SYSTEM AND METHOD FOR DETERMINING OPTICAL ATTENUATION OF AN OPTICAL MEMBER INSERTED INTO TISSUE - Patent application

Abstract

Systems and methods are provided for determining or estimating the presence and effect of inhomogeneities that attenuate light in tissue when performing a medical procedure or diagnosis using optical elements in tissue. The systems and methods include inserting multiple optical elements into tissue and then performing measurements by emitting light through a subset of the optical elements at a time while measuring light collected by another subset of the optical elements. The systems and methods also include combining the measurement data with a model for light propagation in tissue and establishing a system of equations. The systems and methods also include solving for unknown attenuation values ​​from the system of equations.

Description

[Technical field]

[0001] The present disclosure relates generally to determining the presence of inhomogeneities that attenuate light in tissue when performing medical procedures or diagnosis using optical fibers in tissue. More specifically, the present disclosure relates to determining blood clumping in optical fibers that may affect light propagation from or to the optical fiber. In particular, the present disclosure relates to determining light attenuation due to blood clumping to improve light dose control when performing photodynamic therapy or laser thermotherapy using optical fibers or other optical probes in tissue. [Background technology]

[0002] The present disclosure relates to systems and methods for improving light dose control when performing light-based therapy using optical fibers or other optical probes within tissue.

[0003] In the field of medical therapy of oncological diseases, several therapies have been developed for the treatment of malignant tumor diseases. Surgery, cytostatic therapy, treatment with ionizing radiation (gamma or particle radiation), isotope therapy, and brachytherapy using radioactive needles are examples of common therapies. Despite great advances in treatment, oncological diseases continue to be a disease that many suffer from and cause a high percentage of deaths in Western countries. The treatment method, photodynamic therapy (PDT), offers a complement or alternative in the field of treatment. A photoactivatable agent, usually called a sensitizer, is administered to the body transdermally, orally, or topically. The photoactivatable agent may accumulate more in the malignant tumor than in the surrounding healthy tissue. The tumor area is then irradiated with non-thermal red light, usually from a laser, which excites the sensitizer to a more energetic state. Singlet oxygen and other oxidizing species are formed via energy transfer from the activated sensitizer to oxygen molecules in the tissue. Singlet oxygen is known to be particularly toxic to tissue, leading to cell eradication and tissue necrosis. Localization of the sensitizer to tumor cells provides unique selectivity, where surrounding healthy tissue is spared.

[0004] Laser thermotherapy is a related treatment that instead of utilizing photosensitizers uses higher laser power to heat the target tissue, causing tissue death through thermal effects.

[0005] The limited tissue penetration of activating red light is a drawback of PDT, and laser thermotherapy has a similar limitation. As a result, only superficial tumors can be treated with superficial irradiation. To treat thicker and deeper tumors, interstitial light delivery can be used. Here, a light-conducting optical fiber is inserted into the tumor, for example using a syringe needle, with the fiber located in its lumen.

[0006] To achieve an efficient treatment, several fibers may be used to ensure that all tumor cells are exposed to a sufficient amount of light. It has been shown that it is achievable to perform dose calculations of the absorption and scattering properties of tissue. For example, EP 1 443 855 A1 describes a system in which multiple fibers are used for measurement in addition to treatment of the light flux that penetrates the tissue from other fibers and reaches a given fiber. In this way, an improved calculation of the correct light dose for all parts of the tumor can be achieved.

[0007] A problem when performing interstitial illumination as described above is that blood or other material may accumulate at the distal end of the optical fiber, thereby attenuating the light exiting the optical fiber. This has two consequences: first, the attenuation may reduce the intended effect of the procedure as the light dose is reduced further away from the fiber, and second, optical measurements performed through the fiber may be affected by the attenuation of the light.

[0008] Therefore, new and improved devices and methods for determining the effect of the presence of blood clumps on medical optical fibers placed in tissue would be advantageous. Summary of the Invention

[0009] Thus, examples of the present disclosure preferably seek to mitigate, alleviate or eliminate one or more deficiencies, disadvantages or problems in the art, such as those identified above, singly or in combination, by providing a device, system or method according to the appended claims for determining the attenuation of light in tissue, which may be used to determine the effect of the presence of blood clumps on a medical optical element, such as an optical fiber, waveguide, light source or photodiode, disposed in tissue.

[0010] When an optical element is inserted into tissue, trauma to the tissue can cause bleeding, which accumulates at the tip of the optical element or along the length of the optical element. At visible and infrared wavelengths, blood's optical absorption is typically much higher than the average optical absorption of tissue due to the high hemoglobin concentration in blood. Thus, the accumulated blood acts as a light absorbing material that attenuates the light emission from the optical element.

[0011] One objective of the present disclosure is to determine or estimate the attenuation of light in tissue. Another objective of the present disclosure is to determine or estimate the attenuation of light caused by inhomogeneities in medical optical members placed in tissue, for example, blood accumulation at the location where light is emitted from the optical member. Such inhomogeneities may cause localized attenuation of light, which may need to be accounted for. To determine or estimate the attenuation of light, the present disclosure generally consists of two steps, the first step being to perform optical measurements to provide data that can be used to infer the light attenuation. When multiple optical members are used, this step consists of emitting light one member at a time, or by a collection of specific members, and detecting the light collected by other members at some distance from the emitting member.

[0012] In a second step, the attenuation is determined by estimating the attenuation using a model-based algorithm, which may be used to determine or estimate attenuation caused by inhomogeneities such as blood accumulation. The determination or estimation is generally performed by solving an inverse problem where the measurement data set from the first step is used as input and the set of attenuation values ​​is used as output.

[0013] It should be emphasized that the present disclosure is not limited to use in performing the treatment of malignant tumors, but may be used in any situation in which a treatment of tissue using optical elements is performed, or in any situation in which measurements within tissue are performed using optical elements.

[0014] An advantage of using the described method of determining or estimating light attenuation is that the accuracy of the determined or estimated effective attenuation coefficients and attenuation values ​​is improved, which means that dosimetry can be improved.

[0015] The term "comprises / comprising" as used in this specification is used to specify the presence of stated features, integers, steps or components, but does not exclude the presence or addition of one or more other features, integers, steps, components or groups thereof.

[0016] These and other aspects, features and advantages of possible examples of the present disclosure will become apparent and elucidated from the following description of examples of the present disclosure when taken in conjunction with the accompanying drawings. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 illustrates a number of optical elements (11) inserted into tissue (12), the tissue being characterized by light scattering properties denoted μs(r) and light absorption properties denoted μa(r) at geometric coordinate r. [Diagram 2]Figure 2 illustrates the evaluated optical properties (μeff) using the older evaluation method (21) and the new disclosed method (22) in a homogenous tissue phantom. The value of μeff measured by an independent reference measurement method is also shown (23). [Diagram 3] FIG. 3 illustrates the estimated attenuation values ​​using the older evaluation method (31) and the new disclosed method (32) in the same homogenous tissue phantom used in FIG. [Figure 4] FIG. 4 illustrates the optical properties (μeff) of prostate tissue assessed using the older evaluation method (41) and the new disclosed method (42). [Diagram 5] FIG. 5 illustrates attenuation values ​​assessed using the older assessment method (51) and the new disclosed method (52) in the same prostate tissue used in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The following disclosure focuses on examples of the disclosure applicable to determining or estimating light attenuation in tissue. The disclosure may be applicable to determining the effect of the presence of light-attenuating inhomogeneities in medical optical elements, such as optical fibers, waveguides, light sources, and / or photodiodes, disposed in tissue. For example, this is advantageous in determining the effect of the presence of blood clumps in medical optical elements disposed in tissue. However, it is understood that the description is not limited to this application and may be applied to many other systems for determining the effect of the presence of light-attenuating inhomogeneities in medical optical elements disposed in turbid media.

[0019] Consider tissue having light scattering and light absorption properties as illustrated in Figure 1. A number of optical elements (11), such as optical fibers, waveguides, light sources, and / or photodiodes, are placed in the tissue (12) for the primary purpose of delivering a light dose to the tissue or to perform measurements of the optical properties of the tissue. The light scattering properties of the tissue are expressed as μ in geometric coordinate r: s(r). Similarly, the light absorption characteristic can be expressed as μ a The optical fluence at any point r in tissue due to one or more light sources can generally be described by, for example, the Boltzmann transport theory for radiative transfer. The transport equation generally requires a numerical solution. For illustrative purposes, analytical solutions exist for the transport equation in some specific cases. For example, μ s (r)>>μ a Given (r), the optical fluence rate at distance r from a point source in a homogeneous medium can be expressed as: φ(r)=(4πDr) -1 exp(-μ eff r) (1) In the formula, μ eff = [3μ a (μ a +μ s )] 1 / 2 And D = [3(μ a +μ s )] -1 μ eff is the effective attenuation coefficient and D is the diffusion coefficient. Thus, the light fluence rate as a function of distance from a light source is typically expressed as eff The function follows some kind of exponential function, as determined by:

[0020] In the presence of inhomogeneities that attenuate light, absorption may be increased or decreased compared to general tissue. If bleeding occurs at the optical element, the accumulated blood will absorb light to a greater extent than general tissue, as blood has an inherent high light absorption due to high concentrations of hemoglobin. Assuming that blood only accumulates locally around the optical element, the blood acts to attenuate the light emitted from the optical element (and attenuates the light collected by the optical element if used for measurements). The attenuation value A may be incorporated into the optical fluence rate formula. φ(r)=A(4πDr) -1 exp(-μ eff r) (2) where 0≦A≦1. Assuming that the total volume of tissue is close to homogeneous, except for the presence of inhomogeneities such as localized bleeding in each element, and that each element can be considered as a point source, this allows for an attenuation value A i Given a set of i=1..N for N members.

[0021] Attenuation value A i To determine, in a first step, a series of measurements may be performed in which one element at a time emits light and the other elements collect the light that is measured. It should be noted that the method is not limited to one element at a time emitting light and all other elements collecting light, and other measurement regimes are possible, such as using a subset of all elements that emit light, a subset of all elements that collect light, or a combination of both.

[0022] If member i emits light and member i+1 measures the resulting optical fluence, the measured optical power may be expressed as: P i,i+1 =P i K i+1 A i A i+1 (4πD i r i,i+1 ) -1 exp(-μ eff(i) r i,i+1 ) (3) In the formula, P i is the optical power emitted by member i, and K i+1 is the conversion factor for converting the fluence rate to the power collected by element i+1, and r i,i+1 =|r i+1 -r i is the distance between members i and i+1. The coefficient K may be the same for all members, or alternatively may be considered to be known for each member, or relatively known among all members.

[0023] The measurement step provides a series of measurements which in this example can be expressed as follows: (P 1,2 P 1,3 ... P 1,N P 2,1 P 2,3 ... P N,N-1 ) (4)

[0024] In the next step, this data set is i When using this data set in Equation 3, the unknowns, the damping values ​​A i , and the optical properties D and μ eff A nonlinear simultaneous equation is obtained: P i,j =P i K j A i A j (4πD i r i,j ) -1 exp(-μ eff(i) r i,j ) (5)

[0025] This nonlinear system of equations can be solved using a nonlinear solution method, including but not limited to Newton's method, Levenberg-Marquardt method, or trust region method. In general, it is noted that the nonlinear system of equations can be overdetermined or underdetermined. The optical properties D and μ eff can be treated as unknowns or can be considered known from prior knowledge.

[0026] Equation 5 can be linearized, for example, by taking the logarithm of both sides. ln(r i,j P i,j )=ln(A i )+ln(A j )+ln(P i K j (4πD i ) -1 )-μ eff(i) r i,j (6)

[0027] μ a <<μ s and μ s is known and constant, we obtain ln(r i,j P i,j )-ln(P i K j (4π3μ s ) -1 )= =ln(A i )+ln(A j )-μ eff(i) r i,j (7)

[0028] Equation 7 is the unknown A i and μ eff(i) This system of linear equations can be solved by conventional methods for solving systems of linear equations, for example the least squares method if the system of linear equations is under- or over-determined.

[0029] Attenuation value A i To obtain the attenuation value A, the measurement system needs to be calibrated to measure the fluence rate in absolute terms. In practice, this condition may be impractical to achieve. In cases where only relative measurements of the fluence rate are available, the attenuation value A i can still be evaluated, but only in relative values. Relative attenuation values ​​can be used after normalization. For example, the attenuation value A i may be normalized such that the value of A with the smallest attenuation is set to 1. This is a conservative approach since attenuation is typically underestimated, and therefore the resulting light dose. Other normalization approaches are possible, for example based on prior knowledge of the normalized range of attenuation expected in a particular case.

[0030] In other examples, the present disclosure may not be limited to the conditions and approximations applied in the previous description. In the following, some other examples are described.

[0031] In one example, the optical element may not be a point source, but a distributed source such as a diffuser, e.g., an optical fiber with a diffuser. When using a diffuser, it may be necessary to use convolution. The same method as above may then be used to calculate the effective attenuation coefficient and attenuation value, but this may be more complicated. Finite element methods (FEM) may then be applied to resolve the complexity. Alternatively, the diffuser may be approximated as multiple point sources distributed across the dimensions of the diffuser.

[0032] In one example, optical elements may not be used for light delivery, but instead, a light source is placed directly within the tissue. The light source may be a photodiode, e.g., a light emitting diode (LED), or a laser diode.

[0033] In one example, no optical elements may be used for light collection and detection, and instead, a photodetector may be positioned directly inside the tissue. The photodetector may be, for example, a photodiode, a photomultiplier tube, an avalanche photodiode, a charge-coupled device, or a CMOS photosensitive device.

[0034] In one example, the medium may not be considered to have uniform optical properties, but may instead be modeled based on prior knowledge. For example, the medium may be considered to have regions with different optical properties based on tissue anatomy. The tissue anatomy may be known based on imaging data, e.g., X-ray, ultrasound, or magnetic resonance imaging. The optical properties may be known a priori for each region based on prior data, or may be solved with a nonlinear solver along with attenuation values.

[0035] In one example, the model of the optical fluence rate may not be based on analytical equations, but instead, numerical methods may be used to solve the transport equations, examples of such methods include the finite element method, the discrete ordinate method, or Monte Carlo simulations.

[0036] In one example, spectral information obtained by spectroscopic measurements, such as multiple wavelengths or white light, can be used to refine the model to further improve the results. By using known absorption spectra of tissue chromophores, e.g., hemoglobin, oxyhemoglobin, water, and lipids, measurements taken at multiple wavelengths can be used to constrain the model to obtain accurate results for both attenuation values ​​and optical properties.

[0037] In one example, the objective of the method is to i The object of the present invention may be to determine not only the general optical properties of the tissue, light scattering and light absorption, but also the general optical properties of the tissue, light scattering and light absorption.

[0038] In one example, the goal of the method may be to determine not only the attenuation due to inhomogeneities in the tissue, but also the losses in the optics performing the measurements. This approach allows the optics to be calibrated for light losses in a fast and efficient manner. The light may then be increased to compensate for the attenuation of the light either in the optics or in the optical fiber used to transmit the light between the tissues.

[0039] Any method, determination, or calculation described herein may be implemented on a control unit, data processing device, or computing device. A computer implementation may be performed as a computer program or software running on a control unit, data processing device, or computing device.

[0040] Any of the methods, determinations, or calculations described herein may be performed by a control unit, data processing device, or computing device, which may be connected to the optical detection system or may be a stand-alone unit.

[0041] A control unit, data processing device, or computing device may be implemented by dedicated software (or firmware) running on one or more general-purpose or dedicated computing devices. In this regard, it should be understood that each "element" or "means" of such computing devices refers to the conceptual equivalent of a method step, and that there is not always a one-to-one correspondence between the elements / means and specific hardware or software routines. One piece of hardware may sometimes comprise different means / elements. For example, a processing unit functions as one element / means when executing one instruction, but another element / means when executing another instruction. In addition, one element / means may be implemented by one instruction in some cases, but by multiple instructions in some other cases. Such software-controlled computing devices may include one or more processing units, e.g., a CPU ("Central Processing Unit"), a DSP ("Digital Signal Processor"), an ASIC ("Application Specific Integrated Circuit"), discrete analog and / or digital components, or some other programmable logic device, such as an FPGA ("Field Programmable Gate Array"). The control unit, data processing device, or computing device may further include a system memory and a system bus coupling various system components including the system memory to the processing unit. The system bus may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. The system memory may include computer storage media in the form of volatile and / or non-volatile memory such as read only memory (ROM), random access memory (RAM), and flash memory.The dedicated software may be stored in the system memory or on other removable / non-removable, volatile / non-volatile computer storage media contained in or accessible to the computing device, such as magnetic media, optical media, flash memory cards, digital tape, solid state RAM, solid state ROM, etc. The data processing device may include one or more data acquisition devices, such as an A / D converter, as well as one or more communication interfaces, such as a serial interface, a parallel interface, a USB interface, a wireless interface, a network adapter, etc. The dedicated software may be provided to the control unit or data processing device on any suitable computer readable medium, including recording media and read-only memory.

[0042] Aspects of the present disclosure describe a system for determining optical properties, such as, but not limited to, light attenuation at an optical member inserted into tissue and / or light scattering and / or light absorption properties of tissue. The system may include at least two optical members configured to be inserted into tissue, such as interstitially inserted. The at least two optical members may be configured to emit and / or collect light. The system may further include a control unit configured to control the at least two optical members such that light is transmitted from the at least one optical member to the tissue and detected from the tissue by the at least one optical member that collects light. This may result in a data set of measurements for the pair of emitting and collecting optical members.

[0043] The control unit may be further configured to determine an attenuation value at the optical element and / or an optical property of the tissue by using the data set of measurements to define a system of equations using a mathematical model of light propagation in tissue, the system of equations may be solved by the control unit using a numerical solution method.

[0044] The system may utilize any of the methods disclosed herein for determining or estimating attenuation values ​​in optical elements and / or optical properties of tissue.

[0045] In some examples, the system may include multiple optical elements. In some examples, one element emits light at a time and all other elements collect light. Alternatively, in some examples, other measurement regimes may be possible, such as using a subset of all elements that emit, or a subset of all elements that collect, or a combination thereof.

[0046] In some examples of the system, the determined attenuation values ​​at the optical element and / or the optical properties of the tissue can be used to calculate a light dose for photodynamic therapy or laser thermotherapy.

[0047] In some examples of the system, the control unit may be configured to use the determined attenuation value at the optical element and / or the optical properties of the tissue for delivery of a light dose for photodynamic therapy or laser thermotherapy.

[0048] In some examples of such systems, the optical element may be an optical fiber, or an optical fiber with a diffuser. The optical element may transmit the emitted light from the light source to the tissue and transmit the collected light to the detector. The light source and detector may be any type of light source and detector disclosed herein.

[0049] In some examples of such systems, the optical element can be a photodiode configured to be disposed within the tissue, such as interstitially disposed within the tissue.

[0050] In some examples of such systems, the optical element may be configured to emit light at multiple wavelengths, and the control unit may be configured to use the spectral detection and known absorption spectra of tissue chromophores to constrain the solution when solving the simultaneous equations.

[0051] In some examples of such systems, the mathematical model of light propagation in tissue may be based on the Boltzmann transport equation.

[0052] In some examples of the system, the dataset of measurements may be measured optical power, and a mathematical model of light propagation in tissue may be used to represent the measured optical power to set up a system of equations that is solved based on the dataset of measured optical power for a pair of emission and collection optical elements.

[0053] In some examples of such systems, the attenuation values ​​in the optical members and the optical properties of the tissue may be unknown in the mathematical model of light propagation in tissue.

[0054] In some instances of such systems, Newton's method, Levenberg-Marquardt method, or trust region method may be used as a nonlinear numerical solution method for the simultaneous equations.

[0055] In some examples of the system, the least squares method may be used as a linear numerical solution method for the linear simultaneous equations.

[0056] In an aspect of the present disclosure, a method is described for determining optical properties, such as, but not limited to, light attenuation at an optical element inserted in tissue and / or optical properties of tissue, such as light scattering properties and / or light absorption properties. The method may include controlling at least two optical elements such that light can be transmitted from at least one optical element to tissue and detected from tissue by at least one optical element that collects light. This may be used to obtain a data set of measurements for the pair of emitting and collecting optical elements. The method may further include determining the attenuation at the optical elements and / or optical properties of tissue by using the data set of measurements to define a system of equations using a mathematical model of light propagation in tissue, and solving the system of equations by using a numerical method.

[0057] The mathematical model and numerical solution of light propagation in tissue can be any of the models or methods described herein.

[0058] In some examples, the method may include calculating a light dose for photodynamic therapy or laser thermotherapy based on the determined attenuation value at the optical element and / or optical properties of the tissue.

[0059] In some examples, the method can include controlling the delivery of a light dose for photodynamic therapy or laser thermotherapy.

[0060] In some examples of the methods, the mathematical model of light propagation in tissue may be based on the Boltzmann transport equation.

[0061] In some examples of the method, the dataset of measurements may be measured optical power, and a mathematical model of light propagation in tissue may be used to represent the measured optical power to set up a system of equations that is solved based on the dataset of measured optical power for a pair of emission and collection optical elements.

[0062] In some examples of such methods, Newton's method, Levenberg-Marquardt method, or trust region method may be used as a nonlinear numerical solution method for the simultaneous equations.

[0063] In some examples of the method, the least squares method may be used as a linear numerical solution method for the linear simultaneous equations.

[0064] Any of the methods described herein may be computer-implemented methods.

[0065] In some aspects of the present disclosure, a computer program is described for determining the light attenuation at an optical element inserted into tissue, and / or the light scattering and light absorption properties of the tissue. The computer program may include instructions to perform any of the steps of the methods described herein when the computer program is executed by a computer. EXAMPLES

[0066] The disclosed method was applied to measurement data obtained from a system for PDT of prostate tissue, namely the SpetraCure P18 system, IDOSE, J. Swartling, et al “System for interstitial photodynamic therapy with online dosimetry - First clinical experiences of prostate cancer”, J Biomed Opt. 15, 058003 (2010). The system uses 18 individual optical elements that can be used for therapeutic PDT light delivery or optical spectroscopic measurement of tissue for dose planning purposes.

[0067] To obtain attenuation values, the system was calibrated to know the conversion factor K for each optical element, which was calculated by converting each element in the focusing mode to a known optical fluence (W / cm) in a reference tissue phantom. 2 ) and the corresponding readings registered on an internal spectrometer.

[0068] Measurement data was obtained by inserting an optical element into a tissue phantom (a mixture of water, Intralipid, and ink) with scattering and absorption properties similar to tissue at a measurement wavelength of 690 nm. Measurements were performed by the system by cycling through all combinations of emitting and collecting elements to obtain a set of measurements. (P1,2 P1,3 ... P1,18 P2,1 P2,3 ... P18,17) (5)

[0069] This data set was then subjected to evaluation of attenuation values ​​and optical properties. To demonstrate the improvement brought by the new evaluation method, corresponding results using the old model were calculated for comparison. In the old model, the optical properties μ eff was simply determined as the slope (e.g., logarithm of 3) of log(P) around each member as a function of r. A least-squares solution was then used to find the μ of the measured data. eff The attenuation values ​​were estimated based on the deviation to the values.

[0070] μ eff Actual values ​​of were measured independently using time-of-flight spectroscopy for reference.

[0071] FIG. 2 shows the μ of each emitter element using the old and new methods. eff Values ​​are shown. Values ​​obtained by reference measurements are also shown. As the tissue phantom is homogenous, the results for each piece should be the same. Clearly, the results are significantly improved with the new method compared to the old method.

[0072] Figure 3 shows the attenuation values ​​for each emitter element using the old and new methods. In this case, there is no reference value for the actual attenuation caused by losses in the optical element line from the tissue phantom to the detection system. However, with the old method, some of these attenuation losses are added to the μ eff It is clear that this leads to errors in the estimation of attenuation, so the estimated attenuation values ​​cannot be expected to be correct using the old-fashioned methods.

[0073] In another example, the algorithm was applied to real measurements taken from prostate tissue in vivo in a clinical setting. The measurements were obtained in the same way as described in J. Swartling, et al. “System for interstitial photodynamic therapy with online dosimetry - First clinical experiences of prostate cancer”, J Biomed Opt. 15, 058003 (2010). The data set was again based on 18 optical elements.

[0074] FIG. 4 shows the μ-field distribution of each emitter element on prostate tissue using the old and new methods. eff The older algorithm shows much more variation in the obtained values ​​than the newer algorithm. The values ​​obtained with the older algorithm are also generally higher than those obtained with the newer algorithm.

[0075] Figure 5 shows the attenuation values ​​in the prostate for each emitter element using the old and new methods. In this example, the attenuation values ​​are generally lower than the homogenous phantom example, which is expected due to bleeding in the prostate tissue causing increased attenuation.

[0076] The present invention has been described above with reference to specific examples. However, other examples than those described above are equally possible within the scope of the present disclosure. Method steps other than those described above, implementing the method by hardware or software, may be provided within the scope of the present invention. The various features and steps of the present invention may be combined in combinations other than those described. The scope of the present disclosure is limited only by the appended claims.

[0077] The indefinite articles "a" and "an," as used herein and in the claims, unless clearly indicated to the contrary, should be understood to mean "at least one." The phrase "and / or," as used herein and in the claims, should be understood to mean "either or both" of the conjoint elements, i.e., elements that are conjunctive in some cases and disjunctive in other cases.

Claims

1. 1. A system for determining an optical attenuation value around an optical element inserted in tissue or for determining an optical attenuation value at at least one optical element, the system comprising: a plurality of optical elements configured to be inserted into the tissue, the plurality of optical elements configured to emit and / or collect light, the plurality of optical elements configured to form a plurality of pairs of emitting and collecting optical elements, the emitting optical elements emitting light such that light is transmitted from the emitting optical elements to the tissue, and the collecting optical elements collecting light such that light from the tissue is detected; a control unit adapted to detect light from the tissue by the collecting optics to obtain a data set of a plurality of measurements of optical power at different pairs of the emitting and collecting optics from light propagated through the tissue between the plurality of pairs of the emitting and collecting optics; the control unit is further configured to (i) determine a light attenuation value around the optical element inserted in the tissue, and to use the light attenuation value around the optical element inserted in the tissue to determine a light attenuating inhomogeneity around the emission optical element and / or the collection optical element, or (ii) determine a light attenuation value in the at least one optical element, and to use the light attenuation value in the at least one optical element to determine a loss in the at least one optical element; and A system, wherein an optical attenuation value around the optical element inserted in the tissue or an optical attenuation value at the at least one optical element is determined by using the data set of measurements to define a system of simultaneous equations using a mathematical model of light propagation in tissue, and solving the system of simultaneous equations by using a numerical solution method.

2. The system described in claim 1, wherein an optical attenuation value around the optical element inserted into the tissue or an optical attenuation value in the at least one optical element is related to an optical attenuation in tissue proximate to at least one of the plurality of optical elements or a loss in the at least one of the plurality of optical elements.

3. 3. The system of claim 1 or 2, wherein the determined light attenuation value around at least one optical element of the plurality of optical elements is used to calculate a light dose for photodynamic therapy or laser thermotherapy.

4. The system of any one of claims 1 to 3, wherein the control unit is configured to use the determined light attenuation value around at least one of the optical elements of the plurality of optical elements when determining delivery of a light dose to the tissue for photodynamic therapy or laser thermotherapy.

5. The system of any one of claims 1 to 4, wherein the plurality of optical elements are optical fibers, or optical fibers with diffusers, for transmitting emitted light from a light source to the tissue and for transmitting collected light to a detector, or the plurality of optical elements are photodiodes configured to be positioned within tissue.

6. 6. The system of claim 1, wherein at least one of the emitting optical elements of the plurality of optical elements is configured to emit light at multiple wavelengths, and the control unit is configured to use spectral detection and known absorption spectra of tissue chromophores to constrain the mathematical model when solving the simultaneous equations.

7. The system according to any one of claims 1 to 6, wherein the mathematical model of light propagation in tissue is based on the Boltzmann transport equation.

8. 8. The system of claim 1, wherein the mathematical model of light propagation in tissue is used to represent measured optical power to set up the simultaneous equations that are solved based on the data set of multiple measured optical powers for multiple pairs of emission and collection optical elements.

9. The system of any one of claims 1 to 8, wherein the optical attenuation value around at least one optical element of the plurality of optical elements and the optical properties of the tissue are unknown in the mathematical model of light propagation in tissue.

10. The system of any one of claims 1 to 9, wherein the system of equations is solved non-linearly by a non-linear numerical method such as Newton's method, Levenberg-Marquardt method, or a trust region method.

11. The system according to any one of claims 1 to 10, wherein the system of equations is a linear system of equations that is solved by a method for solving linear equations, such as the least squares method.

12. 1. A computer program for determining a light attenuation value caused by inhomogeneities attenuating light around an optical element inserted into tissue and / or losses in at least one optical element, comprising: a plurality of optical elements configured to emit and / or collect light, the plurality of optical elements configured to form a plurality of pairs of emitting and collecting optical elements, the emitting optical elements emitting light such that light is transmitted from the emitting optical elements to the tissue, and the collecting optical elements collecting light such that light from the tissue is detected, when the plurality of optical elements are inserted into the tissue and the computer program is executed by a computer, the plurality of optical elements comprising: detecting light from the tissue with the collecting optics to obtain a data set of multiple measurements of optical power at different pairs of the emission and collecting optics from light propagated through the tissue between the multiple pairs; determining the light attenuation value and using the light attenuation value to determine inhomogeneities that attenuate light around the emission optical element and / or the collection optical element and / or losses in the at least one optical element, wherein the light attenuation value is determined by using the data set of measurements to define a system of simultaneous equations using a mathematical model of light propagation in tissue and solving the system of simultaneous equations by using a numerical solution method.

13. 13. The computer program product of claim 12, further comprising: calculating a light dose for photodynamic therapy or laser thermotherapy by using the determined light attenuation value around at least one optical element of the plurality of optical elements; and controlling delivery of the light dose for the photodynamic therapy or laser thermotherapy.

14. 14. The computer program of claim 12 or 13, wherein the mathematical model of light propagation in tissue is based on the Boltzmann transport equation.

15. 15. The computer program of claim 12, wherein the mathematical model of light propagation in tissue is used to represent measured optical powers to set up the simultaneous equations that are solved based on the data set of multiple measured optical powers for multiple pairs of emission and collection optical elements.

16. The system of equations is a nonlinear system of equations, and the system of equations is solved by a nonlinear numerical method such as Newton's method, Levenberg-Marquardt method, or a trust region method; or The computer program according to any one of claims 12 to 15, wherein the simultaneous equations are linear simultaneous equations, and the linear simultaneous equations are solved by a method for solving linear equations, such as the least squares method.

17. 1. A system for determining an optical attenuation value around an optical element inserted in tissue and an effective attenuation coefficient of said tissue, the system comprising: a plurality of optical elements configured to be inserted into the tissue, the plurality of optical elements configured to emit and / or collect light, the plurality of optical elements configured to form a plurality of pairs of emitting and collecting optical elements, the emitting optical elements emitting light such that light is transmitted from the emitting optical elements to the tissue, and the collecting optical elements collecting light such that light from the tissue is detected; a control unit adapted to detect light from the tissue by the collecting optics to obtain a data set of a plurality of measurements of optical power at different pairs of the emitting and collecting optics from light propagated through the tissue between the plurality of pairs of the emitting and collecting optics; the control unit is further configured to determine an optical attenuation value around the optical element inserted in the tissue and the effective attenuation coefficient in the tissue by using the data set of measurements to define a system of equations using a mathematical model of light propagation in tissue and solving the system of equations by using a numerical solution; and A system, wherein the light attenuation values ​​around the optical element inserted in the tissue and the effective attenuation coefficient in the tissue are used to calculate and / or control a light dose for photodynamic therapy or laser thermotherapy.

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