JP2012517252A - System and method for pretreatment planning for photodynamic phototherapy - Google Patents

Abstract

Disclosed are methods and systems for performing intra-tissue photodynamic therapy and / or photothermal therapy on tissue regions within the body. 3D or 4D image data of the tissue region, wherein the optimized number of light sources, and the individual position of each of the light sources in the tissue region, and the individual control parameters for each of the light sources, are acquired by at least one image modality To be determined. In addition, a computer-based method is provided for virtually planning a tissue photodynamic therapy and / or photothermal therapy session to a tissue region within the body in a virtual environment. A template for guiding a light source into the tissue is based on the data created from the virtual plan.
[Selection] Figure 2

Description

Field of Invention

  The present invention relates generally to the field of photodynamic phototherapy (PDT) and related systems, devices, computer program products, and methods. More particularly, the present invention relates to planning, controlling and adjusting parameters in such PDT systems. Even more particularly, the present invention relates to a system and method for pretreatment and planning of process parameters prior to therapy in a stromal tumor PDT system.

Background of the Invention

  Photodynamic therapy (PDT) is a cancer treatment modality that has shown promising results in terms of selectivity and efficacy, for example, Dougherty TJ et al., Photodynamic therapy, Journal of the National Cancer Institute 1998-88; See 905.

  PDT relies on the use of light sensitive drugs, which are activated by light in the presence of oxygen, resulting in the generation of toxic singlet oxygen radicals. Apoptosis, necrosis, and vascular damage caused by these toxic singlet oxygen radicals result in tissue destruction.

  In order to achieve effective treatment, several fibers have been used to confirm that all tumor cells receive a sufficient radiation dose and a toxic singlet state is obtained.

  Limited transmission of activating light through tissue is a common problem with PDT. Only tumors less than about 5 mm thick can be treated by surface irradiation. In order to treat thicker and / or deeper tumors, intra-tissue PDT (IPDT) can be utilized. In tissue PDT, for example, a photoconductive optical fiber is delivered into a tumor using an injection needle with the fiber disposed in the lumen. This is described, for example, in the same applicant's international application PCT / SE2006 / 050120 as the present application, which is hereby incorporated by reference in its entirety for all purposes. However, international application PCT / SE2006 / 050120 does not provide guidance on effectively positioning a plurality of such optical fibers in the area of tumor tissue.

  In order to maximize the biological effects in intra-organization PDT, accurate dosimetry methods are required and more specifically designed plans prior to the actual treatment of the subject are required.

  A PDT pretreatment plan is disclosed in the same applicant's international application PCT / EP2007 / 058477 as this application. This international application is hereby incorporated by reference in its entirety for all purposes. A method of configuring a pre-treatment module for IPDT on the entire prostate tissue is disclosed. This method involves the reconstruction of the target shape and the optimization of the position of the source fiber within this shape prior to the start of IPDT. However, the method of the international application PCT / EP2007 / 058477 is further improved, especially in terms of determining parameters important for PDT preparation or planning, as well as information or guidance on adjusting parameters for specific patient situations. can do.

  Thus, an alternative or improved preferred method for initially presetting, controlling and adjusting phototherapy and / or related parameters in vivo or ex vivo, prior to and during PDT And / or a system is needed. In particular, the pre-treatment positioning of the light source relative to the treatment area can be improved.

  Accordingly, embodiments of the present invention are provided in the art as specified above by providing systems, methods, and computer programs according to the appended claims, either alone or in any combination. It is preferably pursued to mitigate, mitigate or eliminate one or more defects, inconveniences or problems.

  Even more particularly, the present invention includes a system, method, computer program, and medical workstation incorporating a calculation method for determining an initial state of tissue, ie, a pre-treatment state, prior to PDT treatment. . This calculation method is based on the evaluation of at least one image data set associated with a tumor or sensitizer. This image data set is a combined or superimposed image data set from at least two different image modalities such as MR and ultrasound.

  Also disclosed is a system for performing intra-organophotodynamic therapy on body tissue. This system has the capability to overlay 3D images of treatment areas acquired from different modalities. The integrated 3D image relates to the treatment area, eg, the tumor site of the subject. The superimposed multi-dimensional image forms the basis for the pretreatment and planning processes. For example, a 4D image can be considered to take into account the spatial blood flow distribution. Here, the fourth dimension is time. The 4D image can be used to calculate various 3D parameters over time. For example, the calculation may be a 3D temperature release function, or a 3D washout factor of a sensitizer or oxygen, or a 3D oxygen update parameter. Based on these calculations, the positioning of at least one light source in the region of interest is optimized.

  According to one aspect of the present invention, a system for performing intra-tissue photodynamic therapy and / or photothermal therapy on a tissue region in the body is disclosed. The system has at least one light source configured to irradiate a therapeutic region within a tissue with a therapeutic beam, the light source for interaction with a photosensitive agent and / or for tissue control In order to achieve a controlled thermal environment, it is designed to be interstitially inserted into the tissue. In addition, the system can optimize the number of light sources based on the 3D or 4D image data of the tissue region acquired by at least one image modality, and the individual position of each of the light sources in the tissue region, and Having a unit for determining the individual control parameters.

  In an embodiment, 3D or 4D image data that includes a tissue region is image data combined from at least two different image modalities. In an embodiment, the system is configured to overlay the 3D or 4D image data to obtain combined image data from at least two different image modalities. The above determination can be made in a computer-based virtual environment. This allows user friendly planning and reliable and improved medical procedures.

  In an embodiment, the system includes a unit for evaluating at least one photodynamic therapy parameter of the tissue photodynamic therapy in the light source, and in response to the evaluation of the photodynamic therapy parameter, the therapeutic beam of tissue photodynamic therapy. A unit for changing the characteristics and a control unit configured to at least temporarily limit said irradiation of the therapeutic phototherapy according to at least one attribute of one of the plurality of photodynamic therapy parameters And have.

  The photodynamic therapy parameter may be a parameter related to the condition of the tissue or the condition of the photosensitive agent in the tissue. The photodynamic treatment parameter may be an effective tissue attenuation coefficient.

  The light source may be a distal end region of an optical fiber configured to be inserted into tissue in the tissue region. The distal end region may have a light diffuser, whereby the optical fiber is configured to emit diffused light at the distal end. Alternatively, the light source is an embeddable light source.

  In another aspect, a computer readable storage medium is provided that stores a computer program that includes a plurality of code segments for planning a session of intra-organophotodynamic therapy and / or photothermal therapy to a tissue region within the body. The computer program is a 3D or 4D rendering of a superimposed multidimensional image data set with a first code segment for evaluating at least two sets of 3D or 4D images of two different image modalities of a subject's tumor site. Based on the second code segment for integrating the images and the superimposed image data set, the optimized number of light sources, and the individual position of each light source in the tissue region, and the individual for each light source A third code segment for determining a control parameter of the second code segment.

  The system, method, and computer program can be applied in a computer-based virtual planning environment. In a virtual planning environment, a light source such as an optical fiber end can be positioned. Also, the optimized position and number of light sources can be determined automatically. Alternatively or in addition, the location and number of light sources may be manually adjusted in a virtual planning environment.

  In one aspect, a computer-based method is provided for virtually planning a tissue tissue photodynamic therapy and / or photothermal therapy session to a tissue region within the body in a virtual environment. The method includes providing 3D or 4D data of a region of interest from at least one imaging modality, such as two different image modalities, an optimized number of light sources based on the superimposed image data set, and a tissue region Based on the individual position of each of the light sources and the individual control parameters for each of the light sources, for an optimized treatment, the number of tissue light sources relative to the tissue region, and the spatial distribution, position, And determining a spatial direction, and virtually planning a session based on the determined number of light sources in the tissue and the spatial distribution, position, and spatial direction.

  The 3D or 4D data can include, for example, data for a region that is larger or significantly larger than the area of treatment that includes the tumor. In this case, the virtual plan can include a virtual plan that attaches a surgical template on an anatomically fixed location, eg, bone tissue. The surgical template comprises at least one guide unit such as a guide cylinder having a defined stop unit. For example, the guide cylinder may comprise a stop collar provided against a corresponding coupling collar of a syringe type fiber optic inductor so that a defined direction and depth is provided from the surgical template to the treatment area. .

  Alternatively, or in addition, data for positioning the light source may be provided to a robotic system that automatically or semi-automatically positions the light source in the area of the treated tissue.

  Alternatively, or in addition, data for positioning the light source may be used for real-time feedback during positioning, for example, based on an ultrasound-based image acquired during positioning. Thus, when positioning the light source, adjustments can be made to the patient's current situation. This is advantageous, for example, when the anatomical position should be changed since the first acquisition of 3D data prior to the virtual planning of the number of light sources and the position of the light sources.

  Thus, in another aspect, the system may be a system for performing intra-tissue photodynamic therapy and / or photothermal therapy on a tissue region within the body. The system is at least one light source configured to emit therapeutic light to a tissue region of tissue for interaction with a photosensitive agent and / or to provide a controlled thermal environment for the tissue To optimize the light source based on the 3D or 4D image data of the tissue region acquired by the at least one image modality, and the light source made to be inserted into the tissue into the tissue A unit for determining the number and the individual position of each of the light sources in the tissue region, as well as the individual control parameters for each of the light sources.

  The 3D or 4D image data may be image data that includes a tissue region and is combined from at least two different image modalities.

  As mentioned, the system may be configured to make the above determination in a computer-based virtual environment.

  The system modifies at least one photodynamic therapy parameter of the tissue photodynamic therapy in the light source and a characteristic of the therapeutic beam of the tissue photodynamic therapy in response to the evaluation of the photodynamic therapy parameter. And a control unit configured to at least temporarily limit the radiation of the therapeutic phototherapy depending on at least one attribute of one of the plurality of photodynamic therapy parameters. .

  The light source may be a distal end region of the optical fiber. The distal end region may comprise a light diffuser.

  The light source may also be an implantable light source, such as a photodiode, laser diode or the like.

  In one aspect, a computer-based method for virtually planning a PDT session includes providing a 3D or 4D data of a region of interest from at least one imaging modality and an intra-organizational light source for optimized treatment. Determining the number and distribution of.

  The method may include providing a template for the position of the light source in the region of interest.

  Providing the template may include creating the template based on the creation data output from the virtual plan.

  Based on this virtual plan, the light source is appropriately positioned in the area of the treated tissue.

  This positioning may be performed using a surgical template created from creation data output from the virtual plan. The creation data may be provided in the STL format, for example. Creation can be achieved by free-form methods, including rapid prototyping methods.

  According to another aspect, a computer program for processing by a computer is provided. The computer program includes a code segment for integrating and accurately overlaying multi-dimensional images from different image modalities in a photodynamic pretreatment of a subject in a system for performing intra-tissue photodynamic therapy on body tissue. A computer program for integrating a first code segment for evaluating at least two sets of multi-dimensional images of any image modality of a subject's tumor site and a multi-dimensional image rendering the superimposed multi-dimensions A second code segment and a third code segment for determining the location of the tissue distal end of the optical fiber in the subject's tumor.

  Further embodiments of the invention are defined in the dependent claims, and the features of the second and subsequent aspects of the invention are adapted mutatis mutandis to the first aspect as necessary.

  Some embodiments that provide suitable pre-treatment positioning of the light source relative to the treatment area may be improved.

  Some embodiments of the present invention provide improved treatment accuracy, which leads to avoidance of undertreatment of patients, for example. Some embodiments of the present invention also provide increased patient safety by avoiding damage to a compromised healthy organ.

  As used herein, the term “comprises / comprising” is used to identify the presence of a referenced feature, integer, step, or component, but one or more other features, It is emphasized that the presence or addition of integers, steps, components, or groups thereof is not excluded.

  These and other aspects, features, and advantages made possible by embodiments of the present invention will be apparent from and elucidated with reference to the following description of embodiments of the invention which refers to the accompanying drawings. Will.

It is the schematic of an organization PDT apparatus. FIG. 6 is a flow diagram illustrating a pre-treatment plan and treatment and monitoring sequences that comprise a real-time dosimetry module. FIG. a) is a schematic view of the organs incorporated in the prostate dosimetry model, and b) is a three-dimensional graph showing the reconstructed geometry of the patient's target site. 5 is a flow diagram of an embodiment of a method 400 that includes steps 410-490 and 500-520.

Description of embodiment

  Hereinafter, specific embodiments of the present invention will be described with reference to the accompanying drawings. However, the present invention may 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 numerals refer to like elements.

  The following description focuses on embodiments of the present invention that can be applied to PDT systems and methods, and in particular to tissue PDT systems and methods related to prostate cancer treatment embodiments. However, the present invention is not limited to this application, for example, liver, esophagus, pancreas, breast, brain, lung, trachea, eyeball, urinary tract, brainstem, spinal cord, bone marrow, kidney, stomach, intestine, pancreas, gallbladder, etc. It will be understood that it may be applied to many other organs, including

  In addition or alternatively, the treatment may also include photothermal treatment.

  Photodynamic therapy (PDT) treats certain types of malignant tumors in various organs, in part due to the benefits of repeated treatment feasibility and treatment-induced tissue damage limited to the irradiated site It has become a clinically accepted way to do this. The effects of PDT are brought about by a combination of treatment-induced apoptosis and direct necrosis, vascular damage, and possibly an induced immune response, the extent of tissue damage being affected by light dose, tissue oxygenation, and sensitization It depends on the agent concentration. In the case of PDT, clinical treatment protocols often rely on a light threshold model. This simplified model is based on the premise that only tissue regions exposed to light doses exceeding a predefined threshold are damaged. The threshold light dose tends to depend on the tissue type and the photosensitive material used. In view of the amount of light deposited, it is essential to monitor the optical properties of the tissue before and during PDT treatment. Significant variations in the absorption and scattering coefficients of prostate tissue between multiple patients and within a single patient have been measured by many groups. In addition, any treatment-induced fluctuations in absorption and scattering will directly affect the light distribution during treatment, possibly due to changes in blood content and tissue oxygenation status.

  By applying IPDT, various changing conditions can occur. These conditions may be time dependent and / or may vary within the tissue in response to natural variations in, for example, vascular location and / or neural pathway location. This can result in either overtreatment that can involve serious and undesirable effects, or undertreatment that does not imply a full effect of the treatment. By more accurately adapting the initial characteristics of the prostate histology, such patient variability can be overcome and appropriate and desirable results of treatment can be obtained. Further, by constructing and using an optical fiber having a distal tip configured to emit diffused light relative to a common point source configuration. The distal end of the optical fiber may comprise a diffusing device such as a lens or cone at the end of the optical fiber. Alternatively, the surface of the outer portion of the fiber may be polished to diffuse light. This is called a diffuser. The distal end of the optical fiber may comprise a diffuser, and the implantable light source may comprise a diffuser.

  By using a diffuser, the light is more evenly distributed within the treatment shape compared to a tip or light source constructed with a point source. Therefore, a more time-efficient IPDT treatment result can be obtained. The reason is that the amount of light is scattered more around the distal tip of the optical fiber and unwanted tissue necrosis adjacent to the tip is less with the same amount of energy, thus setting the amount of light to a higher level. As a result, the treatment time can be shortened. Also, using a smaller number of optical fibers compared to a point source by positioning the distal tip of the optical fiber within the region of the treated tissue such as the prostate where different light dispersion characteristics are considered Covering the anatomical geometry can produce the same therapeutic efficiency. Therefore, if an optical fiber configured to emit diffused light is used, fewer percutaneous incisions can be made. In this manner, a surgical template as described herein can include fewer components, thereby reducing manufacturing costs.

  FIG. 1 shows a general IPDT treatment scheme incorporating the present invention. Prior to prostate IPDT treatment, transrectal ultrasonography is performed to assess the target tissue geometry, as well as nearby risk organs (OAR). Multiple cross-sectional slices of the prostate geometry and adjacent tissue types are removed. These slices form the basis for three-dimensional rendering of tissue volume, where the prostate, urethra, rectum, upper and lower sphincter muscles, and areas of the cavernous nerve bundle are delineated by the urologist. Additional image modalities such as MR, CT, SPECT, PET can be used in and around the prostate to further define the tissue. Images taken from different image modalities are superimposed on an integrated 3D model of the geometry to be treated. Based on a 3D model of geometry, a random search algorithm provides a position in the optical fiber. The optical fiber is then positioned at these locations based on its virtual plan.

  A system is provided for performing intra-organophotodynamic therapy on tissue in the body, the system having the capability to overlay 3D images of treatment areas acquired from different modalities. The integrated 3D image is associated with the area of treatment, eg, the tumor site of the subject. The superimposed multi-dimensional image forms the basis for the pretreatment procedure and the planning process. For example, a 4D image may be considered to take into account the spatial blood flow distribution. Here, the fourth dimension is time. The 4D image can be used to calculate various 3D parameters over time. For example, the calculation may be a 3D temperature release function, or a 3D washout coefficient of sensitizer or oxygen, or a 3D oxygen update parameter. Based on these calculations, the positioning of at least one light source in the region of interest is optimized.

  Systems, methods, computer programs, and medical workstations can be applied in computer-based virtual planning environments. In a virtual planning environment, a light source such as an optical fiber end can be positioned. Also, the optimized position and number of light sources can be determined automatically. Alternatively, or in addition, the location and number of light sources may be manually adjusted in a virtual planning environment.

  The 3D or 4D data may include data for an area that is larger or substantially larger than the area of treatment including, for example, a tumor. In this case, the virtual plan may include a virtual plan that attaches a surgical template on an anatomically fixed location, eg, bone tissue. The surgical template comprises at least one guide unit such as a guide cylinder having a defined stop unit. For example, the guide cylinder may comprise a stop collar provided against a corresponding coupling collar of a syringe type fiber optic inductor so that a defined direction and depth is provided from the surgical template to the treatment area. .

  The surgical template may be provided as a 3D structure that matches the 3D structure of the organ. The organ may be the organ to be treated. The surgical template can thus be positioned relative to the tissue to be treated.

  Surgical templates are based on a particular patient and a determined number of light sources / fibers. The treatment is thus advantageously efficient, easy to implement and reliable.

  Alternatively, or in addition, data for positioning the light source may be provided to a robotic system that automatically or semi-automatically positions the light source in the area of the treated tissue.

  Alternatively, or in addition, data for positioning the light source may be used for real-time feedback during positioning, for example, based on an ultrasound-based image acquired during positioning. Thus, when positioning the light source, adjustments can be made to the patient's current situation. This is advantageous, for example, when the anatomical position should be changed since the first acquisition of 3D data prior to the virtual planning of the number of light sources and the position of the light sources.

  Thus, in another aspect, the system may be a system for performing intra-tissue photodynamic therapy and / or photothermal therapy on a tissue region within the body. The system is at least one light source configured to emit therapeutic light to a tissue region of tissue for interaction with a photosensitive agent and / or to provide a controlled thermal environment for the tissue To optimize the light source based on the 3D or 4D image data of the tissue region acquired by the at least one image modality, and the light source made to be inserted into the tissue into the tissue A unit for determining the number and individual position of each of the light sources in the tissue region, as well as individual control parameters for each of the light sources.

  The 3D or 4D image data includes tissue regions and may be combined image data from at least two different image modalities.

  As mentioned, the system may be configured to make the above determination in a computer-based virtual environment.

  The system includes a unit for evaluating at least one photodynamic therapy parameter of the tissue photodynamic therapy in the light source, and in response to the evaluation of the photodynamic therapy parameter, the therapeutic beam of the tissue photodynamic therapy. A unit for changing the characteristics; and a control unit configured to at least temporarily limit the radiation of the therapeutic phototherapy according to at least one attribute of one of the plurality of photodynamic therapy parameters; Can be provided.

  The light source may be a distal end region of the optical fiber. The distal end region may comprise a light diffuser.

  The light source may also be an implantable light source, such as a photodiode, laser diode or the like.

  In one aspect, a computer-based method for virtually planning a PDT session includes providing a 3D or 4D data of a region of interest from at least one imaging modality and an intra-organizational light source for optimized treatment. Determining the number and distribution of.

  The method may include providing a template for the position of the light source in the region of interest.

  Providing a template may include creating the template based on creation data output from the virtual plan.

  Based on this virtual plan, the light source is appropriately positioned in the area of the treated tissue.

  This positioning may be performed using a surgical template created from creation data output from the virtual plan. The creation data may be provided in the STL format, for example. Creation can be achieved by free-form methods, including rapid prototyping methods.

  According to another embodiment of the present invention, a computer program for processing by a computer is provided. The computer program includes a code segment for integrating and accurately overlaying multi-dimensional images from different image modalities in a photodynamic pretreatment of a subject in a system for performing intra-tissue photodynamic therapy on body tissue. A computer program for integrating a first code segment for evaluating at least two sets of multi-dimensional images of any image modality of a subject's tumor site and a multi-dimensional image rendering the superimposed multi-dimensions A second code segment and a third code segment for determining the location of the tissue distal end of the optical fiber in the subject's tumor.

を使用して評価された組織の実効減衰係数、μ_ｅｆｆである。ここで、インデックスｉは、検出器ファイバｉからの測定値を表し、ｒ_ｉは、光源から各検出器ファイバまでの距離であり、ｉは、１以上の整数であって、ＰＤＴシステムにおいて使用されるファイバの数、例えば、６、１２、１８本、又はそれ以上のファイバを表す。さらに、Ｐは、ファイバＩに使用される治療用光源の光出力電力を表し、μ_ａは、吸収係数である。μ_ｅｆｆ及び拡散方程式を使用することによって、このようにして組織におけるフルエンス率が計算され得る。 In one example, a method is used that records the attenuation of transmitted light as the distance increases in the tissue, and the transmitted light attenuation is fitted to a model of light propagation. The embodiment for determining the number and position of light sources is based on such a model. Models that can be used are: J. et al. Welch and M.W. J. et al. C. van Gemert: Transport equation for radiative transfer as described in Optical-Thermal Response of Laser-Irradiated Tissue (Plenum Press 1995), more specifically, an approximation based on the premise of diffuse light propagation, Is the diffusion equation. The resulting data is the equation

_Is the effective tissue attenuation coefficient, μ _eff , evaluated using. Where index i represents the measured value from detector fiber i, r _i is the distance from the light source to each detector fiber, i is an integer greater than or equal to 1 and is used in the PDT system Represents the number of fibers to be used, for example 6, 12, 18 or more fibers. Further, P represents the optical output power of the therapeutic light source used for the fiber I, and μ _a is the absorption coefficient. By using μ _eff and the diffusion equation, the fluence rate in the tissue can thus be calculated.

  Different settings, i.e., initial settings and settings during the treatment procedure, are stored for later calculation and further adjustment of the database containing patient population data. In this work, supplemental resources such as imaging modalities such as MR, CT, ultrasound, and long-term results may be used. The database containing patient population data is continuously updated in this way and further improved to make optimal predictions.

  In addition to the recorded fluorescence measurements, the three-dimensional geometry of the tissue for treatment is taken into account in the calculation as well as the position of the light source and detector, as well as the optical properties of the tissue itself. This data may be provided, for example, at least in part from an imaging modality such as ultrasound, MR, or CT.

  Intra-tissue PDT (IPDT) is considered an alternative to radical prostatectomy, external radiation, and chemotherapy for the treatment of localized prostate cancer. For example, the photosensitizing agent Temopofin (mTHPC, meso-tetra (hydroxyphenyl) chlorin) is used to treat secondary and primary prostate cancer. Using a fiber having a bare end, the amount of light irradiated is 20 J to 100 J per treatment site, resulting in significant treatment-induced necrosis and reduced prostate specific antigen (PSA) levels. did. By using a diffuser, the treatment time and the number of fibers can be reduced. Four of the six primary cases have very mild complications, including transient irritable symptoms, while more severe complications include stress incontinence In one case, sexual function deteriorated. In the case of secondary cases, 13 of 14 patients who needed antiandrogen therapy after PDT eventually began to increase again in PSA and the tumors recurred. According to the authors, more detailed drug and light dosimetry can provide better discrimination between the target tissue and the surrounding sensitivity.

  Thus, there is a need for more accurate and individualized real-time dosimetry, both in PDT to prostate tissue, and in a more general sense. There have been many reports on prostate in vivo spectroscopic measurements of parameters related to PDT effects such as light fluence rate, sensitizer distribution, and tissue oxygenation, and blood flow and blood volume. Such studies have great potential to deepen understanding of the processes associated with PDT in prostate tissue and to expand clinical prostate PDT to also incorporate personalized treatment dosimetry and real-time treatment feedback It has sex.

  Finite element method (FEM) is used to simulate the light transmission signal in a practical prostate model due to temporal and spatially varying tissue optical properties. Based on the simulated data set, the ability of the algorithm to track the increase in effective attenuation coefficient within the prostate is verified. In addition, through tissue importance weighting within the Block-Cimmino algorithm, the possibility of distinguishing between target tissue and risk organs (OAR) in terms of the amount of light deposited is evaluated. Finally, the dose volume histogram (DVH) of the light dose delivered during IPDT treatment and the simulated increase in absorption are compared with and without treatment feedback. Thus, the feasibility of an IPDT dosimetry model that confirms a certain predetermined light dose within the target tissue is determined, regardless of any treatment-induced changes in tissue absorption.

  An IPDT treatment 200, as shown schematically in FIG. 2, includes dosimetry software developed to run on the aforementioned IPDT device that utilizes up to 18 optical patient fibers. The patient fiber may be, for example, a 400 μm diameter optical fiber with a bare end for delivering therapeutic light. Alternatively, or in addition, a diffuser may be used. The therapeutic light may be approximately 652 nm, consistent with one of the absorption bands of the photosensitive substance Temoporin. Using an internal optical unit, the instrument is in a treatment mode during which all fibers emit therapeutic radiation, at which point one fiber is active and six adjacent fibers detect transmitted light. It can be switched between modes. The detection unit consists of six spectrometers covering a spectral interval between 630 nm and 840 nm.

  A therapy session consists of a pretreatment procedure and a therapy procedure, through which a graphical user interface guides the urologist.

  Initially, a first 3D data set including a treatment region is obtained from a first imaging modality. In step (1), for example, an ultrasound examination of the prostate is performed to evaluate the target tissue geometry as well as the nearby OAR. Within a set of 6 to 10 ultrasound images, the urologist draws a line in the computer-based virtual treatment plan for the prostate, urethra, rectum, upper and lower sphincter muscles, and cavernous nerve bundle areas Can do.

  In addition, second 3D data from different image modalities including the treatment area can be used to further improve the virtual plan. The matching of two 3D data sets may be performed by known image processing algorithms based on, for example, grayscale based matching, surface matching, object matching, and the like. A combined 3D data set may facilitate improved virtual planning, for example, because different anatomical structures can be combined in a single 3D image. For example, bone tissue and soft tissue may be provided in a single 3D image (eg, from CT and MR image modalities).

  Then, in step (2), the tissue contour is patched into a three-dimensional voxel representation of the geometry including all organs.

  In step (3), the search algorithm calculates a near-optimal source fiber position within the reconstructed geometry. Virtual planning of light source positioning in the 3D model can be done automatically or semi-automatically. The resulting position can then be transferred from the virtual plan to the actual surgical position as soon as the patient is ready for treatment. By providing a surgical template as described herein, positioning accuracy can be improved.

  FIG. 3 shows a sample 3D geometric model 320 with a 1 mm voxel side length, OAR consisting of target tissue 325 or prostate 311, urethra 313, rectum 315, and normal surrounding tissue, and source fiber. Location 330 is included. This geometry, representing the “test” geometry used in this work, was created based on 8 ultrasound images from a patient with a gland volume of approximately 27 cm 3 and the location of the treatment fiber is , Calculated by the algorithm described in Section C.

  In step (4), using a hollow steel needle, an optical fiber, also called a treatment fiber, is guided into place. This may be done by using a surgical template. Since the fiber position may deviate slightly from the set of positions calculated by the random search optimization algorithm, the opportunity to update the final fiber position within this fourth step is Given to a doctor. In step (5), information about the geometry and actual fiber position is used as input to the Block-Cimmino optimization algorithm to predict the required exposure time for all source fibers.

B. Geometric Model A geometric model is a three-dimensional voxel representation of a target organ, here the prostate, and the adjacent urethra, rectum, upper and lower sphincter muscles and cavernous nerve bundles as risk organs. Several image modalities can be used in rendering an anatomically accurate 3D model of a target organ. For example, by superimposing ultrasound images with MRI or PET images, or SPECT images, or any other suitable image modality. In the following description, an ultrasound image is a reference for explaining the present invention. When determining the position of an organ manually or semi-automatically in a 3D patient data set, the physician marks, for example, 5 to 20 points out of 6 to 10 ultrasound images and is present in that particular section. Draw lines around different tissue types. These points are then connected by linear interpolation to form the contours of the connected organs. From the ultrasonic examination, lateral images are divided head by tail every 5 mm.

  Combining 3D data from several image modalities can improve accuracy.

The tissue contour can be linearly interpolated with respect to the region between the ultrasound cross sections to obtain a voxel side length of 1 mm for all three dimensions. A filling technique is applied to identify the tissue type for the voxels within the outlined line. Initially, all voxels in the three-dimensional matrix are added to normal tissue, except for voxels that contain contours of any other tissue type. The center of each set of contour points is then calculated. The following procedure is performed for each organization type. Initially, the center point of the current tissue type is placed in the buffer. The first point in the buffer is then extracted and set to the same tissue type as the current tissue type. The six connected neighbors are then tested for tissue type. If a point does not belong to the same tissue type as the current contour point and does not belong to another set of contour points, the point is placed in the buffer. This procedure is repeated until the buffer is empty, thus filling all tissue types from its center outward. The reconstructed voxel model has a typical edge length of 60-65 voxels.

C. Fiber Position The task of finding the optimal fiber position is here to maximize the light fluence rate in the target organ, which is the prostate, while minimizing the light distribution in the risk organ (OAR) adjacent to the target organ to be treated Can be constructed to The optimization algorithm is an iterative random search algorithm similar to the simulated annealing type algorithm. The search for the optimal fiber position is initialized by creating a random configuration of source positions within the prostate. In the following description, embodiments will be described with respect to the distal end of the fiber that is the point source. By configuring the distal end to emit diffuse light, the basic concept of rendering the fiber tip position remains the same, but the basic physics of the algorithm changes slightly. However, by using a diffuser, the treatment energy, treatment time, and the number of light sources such as fibers required can be minimized.

ここで、Ｐは、この例では０．１５Ｗに設定された光源効果を表し、実効減衰係数は、μ_ｅｆｆ＝［３μ_ａ（μ_ａ＋μ_ｓ’）］^１／２によって与えられ、ここで、μ_ａ及びμ_ｓ’は、それぞれ０．５及び９．７ｃｍ^−１に設定されている。反復ごとに、それぞれのファイバを、限られた長さだけ無作為の方向に移動する。 A fiber with a bare end is modeled as an isotropic point source. Here, the fluence rate φ _ij in the voxel j by the source in the voxel i is approximated as follows by an analytical solution to the diffusion equation in an infinite homogeneous medium.

Here, P is represents a light source effect set to 0.15W in this example, the effective attenuation _{coefficient, μ eff = [3μ a (} μ a + μ s')] is given by ^1/2, where μ _a and μ _s ′ are set to 0.5 and 9.7 cm ⁻¹ , respectively. Each iteration moves each fiber in a random direction for a limited length.

This movement is limited to voxels within the prostate, and only one source fiber per voxel is allowed. Following fiber movement, a fitness value is calculated as follows to evaluate the quality of this configuration.

は正であり、この特定の領域に光線を放射するときの適合値に建設的に寄与する。これに応じて、公式（２）の第２の和は、最も高いフルエンス率によって特徴づけられる、ＯＡＲ内、即ち尿道、直腸、上部及び下部括約筋、並びに海綿体神経束内のボクセルの２５％を含む。対応する組織重みは上の表１に示されている。ここでは、それぞれ

であり、それにより、リスク器官内のあらゆるフルエンス率が、全体適合関数値にペナルティを与えるようにする。したがって、式（２）は、標的組織外の最も高いフルエンス率値を最小化しながら、前立腺内における最も低いフルエンス率値を最大化するようになっている。 The first sum of equation (2) includes 25% of prostate voxels with the lowest fluence rate. Target tissue weight

Is positive and contributes constructively to the fit value when emitting light to this particular region. Correspondingly, the second sum of formula (2) represents 25% of the voxels in the OAR, namely the urethra, rectum, upper and lower sphincters, and the cavernous nerve bundle, characterized by the highest fluence rate. Including. The corresponding tissue weights are shown in Table 1 above. Here, each

So that every fluence rate in the risk organ penalizes the overall fitness function value. Thus, equation (2) maximizes the lowest fluence rate value in the prostate while minimizing the highest fluence rate value outside the target tissue.

In the iterative scheme, the new fiber position is only accepted if the fiber movement results in a larger fit function value. Since the ray distribution can be regarded as diffusion at a distance 1 / μ _s ′ from the fiber tip at the earliest, the position of the obtained fiber is presented by a depth coordinate shortened by this distance.

  This type of random search algorithm does not guarantee to find an overall optimum. However, this stochastic movement increases the probability that the search can find its way out of the local optimum. In current implementations, the maximum step size is gradually increased from three voxels to one voxel to ensure that the solution converges to the optimum, at the expense of the ability to avoid the local optimum. Be lowered. Typical execution times were approximately 45-60 minutes, but execution time can be minimized by alternative or future computing hardware improvements.

  FIG. 4 further illustrates the method described above in a series of steps 400. However, when reading this disclosure, it should be apparent to those skilled in the art that the same steps may be performed in an overlapping manner. The method begins with acquiring 3D or 4D image data from the first image modality 410. From the acquired image data, anatomical structures are delineated (420) by the physician. The resulting data is stored in the system. This step may also be semi-automatic or fully automatic depending on, for example, the complexity of the image and / or available computer capacity. A subsequent step 430 is for acquiring 3D or 4D image data from a second image modality different from the first image modality. Following this step, the rendering (440) of the data image is performed as 420 above. Subsequent steps 450 and 460 represent the acquisition and further depiction of the image data if additional image modalities different from those above are to be used.

  A matching of the 3D or 4D data set is then performed (470). This matching may be performed by known image processing algorithms based on, for example, grayscale based matching, surface matching, object matching, and the like. A combined 3D or 4D data set can facilitate improved virtual planning, for example because different anatomical structures can be combined in a single 3D or 4D image. Next, at step 480, the tissue contour is patched into a three-dimensional voxel representation of the geometry including all organs. At this stage, the pretreatment method takes into account the OAR and determines the distribution and number of intracellular light sources to be applied in the tissue (490). With the location and number of tissue light sources, the template can be processed (500). However, or alternatively, data for positioning the light source may be provided to a robotic system that automatically or semi-automatically positions the light source in the area of the treated tissue.

  The pretreatment is now complete and a therapy session can be started (510) based on the initial values determined in the previous steps. During the treatment session, intermediate feedback to confirm a predetermined amount of light in the target tissue is performed (520) regardless of any treatment-induced changes in tissue absorption. When reading this disclosure, it should be apparent to one of ordinary skill in the art that step 520 may slightly change the initial value in response to a treatment-induced change in tissue. New values are provided to the treatment setting to optimize the treatment.

  After a healing period or diagnosis to assess the effect of therapy achieved during the treatment session, a new treatment session can be started.

  In conclusion, in embodiments in whole prostate tissue, methods and systems are provided for configuring an initial pretreatment procedure and / or planning process dosimetry module for IPDT. Implemented on an 18 fiber IPDT device is dosimetry software that includes positioning of the individual distal tips of the optical fiber. The dose of light can be initially accurately preset with PDT treatment parameters taking into account patient specific anatomy with superimposed images from several image modalities. Utilizing data on light dispersion simulated by FEM within a practical prostate model shows that increasing levels of light attenuation can be tracked. In other embodiments, a different number of optical fibers may be used.

  As will be appreciated by those skilled in the art, the present invention may be embodied as a device, system, method, or computer program product, ultimately as a medical workstation, or at least as part of a medical workstation. Can be Accordingly, the present invention can take the form of an entirely hardware embodiment, a software embodiment, or an embodiment combining software and hardware aspects, all of which are generally referred to herein as "circuitry." Or, it is called “module”. Furthermore, the present invention may take the form of a computer program product on a computer-usable storage medium embodying computer-usable program code. Any suitable computer readable medium may be utilized including hard disks, CD-ROMs, optical storage devices, transmission media such as media supporting the Internet or Intranet, or magnetic storage devices.

  Embodiments of the present invention are described herein with reference to flowchart illustrations and / or block diagrams. It will be appreciated that some or all of the blocks shown in the figures may be implemented by computer program instructions. Instructions executed via a computer processor, or other programmable data processing device, create a means for implementing the functions / actions specified in one or more blocks of the flowcharts and / or block diagrams. Thus, these computer program instructions can be provided to a general purpose or special purpose computer processor or other programmable data processing device to produce a machine.

  These computer program instructions also produce an article of manufacture in which the instructions stored in the computer readable memory include instruction means that implement the functions / operations specified in one or more blocks of the flowchart illustrations and / or block diagrams. Or a computer or other programmable data processing device may be stored in a computer readable memory that may be operative to function in a particular manner. Instructions for loading computer program instructions onto a computer or other programmable data processing device to be executed on the computer or other programmable device are specified in one or more blocks of the flowcharts and / or block diagrams. A series of operational steps for generating a computer-implemented process may also be performed on a computer or other programmable device to provide steps for implementing the function / operation.

  It should be understood that the functions / operations illustrated in the figures may be performed in an order other than the order described in the operation description. For example, two blocks shown in succession may actually be executed substantially simultaneously, or they may sometimes be executed in reverse order, depending on the functionality / action involved. Is possible. Some of the figures include arrows on the communication path to indicate the main direction of communication, but it is understood that communication in the opposite direction may occur from the arrows shown in the figure. I want.

  The present invention has been described above with reference to specific embodiments. However, embodiments other than those described above are equally possible within the scope of the present invention. Different method steps than those described above, performing the method by hardware or software, can be provided within the scope of the present invention. Different features and steps of the invention may be combined in combinations other than those described. The scope of the present invention is limited only by the appended claims.

Claims (20)

A system for performing intra-organophotodynamic therapy and / or photothermal therapy on a tissue region in the body,
At least one light source configured to irradiate a therapeutic beam to the tissue region within the tissue, for interaction with a photosensitive agent and / or to achieve a controlled thermal environment of the tissue A light source, adapted to be inserted into the tissue into the tissue,
Based on 3D or 4D image data of the tissue region acquired by at least one image modality, an optimized number of light sources, and an individual position of each of the light sources in the tissue region, and each of the light sources A unit for determining individual control parameters for the 3D or 4D image data comprising the tissue region and being combined image data from at least two different image modalities;
A system comprising:   The system of claim 1, wherein the system is configured to overlay the 3D or 4D image data to obtain the combined image data from at least two different image modalities.   The system according to claim 1 or 2, wherein the system is configured to make the determination in a computer-based virtual environment. A unit for evaluating at least one photodynamic therapy parameter of the tissue photodynamic therapy in the light source;
A unit for changing the characteristics of the therapeutic light of the tissue photodynamic therapy in response to the evaluation of the photodynamic therapy parameter;
A control unit configured to at least temporarily limit the irradiation of therapeutic phototherapy according to at least one attribute of one of the photodynamic therapy parameters;
The system according to any one of claims 1 to 3.   5. The system according to any one of claims 1 to 4, wherein the light source is a distal end region of an optical fiber configured to be inserted into tissue in the tissue region.   The system of claim 5, wherein the distal end region comprises a light diffuser and the optical fiber is configured to emit diffused light at the distal end.   The system according to claim 1, wherein the light source is an implantable light source. A computer readable storage medium storing a computer program including a plurality of code segments for planning a session of intra-organophotodynamic therapy and / or photothermal therapy to a tissue region in the body, the computer program comprising:
A first code segment for evaluating at least two sets of 3D or 4D images of two different image modalities of a subject's tumor site;
A second code segment for integrating the 3D or 4D image rendering of the superimposed multi-dimensional image data set;
For determining an optimized number of light sources and respective individual positions of the light sources in the tissue region and individual control parameters for each of the light sources based on the superimposed image data set A computer readable storage medium comprising a third code segment. A computer-based method for virtually planning a tissue photodynamic therapy and / or photothermal therapy session to a tissue region in the body in a virtual environment, comprising:
Providing 3D or 4D data of the region of interest from at least one imaging modality, such as two different image modalities;
Optimized based on the optimized number of the light sources based on the superimposed image data set, and the individual position of each of the light sources in the tissue region, and the individual control parameters for each of the light sources Determining the number of tissue light sources and the spatial distribution, position, and spatial orientation for the tissue region for structured treatment;
Virtually planning the session based on the determined number of light sources in the tissue and the spatial distribution, position, and spatial orientation;
Including methods.   The method of claim 9, comprising providing the virtual template to virtually simulate the positioning of the light source in the region of interest based on the virtual template.   11. The method of claim 10, wherein the step of providing a virtual template includes a sub-step of providing creation data for the template based on the virtual plan. Said virtual planning, wherein comprises the steps of virtually simulate the positioning of the template relative to the tissue region, comprising the steps of virtually simulate introduction into the tissue region in the light source, the, claim 10 or 11. The method according to 11.   The 3D or 4D data includes image data for a treatment region where the tissue region is located or a region larger than the treatment region, and the virtual plan is anatomically fixed as on bone tissue 12. A method according to claim 10 or 11, comprising virtually planning to attach the template to a location.   The virtually planned template comprises at least one guide unit, such as a guide cylinder having a defined stop unit, for example, the guide cylinder has a defined direction and depth from the surgical template to the treatment. 14. A method according to any one of claims 10 to 13, which can comprise a stop collar provided for a corresponding coupling collar of a syringe-type fiber optic inductor, as provided in the region.   Virtually positioning the light source and providing data to a robotic system for automatically or semi-automatically positioning the light source within a region of treated tissue in an actual medical procedure. Item 10. The method according to Item 9. A system for virtually planning intra-tissue photodynamic therapy and / or photothermal therapy to a tissue region in the body,
A unit for processing 3D or 4D data of a region of interest from at least two imaging modalities;
Optimized based on the optimized number of the light sources based on the superimposed image data set, and the individual position of each of the light sources in the tissue region, and the individual control parameters for each of the light sources A unit for determining the number of tissue light sources for the tissue region and the spatial distribution, position, and spatial orientation for the structured treatment;
A unit for virtually planning the session based on the determined number of light sources in the tissue and spatial distribution, position, and spatial orientation;
A system comprising:   A method for creating a template based on creation data from the method for virtually planning according to any one of claims 9-15.   The method of claim 17, wherein the creation of the template is performed without a method that includes a rapid prototyping method.   16. A medical procedure comprising the virtual plan according to any one of claims 9 to 15, and further positioning a light source in a region of treated tissue based on data from the virtual plan.   20. The method of claim 19, comprising positioning a template created from creation data output from the virtual plan with respect to a region of the treated tissue.

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