Systems and methods for distributing radiation for diagnostic purposes

Abstract

A system and method for coupling light into and out of an optical component are described, comprising emitting at least one light beam in the wavelength range of infrared, visible, or ultraviolet light using a light source; coupling the light beam to a proximal end of the optical component via at least one focusing optical element; collecting backscattered light using a distal end of the optical component and emitting the collected light at the proximal end of the optical component, wherein the light emitted by the optical component has an angled sector that is at least partially different from the angled sector of the light beam coupled to the proximal end of the optical component; and detecting the collected light emitted from the proximal end of the optical component using at least one photodetector.

Description

Technical Field

[0001] This disclosure generally relates to systems and methods for photodynamic therapy and / or photothermal therapy and / or diagnosis of sites on and / or within the body of an object, wherein radiation is directed to the site for responding to the radiation, wherein the system includes radiation distributors respectively from at least one radiation source to the responding site and from the responding site to at least one radiation sensor, wherein the responding site is preferably a tissue site, such as a tumor site. Background Technology

[0002] In the medical treatment of cancer, several treatment modalities have been developed to treat malignant tumors. Surgery, cell-suppressing therapy, ionizing radiation (gamma or particle radiation) therapy, isotope therapy, and brachytherapy using radioactive needles are common examples. Despite significant advances in treatment, cancer continues to cause suffering for many and contributes to a high proportion of deaths in Western countries. Photodynamic therapy (PDT) is a treatment modality that complements or replaces this approach. Photoactivators, often called sensitizers, are administered to the body transdermally, or orally, or topically. They can accumulate in malignant tumors to a greater extent than in surrounding healthy tissue. The tumor area is then irradiated with non-thermal red or infrared light, typically from a laser, causing the sensitizer to be excited to a higher energy state. The energy transferred from the activated sensitizer to the tissue creates singlet oxygen and other oxidizing agents. Singlet oxygen is known to be particularly toxic to tissues; cells are eliminated, and tissue necrosis occurs. Due to the sensitizer's localization to tumor cells, it achieves a unique selectivity, where surrounding healthy tissue remains unharmed.

[0003] Laser thermotherapy is a related treatment method that does not use photosensitizers, but instead heats the target tissue with higher laser power, causing tissue death through thermal effects.

[0004] The limited penetration of activating light into tissue is a drawback of PDT, and similar limitations exist for laser thermotherapy. This results in only surface tumors being treatable through surface irradiation. To treat thicker and deeper tumors, interstitial light delivery can be utilized. In this case, an optical fiber is introduced into the tumor using, for example, a syringe needle, with the fiber placed within the lumen of the needle. US5,304,173 discloses a catheter-based system for insertion into arteries. This system is percutaneous and can be used for diagnosing and removing tissue from the vessel wall, rather than for interstitial use.

[0005] To achieve effective treatment, several optical fibers can be used to ensure that all tumor cells receive a sufficient dose of light. Dosing calculations based on the absorption and scattering characteristics of tissue have been demonstrated. To perform these dosage calculations, it is advantageous to first measure the light flux through the tissue in the area where treatment will take place. The measured values ​​can then be used to determine the tissue's absorption and scattering characteristics. These measurements can be performed using separate fiber groups, but it is generally preferred to use the same fiber group as used for treatment because fewer fibers in total must be inserted into the tissue, and the inserted fibers will cover the exact same volume when used for both measurement and treatment. When using the same set of fibers for treatment, some means is needed to switch between measurement and treatment. For example, a system is described in patent EP 1 443 855 A1 in which multiple fibers are used for treatment and for measuring the light flux from other fibers penetrating the tissue to reach a given fiber.

[0006] Patent EP 1 443 855 A1 describes a device that switches between treatment and measurement using an optical fiber and a rotating disk structure. In this way, the correct light dose can be delivered to all parts of the tumor.

[0007] When performing interstitial illumination and measurements as described above, limitations arise because the rotating disk structure can be slow, costly to manufacture, and requires extensive calibration and maintenance. Therefore, a system and method are described in patent EP 1 624 803 A1, in which therapeutic and / or diagnostic radiation is directed to the reaction site via a radiation conductor using a non-mechanical operating mode selector. Several non-mechanical operating mode selectors are described, such as electro-optic switches based on electrically controlled refractive index changes or acousto-optic switches based on sound-generating Bragg deflection. However, while these non-mechanical operating mode selectors are improvements on mechanical switches, they are active components that increase cost and complexity.

[0008] Mode selection using passive components can be achieved by using a beam splitter to calibrate the optical paths of therapeutic and diagnostic radiation. However, when the therapeutic and diagnostic radiation have the same wavelength, the beam splitter will cause radiation loss in both the therapeutic and diagnostic radiation. For example, if the beam splitter has a 50 / 50 transmission / reflection ratio, half of the therapeutic radiation and half of the diagnostic radiation will be lost.

[0009] Therefore, new and improved apparatuses and methods for combining radiation distribution and measurement in the same component would be advantageous. Summary of the Invention

[0010] Therefore, the examples of this disclosure preferably seek to mitigate, alleviate, or eliminate one or more deficiencies, disadvantages, or problems in the art, such as those described above, by providing, individually or in combination, apparatus, systems, or methods according to the appended claims for combining radiation distribution and measurement in the same components.

[0011] Lasers and some light-emitting diodes are known to have high emissivity, i.e., high power per unit emission surface area and per unit solid angle. This property results in light emitted from a laser source being focused into a small area, even with a small numerical aperture (NA). On the other hand, light passing through biological tissue is typically already scattered, resulting in relatively low emissivity once emitted from the tissue. To effectively capture light emitted from biological tissue, a light guide with a relatively high cross-sectional area and high NA is preferably used.

[0012] This disclosure utilizes these properties of light sources and light guides to provide an apparatus for passively calibrating operating modes that distribute light to tissues and measurements of said tissues, without requiring mechanical or active switching elements.

[0013] In one aspect of this disclosure, a system for diagnosing a subject is described. The system may include at least one diagnostic light source for emitting diagnostic light in a wavelength range of infrared, visible, or ultraviolet light, the diagnostic light source being capable of emitting at least one beam. The system may also include at least one photodetector for detecting the light and a plurality of optical components adapted to conduct light to and / or from tissue sites of the subject. The distal ends of the plurality of optical components may be configured to be positioned at different locations within the tissue site to enable effective diagnosis and / or treatment.

[0014] The system may further include each optical element configured such that at least one of the light beams from at least one diagnostic light source is coupled to the proximal end of the plurality of optical elements through at least one focusing optical element. Diagnostic light emitted back from the tissue may be emitted from the proximal end of the plurality of optical elements and has emission in at least part of an angular sector different from the angular sector of the focused light beam, such that the diagnostic light scattered back from the tissue is detected by at least one photodetector.

[0015] In some examples of this disclosure, multiple optical components can be configured to be arranged in the intermediate texture of the tissue.

[0016] In some examples of this disclosure, the system may also be configured for interactive photodynamic or photothermal therapy and includes at least one therapeutic light source for emitting therapeutic light in the wavelength range of infrared, visible, or ultraviolet light, the therapeutic light source emitting at least one beam of light coupled to the proximal end of an optical component via a focusing optical element.

[0017] In some examples of this disclosure, the diagnostic light source may be the same as the therapeutic light source.

[0018] In some examples of this disclosure, the wavelength range of the diagnostic light source may be the same as that of the therapeutic light source.

[0019] In some examples of this disclosure, the system may also include a reflective element for coupling light from the proximal end of the optical element to at least one detector.

[0020] In some examples of this disclosure, the reflective member has at least one aperture for diagnostic light to be transmitted through as it propagates between the at least one diagnostic light source and the proximal ends of the plurality of optical members.

[0021] In some examples of this disclosure, a hole is at least one opening or slit.

[0022] In some examples of this disclosure, one of the plurality of optical components may be a transmission component for transmitting diagnostic light to a tissue site, and at least two other optical components may be receiving components for receiving backscattered light from the tissue site for detection.

[0023] In some examples of this disclosure, the transmission element can be selected sequentially among multiple optical elements.

[0024] In some examples of this disclosure, the system may also include multiple modules, each module including a light-emitting portion, a light-detecting portion, one of at least one focusing optical component, and one of multiple optical components, the light-emitting portion including at least one of at least one diagnostic light source, and the light-detecting portion including at least one of at least one detector.

[0025] In some examples of this disclosure, the transmission component can be selected sequentially among multiple optical components by turning the light-emitting portions of multiple modules on and off in turn.

[0026] In some examples of this disclosure, the system is configured to have an open beam path between the near ends of at least one light source and a plurality of optical components and between the near ends of the plurality of optical components and at least one photodetector.

[0027] In some examples of this disclosure, multiple optical components may be configured to be arranged in a tissue site to perform spatially resolved measurements.

[0028] In some examples of this disclosure, at least one second focusing element may be arranged in front of at least one detector.

[0029] In another aspect of this disclosure, a method for coupling light into and out of an optical component is described. This method may include using a light source to emit at least one light beam within the wavelength range of infrared, visible, or ultraviolet light.

[0030] The method may also include coupling the light beam to the proximal end of the optical component via at least one focusing optical element.

[0031] The method may further include collecting backscattered light at the distal end of the optical component and emitting the collected light at the proximal end of the optical component, wherein the light emitted by the optical component has an angled sector that is at least partially different from the angled sector of the beam coupled to the proximal end of the optical component, and detecting the collected light emitted from the proximal end of the optical component using at least one photodetector.

[0032] It should be emphasized that, when used in this specification, the term "light" is used to specify electromagnetic radiation of any wavelength in the electromagnetic spectrum, including ultraviolet radiation, visible light, and infrared radiation.

[0033] It should also be emphasized that this disclosure is not limited to use in the treatment of malignant tumors, but can be used in any situation where tissue therapy is performed using optical components (such as optical fibers), or in any situation where tissue measurement is performed using optical components.

[0034] It should also be emphasized that this disclosure is not limited to using lasers as a light source, but can use any type of light source with sufficiently high radiation.

[0035] It should also be emphasized that, when used in this specification, the term "comprising" is used to specify the presence of the said feature, integer, step, or component, but does not exclude the presence or addition of one or more other features, integers, steps, components, or groups thereof. Attached Figure Description

[0036] The above and other aspects, features, and advantages that the examples of this disclosure can possess will become clear from the following description of the examples of this disclosure, with reference to the accompanying drawings, wherein...

[0037] Figure 1 An illustrative example of a construction according to this disclosure is shown;

[0038] Figure 2 A schematic example of an arrangement for coupling light into and out of an optical component is shown;

[0039] Figure 3 A schematic example of an arrangement for coupling light into and out of an optical component is shown;

[0040] Figure 4A schematic example of an arrangement for coupling light into and out of an optical component is shown;

[0041] Figure 5 An example is shown of coupling at least two light sources of different wavelengths into and out of an optical component;

[0042] Figure 6 An example is shown of coupling at least two light sources of different wavelengths into and out of an optical component;

[0043] Figure 7 An example is shown of coupling at least two light sources of different wavelengths into and out of an optical component;

[0044] Figure 8 This is an example of how the previously described construction can be arranged to couple light in and out at multiple locations;

[0045] Figure 9 A schematic example of a hole in a reflector is shown;

[0046] Figure 10 A schematic example of a hole in a reflector is shown, which is a slit or two or more separate reflectors forming one or more slits. Detailed Implementation

[0047] The following disclosure focuses on examples of how this disclosure can be applied to combining radiation distribution and measurement within the same component using passive elements. This disclosure can be applied to photodynamic or photothermal therapy of tissues. For example, this is advantageous for accurate dosing of light dose, enabling treatment of a predetermined tissue while protecting surrounding tissues from damage. However, it should be understood that this specification is not limited to this application but can be applied to many other systems in which combining radiation distribution and measurement within the same component using passive elements is useful.

[0048] For reference Figure 1 The laser shown emits light for coupling into an optical component (such as an optical fiber).

[0049] Figure 1 An example of this disclosure is shown. A light source 1 (e.g., a laser) can emit light 4 (e.g., a beam), which can be focused by a focusing element 6 (e.g., a lens or lens assembly) into an optical element 2 (e.g., an optical waveguide or optical fiber). The light can be focused into the proximal end of the optical element 2.

[0050] Due to the characteristics of the light source 1, the numerical aperture NA of the focused beam 8 can be lower than the receiving angle of the optical component 2.

[0051] The distal end (not shown) of optical component 2 can be used to collect backscattered light from the area to be measured or diagnosed (e.g., a tissue site or tumor). The collected backscattered light can be emitted from the proximal end of optical component 2. Optical component 2 can have a higher NA than the focused beam 8, and because the light collected by optical component 2 from the area of ​​backscattered light (e.g., a tissue site) is diffused, the light 9 emitted from optical component 2 fills the NA of optical component 2. Therefore, the light 9 emitted from optical component 2 can result in a wider beam than the focused beam 8.

[0052] At least one detector can be used to detect the emitted light.

[0053] Additionally and / or alternatively, light 4 emitted from at least one light source 1 can pass through a reflecting member 5 (e.g., a mirror), which allows light to pass through an aperture 13 where it can pass through while being reflected elsewhere. Since light 9 emitted backward from the proximal end of the optical member 2 fills the NA of the optical member 2, a major portion of the light 9 emitted from the optical member 2 can be reflected away from the reflecting member 5 and can be detected using at least one detector 3. At least one detector may have a second focusing element 7 (e.g., a lens or lens assembly) arranged in front to focus the light 9 reflected by the reflecting member 5 onto the detector.

[0054] Light transmitted from at least one light source 1 to optical component 2 and light emitted from optical component 2 to at least one detector 3 can be transmitted in an open beam path without the use of waveguides or optical fibers.

[0055] Using the disclosed system and method, light can be distributed via optical fiber and measured at the same wavelength via the same optical fiber without the need for mechanical or active switches.

[0056] The advantage of using this technique in this disclosure is that the measurement of light distribution can be completed instantaneously, which can lead to shorter operation time and shorter total clinical time.

[0057] Another advantage of this disclosure is that it allows for simultaneous light distribution and measurement within the same optical component, which is not possible with a switching module.

[0058] Another advantage of this disclosure is that it has no moving parts, which reduces the possibility of component failure.

[0059] In some of the examples disclosed herein, light 4 from at least one light source 1 can be focused by an optical focusing element 6 onto a near-side optical element 2 (by obtaining a focused beam 8). In some of the examples disclosed herein, light emitted from the optical element can be directly detected by at least one photodetector 3. The detector 3 can be, for example, a photodiode, photomultiplier tube, avalanche photodiode, charge-coupled device (CCD), or CMOS photosensitive device.

[0060] In one example, the light source can be a lamp, a photodiode, such as a light-emitting diode (LED), or a laser diode. The light source can have one or more filters for filtering the wavelengths of the emitted light.

[0061] The light source can be a diagnostic light source, having a wavelength that can be absorbed by one or more chromophores in the tissue (e.g., deoxyhemoglobin and / or oxyhemoglobin). The light source can also be the same as a light source used to treat tissue sites (e.g., to treat tumors).

[0062] Diagnosis and treatment can be performed sequentially. For example, a treatment cycle can be performed first, followed by a diagnostic cycle. In some cases, treatment and diagnosis can be conducted simultaneously.

[0063] In some examples, any type of focusing element 6 is used to focus light from the light source 1 onto the optical component 2 and / or collimate light emitted from the near end of the optical component 2, such as, but not limited to, lenses, curved mirrors, diffractive elements, holographic elements, Fresnel lenses, Fresnel mirrors, and microelectromechanical (MEMS) mirrors. It should be noted that in the examples described with reference to the accompanying drawings in this disclosure, the lens can be replaced with any of these elements.

[0064] In some examples, the focusing component 7, which can be used to focus the light emitted from the optical component 2 onto the detector 3, can be, but is not limited to, a lens, a curved mirror, a diffraction element, a holographic element, a Fresnel lens, a Fresnel mirror, or a microelectromechanical (MEMS) mirror.

[0065] In some examples, any type of optical component 2 (e.g., a light conductor) can be used to conduct light to the reaction site (e.g., a tissue site), including but not limited to optical fibers, liquid light conductors, hollow light conductors, or plastic light conductors.

[0066] In some examples, light from a light source is guided to an optical fiber via a mirror, while light emitted from the optical fiber is detected on the same optical axis as the fiber.

[0067] refer to Figure 2The light from the light source 1 is focused by the optical focusing component 6 (e.g., a lens) to obtain a focused beam 8 that enters the optical component 2 (e.g., an optical waveguide or optical fiber), and a portion of the light emitted by the optical component 2 can be detected by the photodetector 3.

[0068] Light can be detected because the light 9 emitted from the optical component 2 fills the NA of the optical component 2, which results in a beam wider than the focused beam 8. The detector 3 can be arranged at an angle relative to the beam path of the focused beam 8 to collect at least a portion of the light 9 emitted from the optical component 2.

[0069] Figure 3 Another example is shown, in which a beam of light from a light source 1 can be focused by an optical focusing component 6 to obtain a focused beam 8 that is guided to the proximal end of an optical component 2, and light 9 emitted from an optical component 2 can be measured by a disk-shaped photodetector 3 having a hole at its center in which the optical focusing component 6 can be positioned.

[0070] refer to Figure 4 The light beam from the light source 1 is reflected away from the reflective member 10 (e.g., a reflector) and focused by the focusing member 6 onto the near end of the optical member 2, while the light emitted from the optical member 2 is detected by the focusing member 76 and the photodetector 3.

[0071] In some examples of the arrangements described herein, multiple light sources are coupled to the same optical component. For example, to measure the oxygen saturation of a tissue, at least two light sources of different wavelengths are required to distinguish between oxyhemoglobin and nonoxyhemoglobin. Alternatively and / or additionally, in some examples, multiple light sources are coupled to the same optical component, wherein at least one light source is used to measure chromophores, for example, to detect the oxygen saturation of a tissue, while at least a second light source is used for treatment.

[0072] refer to Figure 5 At least two light sources (here shown as three light sources 1a, 1b, and 1c with different wavelengths) are coupled into optical component 2. Beam splitter 11 can be selected such that it transmits the wavelength of light source 1a but reflects the wavelength of light source 1b. Beam splitter 12 can be selected such that it transmits the wavelengths of light sources 1a and 1b but reflects the wavelength of light source 1c. This can be achieved by arranging light sources 1a, 1b, 1c, 2, and 3 with increasing wavelengths, selecting beam splitter 11 as a short-pass filter, and selecting beam splitter 12 as a short-pass filter with a higher cutoff wavelength.

[0073] Alternatively, this can be achieved by configuring light sources 1a, 1b, and 1c with reduced wavelengths, selecting beam splitter 11 as a long-pass filter, and selecting beam splitter 12 as a long-pass filter with a lower cutoff wavelength. It should be noted that the number of light sources is not limited to three; any number of light sources with the same principle can be used. It should also be noted that beam splitters 11 and 12 are not limited to high-pass or low-pass beam splitters; any wavelength-selective beam splitter with appropriate characteristics can be used, such as band-pass beam splitters or notch beam splitters.

[0074] The arrangement for coupling light into and out of optical component 2 is as follows: Figure 1 As shown, this is just an example, and other methods are also possible, such as those described in the references. Figures 2 to 4 As described.

[0075] In some examples, multiple light sources 1a, 1b, 1c can be coupled into optical component 2 without the need for a beam splitter. (Reference) Figure 6 In the example, the light (e.g., beams) from each light source 1a, 1b, 1c is spatially separated, and each of them passes through holes 13a, 13b, 13c in the reflecting member 5 (e.g., a mirror) and is then focused into the optical member 2 by the focusing member 6.

[0076] The collected light can then be emitted from the proximal end of the optical component 2, collimated by the focusing component 6, and reflected by the reflecting component 5 to be directed toward at least one detector 3. At least one detector may have a second collecting component 7 arranged in front to focus the light onto at least one detector 3.

[0077] In some examples, a slit may be used in the reflective member 5 as an alternative to using a single aperture 13 for each optical path and / or beam.

[0078] exist Figure 9 The arrangement of using holes as apertures 13 is further illustrated in the image, while... Figure 10 The diagram further illustrates the use of a slit as an alternative to aperture 13. In these examples, the reflective element 5 is used with a single light source 1, but the principle remains the same for multiple light sources. Figure 9 When multiple light sources 1 are used, the reflective member 5 may have additional apertures 13, for example, one aperture 13 for each light source and / or optical path and / or beam. Figure 10In this configuration, a single slit can be used with multiple light sources, provided that the slit is long enough to accommodate the individual optical paths from each light source 1. Alternatively, the reflective member 5 may have a slit 13 for each light source and / or optical path and / or beam. The slit can be formed in a reflective member (e.g., a mirror) or by positioning two mirrors adjacent to each other with a gap between them, where the gap will serve as the slit.

[0079] refer to Figure 7 The example illustrates how reflective elements 13 and 14 can be used to spatially separate light beams from each of the light sources 1a, 1b, and 1c. In this example, one of the light sources 1a is arranged along the optical axis, while the other two light sources are arranged at an angle to the optical axis (e.g., perpendicular to the optical axis). By arranging the reflective elements 13 and 14 at different distances from the optical axis, light can be reflected from the other two light sources 1b and 1c to obtain three parallel light paths and / or beam paths.

[0080] Each parallel optical path and / or beam path can pass through the aperture (e.g., as shown in the image). Figure 9 (Or as shown in Figure 10, in the hole in the reflecting member 5). Light can then be focused into the optical member 2 by the focusing member 6. Most of the light returning from the optical member 2 can be reflected by the reflecting member 5 to the beam splitter 15, which reflects light having the wavelength (shortest wavelength) of the light source 1a, while light having a wavelength longer than that of the light source 1a can be transmitted and detected by the detector 3a. The light reflected by the beam splitter 15 can be detected by the detector 3b, or it can be reflected by another reflecting element 16 (e.g., a mirror) that directs the light to the detector 3b. With this arrangement, light from the light source 1b or 1c can be detected simultaneously with light having the wavelength of the light source 1a. Alternatively, light from the light source 1a can induce fluorescence in tissue having a wavelength longer than that of the light source 1a, for example, by photosensitizer-induced fluorescence. In this case, the fluorescence can be detected by the detector 3a, which is separated from the light from the light source 1a that will be detected by the detector 3b. Light sources 1b and 1c can be turned on sequentially after the light source 1a, and the detected light can be detected by the detector 3a.

[0081] In some examples, such as those described in this disclosure, multiple modules are combined into a single complete system, such that these modules can interact in the manner described in patent EP 1.443 855A1. Figure 8 It shows a model based on multiple modules (e.g.) Figures 1 to 7A system (as shown in any of the modules) where multiple optical fibers can be connected to the system. The system may include at least two optical elements configured to be inserted into tissue, such as interstitially. The at least two optical elements may be configured to emit and / or collect light. The system may also include a control unit configured to control the system such that light is transmitted from at least one optical element to the tissue and that light from the tissue is detected by collecting light through at least one optical element. This yields a dataset of measurements of the emitting and collecting optical element pairs.

[0082] For example, the transmission component of an optical component can be selected sequentially among multiple optical components. This can be accomplished by sequentially turning on and off the light-emitting parts of multiple modules.

[0083] In some examples, the system may include multiple optical components. In some examples, at a time, a single optical fiber may emit light, while all the other optical fibers collect the light. Alternatively, in some examples, other measurement schemes are also feasible, such as using a subset of all the optical fibers that emit light, or a subset of all the optical fibers that collect light, or a combination of these.

[0084] In some examples of the system, the optical properties of the measured and / or determined tissues can be used to calculate the light dose for photodynamic therapy or laser thermotherapy.

[0085] In some examples, multiple optical components are configured to be arranged on the tissue site, enabling spatially resolved measurements. The optical properties can then be obtained from the measurements by solving the transmission equations for radiative transmission.

[0086] In some examples of the system, the optical components may be optical fibers or optical fibers with diffusers. The optical components can be configured to be interstitially disposed within the tissue to allow for treatment and / or diagnosis of deep tissue sites. In one example, this can be accomplished using a needle, syringe, and / or catheter.

[0087] Alternatively, in some examples, the optical components are configured to transmit light to and from the surface of a tissue site (e.g., the surface of the skin or a surface in a body cavity).

[0088] The optical components can transmit light emitted from the light source to the tissue and transmit the collected light to the detector. The light source and detector can be any type of light source and detector disclosed herein.

[0089] In other examples, this disclosure may not be limited to the conditions applied in the preceding description. Several other examples are described below.

[0090] In some examples, it is advantageous to detect not only light from one light source but also light of other wavelengths at the same time. Figure 1-10 The detector in the optical fiber can be replaced by a device that performs spectral decomposition on the light emitted from the optical fiber (e.g., by using a spectrometer or multiple wavelength-selective optical filters and detectors).

[0091] In some examples, one or more holes in the mirror are transparent areas on the mirror, while the rest of the mirror surface is coated with a reflective material.

[0092] In some examples, one or more holes in the mirror are openings in the mirror, such as... Figure 9 As shown.

[0093] In some examples, one or more holes in the mirror are slits in the mirror, or two or more separate mirrors form one or more slits, such as... Figure 10 As shown.

[0094] In the following sections, the basic principles relating to the system according to this disclosure will be described, wherein the description is based on an exemplary system having three diagnostic light sources and six optical components, such as six modules, each module including three diagnostic light sources coupled to a single optical component (preferably multiple optical fibers).

[0095] In this text, the reaction or treatment site refers to the site where treatment (e.g., photothermal therapy) is performed, or the site where a photodynamic active compound can react in the tumor when subjected to therapeutic radiation (e.g., performed by individual optical components, which pass through the lumen of an injection needle or catheter, for example, placed in the tumor). These optical components can then be fixed in the reaction site. The optical components can then be moved forward to reach beyond the distal end of the needle or catheter. The same optical components are used continuously during treatment for integrated diagnosis and dosing, and to avoid subjecting the patient to multiple stings.

[0096] Preferably, each diagnostic light source is a laser and / or a light-emitting diode, one of which has the same wavelength as the laser used for photothermal therapy or photodynamic tumor therapy, but may have a lower output power. Suitable filters can be arranged to be inserted into the optical path to ensure that the correct dynamic range is used for all measurement tasks and to prevent radiation detector saturation.

[0097] Certain diagnostic light sources are used to study how radiation with corresponding wavelengths penetrates tumor tissue at the treatment site.

[0098] When radiation from a radiation source is transmitted into the tissue via the aforementioned arrangement through specific optical components, one of the optical components acts as a transmitter into the tissue site (e.g., a tumor), while in this example, five optical fibers in the tissue site (e.g., a tumor) act as receivers and collect the diffusion flux of the radiation arriving at them. The optical components transmit the collected light and emit light, making it detectable by at least one detector as described above, and five different light intensities can be recorded for each wavelength.

[0099] As an alternative for specific wavelengths, light from optical broadband sources such as white light sources and / or broadband light-emitting diodes and / or line sources can be coupled into specific active optical components. As the optical components pass through the tissue to reach the patient, the known spectral distribution of the light source can be corrected by tissue absorption. Oxygenated blood then produces characteristics distinct from deoxygenated blood, allowing for the chromatography determination of oxygen distribution using thirty different spectral distributions read out, five spectra at a time in six possible contellations. This determination of oxygenation in tumors is important because the PDT process requires the acquisition of oxygen from the tissue.

[0100] Finally, when one of the light sources can induce fluorescence in the tissue, the sensitizer given to the tissue exhibits a fluorescence distribution characteristic shifted towards longer wavelengths. The intensity of the corresponding signal allows for approximate quantification of the sensitizer level in the tissue. For some substances, red light used for light propagation studies can be used to induce red or near-infrared fluorescence. This fluorescence travels through the tissue to the end of the receiving optics and is simultaneously displayed as a spectrum obtained by one of the detectors. Chromatographic calculations of the sensitizer distribution can be performed based on a total of 30 measurements at each measurement time.

[0101] If the ends of the components are additionally treated with a material whose fluorescence properties depend on temperature, sharp fluorescent lines are obtained upon excitation, and the intensity of these lines and their relative intensities depend on the temperature of the ends of the optical components used for treatment. Examples of such materials are salts of transition metals or rare earth metals. Therefore, the temperature can also be measured one at a time or simultaneously at six locations on six optical components. The measured temperatures can be used to determine whether blood coagulation has occurred at the ends of the optical components (related to light attenuation), and for studies utilizing possible synergies between PDT and thermal interactions. Because the obtained lines are sharp, they can be readily extracted from a broader broadband distribution of intrinsic fluorescence from the tissue.

[0102] After diagnostic measurements and calculations have been performed, the optical components coupled to the patient can be used for treatment by turning off the diagnostic light source and turning on the therapeutic light source, thus coupling the therapeutic light source to the patient's optical components. The therapeutic light source is preferably a laser source with a wavelength selected to match the absorption band of the sensitizer. In photodynamic tumor therapy, dye lasers or diode lasers are preferred, with their wavelengths selected according to the sensitizer used. For example: for The wavelength is 630 nm for anthraquinone (ALA), 635 nm for phthalocyanine, and approximately 670 nm for other sensitizers with similar wavelengths. During treatment, each laser is adjusted to its desired output power. They can have built-in or external monitoring detectors if needed.

[0103] Therapeutic treatment may be interrupted, and new diagnostic data may be processed in an interactive manner until optimal treatment is achieved. This method may include a synergistic effect between PDT and thermotherapy, where increased temperature is achieved with increased laser radiation flux. The entire process can be controlled using, for example, a computer control unit that not only performs all calculations but also regulates and controls the system. The invention has been described above with reference to specific examples. However, other examples besides those described above are also possible within the scope of this disclosure. Method steps different from those described above may be provided within the scope of this invention. Different features and steps of the invention may be combined in combinations other than those described. The scope of this disclosure is defined only by the appended claims.

[0104] As used in this specification and claims, the words “a” and “an” should be understood to mean “at least one” unless explicitly stated to the contrary. The phrase “and / or” as used in this specification and claims should be understood to mean “one or two” of the elements so combined, that is, elements that exist in combination in some cases and independently in others.

Claims

1. A system for diagnosing a subject, the system comprising a plurality of modules and a plurality of optical components adapted to conduct light to and / or from a tissue portion of the subject, wherein distal portions of the plurality of optical components are configured to be intermittently positioned at different locations within the tissue portion; Each of the plurality of modules is connected to the proximal end of one of the plurality of optical components, and each of the modules includes: At least one diagnostic light source for emitting diagnostic light in the wavelength range of infrared, visible, or ultraviolet light, said diagnostic light source emitting at least one light beam; At least one photodetector for detecting light; Focusing optical components; Each module is characterized by: The optical component connected to the module is configured such that at least one of the light beams from the at least one diagnostic light source is coupled to the proximal end of the connected optical component through the at least one focusing optical element, and the diagnostic light emitted back from the tissue is emitted from the proximal end of the connected optical component, the connected optical component having a higher numerical aperture (NA) than the focused light beam coupled to the optical component to provide at least partially emission in an angled sector different from the angled sector of the focused light beam, such that the at least one photodetector detects the diagnostic light scattered back from the tissue.

2. The system according to claim 1, characterized in that, The system includes at least two diagnostic light sources coupled to each of the plurality of optical components.

3. The system according to any one of claims 1 to 2, characterized in that, The system includes at least one diagnostic light source and at least one therapeutic light source coupled to each of the plurality of optical components.

4. The system according to any one of claims 1 to 3, characterized in that, Each of the plurality of optical components has a distal portion configured for interfacial positioning, and wherein each of the plurality of optical components is separated to be positioned at different locations in the tissue site.

5. The system according to any one of claims 1 to 4, characterized in that, At least one of the plurality of optical components transmits light to the tissue site, and a group of optical components that do not transmit light to the tissue site collects the light detected by the at least one detector.

6. The system according to claim 5, characterized in that, The transmission component of the optical component is selected sequentially among the plurality of optical components.

7. The system according to any one of claims 1 to 6, characterized in that, The system is further configured for interactive photodynamic or photothermal therapy and includes at least one therapeutic light source for emitting therapeutic light in the infrared, visible, or ultraviolet wavelength range, the therapeutic light source emitting at least one beam that is coupled to the proximal end of the optical component via the focusing optics.

8. The system according to claim 7, characterized in that, The diagnostic light source is the same as the therapeutic light source, or the wavelength range of the diagnostic light source is the same as the wavelength range of the therapeutic light source.

9. The system according to any one of claims 1 to 8, characterized in that, The reflective member is used to couple the light from the proximal end of the optical member to the at least one detector.

10. The system according to claim 9, characterized in that, The reflective member has at least one aperture through which the diagnostic light is transmitted as it propagates between the at least one diagnostic light source and the proximal ends of the plurality of optical members.

11. The system according to claim 10, characterized in that, The hole is at least one opening or slit.

12. The system according to any one of claims 1 to 11, characterized in that, One of the plurality of optical components is a transmission component for transmitting the diagnostic light to the tissue site, and at least two other optical components are receiving components for receiving backscattered light from the tissue site for detection.

13. The system according to claim 12, characterized in that, The transmission component is selected sequentially among the plurality of optical components.

14. The system according to claim 12, characterized in that, The transmission component sequentially selects among the plurality of optical components by turning the light-emitting portions of the plurality of modules on and off in turn.

15. The system according to any one of claims 1 to 14, characterized in that, The system has an open beam path between the at least one light source and the proximal ends of the plurality of optical components and between the proximal ends of the plurality of optical components and the at least one photodetector.

16. The system according to any one of claims 1 to 15, characterized in that, The plurality of optical components are configured to be arranged on the tissue site to perform spatially resolved measurements.

17. The system according to any one of claims 1 to 16, characterized in that, At least one second focusing element is arranged in front of the at least one detector.

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