HK1152001B - Light coupling adapter device for photodynamic or photothermal therapy or photodynamic diagnosis, corresponding system and method - Google Patents

Abstract

A system configured for photodynamic or photothermal therapy and photodynamic diagnosis of a tissue is 5 disclosed. The system comprises in combination an assembly of: a proximal end adapter for a catheter comprising an adapter body (32), having proximal and distal ends, defining an axial lumen extending between the proximal and distal ends, a catheter mounting element at the distal end of the adapter body (32) for sealingly mounting a catheter to the adapter body, and a hollow catheter (31), wherein the catheter mounting element connects a catheter body to the hollow catheter so that the hollow catheter extends from the distal end of the catheter body; a first light 15 guide (36) having proximal and distal ends, wherein said first light guide is sealingly contained in said axial lumen defining an axial optical path extending between the proximal and distal ends of the adapter body (32) towards said tissue (8) and into close proximity thereof or 20 interstitially into said tissue; an optical connector mounting element at the proximal end having mounted an optical connector (37) to the adapter body, and wherein said optical connector (37) is coupled to a light source via a second light guide (38), such that light from said 25 light source is transmittable from said light source via said second light guide (38) and further via said optical connector (37) to said first light guide (36) via said proximal end adapter towards said tissue (8) through said catheter (31).

Description

Optocoupler adapter device for photodynamic or photothermal therapy or photodynamic diagnosis, corresponding system and method

Technical Field

The present invention relates to a system for interactive interstitial photodynamic or photothermal therapy and/or tissue diagnosis by means of a device having at least one therapeutic or diagnostic light source, e.g. a laser radiation source, and at least one radiation conductor, e.g. an optical waveguide in the form of an optical fiber, for transmitting light between the tissue and the device, e.g. from laser radiation to the tissue, and an optical coupler adaptation mechanism for conveniently connecting an optical path, e.g. above the laser source, including the optical fiber between the tissue and the device.

Background

Systems and methods for therapy and diagnosis using interactive interstitial photodynamic tumour therapy (PDT) and/or Photothermal Tumour Therapy (PTT) and photodynamic diagnosis (PDD) are disclosed in WO 03/041575. The system includes a plurality of optical fibers inserted directly into the interstitium of a selected tissue to be treated and/or diagnosed, such as a cancerous tissue.

In WO03/041575 it is disclosed that for diagnosis a diagnostic laser source is connected to one of the fibres as a diagnostic transmission fibre for transmitting diagnostic laser light into the tissue. The remaining fibers act as receivers for light transmitted from the distal end of the diagnostic transmission fiber through the tissue to the distal end of the remaining fibers and on to the detector. Each fiber is used in succession as a transmitter, while the remaining fibers act as receivers. By calculation, tomographic images of certain properties of the tissue can be obtained, such as fluorescence properties caused by certain sensitizers.

In addition, WO03/041575 discloses that the same system can be used in therapy, whereby light is transmitted simultaneously through all optical fibers to the tissue for activation of an agent, such as a sensitizer located in tumor cells. By treatment, the cells are eradicated and the tissue becomes necrotic. Also, it is disclosed that the system can be used as a photothermal therapy, including transmitting radiation through an optical fiber, which heats the tissue sufficiently and kills tumor cells. It is noteworthy that tumor cells may be more sensitive to heat than other cells.

In the diagnostic and therapeutic system of WO03/041575, optical fibres are used, which are inserted directly into the interstitium to be treated. Agents that will be activated or sensitized can be delivered to the tissue by systemic administration, for example, intravenously or orally, and accumulated in the relevant tissue by any mechanism. The remaining agents are usually removed by body action, for example through the liver or kidneys, which places a considerable burden on these organs or systems.

Another method of providing an agent to tissue is to inject a substance directly with a needle and syringe, which is applicable when the location of the tissue to be treated is well-defined and known.

The agent may also be applied topically to the skin, and therefore iontophoresis techniques may be used to improve delivery of the agent into the relevant tissue. Here, the current is generated by electrodes arranged in a suitable manner, and the reagent transfer is performed by the current, depending on the ionic properties of the reagent.

In the PDT/PTT and PDD described above, the optical fiber is inserted directly into the interstitium to be diagnosed/treated, i.e. the distal end of the optical fiber, which is connected at its proximal end to a radiation generator, is stuck into the tissue, exhibiting interstitial distribution therein. However, this distribution has some drawbacks. For example, the fibers, or at least the distal ends thereof, must be sterilized between subsequent treatments or patients. However, sterilization methods often deteriorate the optical properties of the fiber, for example, solvents are aggressive when using plastic fibers or residues are left on the surface of the optical fiber after sterilization or disinfection. Alternatively, the patient-contaminated fibers can be discarded, but this is costly. When the distal end of the fiber is inserted through the lumen of the cannula, it sticks to the tissue to be treated/diagnosed, where leakage may need to be noted. Also, in case a drug needs to be delivered to the tissue during treatment, e.g. in order to increase the amount of sensitizer in the tissue, it would be convenient if the same route as the fibres could be used to get the drug into the tissue. While additional syringes are currently used to pierce the tissue, this can cause inconvenience and injury to the patient, for example, increasing the chance of infection and blood loss. Therefore, there is a need to provide a convenient way to interstitial PDT/PTT and PDD into the body, thereby creating a minimum number of entry points by providing easy access to the tissue from the outside, either at the time of treatment/diagnosis or between repetitions of the same treatment/diagnosis. In addition, there is also a need to provide a more cost effective way of disinfecting between treatments or patients.

Some attempts to solve these problems will be described below. However, to date, these attempts have not been successful.

EP 523417 discloses a system in which a radiator can be inserted into a sleeve so that the surrounding tissue is radiated, and a sensor can be introduced into another sleeve to determine the radiation effect.

US 5,454,794 discloses a steerable light-scattering catheter. More particularly, steerable catheters are disclosed that can treat luminal surfaces, such as those in the vascular tree (vascular tree), pulmonary artery tree (pulmonary tree), gastrointestinal tract, urinary organs, and the like, with photodynamic therapy (PDT) or other light scattering treatment methods. The catheter has a light scattering tip that can be deflected to enable precise steering of the catheter. A light scattering tip on a steerable catheter can enter the luminal system to be treated. The catheter does not require a guide lumen for insertion, thereby reducing the size. Such a small form factor device is capable of delivering process light to the walls of the most distal small diameter lumen. However, US 5,454,794 is not suitable for photodynamic diagnosis. Also, the catheter of US 5,454,794 is not capable of interstitial insertion and is only capable of endoluminal delivery. Direct percutaneous insertion into a tumor, for example a tumor close to the skin, is not possible with such catheters. Partly because of their flexible design and are not suitable for this purpose.

US 5,304,171 also discloses a catheter apparatus and method for delivering laser energy to the body. An apparatus for delivering laser energy to a body part is disclosed, comprising: a flexible tube, a liquid, means for providing a flow of liquid into the tube, and a laser energy source, the tube having an opening at a first end through which the liquid can flow, the laser energy source being operatively connected to a second end of the tube, wherein, when the tube contains the liquid, the tube and the liquid cooperate to conduct laser energy from a laser source and emit a portion of the laser energy from the first end of the tube containing the liquid. According to the disclosed method, laser energy is conducted to a site by bringing a proximal end of a flexible tube into proximity with the site, introducing a liquid into the tube to fill at least the proximal end of the tube with the liquid, and flowing a portion of the liquid from the proximal end of the tube to the site, directing laser energy from a laser energy source into the distal end of the tube so that a portion of the laser energy exits the proximal end of the tube at the site. The liquid is for example a radiographic contrast medium. The method is used, for example, to remove an obstruction from a blood vessel of an animal.

The device of US 5,304,171 is neither suitable for photodynamic diagnosis nor photodynamic therapy. Also, the catheter of US 5,304,171 does not allow for inter-tissue insertion. In addition, direct percutaneous insertion into tumors, for example near the skin, is not possible with such catheters.

EP 1334748 discloses a device for photodynamic therapy. Light emitted by the implantable detector is used to illuminate a treatment site that has been perfused with a photoreactive agent. Various embodiments of implantable probes are disclosed. Preferably, an array of Light Emitting Diodes (LEDs) or solid state Laser Diodes (LDs) is mounted on a light bar inside the implantable probe and powered by using a battery power supply, an inductively coupled external transformer, or by using current supplied in leads running through a flexible catheter extending to an external power supply outside the patient. Implantable probes are typically placed at a treatment site within a patient during surgery and left for several days (or longer) after the incision is closed while the treatment site is irradiated by an array of LEDs or solid LDs. The device of EP 1334748 is not provided for photodynamic diagnosis. In addition, the inter-tissue insertion and removal of the probe must be performed surgically. And does not provide easy delivery of light to the tumor for short-term diagnosis and treatment.

WO2004/012589 discloses catheters and methods for diagnosing and treating diseased vessels. Catheters for detecting and treating diseased tissue in blood vessels or other hollow body organs are provided. The catheter includes an elongated tubular catheter shaft having a distal end including a light transmission region. A diagnostic optical fiber having a distal end and terminating in a light transmitting region is contained within a first fiber lumen in the catheter shaft for emitting and receiving light through the light transmitting region. A diagnostic subassembly, located at the proximal end and in communication with the diagnostic optical fiber, processes the diagnostic light for use in connection with a diagnostic method for detecting diseased tissue. A second fiber lumen may be provided in the catheter shaft containing a treatment optical fiber for transmitting treatment light from a light source located at the proximal end of the catheter shaft to the light transmission region. The treatment fiber has a distal end and terminates in a light transmission region for emitting light for treating diseased tissue. An occlusion balloon is disposed at the distal end of the catheter shaft proximal to the light transmission region and in fluid communication with the inflation lumen. One or more infusion ports formed on or near the light transmission region in fluid communication with the plenum chamber deliver infusion fluid into the hollow body organ.

The catheter of WO2004/012589 does not allow interstitial insertion. In addition, direct percutaneous insertion into tumors, for example near the skin, is not possible with such catheters.

The catheter devices described above are indeed not suitable for systems comprising a plurality of optical waveguides inserted into tissue, such as the system disclosed in WO03/041575 of the same applicant as the present application. WO03/041575 discloses systems and methods for interactive interstitial photodynamic and/or photothermal tumour therapy. The system includes a distributor for distributing radiation between the at least one radiation source and the reaction site, or between the reaction site and the at least one radiation sensor. A plurality of first radiation conductors are arranged to conduct radiation between the reaction sites and a plurality of second radiation conductors are arranged to emit radiation from the radiation source and/or to conduct radiation to the radiation sensor. The distributor comprises two planar discs mounted adjacent to each other, one fixed and the other rotatable relative to the first, each disc having holes arranged equidistantly on a circular line, the number of holes in the rotatable disc being several times the number of holes in the fixed disc. One end of the first radiation conductor is fixed on the hole of the fixed disc, and one end of the second radiation conductor is fixed on the hole of the rotatable disc.

Accordingly, there is a need to provide improved devices and methods that provide more advantageous access to tissue, interactive interstitial photodynamic or photothermal therapy and/or diagnosis of tissue, and in particular, devices and methods that are more advantageous in terms of increased flexibility, reduced cost, or user friendliness.

Disclosure of Invention

Accordingly, the present invention preferably seeks to mitigate, alleviate or eliminate one or more of the above-identified deficiencies in the art and disadvantages singly or in any combination and solves at least some of the above mentioned problems by providing a device, a system, a method and a use according to the appended patent claims.

It is an object of the present invention to provide a system in which at least one radiation conductor for photodynamic or photothermal therapy and/or diagnosis can be conveniently arranged.

The present invention provides a disposable unit for interstitial insertion of an optical fiber into tissue, wherein the disposable unit is configured as a system for interstitial photodynamic or photothermal therapy and/or diagnosis of the tissue, the disposable unit comprising the following components:

the optical fiber having a distal end and a proximal end;

a hollow needle in the form of a hollow cannula;

an adapter having a proximal end and a distal end defining a lumen extending axially therebetween, the lumen containing the optical fiber, the adapter configured to be mounted at the proximal end of the hollow needle, whereby the adapter is configured to position the optical fiber into the hollow needle, whereby the distal end of the optical fiber is disposed in a correct position towards the tissue; the adapter is further configured to connect the optical fiber at a proximal end to a primary fiber; and

wherein light can be coupled from the primary fiber to the optical fiber, whereby the optical fiber is arrangeable at its distal end to receive light from and/or transmit light to the tissue.

Wherein the hollow needle is made of metal.

Wherein the hollow needle is straight.

Wherein the adapter is mounted to the hollow needle by being inserted into the hollow needle.

Wherein the hollow needle with the adapter therein is disposed in a catheter with a cannula.

Wherein the optical fiber terminates before the distal end of the cannula, and wherein light emitted from the optical fiber propagates through the cannula before reaching the tissue.

Wherein the optical fiber extends out of the ferrule and whereby the optical fiber has a lens or taper disposed at the distal end of the optical fiber.

Wherein the optical fiber has an outer portion configured to be polished to scatter the emitted light.

Wherein the primary fiber is disposed in a screw lock connector for coupling to the optical fiber of the adapter.

Wherein the primary fiber is disposed in an optical contact configured to mate with the proximal end of the adapter.

The present invention also provides a method of installing the above-described disposable unit, comprising:

providing an adapter having a proximal end and a distal end defining a lumen extending axially therebetween, the lumen containing an optical fiber;

mounting the adapter at the proximal end of the hollow needle;

positioning the optical fiber in the hollow needle;

connecting the proximal end of the adapter to a distal end of a connector, thereby coupling the optical fiber of the adapter to a primary fiber of the connector.

Wherein the connector is a twist lock connector comprising the primary fiber, and further comprising:

connecting the adapter with the screw lock connector by mounting the hollow needle containing the adapter to the screw lock connector.

The method further includes disposing the hollow needle (111) containing the adapter (132, 230) in a catheter.

An example system of apparatus for photodynamic or photothermal therapy and/or diagnosis of tissue includes: at least one laser radiation source, at least one radiation conductor for conducting laser radiation to the tissue, and means for connecting the radiation conductor and the laser source. The system comprises: an arrangement for arranging the radiation conductors from the tissue to the organ, the arrangement comprising at least part of the radiation conductors. The arrangement may comprise a sleeve arranged from the tissue to the organ, such that the radiation conductor is insertable into the sleeve after the sleeve has been placed in the tissue. The system may further comprise a supply means for supplying an agent to said tissue via said arranging means. The cannula may have a port for providing the reagent. The supply device may be a syringe. A first cannula may be arranged from the tissue to a distribution plate of the mechanism and a second cannula may be arranged from the distribution plate to the laser source, the second cannula having a port for providing the reagent. The system may further comprise a pad containing said agent and being distributed at the skin adjacent to said tissue and forming a first electrode connected to a first potential, whereby a second potential is connected to an electrically conductive lining arranged on at least one radiation conductor, forming the current needed for iontophoretic introduction of said agent into said tissue. The conductive liner may be of metal, for example silver.

An example method for photodynamic or photothermal therapy and/or photodynamic diagnosis of tissue by the above apparatus comprises: at least one laser radiation source, at least one radiation conductor for conducting laser radiation to the tissue, and a mechanism for connecting the radiation conductor and the laser source. The method can comprise the following steps: placing the deployment device within the tissue such that the distal end thereof is within or adjacent to the tissue to be treated; inserting radiation conductors into the arranging means; and connecting the radiation conductor to the device. The method may further comprise supplying an agent to said tissue to be treated via the arranging means.

According to a first aspect of the present invention, a proximal end adapter for a catheter is provided. The adapter includes: an adapter body having a proximal end and a distal end defining an axial lumen extending therebetween, a catheter mounting element at the distal end of the adapter body for sealingly mounting a catheter to the body; an optical connector mounting element at the proximal end for mounting the optical connector to the adapter body; and an optical waveguide having a proximal end and a distal end, wherein the optical waveguide is sealed within the shaft lumen defining an axial optical path extending between the proximal end and the distal end of the adapter body. The proximal end adapter is configured for use in a system for interactive interstitial photodynamic or photothermal therapy and/or diagnosis of tissue.

An optical connector mounting element at the proximal end for mounting an optical connector to the adapter body may be provided directly on the adapter body.

The catheter mounting element at the distal end of the adapter body may include a mounting surface for sealing engagement with the optical connector. The mounting surface may be an internal tapered surface that matingly sealingly engages an external tapered surface of a Luer lock (Luer lock) connector included in the optical connector. The mounting surface may be threaded so as to matingly sealingly engage a threaded surface included in the optical connector.

The proximal adapter may include a radially compressible seal having a central bore for receiving the optical waveguide therein and located within the adapter body along the axial lumen distal to the proximal end, wherein the seal is compressed by the optical waveguide to extend radially outward to provide the seal.

The optical waveguide may be sealingly attached within the shaft cavity by fastening means, such as glue.

According to an embodiment, the catheter is a percutaneous, intravenous catheter device. The catheter may have a relatively short length, on the order of less than 10 cm.

When mounted on the catheter, the adapter forms a seal between the lumen and a fluid connection from the proximal side of the adapter and provides an optical connection from the proximal side of the adapter to the lumen through the optical waveguide.

According to a further first aspect of the present invention there is provided a combination of an adapter and a hollow catheter as mentioned above. The adapter mounting element connects the adapter body to the hollow catheter such that the hollow catheter extends from the distal end of the adapter body.

The proximal end of the optical waveguide may be located within the adapter body distal to the adapter body proximal end, wherein the distal end of the optical waveguide extends from the distal end of the adapter body into the hollow catheter.

The hollow catheter may define an axially extending catheter lumen, wherein the optical waveguide is in radial contact with an inner wall of the axially extending catheter lumen.

The hollow catheter may define an axially extending catheter lumen, wherein the optical waveguide has a diameter smaller than an inner diameter of the catheter lumen, such that coaxial, radially offset channels are formed in the catheter lumen.

The second lumen may include an inlet opening into the shaft lumen portion of the catheter body.

The combination may further comprise a needle insertable into and removable from the hollow catheter for aligning the catheter to the tissue when separation of the adapter from the catheter occurs, such that the radiation fiber can be inserted into the tissue through the catheter or needle.

According to another aspect of the invention, a system for photodynamic or photothermal therapy and/or diagnosis of tissue is provided. The system comprises the following combination of components: a proximal end adapter for a catheter comprising an adapter body having a proximal end and a distal end and defining an axial lumen extending therebetween, a catheter mounting element at the distal end of the adapter body for sealingly mounting the catheter to the adapter body, and a hollow catheter, wherein the catheter mounting element connects the catheter body to the hollow catheter such that the hollow catheter extends from the distal end of the catheter body; a first optical waveguide having a proximal end and a distal end, wherein the first optical waveguide is sealed within the shaft lumen defining an axial optical path extending between the proximal end and the distal end of the adapter body to the tissue and to access the tissue or into the interstitium; an optical connector mounting element at the proximal end and mounting an optical connector on the adapter body, wherein the optical connector is coupled with a light source through a second optical waveguide such that light from the light source can pass from the light source, through the second optical waveguide and further through the optical connector to the first optical waveguide, through the proximal end adapter through the catheter to the tissue.

After the cannula is disposed in the tissue, a first optical waveguide may be inserted into the catheter.

The system may further comprise a supply device for providing an agent to the tissue through the catheter.

The catheter may have a port for providing the reagent.

The system may further comprise a pad containing said agent and being arranged at the skin adjacent to said tissue and forming a first electrode connected to a first potential, whereby a second potential is connected to an electrically conductive lining arranged on at least one radiation fiber, forming the current needed for iontophoretic introduction of said agent into said tissue. The conductive liner may be of metal, for example silver.

The system may further comprise a second adapter for releasably connecting the proximal end of the adapter body to another optical connector located proximally to the optical connector, thereby ensuring patient safety and avoiding contamination of the reusable contents of the system.

According to another aspect of the present invention, a method of using a proximal adapter of a catheter is provided. The adapter having an adapter body having a proximal end and a distal end and defining an axial lumen extending therebetween, a catheter mounting element at the distal end of the adapter body for sealingly mounting the catheter to the body; an optical connector mounting element at the proximal end for mounting the optical connector to the adapter body; and an optical waveguide having a proximal end and a distal end, wherein the optical waveguide is sealed within the shaft lumen defining an axial optical path extending between the proximal end and the distal end of the adapter body. The method comprises the following steps: mounting an adapter on the catheter housing through the catheter mounting element, providing an optical waveguide in the catheter lumen; mounting an optical connector to the optical connector mounting element of the adapter to provide an optical path through the adapter.

The mounting of the adapter and the mounting of the optical connector may include mounting them with threads.

According to another aspect of the invention, a method of photodynamic or photothermal therapy and/or diagnosis of tissue is provided. The method comprises the following steps: providing at least one source of laser radiation and providing at least one radiation fiber for conducting laser radiation to the tissue and arranging a conduit in the interstitium; mounting a proximal adapter on the proximal end of the catheter, said adapter having a radiation fiber mounted in the lumen of the catheter to reach said tissue, said adapter being connected to a distal radiation fiber by an optical connector coupled to said at least one laser radiation source, such that when said adapter is connected to said connector, laser radiation emitted from said at least one laser radiation source is transmitted through said distal optical fiber to said at least one radiation fiber and to said tissue.

Prior to mounting the adapter to the catheter, the method may comprise: inserting a needle into tissue, the needle having a catheter sheath surrounding the needle, and removing the needle and inserting at least one radiation fiber into the sleeve.

The method may include withdrawing the proximal adapter from the lumen, draining fluid from the tissue through the lumen, and reinstalling the proximal adapter to the proximal end of the catheter.

According to another aspect of the present invention, there is provided use of an intravenous access device for interstitial light coupling to tissue.

The present invention thus provides advantageous devices, systems, applications and methods.

Drawings

Further objects, features and advantages of the present invention will become apparent from the following detailed description of several embodiments of the invention, when read in conjunction with the accompanying drawings, wherein:

FIG. 1 is a schematic diagram of a known system in which the present invention may be employed;

FIG. 2 is a schematic view of the system of FIG. 1 suitable for diagnostic use;

FIG. 3 is a cross-sectional view of a fiber optic ferrule;

FIG. 4 is a schematic diagram of an embodiment of the present invention;

FIG. 5 is a schematic diagram of an embodiment of the present invention;

FIG. 6 is an enlarged partial view of FIG. 5;

FIG. 7 is a schematic plan view of a conventional percutaneous intravenous catheter device;

FIG. 8a is a cross-sectional view of a proximal end adapter for a catheter;

FIG. 8b is a cross-sectional view of another proximal end adapter; and

FIGS. 9a, 9b, 10a, 10b and 11-16 are cross-sectional views of various proximal adapters and catheter assemblies.

Detailed Description

Fig. 1 is a schematic view of an apparatus for interactive interstitial photodynamic light therapy (PDT) or photothermal therapy (PTT) and photodynamic diagnosis (PDD) of a body surface or an internal body part of a human or animal. A plurality or at least two radiation conductors, such as optical waveguides or optical fibers 6, are inserted directly into the tissue 8, which may be an organ, a tumor or any other tissue. The fibers 6 may be inserted into the tissue 8 with their distal ends, respectively, and interstitially, in a geometric pattern. Thus, the fibers 6 are patient fibers. As shown in fig. 1, the distal ends of the patient fibers 6 are arranged in a geometric pattern, covering a certain area to be studied and/or treated. As shown in fig. 1, the proximal end of the patient fibers 6, which are arranged distally from the tissue, are inserted into and attached to the flat disc 3 of the converting means 1. The flat discs 3 are arranged adjacent to the second flat disc 4 and the flat discs are rotatable relative to each other about the axis 2.

As shown in fig. 1, a plurality or at least two optical fibers 7 are connected to the opening 5 of the second flat disc 4. In fig. 2, the first diagnostic fibre 7a is connected to a diagnostic light source 9a at its proximal end remote from the disc 4. The diagnostic light source may be a laser emitting light at a specific wavelength. The diagnostic light is passed by the diagnostic light source 9a through the diagnostic fibre 7a and through the two flat discs, which are well light-transmissive with suitable adjustment, to the patient fibre 6a and further through the patient fibre 6a to the tissue 8.

The diagnostic light is emitted through the distal end of the patient fiber 6a into the tissue 8 and is scattered within the tissue. The scattered diagnostic light is collected by the distal ends of the remaining patient fibres 6b and from there passes to a diagnostic sensor placed in the diagnostic sensor unit 12. As shown in fig. 2, the diagnostic sensor unit 12 is connected to the second flat disc 4 by means of fibres 7 b. The scattered light collected by the distal end of the patient fibre 6a passes through the patient fibre 6b and the diagnostic fibre 7b, respectively, via the two flat discs 3, 4 to the diagnostic sensor located in the unit 12.

By rotating the second disc 4, a set of diagnostic fibres 7 is placed in a different order opposite the fibres 6, whereby the other patient fibre 6 acts as a transmitting fibre 6a and the remaining fibres act as receiving fibres, respectively.

The combined response of the diagnostic sensors in unit 12 can be evaluated and a diagnostic image of tissue 8 obtained therefrom. The diagnostic image may include information about the flow of light through the tissue, the autofluorescence of the tissue, or a fluorescence signal obtained from a tumor sensitizer when the tissue is excited with visible or ultraviolet radiation. The last-mentioned fluorescence signal is shifted to longer wavelengths and clearly shows a clear difference from the endogenous fluorescence of the tissue. This information is used to determine the location of the tumor and to quantify how much sensitizer is absorbed within the tissue. In this way, the correct amount of light can be calculated or measured. The micro-thermistors may be arranged in association with the fibers 6 to measure tissue temperature, or alternatively may be temperature measured by custom-made fibers.

The device of fig. 1 and 2 can also be adjusted to the treatment position. At the treatment site, the proximal ends of all the fibers may be connected to one or several laser sources in order to obtain sufficient laser radiation of the tissue to be treated. In this case, the therapeutic light source may be conveniently fixed to a hole in the flat disc 4 as shown in fig. 2, with the end remote from the disc 4 being connected to the therapeutic light source as shown in fig. 1. The therapeutic light thus passes through a set of therapeutic fibres (part of fibres 7) and via the flat discs 4 and 3, respectively, to the patient fibres 6 and into the tissue 8.

The optical radiation may be infrared, Near Infrared (NIR), visible or Ultraviolet (UV), which may be both therapeutic and diagnostic.

The optical fiber, i.e. the patient fiber 6, may be arranged directly or by means of an insertion needle, typically in the form of a metal hollow cannula with a tip, within the tissue 8. Such metal needles may be arranged in the correct position with the aid of, for example, X-rays, ultrasound or visible light.

The patient's optical fiber 6 can be inserted from the distal end through the lumen of the metal needle so that the fiber tip at its distal end is in the correct position in the tissue 8. The needle may be retained there or may be removed during PDT, PTT and PDD or during their mutual deformation. The optical fiber is typically covered by a liner or cladding, which avoids its exposure to body tissues and fluids, and does not experience radial dissipation of light, i.e., light is only transmitted or collected from the tip of the fiber. The proximal ends of the patient fibers 6 remote from the tissue 8 are distributed in the holes of the flat disc 3.

Since the needle used to insert the fiber is passed into the tissue 8, the needle can be used to add reagents that can be used for subsequent diagnosis and/or treatment.

Another method of aligning the optical fibres may be to insert a needle as described above so that a plastic cannula can be inserted over the needle and the optical fibres inserted into the plastic cannula with the needle after it has been withdrawn. The optical fiber may then be permanently placed in the ferrule. Thus, the plastic sleeve protects the optical fiber.

During medical treatment, patients often require medication, blood, or fluids. The most effective method of administering these substances is to introduce them directly into the patient's blood so that the circulatory system can rapidly deliver the substances to the target tissue or organ. The most common method of directly administering a substance into the blood of a patient is injection with a conventional needle and syringe. However, during treatment, patients often require repeated or continuous doses of the drug. Repeated injections with conventional syringes will damage the vascular tissue and cause considerable discomfort to the patient.

Therefore, when a patient requires repeated doses of a drug or other substance, a catheter is typically employed by the medical care provider. However, to date, catheters have not been used to deliver light to the stroma in systems for interactive interstitial photodynamic diagnosis and tissue treatment of tissue.

Thus, an alternative system to the above-described system is disclosed in FIG. 3, which includesA cannula of an intravenous access device; however, this is for a different use than the conventionally known use.

In general, as shown in figure 7,the device may be classified as an oral Intravenous (IV) catheter when it is located in a patient. The IV catheter includes a catheter having a wall 110 defining a lumen, a proximal end and a distal end, and a catheter adapter body in fluid communication with the catheter lumen. From the beginningThe device also includes a very thin needle 111 for inserting the catheter into the blood vessel. More precisely, "intravenous" means knownArranged for access from outside the body to inside the vein by means of a sharp needle that penetrates the vein. This is typically done in order to obtain a blood sample intravenously or to deliver a drug into the circulatory system. The needle enters the vein at the skin surface near the arm or back of the patient's hand. The needle 111 is wrapped with a flexible plastic tube and arranged as a sleeve 110 around the needle. The needle is advanced into the vein and then withdrawn leaving the flexible tube in the vein. The drug enters through a tube 110, which is properly called an "endo-irradiation indwelling catheter", but is generally known under the trade name thereofThe tube is typically left for a longer period of time, for example, throughout the surgical procedure.

However, it should be noted thatThe device is not suitable for insertion into the interstitium. Conversely, events such as a punctured vein that causes blood leakage into the body that pose a serious threat to patient health should also be avoided. This type of catheter, i.e., an Intravenous (IV) catheter, is commonly used for infusion of fluids, such as for example, for delivery of common saline solutions, various drugs and complete parenteral nutrition to a patient, as well as for withdrawal of blood from a patient or monitoring of various parameters of the patient's vasculature, but is not used for insertion of an optical waveguide intravenously into tissue. Peripheral IV catheters are relatively short and are typically about 5cm or less.

More specifically, referring to fig. 7, an IV catheter generally includes a housing 102, an introducer needle 111, and a catheter 110. The housing is used to pinch the vascular access device during catheter insertion, such as at pinch region 104. The introducer needle is attached to the proximal end of the catheter housing, such as by an intermediate catheter needle adapter 103, and is used to penetrate the patient's skin and enter the blood vessel. The catheter is concentrically fitted over the introducer needle and placed there by means of frictional engagement between the catheter needle adapter 103 and the catheter housing 102. The relative lengths of the needle and the catheter cannula are such that the tip of the needle extends beyond the end of the catheter cannula when the needle is attached to the housing. In use, a medical professional penetrates the skin of a patient with a needle and finds a blood vessel of the patient. As the introducer needle is advanced into the patient's blood vessel, the medical professional withdraws catheter needle adapter 103 from the housing. The health care provider then retracts the introducer needle 111, leaving the catheter and attaches a suitable device to the catheter. The catheter is typically provided with a lock 101 for sealing the proximal end of the catheter device when required during the procedure. There are a number of different locking mechanisms that can be used, and a sliding locking cap, such as a screw type locking mechanism, is often used. The lock 101 has a grip region 105, an intermediate region 106, and an insertion region that mates with the proximal region 108 of the catheter housing 102 or the catheter needle adapter 103. Engagement of the lock 101 with the catheter is provided by elements 109, 106 on the lock 101 and the catheter housing 102 or catheter needle adapter 103, respectively, being mated, for example by bayonet closure or mating threads.

According to an embodiment of the present invention, a proximal end adapter for an IV catheter is provided. Referring to fig. 3 and 8a, the adapter has an adapter body 32 having a proximal end and a distal end and defining an axial lumen 33 extending therebetween. A catheter mounting element is provided at the distal end of the adapter body 32 for sealingly mounting a catheter to the body. An optical connector mounting element is provided at the proximal end of the adapter body for mounting an optical connector 37 directly to the adapter body. In addition, the adapter has a light guide 36 having a proximal end and a distal end. An optical waveguide 36 is sealingly located within the shaft lumen, defining a shaft optical path extending between the proximal and distal ends of the adapter body 32.

To ensure that the optical waveguide 38 transmits light between the adapters 32 and 37, a fiber, hereinafter also referred to as the primary fiber, that is not contaminated during use, another proximal end, and a second adapter may be used to enhance patient safety and simplify use. In this case, for example, an SMA connector (SMA is an abbreviation for miniature version a) (not shown in the figures) may be provided for proximal attachment to the fibre 38 and then distal attachment to the fibre 36 by means of a threaded portion 37 on the component 32. In this way it is ensured that the fibres leading to the means for providing light to the fibres 36 or receiving light from the fibres 36 are true reusable fibres. The fibers 36, and ultimately the proximal threads of the adapter, can become contaminated with bodily fluids during use. The first adapter comprising components 32 and 36 may then be a single use device and disposed of after use. The first adapter may be manufactured from a plastic material at low cost. The second adapter may have a metal housing and a glass optical waveguide therein for easy sterilization. In this way, the second adapter is a reusable adapter. In addition to SMA type connectors, other commercially available optical connector types may be used, such as ST, FC or SC connector types. Optical connectors are used to match fibers to each other or to devices.

All of the connectors described herein provide good coupling efficiency, which requires precise positioning of the fibers relative to each other. Connectors are used to provide a convenient system since the connection of devices for photodynamic or photothermal therapy and/or diagnosis must be interrupted from time to time, for example between patients or during treatment, for example to drain fluid from tissue. The optical connectors described herein have the fibers all centered so that their light transmitting portions pass directly through the connector and are in line.

According to one embodiment, the adapter is combined with a catheter comprising a plastic pliable sleeve 31 attached to a body portion 32 of the adapter. In addition to the body portion, a needle may also be inserted within the catheter lumen. The needle is long enough and extends outside the plastic cannula. A needle with a plastic cannula is threaded into the skin and into the tissue. The plastic cannula has a diameter such that it closely surrounds the needle and is sufficiently rigid to follow the needle into the skin and tissue. When the plastic cannula 31 is placed in the desired position, the needle can be withdrawn and the catheter left. Typically, the catheter is secured to the skin by adhesive tape so that it does not become dislodged by accident. The conduit may include a port 34 which is normally closed by a lid 35. Reagents or drugs can be added to the plastic cannula through the hole, for example by means of a syringe. Such addition may be performed as a bolus, intermittent addition, or continuous addition of the agent prior to diagnosis or treatment. In addition, excess fluid may also be expelled from the tissue through the port. However, according to some embodiments, the presence or absence of the port is optional.

When the needle is withdrawn, as shown in FIG. 3, the optical fiber 36 may be inserted into the location of the needle. The insertion may be performed after the bolus addition is made or before any reagent addition is made. According to this embodiment, the optical fiber is attached to the adapter body 32, and the assembly is in turn attached to the catheter. In this way, the optical fiber 36 is conveniently inserted into the catheter and further to the tissue to be diagnosed and treated. According to a specific embodiment, the distal end of the adapter body is attached to the proximal end of the catheter housing. Attachment may be accomplished by mating of a luer lock connector, such as a male luer lock connector on the proximal catheter housing and a female luer lock connector on the distal adapter body 32, or vice versa. An example of an adapter with a screw lock connection 141 is given in fig. 8b, parts 145, 146, 147 corresponding to parts 105, 106, 107 (fig. 7), respectively. However, as shown in FIGS. 9a, 9b, 10a, 10b and 11-16, a twist lock coupler 141 is rotatably attached to the adapter housing 132 for connection to a catheter, which are cross-sectional views of various proximal adapters and catheter assemblies.

Finally, a connector 37 having an optical connector 38 may be attached to the proximal end of the adapter body 32 and then to the catheter to couple the laser radiation or light into the optical fiber 36. The optical connector 37 has a centrally arranged optical fibre 38 and is located at its other end, as shown in figure 1, connected to the flat disc 3. Thus, the optical path between the disc 3 and the tissue 8 is ensured by the fibres 38, the adapter 32 and the fibres 36. The connection may be conveniently released and reconnected by detaching the adaptor body 32, and thereby the fibre 36, from the catheter 31, for example as may be used when adding a new sensitizer partway to the tissue 8. At the end of the treatment, the adapter 32 and catheter 31 may be discarded. Thus, when the adapter device is used for disposable use in a single-use process, the occurrence of contamination is avoided.

According to an embodiment, the catheter mounting element of the proximal adapter at the distal end of the adapter body 32 includes an inner tapered surface that matingly sealingly engages with an outer tapered surface of the screw lock connector.

According to other embodiments, the proximal adapter has a radially compressible seal with a central bore that receives the optical waveguide 36 therein. A seal is located within the adapter body and along the axial lumen distal to the proximal end, wherein the seal is compressed by the optical waveguide to extend radially outward to provide a sealing effect to prevent leakage from the catheter through the adapter mounted thereto.

According to an embodiment of the proximal adapter, the optical waveguide is sealingly attached within the shaft lumen by fastening means, e.g. by glue, clips or local melting of the adapter housing around the fiber 36.

According to an embodiment, a combination of an adapter hollow conduit is provided. The adapter mounting element is configured to couple the adapter body to the hollow catheter such that the hollow catheter extends from the distal end of the adapter body. The proximal end of the optical waveguide may be located within the adapter body distal to the adapter body proximal end, and the distal end of the optical waveguide extends from the distal end of the adapter body into the hollow catheter. The hollow catheter defines an axially extending catheter lumen, wherein the optical waveguide is radially contactable with an inner wall of the axially extending catheter lumen to provide a tight fit therein. In addition, the optical waveguide has a diameter that is smaller than the inner diameter of the catheter lumen such that when the optical waveguide is inserted, coaxial, radially offset channels are formed in the catheter lumen. The coaxial lumen may include an inlet opening 34 to the lumen portion of the catheter body, e.g., for administration of a drug.

As shown in fig. 3, the optical fiber 36 may terminate a few millimeters before the end of the ferrule 31. In this way, light is emitted from the optical fiber and is spread out through the cannula before reaching the tissue.

In another embodiment, the optical fiber extends beyond the end of the ferrule, so that a spreading means may be provided for the optical fiber, such as a prism or a taper at the end of the optical fiber. In addition, the outer surface of the fiber may be polished for light scattering.

Fig. 9a shows the proximal end adapter 132 connected to the catheter body 102. In this embodiment, the optical fiber 136 is arranged in the lumen 110 of the catheter 102 and is in turn located in the hollow needle 111. Fig. 9b shows how the optical connector 137 is threadably mounted on the proximal end of the adapter 132. In fig. 9b and 16, the ends of the optical fibers 136 or 236, respectively, are shown as converging to the tip of the needle 111. However, in practice, the needle is slightly wider than the optical fiber to receive the fiber therein; this is different from that shown in fig. 9b and 16, in that for the illustrative purposes mentioned, the tip of the needle appears to be part of the fiber 136 or 236, respectively.

In fig. 10a and 10b, the fibers 136 are distributed directly in the lumen 110 of the catheter 102, the needle being omitted. Fig. 11 shows the tip adaptor 230 insertable into the hollow needle 111, fig. 12, or into the catheter, fig. 13-16. Here, the screw lock connector 237 includes optical fibers arranged therein for coupling the adapter 230 to the fibers 236. Adapter 230 is inserted into needle 111 (fig. 12) or lumen 110 (fig. 14). In addition, referring to fig. 16, a needle 111 having an adapter 230 therein may also be disposed within the catheter 102.

All embodiments of the adapter described herein can be used in the systems described in fig. 1 and 2 above.

Fig. 4 discloses a system for adding a substance to tissue in photodynamic diagnosis or therapy or photothermal therapy. The distal tip portions of the plurality of optical fibers 41 terminate in the tissue 8 to be treated and extend through a flexible or rigid sleeve 42. The distal end of each optical fibre and the corresponding sleeve, which is remote from the tissue 8, is attached to a disc 43, similar to the disc 3 shown in figure 1. Although only two optical fibers are shown in fig. 4, any number of fibers may be used. The sleeve may be a plastic material or a metal material.

Another disc 44 is arranged adjacent to disc 43. The disc 44 may be similar to the disc 4 in fig. 1. A ferrule 45 including an optical fiber 46 is attached to the disk 44. The optical fiber 46 may be similar to the optical fiber 7a shown in fig. 2.

The cannula 45 has a port 47 that is normally closed with a cap (not shown) and to which a syringe 48 may be attached. The syringe may deliver a substance or agent into the tissue 8 through the port 47 and cannulae 45 and 42. The administration may be bolus, or intermittent or continuous. The administration can be performed before or during diagnosis or during treatment.

In fig. 4, only one cannula with port 47 is shown. Such a cannula may be connected to each cannula 42 during the diagnostic steps described above. In addition, a plurality or all of the sleeves 45 may have ports.

Figure 5 illustrates an additional method of delivering a substance to tissue. The optical fiber may be covered by a liner having electrical conductivity. This property can be used to electrophoretically supply substances to tissue. The ends of the optical fibers are distributed within the tissue as described above with reference to fig. 3.

In one embodiment, the optical fiber is covered with a suitable metal such as silver (Ag) liner. The metal bushing serves multiple functions.

1) The metal liner acts as a fully reflective medium, meaning that the optical fibers can be distributed directly into the tissue without the need for a protective sleeve. The optical fiber may be in direct contact with any fluid surrounding the tissue.

2) The metal is an electrical conductor, which means that the optical fiber can be used as an electrode, for example for introducing substances in tissue by iontophoresis.

FIG. 5 is a schematic view of a system for introducing a substance to tissue by iontophoresis. The tumor 81 is confirmed to be located under the skin 82 of the patient. The tumor may be located close to the skin or at a considerable depth. The effect of introducing substances by iontophoresis is more pronounced if the tumor to be treated is closer to the skin.

A pad 83 containing the agent to be introduced is placed on the skin surface over the tumor to be treated. The pad may simultaneously function as an electrode, which is indicated by connector 84 being connected to a galvanic positive electrical connection.

In fig. 5 two optical fibers 85, 86 covered with a metal layer are shown, which are arranged in plastic ferrules 87, 88. However, any number of optical fibers may be used, such as 3, 4, 5, or 6 optical fibers and ferrules. The optical fibers 86, 87 may be distributed in the tissue 81 through the adapter 32 and catheter 31 described above. Each cannula is connected at one end to a disc, similar to disc 43 in fig. 4, and the other end terminates at a position in the tissue of tumor 81. The optical fibers 85, 86 extend through ferrules 87, 88. At the distal end of the tumor, each fiber is electrically connected to ground potential. The distal end thus extends out of the cannula and into contact with the tissue. An electrical current is generated between the pad 83 and the respective ends of the fibers. The current carrying agent passes through the skin and into the tumor. The reagent may be ALA-solution, phthalocyanine, chlorine, etc. For some agents, the polarity may be reversed.

These agents treat tumors in the following manner.

ALA or aminolevulinic acid is a precursor of a photosensitizer. When administered, ALA is enriched in tumor cells due to their high activity and is converted to protoporphyrin ix (ppix), which is a photosensitizer. By irradiating the tumor with a laser beam having a wavelength of about 635nm, PPIX is excited, exciting the oxygen in the cells to a singlet state. Singlet oxygen will cause devastating damage to the cells and within a few days cause the cells in the affected area to die.

Phthalocyanines are the second generation of photosensitizers with improved pharmaceutical profiles. They have a strong absorption in the red region, where the tissue is very transparent, which makes them suitable for PDT.

Chlorine is also a second generation photosensitizer suitable for PDT.

Other sensitizers are Foscan and tokoad.

The metal layer, particularly the silver layer, acts to inhibit bacterial growth when in contact with tissue or tumors, thereby preventing infection.

As shown in fig. 5 and 6, the distal end of the fiber extends out of the plastic cannula and into contact with the tissue. The distal end 93 may also be free of a metal bushing, at least on the outside of its end. Fig. 6 shows an optical fiber 91 coated with a metal liner 92, which reflects light passing inside the fiber and acts as a current conductor layer. The fibers are arranged within a plastic sleeve 94 that protects the fibers and forms a barrier to the body portion surrounding the sleeve. Since the end 93 is not covered by silver and is in contact with the liquid in the tissue, light in the fiber will partially pass out of the side walls of the fiber. Thus, the end 93 will scatter light. This is an advantage in PDT and PDD.

When the optical fiber is used for optical diagnosis or treatment, light passing through the fiber is diffused in a region surrounding the tip or collected from this region, which is advantageous. The same applies to the optical therapy.

The above methods of supplying reagents may be used instead or in combination.

The sleeves 87 and 88 may be plastic sleeves or tubes made of a material compatible with the human body. It may have some flexibility or elasticity.

The sleeves 87, 88 may be steel pins attached in a suitable arrangement to a disc, here similar to the disc 43 in fig. 4. There may be 6 needles arranged in a geometric configuration. The needle may penetrate the skin and into the tumor.

The sleeve may be made of polyurethane or polyvinyl chloride containing a suitable softener. The cannula may contain barium so that the position of the cannula can be monitored by X-ray.

In another embodiment, each sleeve is so-calledDevices which are of the intravenous catheter type described above.

In cases where it is not necessary to administer the agent through the cannula, the cannula may be eliminated and the fiber passed directly into the tissue. In this case, it may be more advantageous to coat the metal liner with an electrically insulating layer, leaving only a small exposed area of the silver liner at the ends, so that iontophoretic use of the substance can be made.

The term "proximal" as used herein refers to the location on the catheter that, in normal use, is closest to the medical professional using the device and farthest from the patient in connection with whom the device is used. Conversely, the term "distal" refers to the location on the catheter that, in normal use, is furthest from the medical professional using the device and closest to the patient using the device.

Threads and tapered surfaces suitable for use with a screw lock type connector are referenced herein. Typically, the screw lock has a taper with an included angle of 6%, as fully characterized in publication ISO 594/1, first edition, 1986-06-15, some of which are incorporated herein by reference. The screw lock connector has a double right hand thread, which is fully characterized in publication ISO 594/-2, first edition, 1991-05-01, the contents of which are incorporated herein by reference.

The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the invention may be varied within the scope of the disclosed embodiments. Various individual features may be combined with other features not specifically disclosed. The invention is only limited by the appended patent claims.

Claims (13)

1. A disposable unit for interstitial insertion of optical fibers (136, 236) into tissue (8), wherein the disposable unit is configured as a system for interstitial photodynamic or photothermal therapy and/or diagnosis of the tissue (8), the disposable unit comprising the following components:

the optical fiber (136, 236) having a distal end and a proximal end;

a hollow needle (111) in the form of a hollow cannula, the hollow needle (111) having a proximal end and a distal end;

an adapter (132, 230), said adapter (132, 230) having a proximal end and a distal end and defining a lumen extending axially therebetween, said lumen containing said optical fiber (136, 236), said distal end of said adapter (132, 230) being configured to be mounted at said proximal end of said hollow needle (111), whereby said adapter (132, 230) by being inserted into said hollow needle is configured to position said optical fiber (136, 236) into said hollow needle (111), whereby said distal end of said optical fiber is disposed in a correct position towards said tissue (8); the adapter (132, 230) is further configured to connect the optical fiber (136, 236) to a primary fiber at the proximal end; and

wherein light can be coupled from the primary fiber to the optical fiber (136, 236), whereby the optical fiber is arrangeable at its distal end to receive light from the tissue (8) and/or to transmit light to the tissue (8).

2. The disposable unit according to claim 1, wherein the hollow needle (111) is made of metal.

3. The disposable unit according to claim 1, wherein the hollow needle (111) is straight.

4. The disposable unit of claim 1 wherein the adapter (132, 230) is mounted to the hollow needle (111) by being inserted into the hollow needle (111).

5. The disposable unit according to claim 1, wherein the hollow needle (111) with the adapter (132, 230) inside is arranged in a catheter with a cannula (110).

6. The disposable unit according to claim 5, wherein the optical fiber (136, 236) terminates before the distal end of the cannula (110), and wherein light emitted from the optical fiber (136, 236) propagates through the cannula (110) before reaching the tissue (8).

7. The disposable unit according to claim 5, wherein said optical fiber (136, 236) extends out of said cannula (110), and whereby said optical fiber (136, 236) has a lens or taper disposed at said distal end of the optical fiber.

8. The disposable unit of claim 1, wherein the optical fiber (136, 236) has an outer portion configured to be polished to scatter the emitted light.

9. The disposable unit of claim 1, wherein the primary fiber is disposed in a screw lock connector (237) for coupling to the optical fiber (136, 236) of the adapter (132, 230).

10. The disposable unit of claim 1, wherein the primary fiber is disposed in a light contact configured to mate with the proximal end of the adapter (132, 230).

11. A method of installing the disposable unit of claim 1, comprising:

providing an adapter (132, 230), said adapter (132, 230) having a proximal end and a distal end and defining a lumen extending axially therebetween, said lumen containing an optical fiber;

mounting the distal end of the adapter (132, 230) at the proximal end of a hollow needle (111) having a proximal end and a distal end;

positioning the optical fiber (136, 236) in the hollow needle (111) by inserting the adapter containing the optical fiber into the hollow needle;

connecting the proximal end of the adapter (132, 230) to a distal end of a connector, thereby coupling the optical fiber (136, 236) of the adapter (132, 230) to a primary fiber of the connector.

12. The method of claim 11, wherein the connector is a screw lock connector (237) comprising the primary fiber, and further comprising:

connecting the adapter (132, 230) with the screw lock connector (237) by mounting the hollow needle (111) containing the adapter (132, 230) to the screw lock connector (237).

13. The method of claim 11, further comprising

Disposing the hollow needle (111) containing the adapter (132, 230) in a catheter.