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WO1999042179A1 - Procede pour le traitement photodynamique de tissu humain - Google Patents

Procede pour le traitement photodynamique de tissu humain Download PDF

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Publication number
WO1999042179A1
WO1999042179A1 PCT/EP1999/001155 EP9901155W WO9942179A1 WO 1999042179 A1 WO1999042179 A1 WO 1999042179A1 EP 9901155 W EP9901155 W EP 9901155W WO 9942179 A1 WO9942179 A1 WO 9942179A1
Authority
WO
WIPO (PCT)
Prior art keywords
ultrasound
light
applicator
body tissue
tissue
Prior art date
Application number
PCT/EP1999/001155
Other languages
German (de)
English (en)
Inventor
Klaus M. Irion
Original Assignee
Karl Storz Gmbh & Co. Kg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Karl Storz Gmbh & Co. Kg filed Critical Karl Storz Gmbh & Co. Kg
Publication of WO1999042179A1 publication Critical patent/WO1999042179A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/30—Surgical pincettes, i.e. surgical tweezers without pivotal connections
    • A61B2017/306—Surgical pincettes, i.e. surgical tweezers without pivotal connections holding by means of suction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the invention relates to a device for the treatment of body tissue, in particular soft tissue, by means of a reaction which is light-induced by a photosensitizer contained in the body tissue, with a light-supplying unit and an applicator which has an applicator surface in the distal region from which the light emerges directed towards the body tissue .
  • PDT photodynamic therapy
  • malignant, but also benign tissue degenerations, such as tumors are treated with photodynamic therapy.
  • photosensitizers are administered to the patient, which accumulate specifically in the tissue to be treated and which, when illuminated with excitation light of high light intensity, lead to a phototoxic effect by which the degenerated tissue is destroyed.
  • Substances are used as photosensitizers which either contain a hematoporphyrin backbone or delta-aminolevulinic acid (ALA), a precursor of the fluorescent protoporphyrin IX.
  • the photosensitizer is administered in a concentration of a few mg / kg of body weight, for example intravenously, or is applied locally to the body tissue to be treated.
  • the photosensitizers accumulate in tumor tissues in a multiple concentration. This preferential accumulation in the tumor tissue represents the crucial basis for photodynamic therapy.
  • Irradiation with light in the red spectral range is preferably carried out in the case of photodynamic therapy.
  • Long-wave light is more suitable for photodynamic therapy than short-wave light because the depth of penetration of long-wave light into the body tissue is greater.
  • the phototoxic effect of the photosensitizer enriched in the body tissue is based on the fact that this is converted into an excited state when irradiated with light. From the excited state, the photosensitizer returns to the ground state with the release of energy, the released energy being transferred to molecular oxygen, which absorbs this energy with the formation of excited singlet oxygen.
  • This aggressive singlet oxygen destroys the cell structures in the tissue concerned by photo-oxidation. This cellular damage, together with a simultaneous collapse of the tumorous vascular system, leads to complete tumor destruction.
  • photodynamic diagnosis In addition to the therapeutic effect of the light-induced reaction by the photosensitizer, it is also known that the use of a photosensitizer can serve diagnostic purposes in order to better or earlier recognize degenerated tissue. Such a diagnostic procedure is called photodynamic diagnosis (PDD).
  • PDD photodynamic diagnosis
  • the body tissue to be examined is irradiated with light of lower intensity and shorter wavelength, whereby the photosensitizer is excited to fluoresce.
  • the fluorescent light can be observed using an endoscope.
  • a device for photodynamic diagnosis is described in the aforementioned DE-A-195 48 913, but it can also be used for photodynamic therapy.
  • An endoscope is known from DE-A-44 43 947, which has optical examination means and a source of therapeutic ultrasound, the source having an ultrasound transducer arranged at the distal end of the endoscope.
  • the ultrasound radiation is carried out laterally across the longitudinal axis of the endoscope through the endoscope shaft, while the optical examination means at the distal end of the endoscope have optics with a view in the direction of the longitudinal axis of the endoscope.
  • the ultrasound radiation area and the field of view of the optics are therefore spatially separated from one another.
  • This endoscope is only suitable for therapy with ultrasound, while the optical examination means only serve to visually control the ultrasound treatment of the body tissue.
  • DE-A-35 32 604 discloses a laser probe for the treatment of surface tumors which are present in a large area within a body cavity.
  • the laser probe has a substantially hollow spherical light diffusion part at the tip, which includes a light dispersion medium.
  • Light guides are guided in this light diffusion part, the laser light exit ends of which are arranged essentially in the middle of the light diffusion part.
  • Such a laser probe scatters laser light emitted from the exit end of the light guide over a large area, as a result of which the objects are irradiated with a uniform intensity.
  • the position of the hollow spherical light diffusion part of the laser probe can be within the Body cavity can be freely set outside of the body, for example by means of an ultrasound diagnostic device. The ultrasound is used only for diagnostic purposes. Furthermore, it is not disclosed how the ultrasound is irradiated.
  • WO-A-96/27341 discloses a method for the improved absorption of a photosensitizer in a tissue to be treated by means of ultrasound.
  • Ultrasound generated in an ultrasound device is irradiated onto the photosensitizer after its absorption in the tissue in order to excite it.
  • the photosensitizer is excited with ultrasound instead of light.
  • This possibility of stimulating a photosensitizer with ultrasound instead of light is also in Jpn. J. Appl. Phys. Vol. 33 (1994), pages 2846-2851, Part 1, No. 5B, May 1994, "Sonochemical Application of Ultrasound to Tumor Treatment".
  • an instrument is known from the DE company publication of Laser- undtechniktechnologie gGmbH, Berlin, "Laser Ultrasound Surgical Therapy, Transmission of Ultrasound and Laser via Silica Glass Fibers", which has a long flexible fiber with a diameter of 300 - 1,300 ⁇ m, by means of which ultrasound and laser light can simultaneously be radiated into the body tissue to be treated to a limited area.
  • the ultrasound is generated on the proximal side using an ultrasound transducer and transmitted distally via the flexible glass fiber; the oscillator frequency is in the lower kHz range (20-50 kHz) because the damping in the waveguide is too strong at higher frequencies.
  • Tissue is supposed to coagulate with the laser light and with the Ultrasound tissue can be removed.
  • This known instrument is used in neurosurgery. However, it is not possible to use this known instrument for photodynamic therapy, because for this purpose it is necessary to irradiate the body tissue over a wide area in order to achieve the phototoxic effect.
  • the invention is therefore based on the object of developing a device of the type mentioned at the outset in such a way that a higher effect of the photodynamic therapy is achieved, so that it can in particular be accelerated and carried out with less light intensity and energy.
  • the technical effort and cost should be kept as low as possible.
  • an ultrasound generation unit is provided for generating ultrasound of high intensity, the ultrasound likewise emerging from the applicator surface in such a way that the radiation areas of ultrasound and light overlap at least partially in the body tissue .
  • the device according to the invention now for the first time creates a system with which the effect of photodynamic therapy is improved by simultaneous use of therapeutic ultrasound, which is achieved in that the radiation areas of the light and ultrasound emerging from the applicator surface at least partially overlap in the body tissue, ie that the ultrasound in the body tissue is superimposed on the light. Due to the overlay, the previously mentioned supporting effect of ultrasound in photodynamic therapy.
  • High intensity ultrasound is understood to mean ultrasound in the therapeutic power and frequency range.
  • Another advantage of the device according to the invention is that the photosensitizer or a precursor thereof does not have to be administered to the patient beforehand, as in the conventional devices for photodynamic therapy, since the photosensitizer diffuses faster into the tissue as a result of the application of ultrasound, as a result of which the Photosensitizer or the precursor can optionally be administered during the treatment.
  • the device according to the invention Compared to a system configured from a conventional PDT catheter and an extracorporeal ultrasound applicator, the device according to the invention also has the advantage of being less complex and cost-intensive, since overall only one applicator is provided both for the irradiation with light and for the irradiation with ultrasound .
  • the ultrasound generating unit has at least one electrically excitable vibrating element which is arranged in the applicator surface.
  • the arrangement of the at least one vibrating element in the applicator surface has the advantage that the ultrasound is generated in the immediate vicinity of the body tissue, thereby avoiding losses or undesirable heat development that can occur when ultrasound is supplied via an ultrasound transmission system to the applicator surface .
  • the ultrasound from the vibrating element can be better coupled into the body tissue if the applicator surface is brought into contact with the body tissue.
  • This arrangement of the vibrating element also enables the coupling of ultrasound of a relatively high frequency (approx. 0.5-10 MHz) into the body tissue, which would otherwise be dampened too much by transmission losses.
  • this measure opens up the possibility of designing the oscillating element geometrically such that the ultrasound is already emitted in a focused manner. ⁇
  • an opening is provided in or next to the at least one oscillating element in the applicator surface, through which an optical fiber of the light-supplying unit is guided.
  • This measure now has the advantage that light and ultrasound are emitted spatially close to one another from the applicator surface, as a result of which a suitable superimposition of light and ultrasound on the radiation side is achieved directly in front of the applicator surface.
  • This in turn has the advantage that the applicator surface can be brought close to the body tissue and the emitted light and the ultrasound overlap optimally in the entire treatment area, so that the effect of the ultrasound, which has a positive influence on the photodynamic therapy, in as large an area of the body tissue as possible 10
  • the oscillating element can be designed with a central bore or opening in which the exit surface of the light guide is arranged.
  • the ultrasound emerges from the applicator surface in a slightly focused manner.
  • This measure has the advantage that the focusing achieves a better depth effect of the ultrasound.
  • Slightly focused means that the ultrasound is not focused on a point, but rather on a flat or spatial focus area in the body tissue in order to allow the ultrasound to act in a specific area of the body tissue.
  • the at least one oscillating element has a geometry on the radiation side, through which the ultrasound is emitted in a slightly focused manner.
  • Focusing the ultrasound through the geometric configuration of the oscillating element has the advantage that no ultrasound-refractive elements have to be switched into the beam path of the ultrasound.
  • the ultrasound additionally serves for the thermal coagulation of the body tissue.
  • the aforementioned focusing is also used so that in addition to the purely mechanical effect of ultrasound, which causes an improved diffusion of the photosensitizer into the tissue, there is also a deeply effective thermal treatment of the tissue. Tissue coagulation in different tissue depths is possible via appropriately focused power ultrasound, which supports the phototoxic destruction of the tissue area to be treated.
  • an additional coagulation effect is achieved by coupling in high-power laser light, e.g. achieved via the existing light guide system, or by combination with HF current or microwave application.
  • an image transmission unit which transmits fluorescent light emanating from the body tissue into an image recording unit which receives the fluorescent light for evaluation and reproduction by an image reproduction unit.
  • the duration of the photodynamic therapy can be controlled or monitored by detecting the fluorescence.
  • the image transmission unit has an image-transmitting optical arrangement, for example a lens system, which transmits the fluorescent light from the applicator into the image recording unit.
  • an image-transmitting optical arrangement for example a lens system, which transmits the fluorescent light from the applicator into the image recording unit.
  • This measure has the advantage that an endoscopic visual inspection of the treatment area is made possible for the doctor at the same time.
  • this system can preferably also be reduced to a one-dimensional, non-imaging system, i.e. for example, on an optical fiber that receives light distally and transmits it proximally, for example, feeds it to a spectrometer. As long as the spectrometer detects fluorescent light, the PDT can be continued (spectral feedback for PDT control).
  • the applicator has an imaging unit that determines depth-dependent information from the radiation area of ultrasound and light.
  • the sono-photodynamic therapy carried out with the device according to the invention possibly also combined with another therapy method (high frequency, thermotherapy, cryotherapy) - is simultaneously controlled by means of a rapid imaging method 13
  • the depth effect of the therapy can be visualized, while only the superficial effect of light and ultrasound can be described using the aforementioned endoscopic image.
  • the imaging unit in the applicator has at least one ultrasound element which operates according to the pulse-echo method, which generates ultrasound in the diagnostic power range, couples it into the body tissue and in turn detects the reflected ultrasound information.
  • the ultrasound pulse-echo method with miniaturized ultrasound transducers which generate ultrasound with frequencies above 1 MHz, is particularly suitable as an imaging method for endoscopic implementation in order to obtain the corresponding resolution.
  • the one-dimensional A-mode or the two-dimensional B-mode is suitable as an image representation of the depth-dependent tissue information.
  • the imaging unit in the applicator has a unit which operates according to the optical coherence method, which couples coherent light pulses, which are generated by at least one superluminescence diode, into the tissue and in turn detects the reflected light information and reproduces it as an image signal.
  • optical coherence tomography is also suitable as an endoscopic protective image method.
  • the method has a lower one compared to the ultrasonic method 14
  • both the one-dimensional A-mode and the two-dimensional B-mode are suitable for image display.
  • the light pulses generated preferably have wavelengths of at least 60 nm.
  • a suction device is provided for sucking the body tissue onto the applicator surface.
  • This measure has the advantage that the body tissue is fixed on the applicator surface, as a result of which the light and the ultrasound can be optimally radiated into the body tissue. Furthermore, the suction of the body tissue has the advantage that the treatment area in the body tissue is fixed in terms of distance. The ultrasound can thus be coupled into the body tissue in a targeted and controlled manner because the distance between the exit surface of the ultrasound from the applicator surface and the body tissue is defined. Another advantage of suction is that the body tissue to be treated is not displaced when the applicator is brought up to the body tissue, but rather is drawn vice versa into the coupling area of the ultrasound, so that as much tissue as possible is captured by the light and by the ultrasound and the area of action is thus is enlarged.
  • the suction device has at least one suction channel which opens into the applicator surface and which is connected to a suction device. 15
  • suction of the body tissue onto the applicator surface can be achieved in an advantageously simple manner, which also has the advantage that the suction power can be adjusted, for example by means of a regulator on the suction device, in order to adapt the suction effect to the respective flexibility of the body tissue to be treated adapt.
  • the suction channel is guided through the opening in or next to the at least one oscillating element.
  • This measure has the advantage that the suction of the body tissue can be provided in a central region of the applicator surface, whereby a uniform suction of the body tissue on the applicator surface is achieved.
  • the applicator surface is curved inwards.
  • This measure has the advantage in connection with suction that the body tissue can be partially or completely sucked into the bulge. This is particularly advantageous in the treatment of soft tissue, since soft tissue has a high degree of flexibility, so that such soft tissue can be sucked well into the bulge.
  • Another advantage of the curved applicator surface is that it can cause the ultrasound to focus due to geometry.
  • a suction and rinsing line for a fluid opens into the applicator surface.
  • This measure has the advantage that the treatment area of the body tissue can be rinsed during the photodynamic therapy and degenerated tissue degraded by the photodynamic therapy can be suctioned off.
  • the suction and rinsing line is guided through the opening in or next to the oscillating element.
  • This measure in turn has the advantage that the introduction of the fluid for rinsing the treatment area and the suction of the fluid and of degraded body tissue can preferably take place in the center of the applicator surface and thus preferably also uniformly.
  • a seal is provided on the edge of the applicator surface.
  • This measure has the advantage in particular in connection with suction of the body tissue on the applicator surface that the suction effect for suctioning the body tissue can be improved.
  • this measure has the advantage that the fluid can be held securely in the area between the applicator surface and the body tissue.
  • the edge seal is designed as a suction device. 17
  • edge-side seal itself represents a peripheral suction system, which completely surrounds the application-side surface of the oscillating element.
  • suction has only a full peripheral effect and at the same time seals the area of application between the surface of the oscillating element and the tissue surface to the outside, so that a fluid medium in which e.g. the photosensitizer is contained, can be held between the surface of the vibrating element and the tissue surface and serves as a coupling medium for the ultrasound transmission.
  • a coupling medium which is permeable to ultrasound and light is arranged on the distal side of the applicator surface.
  • This measure has the advantage that ultrasound and light can be coupled into the body tissue without loss or with only a slight weakening.
  • the coupling medium contains scattering elements that cause diffuse scattering of light.
  • the coupling medium effects a focusing of the ultrasound.
  • This measure has the advantage that in the case of focusing that is not already brought about by the geometric configuration of the oscillating element, the ultrasound can be focused using simple means.
  • the coupling medium consists of a structured glass, a glass ceramic, a gel or of silicone with scattering particles.
  • These coupling media are suitable agents in the form of solid bodies or substances similar to solid bodies in order to cause diffuse scattering of the light.
  • the coupling medium is a fluid that contains scattering particles.
  • a fluid as a coupling medium, in which scattering particles are contained, has the advantage that the fluid can be used on the one hand as a rinsing liquid and on the other hand causes diffuse scattering of the incident light.
  • Another advantage of using a fluid as the coupling medium is that the photosensitizer or the precursor thereof can be added to the fluid, which then diffuses into the tissue to be treated accelerated under the action of ultrasound. This has the further advantage that the photosensitizer or precursor does not have to be administered to the patient beforehand. This saves time-consuming preparation of photodynamic therapy. 19
  • the fluid is led to the applicator surface by means of the suction and rinsing line and is then sucked off again.
  • This measure has the advantage that continuously new fluid can be brought into the area between the applicator surface and the tissue surface, whereby on the one hand cooling of the tissue surface is achieved and on the other hand photosensitizer can be continuously fed into the coupling area so that a sufficient amount of photosensitizer is added to it Tissue can diffuse.
  • the coupling medium contains a photosensitizer or a precursor of the photosensitizer.
  • the admixture of a precursor in the coupling medium has the advantage that the light-induced reaction does not already occur in the coupling medium, but only in the tissue, where the photosensitizer is produced from the precursor.
  • the applicator surface is designed such that light and ultrasound are emitted laterally in the longitudinal direction of the applicator.
  • This measure has the advantage that overall a larger applicator area is formed and thus a larger area of the tissue can be treated with light and ultrasound, because such an applicator area can be extended over an extended area in the longitudinal direction of the applicator.
  • Another advantage of this measure is that malignant tissue in tubular hollow organs, such as the intestine, esophagus, etc., can be treated.
  • the applicator can then be inserted into such hollow organs, and the hollow organ wall in which the malignant tissue is contained can then be treated by the laterally emerging ultrasound and the laterally emerging light.
  • the light and / or the ultrasound is irradiated laterally from the applicator into the tissue via a light and / or ultrasound deflecting, for example reflecting, element.
  • the light and the ultrasound can be fed in the longitudinal direction of the applicator and then coupled laterally out of the applicator into the tissue via the beam-deflecting element, for example a reflector in the form of a metal mirror.
  • the beam deflecting element simultaneously creates a superimposition of light and ultrasound.
  • the beam-deflecting element is preferably positionally adjustable, preferably from the proximal end of the applicator, so that by adjusting the position of the light and / or ultrasound deflecting element, the light and the ultrasound can be moved overlapping one another over an extensive treatment area.
  • Another advantage is that the direction of radiation of light and ultrasound can be specifically adjusted or readjusted to a treatment area, especially if the treatment area is difficult to access due to anatomical conditions and a change in position of the applicator is not possible at all or only with difficulty.
  • the ultrasound has a frequency of more than 20 kHz and / or an energy density in the range of at least 50 mW / cm 2 .
  • the photodynamic therapy can be improved in a particularly effective manner by the application of ultrasound.
  • the applicator is designed as an endoscope.
  • This measure has the advantage that the photodynamic therapy with simultaneous application of ultrasound can be carried out minimally invasively under endoscopic control.
  • the applicator is designed as an endoscopic catheter.
  • An endoscopic catheter does not necessarily have an image relay system.
  • a catheter with light and ultrasound emitting functions can be positioned, for example, under external X-ray, MR, CT or ultrasound control and can treat the corresponding tissue.
  • a further position control of the correct position of the catheter and the light / ultrasound-radiating area can be carried out, for example, by means of the fiber optic measurement of the fluorescence of the tissue area enriched with the photosensitizer, as already previously in connection with an embodiment of the 22
  • the applicator surface is arranged in the distal area of the endoscope or the endoscopic catheter.
  • Figure 1 shows an inventive device for the treatment of body tissue in a schematic overall view.
  • FIG. 2 shows a longitudinal section through the distal end of the applicator of the device in FIG. 1 according to a first exemplary embodiment
  • FIG. 3 shows the distal end of an applicator of the device in FIG. 1 according to a second exemplary embodiment in a longitudinal section along the line III-III in FIG. 4;
  • Figure 4 is a front view of the distal end of the applicator in Figure 3;
  • FIG. 5 shows the distal end of an applicator according to a further exemplary embodiment for use in the device in FIG. 1 in longitudinal section;
  • FIG. 6 shows the distal end of an applicator according to a further exemplary embodiment in longitudinal section
  • Fig. 7 shows the distal end of an applicator according to another embodiment in longitudinal section.
  • reference numeral 10 overall shows a device for treating body tissue, in particular soft tissue, by means of a reaction which is light-induced by a photosensitizer contained in the body tissue.
  • the device 10 is used in photodynamic therapy in which the degenerated body tissue, for example tumor tissue, in which the photosensitizer is enriched in increased concentration, is destroyed by a phototoxic effect.
  • the device 10 has an applicator 12.
  • the applicator 12 is designed as an endoscope 14, which has an endoscope shaft 16 and an endoscope optics 18.
  • the endoscope shaft 16 can be guided through an incision artificially created on the human body or through a natural body walk to the body tissue to be treated in the human body.
  • the device 10 furthermore has a light-supplying unit 20.
  • the light supply unit 20 comprises a light source 22 which generates light in a wavelength range suitable for photodynamic therapy with a suitable intensity.
  • the wavelength range suitable for photodynamic therapy depends on the photosensitizer used.
  • a broadband light source or even a white light source is preferably used, but inexpensive diode lasers which emit in the red or infrared spectral range can also be used.
  • the light generated in the light source 22 is guided into the applicator 12 via a light guide 24 and a light guide connection 26.
  • the light generated by the light source 22 is guided further to the distal end of the applicator 12 or endoscope 14, where it emerges from an applicator surface 28, directed flatly onto the body tissue.
  • the light guide 24 has at least one optical fiber, for example a quartz fiber.
  • the applicator surface 28 is shown arranged on the end face at the distal end of the applicator 12, it goes without saying that the applicator surface is also proximally in 25th
  • the endoscope shaft 16 can be arranged offset, or that the applicator surface 28 is designed such that the light and ultrasound, as will be described in more detail later, are emitted laterally from the circumferential surface of the endoscope shaft 16.
  • the device 10 has an ultrasound generation unit 30.
  • the ultrasound generating unit 30 comprises a control unit 32, from which an electrical line 34 is guided through a connection 36 into the endoscope 14.
  • a vibrating element of the ultrasound generating unit 30 (not shown in FIG. 1 and explained later), for example a piezoceramic ultrasound transducer, which generates ultrasound in the therapeutic power and frequency range and is accordingly electrical by the control unit 32 is excited.
  • the therapeutic ultrasound generated likewise emerges from the applicator surface 28 at the distal end of the endoscope 14, in such a way that the radiation areas of ultrasound and light overlap at least partially in the body tissue.
  • the applicator 12 can also be designed as an endoscopic catheter instead of in the form of the endoscope 14. Both in the endoscope 14 and in the configuration of the applicator 12 in the form of an endoscopic catheter, the applicator surface 28 is arranged in the distal region of the endoscope 14 or the endoscopic catheter. In the event that the applicator 12 is designed as an endoscopic catheter, the catheter can be positioned under external X-ray, MR, CT or ultrasound control and the body tissue 14 can be treated. 26
  • the device 10 further comprises an image recording unit 38, with which light emanating from the body tissue, essentially fluorescent light, which is transmitted from the distal end of the endoscope 14 via the endoscope optics 18, is recorded.
  • the image recording unit 38 comprises a video camera 40 connected to the endoscope optics 18, which in turn is connected to an image display unit 42, for example a screen, in which the output signal of the video camera 40 is processed and displayed.
  • the distal end of the endoscope shaft 16 is shown on an enlarged scale in longitudinal section.
  • a light guide 44 is guided in the endoscope shaft 16 up to the applicator surface 28.
  • the light guide 44 has at least one optical fiber, for example quartz fiber.
  • the light guide 44 is connected to the light guide 24 and thus to the light source 22.
  • the light generated by the light source 22 is guided through the light guide 44 to the applicator surface 28, exits there with a relatively large aperture, for example> 20 °, and penetrates into the body tissue shown in FIG. 2 and designated 46 with a penetration depth of a few mm, as indicated by dash-dotted arrows 48.
  • a fluorescence induced by the irradiation of the light in the body tissue 46 and by the photosensitizer that has been introduced into the body tissue 46 is transmitted from an image-transmitting optical arrangement 50, for example an image guide bundle or a relay lens system, to the endoscope optics 18 and via the video camera 40 Image display unit 27
  • the fading of the photosensitizer, which is associated with the destruction of the degenerated body tissue 46, can be observed over the course of the intensity of the fluorescent light over time. In this way, it can be determined how far the process of breaking down the body tissue 46 has progressed.
  • the fluorescent light emanating from the body tissue 46 is indicated by an arrow 49 with a broken line.
  • a vibrating element 52 is arranged in the applicator surface 28 and is connected to the control unit 32 via an electrical line 54 and via the electrical line 34.
  • the vibrating element 52 for example a piezoceramic vibrator, is electrically excited by the control unit 32 to generate ultrasound in the therapeutic power and frequency range.
  • the ultrasound is radiated from the vibrating element 52 from the applicator surface 28 into the body tissue 46, as indicated by broken lines 56.
  • the light emerging from the light guide 44 and the ultrasound emerging from the vibrating element 52 overlap in a spatially extended area.
  • the light guide 44 has optics at its distal end through which the light is emitted at an angle to the longitudinal axis, so that the light and the ultrasound overlap in the largest possible radiation area.
  • the optical arrangement 50 has an oblique view optics at its distal end in order to be able to receive as much fluorescent light as possible from the ultrasound and light irradiation area.
  • the applicator 12 has an imaging unit, not shown in more detail, which determines depth-dependent information from the radiation area of ultrasound and light.
  • the imaging unit has in the applicator 12 at least one ultrasound element operating according to the pulse-echo method, which generates ultrasound in the diagnostic power range, preferably with frequencies above 1 MHz, couples it into the body tissue 46 and in turn detects the reflected ultrasound information.
  • the imaging unit in the applicator 12 has a unit which operates according to the optical coherence method and which couples coherent light pulses, which are generated by a superluminescence diode, preferably with a wavelength of more than 600 nm, into the tissue and the reflected light information is again acquired and reproduced as an image signal.
  • FIGS. 3 and 4 show a further exemplary embodiment, modified compared to FIG. 2, which shows the distal end of the endoscope shaft 16 in FIG. 1.
  • an applicator surface denoted by 60 is curved inwards. As can be seen from FIG. 3 in connection with FIG. 4, the applicator surface 60 has a spherical cap configuration. From the applicator surface 60, light supplied via an optical fiber 62 and generated in the light source 22 in FIG. 1 emerges. 29
  • An optical arrangement 64 in turn transmits light coming from the body tissue to the endoscope optics 18 and from there via the video camera 40 into the image display unit 42 in FIG. 1.
  • An electrically excitable oscillating element 66 which is connected to the control unit 32 via an electrical line 65, is arranged in the applicator surface 60.
  • the vibrating element 66 is formed by a round piezoceramic vibrator, as can be seen in FIG. 4. Approximately in the middle, the vibrating element 66 has an opening or bore through which the distal end of the light guide 62 and the optical arrangement 64 is guided.
  • the ultrasound generated by the vibrating element 66 in the therapeutic power and frequency range experiences a " geometrical focusing " due to the geometrical configuration of the vibrating element 66 on the radiation side, which is adapted to the spherical cap-shaped configuration of the applicator surface 60, so that the generated ultrasound is focused on a focus area F is radiated concentrated, as indicated by broken lines 67.
  • a coupling medium 70 is also arranged in front of the applicator surface 60.
  • the coupling medium 70 is geometrically adapted to the geometry of the applicator surface 60.
  • the coupling medium 70 is not shown in FIG. 4.
  • the coupling medium 70 is permeable to ultrasound and causes diffuse scattering of the light emerging from the distal end of the light guide 62.
  • the diffuse scattering of the light is indicated in FIG. 3 with dash-dotted arrows 72.
  • the diffuse scattering causes the light to shine evenly into the body tissue.
  • a large-area radiation of the light into the body tissue is achieved.
  • a suction device which has a suction channel 74 which opens into the applicator surface 60 and which is connected on the proximal side to a suction device 76 shown in FIG. 1.
  • the suction channel 74 serves to suck the body tissue to be treated into the bulge of the applicator surface 60, at least partially, but as completely as possible.
  • a corresponding opening 78 is provided in the coupling medium 70.
  • a suction and rinsing line 80 for a fluid is provided, which is connected to a suction and rinsing device 82 shown in FIG. 1.
  • a fluid can be introduced into the coupling area between body tissue and applicator surface 60 or coupling medium 70 in order to cool the body tissue, which can heat up through the application of ultrasound, the coupling of light and ultrasound to improve in the tissue and / or to introduce into the tissue photosensitizer or a precursor thereof contained in the fluid.
  • body tissue that has been broken down during the photodynamic therapy can be suctioned off through the suction and rinsing line 80.
  • suction channel 74 and the suction and rinsing line 80 for the fluid are separate lines in FIG. 3, as indicated by a broken line 79, it can also be provided to provide only one line as a whole, which is then used both for suctioning the body tissue as well as for sucking and flushing the operating area.
  • several suction channels can also be provided for sucking in the body tissue 31
  • a seal 86 is arranged circumferentially on an edge 84 of the applicator surface 60 in order to seal the applicator surface 60 against the body tissue at the edge.
  • the seal 86 is designed, for example, in the form of a sleeve made of an elastic material, for example as a sealing lip.
  • a sealing of the applicator surface 60 can, however, also be achieved by the edge 84 itself being made elastic. 4, the seal 86 is not shown.
  • a photosensitizer which has, for example, a hematoporphyrin backbone, or delta-aminolevulinic acid (ALA) as a precursor of the fluorescent protoporphyrin IX, is administered to the patient beforehand.
  • ALA delta-aminolevulinic acid
  • Hematoporphyrin derivatives can be administered intravenously.
  • the applicator 12, i.e. the endoscope shaft 16 of the endoscope 14 in FIG. 1 is guided through an artificially created incision or through a natural body path to the body tissue to be treated, the applicator surface 28 or 60 being brought as close as possible to the body tissue.
  • the body tissue to be treated is radially irradiated by means of light generated by the light source 22 through the light guide 44 in FIG. 2 or light guide 62 in FIG. 3.
  • Therapeutic ultrasound generated by the vibrating element 52 in FIG. 2 or vibrating element 66 in FIG. 3 is superimposed on the light thus irradiated, ie the radiation areas of light and ultrasound in the body tissue at least partially overlap.
  • the ultrasound has an energy density in the range of 50 mW / cm 2 and above and a frequency of 20 kHz and more.
  • the ultrasound which is additionally radiated into the body tissue now causes the photosensitizer to be distributed more rapidly in the cells of the body tissue to be treated, or is transported better through the cell walls. As a result, the light energy required for the photodynamic therapy of the light generated by the light source 22 can be reduced and the duration of the photodynamic therapy can also be reduced.
  • Fluorescence light emitted by the photosensitizer in the body tissue is evaluated in the image display unit 42 during the therapy via the image recording unit 38 in order to control the respective stage of the therapy.
  • the image display unit 42 can also be coupled to the light source 22 in such a way that the energy of the light generated by the light source 22 is correspondingly reduced by the decrease in fluorescence.
  • the decrease in fluorescence follows 33
  • the therapy is controlled with the previously described imaging unit, which enables a rapid imaging method.
  • the depth effect of the therapy can be visualized, while the endoscopic image is used to describe the superficial effect.
  • the ultrasound pulse echo method with ultrasound frequencies of over 1 MHz is used as the imaging method in order to obtain a correspondingly high resolution.
  • the one-dimensional A-mode or the two-dimensional B-mode is suitable for the image display of the depth-dependent tissue information.
  • optical coherence tomography can also be used as an endoscopic quick image method.
  • one or more superluminescent diodes generate coherent light pulses with wavelengths of 600 nm and above, which are injected into the tissue, the reflected light information again being recorded and reproduced as an image signal.
  • the body tissue to be treated is also sucked into the bulge towards the applicator surface 60. Furthermore, the ultrasound is irradiated onto the focus area F in a slightly focused manner in order to achieve a better depth effect of the ultrasound. At the same time, a fluid is passed through the suction and irrigation line 80 into the coupling space between the body tissue and the applicator surface 60, more precisely the inside of the coupling medium 70, in order to do this 34
  • FIG. 5 shows the distal end of an applicator 90 as a further exemplary embodiment, which is used instead of the applicator 12 in the device 10 in FIG. 1.
  • a vibrating element 92 is arranged as part of the ultrasound generating unit 30 in FIG. 1, specifically in an applicator surface 94, which in this case is formed by the surface of the vibrating element 92 itself on the radiation side.
  • the vibrating element 92 is round.
  • a hole or opening 96 is formed approximately centrally in the oscillating element 92, through which the distal end of a light guide 98 is guided as part of the light-supplying unit 20 in FIG. 1.
  • a wall 100 of the applicator 90 is double-walled, with an outer wall 102 and an inner wall 102, between which the wall 100 defines a cavity 106, which is connected to the suction device 76 in FIG. 1, for tissue 108 to the applicator 90 suck.
  • the suction acts peripherally over the entire circumference of the applicator 90.
  • a seal 110 in the form of sealing lips 112 provides a corresponding seal of the surface of the tissue 108 against the distal end of the applicator 90.
  • the suction of the tissue 108 or the suction effect is indicated by an arrow 111 and an arrow 113.
  • a fluid coupling medium 114 can be brought via a feed line 116 according to an arrow 117 and can be sucked out of this area again via a discharge line 118 by a discharge line 118 according to an arrow 119.
  • Scattering particles are contained in the coupling medium 114, which cause a diffuse scattering of the light radiated through the light guide 98.
  • the coupling medium 114 is permeable to the ultrasound emitted by the oscillating element 92.
  • the feed line 116 and the discharge line 118 can be connected to the suction and rinsing device 82 shown in FIG. 1.
  • the coupling medium 114 can be continuously circulated in the manner of a circulation circuit by means of the suction and rinsing device 82 in FIG. 1, the coupling medium 114 also being admixed with the photosensitizer or a precursor thereof, which then also enters the area between the surface of the fabric 108 and the applicator surface 94 is brought and can diffuse into the tissue 108, which is accelerated under the action of the ultrasound.
  • FIG. 6 shows the distal end of an applicator 120 as a further exemplary embodiment, which in turn is used in the device 10.
  • the applicator 120 has a vibrating element 122 as well as a light guide 124 and a light guide 126.
  • an applicator area is defined by the areas 128, 130, 132. This applicator surface is designed such that the ultrasound and the light in the longitudinal direction of the applicator 120 are laterally irradiated into a tissue 134 to be treated.
  • a coupling medium 136 which is in turn a fluid and can be brought between this applicator surface and the tissue 134 via a supply line 144 and a discharge line 146 and then suctioned off again, causes diffuse scattering and thus a flat radiation of the light into the tissue 134 .
  • a window 140 is formed in the applicator 120 in a wall 138, through which ultrasound and light are irradiated into the tissue 134.
  • a seal 142 in the form of a sealing lip is formed on the edge of the window 140.
  • the applicator 120 is used, for example, for the photodynamic treatment of tissue 134 in the wall of a hollow organ, for example the intestine or the esophagus.
  • FIG. 7 Another exemplary embodiment of an applicator 150 is shown in FIG. 7, in which ultrasound and light are also irradiated laterally from the applicator 150 into tissue not shown in FIG. 7. 37
  • a light guide 152 for supplying light from the light source 22 shown in FIG. 1 and a vibrating element 154 are arranged in the distal region of the applicator 150.
  • the beam-deflecting element 156 is preferably arranged in a position-adjustable manner in the applicator 150, for example pivotably.
  • an applicator surface 157 is defined by the reflecting surface of the light and / or ultrasound deflecting element.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Radiation-Therapy Devices (AREA)
  • Laser Surgery Devices (AREA)

Abstract

Un dispositif pour le traitement de tissu humain, notamment de tissu mou, au moyen d'une réaction photo-induite par un photosensibilisateur introduit dans le tissu humain, comporte une unité acheminant la lumière (20) et un applicateur (12) d'où sort la lumière dirigée sur le tissu humain. L'applicateur (12) présente dans sa région distale une surface (28) d'où sort la lumière. Une unité ultrasonore (30) produit des ultrasons de haute intensité qui sortent également de la surface d'applicateur (28) de telle manière que les régions d'exposition à rayonnement ultrasonore et lumineux se chevauchent au moins partiellement dans le tissu humain.
PCT/EP1999/001155 1998-02-23 1999-02-23 Procede pour le traitement photodynamique de tissu humain WO1999042179A1 (fr)

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DE19807583.9 1998-02-23
DE1998107583 DE19807583C1 (de) 1998-02-23 1998-02-23 Vorrichtung zur Behandlung von Körpergewebe, insbesondere Weichgewebe, mittels einer durch einen in dem Körpergewebe enthaltenen Photosensibilisator lichtinduzierten Reaktion

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WO1999042179A1 true WO1999042179A1 (fr) 1999-08-26

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DE10343808A1 (de) * 2003-09-22 2005-05-04 Siemens Ag Medizinisches Untersuchungs- und/oder Behandlungssystem
WO2006022970A1 (fr) * 2004-07-22 2006-03-02 Ondine International Ltd. Traitement sonophotodynamique pour applications dentaires
RU2433785C1 (ru) * 2010-03-15 2011-11-20 Валерий Викторович Педдер Устройство для термо- и фотохромо-ультразвуковой обработки биотканей
RU2496537C2 (ru) * 2011-07-26 2013-10-27 Валерий Викторович Педдер Устройство для термо- и фотохромо-ультразвукового лечения остеоартрозов
EP2527828A4 (fr) * 2010-01-18 2017-08-16 Humanscan Co., Ltd. Sonde à ultrasons

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DE10220849A1 (de) * 2002-05-08 2003-11-27 Forschungszentrum Juelich Gmbh Vorrichtung und Verfahren zur fluorimetrischen Erfassung von Substanzen in Medien

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10343808A1 (de) * 2003-09-22 2005-05-04 Siemens Ag Medizinisches Untersuchungs- und/oder Behandlungssystem
US7289842B2 (en) 2003-09-22 2007-10-30 Siemens Aktiengesellschaft System for medical examination or treatment
DE10343808B4 (de) * 2003-09-22 2017-06-01 Siemens Healthcare Gmbh Medizinisches Untersuchungs- und/oder Behandlungssystem
WO2006022970A1 (fr) * 2004-07-22 2006-03-02 Ondine International Ltd. Traitement sonophotodynamique pour applications dentaires
EP2527828A4 (fr) * 2010-01-18 2017-08-16 Humanscan Co., Ltd. Sonde à ultrasons
RU2433785C1 (ru) * 2010-03-15 2011-11-20 Валерий Викторович Педдер Устройство для термо- и фотохромо-ультразвуковой обработки биотканей
RU2496537C2 (ru) * 2011-07-26 2013-10-27 Валерий Викторович Педдер Устройство для термо- и фотохромо-ультразвукового лечения остеоартрозов

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