optical fiber scanning system is operating in the current mode; And an optical sensor that generates an output signal indicating at least one parameter of the light received from the portion. At least two different modes are
(A) a diagnostic mode in which diagnostic light is carried through the illumination optical fiber;
(B) an imaging mode in which imaging light is carried through the illumination optical fiber;
2. The optical fiber scanning system according to claim 1, wherein (c) a relatively high power treatment light is selected from the group consisting of a treatment mode carried through the irradiation optical fiber.   Responsive to the output signal, further comprising a display device coupled to the photosensor to receive the output signal from the photosensor for creating an image of at least the portion of the internal location. The optical fiber scanning system according to claim 1.   Light received from at least the portion of the internal location and entering the end of the scanner optical fiber is carried through the illumination optical fiber and the light sources illuminate the internal location in operation in the current mode 2. The fiber optic scanning system of claim 1, wherein the optical fiber scanning system has a wavelength that is substantially different compared to light generated by one of the two. The at least one parameter is
(A) the intensity of the received light;
(B) the direction in which the received light is transmitted from the internal position;
(C) the angle at which the received light is transmitted from the internal position;
(D) the distance that the received light travels from the internal position;
(E) a period during which the received light is transmitted from the internal position;
(F) the depth in the tissue at the internal position through which the received light is transmitted;
The optical fiber scanning system according to claim 1, comprising at least one of (g) a wavelength of received light.   The irradiation optical fiber is coupled to the irradiation optical fiber and selectively displaces the irradiation optical fiber by a non-resonant motion, so that the irradiation optical fiber is not in the previous position. The optical fiber scanning system according to claim 1, further comprising an irradiating optical fiber displacement device configured to illuminate regions having different internal positions.   The illumination fiber optic displacer changes the direction in which the illumination optical fiber emits one of the plurality of different types of light directed toward the internal position, and the plurality of different in the current mode. 7. The fiber optic scanning system of claim 6, wherein the different areas are illuminated with the one type of light.   The irradiating fiber optic displacer changes the depth of focus of the different types of the one light emitted by the irradiating optical fiber within the tissue at the internal location, and different depths within the tissue. 7. The fiber optic scanning system of claim 6, wherein the different areas are illuminated.   The optical fiber scanning system according to claim 6, wherein the irradiation optical fiber displacement device includes a cable moving with respect to the scanner optical fiber, and displaces the end of the irradiation optical fiber.   The irradiating optical fiber displacement device is an elastic material film that defines a volume coupled to exchange information with a pressurized fluid source, and the amount of pressurized fluid in the volume is selectively changed. 7. The optical fiber scanning system according to claim 6, further comprising an elastic material film disposed in the vicinity of the distal end of the irradiation optical fiber so as to displace the distal end.   The illumination fiber optic displacer comprises an electromechanical actuator disposed proximate the distal end of the illumination optical fiber to displace the distal end in response to a selectively applied electrical signal. The optical fiber scanning system according to claim 6.   The irradiating optical fiber displacer includes a wire and a restoring spring actuator, and is disposed near the end of the irradiating optical fiber so as to displace the end when a force is selectively applied to the wire. The optical fiber scanning system of claim 6, wherein the optical fiber scanning system is disposed.   2. The scanning driver of claim 1, wherein the scanning driver drives the end of the scanner optical fiber to move in the desired pattern near a resonant frequency of the end of the scanner optical fiber. Fiber optic scanning system.   A movable reflective surface arranged to reflect light for receiving light transmitted from at least the portion of the internal position to the distal end of the scanner optical fiber, the movable reflective surface being near a resonant frequency; 2. The fiber optic scanning system of claim 1, wherein said optical fiber scanning system is driven to move by said scan driver, thereby scanning at least said portion of said internal location in said desired pattern.   Measuring the position of reflected light in the image field generated from the position and orientation of the illumination optical fiber in the fiber optic scanning system for at least a portion of the internal position that causes reflection of one of the plurality of different types; The optical fiber scanning system according to claim 1, further comprising a processor.   The optical fiber scanning system according to claim 1, wherein the irradiation optical fiber includes a multimode optical fiber.   The optical fiber scanning system according to claim 1, wherein the irradiation optical fiber comprises a single mode optical fiber. The scanner optical fiber is:
(A) a multimode optical fiber;
(B) a single mode optical fiber;
(C) a multilayer clad optical fiber;
The optical fiber scanning system of claim 1, further comprising: (d) an optical fiber selected from the group consisting of both multimode and single mode optical fibers.   A processor for determining the size of the particulate in the tissue at least in the portion of the internal location as a function of the scattering angle of the light received by the scanner optical fiber, wherein the size of the particulate is the internal 2. The optical fiber scanning system according to claim 1, wherein the optical fiber scanning system is proportional to the intensity of light received from the fine particle including the tissue at a position and the scattering angle of the received light.   The optical fiber scanning system according to claim 19, wherein the microparticle is a component of a cell.   The desired pattern of scanning is a spiral and further comprises a processor for determining a characteristic of the tissue at the internal location, wherein the characteristic is illuminated by the light of the plurality of different types Reflectivity measured as a function of distance from a point, the reflectivity determining a parameter selected from the group consisting of absorption, scattering, and effective scattering coefficient of the illuminated tissue The optical fiber scanning system according to claim 1, wherein the optical fiber scanning system is used.   The desired pattern of scanning is a spiral and further comprises a processor for determining a characteristic of the tissue at the internal location, the characteristic being a function of the propagation time of light from the point where the tissue is illuminated And the propagation time is determined by the processor to determine one parameter selected from the group consisting of absorption, scattering, and effective scattering coefficients of the tissue illuminated by the light. The optical fiber scanning system according to claim 1, wherein the optical fiber scanning system is used. The desired pattern of scanning is
(A) spiral scanning;
(B) propeller scanning;
(C) linear scanning;
(D) raster scanning;
The optical fiber scanning system of claim 1, wherein the optical fiber scanning system is selected from the group consisting of: (e) Lissajous scanning.   The at least one parameter comprises at least one of a distance and an angle between the fiber optic scanning system and the surface of the tissue at the internal location, and the at least one parameter is detected in the received light The fiber optic scanning system of claim 1, wherein the optical fiber scanning system is determined in response to specular reflection from a surface of the tissue at the measured internal location.   One light source of the plurality of light sources coupled to the illumination fiber in the current mode generates light having at least one characteristic selected for treatment at the internal location, the characteristic being an output level And at least one selected from the group consisting of a wavelength band and an optical fiber scanning system according to claim 1.   The lens of claim 1, further comprising a lens disposed near the distal end of the illumination optical fiber to collect the light directed toward the internal position in the current mode. An optical fiber scanning system as described. A method of scanning an internal position of a patient's body in a plurality of different modes, wherein for each of at least two of the plurality of different modes implemented, the method comprises:
(A) carrying a plurality of different types of light from a light source selected for use in the current mode of the at least two modes to the end of the illuminating optical fiber, emitted from the end Directing the light onto the internal position, the distal end of the illumination optical fiber being stationary or non-resonant and moving relatively slowly;
(B) scanning at least one portion of the internal location to collect light received from at least the portion of the internal location;
(C) carrying the received light from at least the portion of the internal location through a scanner optical fiber to a proximal end of the scanner optical fiber;
(D) detecting the received light and generating an output signal in response to the received light;
(E) using the output signal to determine at least one parameter of at least the portion of the internal position during the current mode currently implemented. The at least two modes are:
(A) a diagnostic mode in which diagnostic light is carried through the illumination optical fiber;
(B) an imaging mode in which imaging light is carried through the illumination optical fiber;
28. The method of claim 27, wherein (c) a relatively high power treatment light is selected from the group consisting of a treatment mode carried through the irradiating optical fiber.   Using the output signal comprises displaying an image of at least the portion of the internal location in response to the output signal, and wherein the at least one parameter comprises an appearance of at least the portion of the internal location. 28. The method of claim 27, wherein:   The received light has a wavelength that is substantially different from the light directed from the illumination optical fiber to the internal location, and the step of using the output signal is characterized by the tissue at the internal location. The method of claim 27, comprising the step of determining. The at least one parameter is
(A) the intensity of the received light;
(B) the power of the received light;
(C) the direction in which the received light is transmitted;
(D) an angle at which the received light is transmitted from the internal position;
(E) the depth in the tissue at the internal position where the received light is transmitted;
(F) the wavelength of the received light;
28. The method of claim 27, wherein the method is selected from the group consisting of: (g) a propagation time of the received light.   28. The method of claim 27, further comprising selectively displacing the illuminating optical fiber to illuminate different regions of the internal location.   The selectively displacing step comprises changing a direction in which the illumination optical fiber emits light toward the internal position to illuminate the different areas. the method of.   The selectively displacing step comprises a depth of focus of light emitted by the irradiating optical fiber in the tissue at the internal location to illuminate the different regions at different depths in the tissue. The method of claim 32, comprising the step of changing:   28. The method of claim 27, wherein the step of scanning comprises driving the end of the scanner optical fiber to move near a resonant frequency of the end of the scanner optical fiber.   The step of scanning comprises driving a movable reflective surface arranged to reflect the received light from at least a portion of the internal location toward the distal end of the scanner optical fiber; 28. The method of claim 27, wherein the movable reflective surface is driven to move near a resonant frequency of the movable reflective surface.   The step of using the output signal includes determining a position of reflection of the light that illuminates the tissue within a field of view of the received light collected by the scanner optical fiber. Item 28. The method according to Item 27.   The step of using the output signal comprises determining the size of the particulate in the tissue at the internal location as a function of the scattering angle of the received light, the size of the particulate being the intensity of the received light 28. The method of claim 27, wherein the method is proportional to the scattering angle of the received light.   40. The method of claim 38, wherein determining the size of the microparticle comprises determining the size of a cellular component in the tissue.   The desired pattern of scanning is a spiral, and the step of using the output signal comprises determining a characteristic of the tissue at the internal position, the characteristic comprising light emitted from the illumination optical fiber Reflectivity measured as a function of distance from a point incident on the tissue, the reflectivity being selected from the group consisting of absorption, scattering, and effective scattering coefficient of the tissue illuminated with the light The method of claim 27, wherein the method is used to determine a parameter to be performed. The scanning step includes:
(A) a spiral pattern;
(B) a propeller pattern;
(C) a linear pattern;
(D) a raster pattern;
28. The method of claim 27, comprising scanning with a pattern selected from the group consisting of: (e) a Lissajous pattern.   The step of using the output signal is responsive to specular reflection of the surface of the tissue included in the received light, the distance and angle between the fiber optic scanning system and the surface of the tissue at the internal location. 28. The method of claim 27, comprising determining at least one parameter selected from the group consisting of:   When operating in a treatment mode, the method further comprises emitting light from the irradiating optical fiber having at least one characteristic selected for treatment at the internal location, the at least one characteristic comprising: 28. The method of claim 27, comprising at least one selected from the group consisting of relatively high power and wavelength bands.   28. The method of claim 27, further comprising focusing the light from the illumination optical fiber toward the internal location. A fiber optic scope for illuminating an internal location of a patient's body with a plurality of different types of light between a plurality of different modes and responding to light received from the internal location,
(A) a plurality of different light sources that generate different types of light for illuminating the internal location;
(B) an elongated casing disposed at the end of the optical fiberscope;
(C) a generally centrally located scanner at the distal end of the fiber optic scope, wherein the scanner is driven to move near a resonant frequency in a desired pattern and is at least desired in the internal position A light configured to be collected by the scanner and carried through the scanner optical fiber to a near end of the scanner optical fiber;
(D) a plurality of illuminating optical fibers spaced from the scanner in the elongated housing and having a distal end disposed about the scanner, the optical fibers being emitted from the distal end of the illuminating optical fiber; A plurality of illumination lights that carry light from a selected one of the plurality of different light sources to the end of the illumination optical fiber operating in a current mode so that the light is directed to the internal location Fiber,
(E) a sensor coupled to the scanner optical fiber and responsive to the received light carried through the scanner optical fiber during the current mode being implemented by the fiber optic scope; And a sensor for generating an output signal that can be processed to provide data regarding tissue at the internal location. The at least two different modes are:
(A) a diagnostic mode in which diagnostic light is carried through the plurality of irradiation optical fibers;
(B) an imaging mode in which imaging light is carried through the plurality of illumination optical fibers;
46. The fiber optic scope of claim 45, wherein (c) a relatively high power treatment light is selected from the group consisting of a treatment mode carried through the plurality of illumination optical fibers.   In order to selectively scan the desired portion of the internal location, the scanner includes a driver coupled to the distal end of the scanner optical fiber, the driver in the desired pattern the distal end. 46. The optical fiber scope according to claim 45, wherein a force to resonate is applied.   The apparatus further comprises a displacer for selectively displacing the distal end of the illumination optical fiber to control where light emitted from the illumination optical fiber is incident on the internal position. Item 46. The optical fiber scope according to Item 45.   The sensor is responsive to the received light in a particular wavelength band substantially different from the wavelength band of the light emitted by the plurality of illumination optical fibers operating in the current mode. The optical fiber scope according to claim 45, wherein   The scanner includes a reflective surface that reflects the received light into the end of the scanner optical fiber, and includes a driver for moving the reflective surface near a resonant frequency. The optical fiber scope according to claim 45. The scanner includes an optical fiber that transmits the received light, and the optical fiber includes:
(A) a multimode optical fiber;
(B) a single mode optical fiber;
(C) a multilayer clad optical fiber;
46. The fiber optic scope of claim 45, wherein the fiber optic scope is of a type selected from the group consisting of: (d) multimode and single mode coupled optical fibers.   The scanner has a position of reflected light within an image field resulting from the position and orientation of the plurality of illumination optical fibers in the optical fiber scanning system with respect to at least a portion of the internal position from which the received light is reflected. 46. The fiber optic scope of claim 45, further comprising a processor for measuring. The desired pattern for scanning is
(A) a spiral pattern;
(B) a propeller pattern;
(C) a linear pattern;
(D) a raster pattern;
46. The fiber optic scope of claim 45, comprising a pattern selected from the group consisting of: (e) a Lissajous pattern.   46. The optical fiber of claim 45, wherein the output signal generated by the sensor is usable to display an image of at least the portion of the internal location in both an imaging mode and a monitoring mode. scope.   46. The light of claim 45, wherein the output signal generated by the sensor can be used to calculate absorption for the penetration depth of the light emitted from the plurality of illumination optical fibers. Fiberscope.   The output signal generated by the sensor is responsive to specular reflection from the surface of the tissue in a group of distances and angles between the fiber optic scope and the tissue surface at the internal location. 46. The fiber optic scope of claim 45, wherein the specular reflection includes the received light that can be used to determine at least one parameter selected from:   The output signal generated by the sensor can be used to determine the size of the particulate in the tissue at the internal location as a function of the scattering angle of the received light, wherein the size of the particulate is The optical fiber scope according to claim 45, which is proportional to the intensity of the received light and the scattering angle of the received light.   58. The fiber optic scope of claim 57, wherein the size of the microparticles corresponds to the size of a cell component.   As a function of reflectivity measured from where the tissue is illuminated by the light emitted from the plurality of illumination optical fibers in the current mode, the output signal generated by the sensor is at the internal location. 46. The fiber optic scope of claim 45, wherein the fiber optic scope is usable to calculate a parameter selected from the group consisting of absorption, scattering and effective scattering coefficients of the tissue.

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