WO2012048891A1

WO2012048891A1 - Device, system and method for emission of light and detection of light in a therapy system

Info

Publication number: WO2012048891A1
Application number: PCT/EP2011/005170
Authority: WO
Inventors: Sune Svanberg
Original assignee: Spectracure Ab
Priority date: 2010-10-14
Filing date: 2011-10-14
Publication date: 2012-04-19

Abstract

A medical device for emission of therapeutic light from a light emitting unit and wherein the light emitting unit is devised to be reversed for detection of light when no light is emitted.

Description

SPECIFICATION

TITLE: Device, system and method for emission of light and detection of light in a therapy system

BACKGROUND OF THE INVENTION

Field of the Invention

The present document pertains to combined use of a unit that emits light in one operational mode and detects light (produces a signal for further processing) in a second operational mode. In more particular, some

embodiments relate to combined use of Light-emitting diodes or diode lasers in therapeutic medical systems . Such devices are in a particular application used in a system or method for treatment and diagnostics in photodynamic therapy, in particular interstitial photodynamic therapy and control of said therapy.

Description of the Prior Art

Photodynamic therapy (PDT) is a powerful, non-thermal treatment modality for malignant disease and some other medical conditions, such as angioplastic interventions of vessels, disinfection from microbial and bacterial

infection. Also, the technique is used for photochemical internalisation (PCI) providing improved access to tumour cells for conventional cytotoxic tumour agents. For deep- lying tumors, interstitial photodynamic therapy has been developed, where optical fibers are inserted into the tumor mass, either directly or guided in hollow metal needles (troachards) . The laser or other light source is normally placed external of the irradiated tissue, the light is guided through the fiber and exits at its bare end or along a diffusing section of the fiber inside the tumor.

Alternatively, the light source can be integrated at the end of a thin, fiber-like probe, or light sources can be placed along the probe with electrical power supplied through wires in the probe connected to an external power supply. Some examples of such therapeutic devices are given in WO2000015296 (Al) , US20110077464 (Al) , US20110008372 (Al) , or EP1334748 (B2) , all of Life Sciences Oncology.

Dosimetry is a very important aspect of interstitial

PDT, regarding light flux, sensitizer distribution and tissue oxygenation. Frequently this is performed in a very rudimentary manner and mostly concerning light flux, and then pursued through separate monitoring fibers. The applicant of the present disclosure, SpectraCure AB, has patented and implemented a novel approach for integrated light delivery and diagnostics. Examples can be found in PCT/SE2002/002050, PCT/SE2004/000755 , PCT/SE2004/000756 , PCT/SE2004/000758, or PCT/EP2007/058477 , which all are incorporated herein in their entirety for all purposes. This is a major improvement to therapy only. In some example of Spectracure' s technology, optical fibers are used to transmit non ionizing radiation to certain

treatment sites. The same fibers may be used for all therapeutic and diagnostic purposes. This is accomplished through a novel switching/interconnecting device based on mechanical, optical and/or electro-optical components.

In the approach using light sources inside the tissue, the option of integrated light delivery and

dosimetry was hitherto not available.

Hence, an improved system for light based therapy and diagnosis would be advantageous .

SUMMARY OF THE INVENTION

Accordingly, embodiments of the present invention preferably seek to mitigate, alleviate or eliminate one or more deficiencies, disadvantages or issues in the art, such as the above-identified, singly or in any combination by providing a device and method according to the appended patent claims. Recently it has been recognized by the present inventors that a light emitting diode (LED) , while normally used to generate light driven by an electric current, can also act as a detector, which generates an electric current proportional to the light flux when irradiated by light.

According to aspects of the disclosure, a medical device is provided for emission of therapeutic light from a light emitting unit and wherein said light emitting unit is devised to be reversed for detection of light when no light is emitted.

According to aspects of the disclosure, a method is provided for controlling delivery of therapeutic light, comprising, providing a device having a light emitting unit devised to be reversed for detection of light when not emitting light, wherein the light emitting unit is used for both therapy and diagnostics/dosimetry. According to further aspects of the disclosure, a system is provided for treatment and diagnostics in

interstitial photodynamic therapy comprising the disclosed device . According to yet another aspect of the disclosure, a method is provided for treatment and diagnostics in

interstitial photodynamic therapy comprising the disclosed method or using the disclosed system. According to some examples of the disclosure, Use of the provided device, or method, or system is provided for targeting treatment, wherein a light emitting mode is activating the target treatment, and/or a detecting mode is establishing a quantity of light delivered for activation, and/or diagnosing an effect of a treatment. Further embodiments of the invention are defined in the dependent claims, wherein features for the second and subsequent aspects of the invention are as for the first aspect mutatis mutandis.

Some embodiments of the invention provide for a compact array which where the units may be switch between a light emitting mode and a light receiving mode. This may enhance therapy since the same unit may be used both for treatment and for diagnosis/dosimetry .

Some embodiments of the invention provide for a further enhanced treatment by using a matrix of the

disclosed units where the units may be controlled to emit light in directional patterns for controlling the amount of light to specific regions. Also, some patterns may

simultaneously be used for receiving light from specific regions for dosimetry. The information from the dosimetry may be used as feedback to the emitted light to further enhance therapy .

It is pointed out that the application of

interstitial light is generally little invasive. This may be accomplished by using templates and needles to insert the light sources into the tissue. Such insertion should not be life threatening in general, e.g. by using devices disclosed in PCT/SE2006/050120 of the same applicant which is incorporated herein in its entirety for all purposes.

It should be emphasized that the term

"comprises/comprising" when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof .

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects, features and advantages of which embodiments of the invention are capable of will be apparent and elucidated from the following description of embodiments of the present invention, reference being made to the accompanying drawings, in which

Fig. 1 is a schematic diagram of an embodiment;

Fig. 2 is a schematic illustration of a planar light emitting matrix comprising a plurality of light emitting units that may have two operational modes;

Fig. 3 is a schematic illustration of a linear light emitting matrix comprising a plurality of light emitting units that may have two operational modes;

Fig. 4 is a further schematic illustration of a planar light emitting matrix comprising a plurality of light emitting units that may have two operational modes;

Fig. 5 is a schematic illustration of a light

emitting matrix comprising a plurality of light emitting units that may have two operational modes, wherein light is conveyed to and from the matrix by means of light guides, such as optical fibres; and

Fig. 6 is a schematic illustration of an implantable probe having a light emitting matrix comprising a plurality of light emitting units that may have two operational modes . DESCRIPTION OF THE PREFERRED EMBODIMENTS

Specific embodiments of the invention will now be described with reference to the accompanying drawings .

This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the embodiments illustrated in the accompanying drawings is not intended to be limiting of the invention. In the drawings, like numbers refer to like elements . The following description focuses on an embodiment of the present invention applicable to a unit for treatment and/or diagnosis of a tumor and in particular to a LED based array emits light in one operational mode and detects light in a second operational mode.

Recently it has been recognized by the present inventors that a light emitting diode- (LED), while normally used to generate light driven by an electric current, can also act as a detector, which generates an electric current proportional to the light flux when irradiated by light.

There is an analogy between an electrical generator and an electrical motor, which essentially are identical devices, generating current when the shaft is mechanically rotated, or with the shaft rotating when the device is fed by an electrical current. Thus, when using LEDs implanted in tissue as discussed above for delivering the therapeutical light dose, they can alternatingly be used for detecting the surrounding light level due to other surrounding light sources. Primarily this would be for detecting light at the same wavelength where the LEDs are emitting.

Means are be provided to switch between delivering an electric current through the feeding LED wires and

detecting the much weaker current generated by the same LED and running through the same wires. This switching may be done electronically or

mechanically .

In this way the approach with implanted LEDs for therapeutic light delivery is transformed into an

integrated approach where the same arrangement is used for both therapy and diagnostics/dosimetry . The LEDs are controlled by a control unit with sequential activation of the different LEDs. The control unit may be externally to the implanted LEDs and connected to it via a communication link, e.g. cable based or wireless.

In principle also implanted diode lasers can be used in the same dual way as LEDs, and this aspect is also covered by the present disclosure.

Also for the case when the light sources are placed externally to the tissue as is the case in the SpectraCure system, illuminating LED or diode laser sources could be used for light detection of the diagnostic light flowing back through the optical fiber, thus eliminating the need for switching between light delivery and light detection optical paths.

Instead electrical switching of the LED/diode laser for source or detector function is provided.

For oxygenation, separate multiple fibers may be used in embodiements where for instance two LED wavelengths are used, one non-restrictingly at the isobestic point where oxy- and deoxyhemoglobine have the same absorption, and the other one where they differ substantially. Then tomograhic mapping of the oxygenation could be done through the tumor mass in the same way as it would be done for the

therapeuting light flux as described above.

It is noted, that for the detection of the weak currents due to light emanating from different sources these could be modulated enabling sensitive lock- in

detection. Monitoring phase and partial demodulation would provide information on light propagation. Further, by using different modulation frequencies this information could become more comprehensive. Knowledge of which source is being modulated on which frequency at a particular instance of time also provides spatial tagging allowing even

simultaneous tomographic assessment of the three- dimensional flux field.

In Fig.l an embodiment 1 of the present invention is illustrated. A selector unit 100 is shown for switching between a light emitting mode 110 and a light detecting mode 111. Selector unit may be controlled by a control unit (not shown) . When selected to be in light emitting mode, therapeutic light is emitted from light emitting unit 120 by delivering an electric current from unit 110 to the light emitting unit 120. When light emitting unit 120 is selected to be in detection mode a unit 111 will detect an electric current generated by the light emitting unit 120. Thus, the same light emitting unit 120 can be used for both therapy and control of said therapy. The control may be dosimetry based. Moreover, diagnostics of surrounding tissue may be performed by a particular compact unit.

Separate detector units are not necessary thanks to the dual mode light emitting and detecting units 120.

The light emitting unit 120 is adapted to be used interstitially either internally by implanting the light emitting unit 120 in the tissue or place it externally to the tissue. Light guides may be used for conveying light to and from a light emitting and detecting unit 120, see .e.g. Fig. 5

The selector unit may be arranged remote from the light emitting unit.

When arranging a plurality of said light emitting units in an array, a plurality of such light emitting units may be switched independently. A sub-set of said plurality of said light emitting units is thus selectable to emit light, while at least one of the remaining light emitting units is at the same time selectable to be in the second mode of operation for detection of light, such as light scattered from tissue receiving said therapeutic light.

The array may be provided extracorporeally or

implanted, or divided into an extracorporeally arranged unit and an implanted unit .

Detection may thus be provided inside the body and/or external thereto.

Alternatively and/or additionally, if partly or fully positioned extracorporeally the array of LEDs may be positioned on a flexible or resilient element to be

fastened on a skin site for diagnosing and/or therapeutic use. The flexible or resilient element may be self-adhesive or fastened using for example an adhesive spray. The flexible or resilient element may be made form a flexible or resilient material. Alternatively and/or additionally the flexible or resilient element may comprise slits in different directions in such way that it becomes flexible.

Examples of such arrays which can be modified to incorporate the present invention may be found in the following disclosures, which all are incorporated herein in their entirety for all purposes: O2000015296 (Al) ,

US20110077464 (Al) , US20110008372 (Al) , or EP1334748 (B2) .

Various patterns of the plurality of light emitting units may be activated over time to tailor efficacy of the therapy.

The invented unit may be used in conjunction with photo reactive agent, such as talaporfin sodium or

porphyrin, for a light activated therapy treatment, such as target treatment of a tumor. The light emitting mode of the invented unit may be used for activation. The diagnostic/dosimetry mode may be used to establish if a sufficient quantity of light has been delivered and/or the effect of the treatment. In this manner a feedback for ongoing therapy may be provided. Therapy is advantageously controlled by

diagnostic measurements of one and the same arrangement comprising the dual mode light sources and detector units (e.g. LEDs or laser diodes).

Some examples of light emitting units are shown in Figures 2-6.

Fig. 2 is a schematic illustration of a planar light emitting matrix 2 comprising a plurality of light emitting units that may have two operational modes.

The matrix is in this example a flexible substrate 15 having slots or weaknesses in a vertical direction 18 or a horizontal direction 17 to enhance the flexibility. LEDs are positioned the surface of the substrate 16.

Alternatively the LEDs may be positioned in adjacent pairs coupled in such way that the LEDs of each pair may be alternated between. Thereby may one LED act as a emitter and one as a receiver.

The LEDs or groups of LEDS may be controlled for directional pattern of light. This may be employed to archive desired light distributions to specific regions during therapy. The directional patterns may also be used to control and vary intensity over different portion of a region.

Additionally some LEDs in one pattern may be used in an emitting mode while some LEDs in another pattern may simultaneously be used for detection. By switching between different patterns of emitting and detecting light treatment and dosimeter may be simultaneously be conducted to enhance therapy of e.g. a tumor site.

Various constellations of patterns for emitting light and/or for detecting light may be selectable. Additionally, different directional patterns may be switched bwteen sequentially .

Additionally, by using pairs even more complex patterns may be used to further enhance the treatment and/or diagnostic/dosimetry.

An advantage with the matrix is that a single cable may be used for controlling the in and/or out signal.

Further multiplexing may be possible to control the light emitting units of the matrix 2. The multiplexing may be embedded in the matrix 2.

The control unit may be integrated in probe or be an external unit .

Fig. 3 is a schematic illustration of a linear light emitting matrix 3 comprising a plurality of light emitting units that may have two operational modes.

The linear array 3 may be an elongated probe 20 implanted internally either within a tumor or adjustment to a tumor during conventional minimally invasive procedures.

The probe 20 may either be rigid or flexible, as appropriate for facilitate the probes positioning. The probe includes a plurality of LED 26 which may be switched between emitting light for therapy or for receiving light for diagnostic/dosimetry.

The LEDs 26 are located on opposite side of a

substrate 24 for conducting for Bi-directional illumination and detection for effective control.

Additionally the probe may have an optically

transparent sheath 28 enclosing the LEDs 26 and the

substrate 24. Preferably the sheath is biocompatible. Fig. 4 is a further schematic illustration of a planar light emitting matrix 4 comprising a plurality of light emitting units 42 on a substrate 40 that may have two operational modes. The matrix 4 is very compact and may be implantable. The light emitting units are generally

directed toward a tumor. The matrix 4 is working in a similar fashion as the exemplary matrix in fig. 2. The Matrix may be energized from outside the body if implanted. Additionally the matrix 4 may include integrated chip technology or surface mounted device (smd) light units.

The probe may be covered with an optical transparent sheath which may be biocompatible.

The probe may work in conjunction with a photoreactor which is preferably absorbed by the cells of a tumor. Once at least an initial light activated therapy treatment has then been delivered, killing some of the abnormal tumor cells, immune system stimulating factor/factors is

administered (it being understood that the administration of other therapeutic agents to the patient can occur before, concurrently with, or after the light activated therapy. By also using the matrix for detecting light for dosimetry the therapy may be very effective. The dosimetry may be employed as feedback for controlling the directional patterns and the intensity of the emitted light. Thus, delivery/administration of emitted light to a tumor site may be further enhanced to ensure effective therapy.

Fig. 5 is a schematic illustration of a light

emitting matrix 5 comprising a plurality of light emitting units 216 positioned on a substrate 218. The light emitting units 218 may have two operational modes, wherein light is conveyed to and from the matrix 5 by means of light guides 214, such as optical fibers. Additionally, the fibers may convey light bi-directionally. The light emitting units of the matrix may be switchable to obtain different patterns of units emitted light and detecting light. The bundle of fibers 210 connected to the light emitting units of the matrix 5 is compact to be entered into body. The bundle may then get broader in probe in the body. Various patterns of light switchable to ensure effective therapy according to what has previously been disclosed herein.

Fig. 6 is a schematic illustration of an implantable probe 6 having a light emitting matrix comprising a

plurality of light emitting units 344' , 344 located on a substrate 342. The light emitting units may have two operational modes. The light emitting units may be

energized through conductor 348a and b extending through the lumen 350a and 350b in a catheter 352. The implantable probe with integrated light emitting units in an array may be configured to have a flat configuration, thereby easily implanted. The probe 6 may also have embedded multiplexing (alternatively, modulator) circuit 354 which selectively energizes any of the light emitting units to provide desired geometrical patterns of light. The multiplexing may also be used to provide desired geometrical patterns for detecting light, such as fordosimetry .

The illustrated probe may be employed for a PDT system. Additionally, the illustrated probe 6 may be implanted for long term treatment.

Some units 120 can be permanently detecting while others illuminate light Units 120 are selectively controllable between the two operational modes (or a third mode: OFF)

The present invention has been described above with reference to specific embodiments. However, other

embodiments than the above described are equally possible within the scope of the invention. Different method steps than those described above, performing the method by hardware or software, may be provided within the scope of the invention. The different features and steps of the invention may be combined in other combinations than those described. The scope of the invention is only limited by the appended patent claims.

Claims

1. A medical device for emission of therapeutic light from a light emitting unit and wherein said light emitting unit is devised to be reversed for detection of light when no light is emitted.

2. The device of claim 1, comprising a selector unit for a selection between a light emitting mode and a light detecting mode is performed by utilizing a selector unit.

3. The device of claim 2, wherein said selection unit is configurated to select either to deliver an

electric current to said light emitting unit or to detect an, by the light emitting unit, generated electric current.

4. The device according to claim 1 or 2 , wherein said selection is performed either electronically or mechanically .

5. The device according to any of claims 1 to 4 , wherein said light emitting unit is arranged be placed either externally or internally to a tissue, such as on a probe or in an array of a plurality of light emitting sources.

6. The device according to claim 5, wherein said light emitting unit is implantable in tissue.

7. The device of any of claims 1-6, wherein said light emitting unit is comprised in an array of a plurality of said light emitting units.

8. The device of claim 7, wherein a sub-set of said plurality of said light emitting units is selectable to emit light, while at least one of the remaining light emitting units is at the same time selectable to be in the second mode of operation for detection of light, such as light scattered from tissue receiving said therapeutic light.

9. A method for controlling delivery of therapeutic light, comprising

providing a device having a light emitting unit devised to be reversed for detection of light when not emitting light, wherein said light emitting unit is used for both therapy and diagnostics/dosimetry.

10. A method for therapeutic light delivering according to claim 9, comprising at least two light emitting units for both therapy and diagnostics/dosimetry with sequential activation between said at least two light emitting units to either emit or to detect light.

11. A method for treatment and diagnostics in interstitial photodynamic therapy comprising the method of claim 9 or 10.

12. The method of claims 9 to 11 wherein said light emitting unit is a light emitting unit comprised in the device of any of claims 1-8.

13. A system for treatment and diagnostics in interstitial photodynamic therapy comprising the device of any of claims 1-8.

14. A method for treatment and diagnostics in interstitial photodynamic therapy comprising the method of any of claims 9-12 or using the system of claim 13.

15. Use of a device according to any of claims 1-8, or a method according to any of claims 9-13 or a system according to claim 14 for target treatment, wherein a light emitting mode is activating said targeting treatment, and/or a detecting mode is establishing a quantity of light delivered for activation, and/or diagnosing an effect of a treatment .