Intrinsic fluorescence generation using exogenous fluorescence agent

Abstract

Methods, systems, and devices determine a glomerular filtration rate (GFR) by obtaining a measurement data set. Further, the present disclosure includes obtaining a measurement dataset comprising a plurality of measurement entries obtained before and after administration of the exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the intensity of the detected fluorescence emitted from the exogenous fluorescent agent within the diffusely reflecting medium; determining whether the IF signal includes a portion of the early fluorescence data; upon determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering an IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change of the operable IF signal; a GFR value is provided.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480070703.3 (22) Application Date 2024.09.26 (30) Priority Data 63 / 540,510 2023.09.26 US (85) PCT International Application Entering National Phase Date 2026.05.06 (86) PCT International Application Application Data PCT / US2024 / 048614 2024.09.26 (87) PCT International Application Publication Data WO2025 / 072487 EN 2025.04.03 (71) Applicant Medibecon Ltd. Address Missouri, USA (72) Inventors Jesse Ross-Jones, Jochen Friedman (74) Patent Agency Beijing Kangxin Intellectual Property Agency Co., Ltd. 11240 Patent Attorney Chen Rui (51) Int.Cl. G01N 21 / 64 (2006.01) A61B 5 / 20 (2006.01) A61B 90 / 00 (2006.01) A61K 49 / 00 (2006.01) G02B 5 / 02 (2006.01) G02B 5 / 22 (2006.01) A61B 5 / 1455 (2006.01) (54) Invention Title Intrinsic Fluorescence Generation Using Exogenous Fluorescent Agents (57) Abstract Methods, systems and apparatus for determining glomerular filtration rate (GFR) by obtaining a measurement dataset. Furthermore, this disclosure includes: obtaining a measurement dataset comprising multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from the exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change of the operable IF signal; and providing the GFR value.Claims 3 pages, Description 17 pages, Drawings 8 pages, CN 122139117 A 2026.06.02 CN 1 22 13 91 17 A 1. A method for determining glomerular filtration rate (GFR) in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of the exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal representing a detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining the portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change across the operable IF signal range; and providing the GFR value. 2. The method of claim 1, wherein determining whether the IF signal includes the portion of the early fluorescence data includes determining a falling segment of the IF signal. 3. The method of claim 2, wherein determining whether the IF signal includes the portion of the early fluorescence data comprises: determining a preliminary GFR value (GFRprel) occurring at a preliminary GFR time (tGFRprel), wherein determining GFRprel comprises calculating the renal decay time constant (RDTC) by: performing an initial estimation of a single exponential curve fit for the IF signal across at least a sequential or overlapping portion of the IF signal based on determining when a segment of the IF signal prior to tGFRprel exceeds a quality threshold. 4. The method of claim 3, further comprising: determining a start time tstart, the start time representing a point in time prior to the evaluation of tGFRprel and during the determined IF signal decline segment; determining the start of a fitting interval for the single exponential curve fit of the operable IF signal, the fitting interval being the sum of the start time tstart and a calculated value of a first constant multiplied by the exponent of the Euler number plus a second constant (ttoeq); setting the fitting interval as the single exponential curve fit of the operable IF signal. 5. The method of claim 4, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time tinterpol, said time tinterpol being determined using GFRprel by linear interpolation between: a low GFR boundary (GFRlow) with associated time tlow and / or a high GFR boundary (GFRhigh) with associated time thigh.6. The method of claim 3, further comprising: determining a start time (tstart), the start time representing a point in time prior to the single exponential curve fitting of the operable IF signal and during a determined falling segment of the IF signal; setting a starting point (teq) for the single exponential curve fitting of the operable IF signal range; wherein teq = tstart + ttoeq, and wherein A, B, and C are constants. 7. The method of claim 3, wherein determining the falling segment of the IF signal comprises: identifying a predetermined fitting window; performing a single exponential curve fitting of the IF signal according to the following formula: IFfit = C0 + C1 e⁻t / RDTC, where IFfit represents the fitting of a portion of the IF, C0 and C1 are curve fitting constants, t is time, and RDTC is a time parameter; calculating RDTC values ​​in at least two segments of the predetermined fitting window; comparing the RDTC values ​​from the at least two segments until all RDTC values ​​correspond to positive values. 8. The method of claim 7, further comprising: determining a start time (tstart), the start time representing a point in time prior to the single exponential curve fitting of the operable IF signal and during a determined IF signal descent segment; setting a starting point (teq) for the single exponential curve fitting of the operable IF signal; wherein teq = tstart + ttoeq, and wherein A, B, and C are constants. 9. The method of claim 8, wherein teq is set based on determining when the single exponential curve fitting according to the IFfit equation exceeds a quality threshold. 10. The method of claim 8, wherein tstart is determined once GFRprel is determined at tGFRprel, and tstart is tGFRprel minus time (tinterpol), the time being determined using GFRprel by linear interpolation between: a low GFR boundary (GFRlow) with an associated time low and / or a high GFR boundary (GFRhigh) with an associated time thigh. 11. The method of claim 3, wherein determining whether the IF signal includes the portion of the early fluorescence data further comprises performing a reverse look-through component filter. 12. The method of claim 1, wherein determining the GFR value comprises calculating the renal decay time constant (RDTC) by performing a single exponential curve fitting of the operable IF signal across at least a sequential or overlapping portion of the operable IF signal.13. The method of claim 12, wherein the single-exponential curve fitting of the operable IF signal comprises performing a logarithmic transformation on the operable IF signal and subsequently fitting a linear function to the logarithmically transformed operable IF signal. 14. The method of claim 12, wherein determining the GFR value begins at the start point (teq) of the single-exponential curve fitting of the operable IF signal. 15. The method of claim 12, wherein determining the GFR value is based on the rate of change of the operable IF signal after the start of the single-exponential curve fitting of the operable IF signal. 16. The method of claim 1, wherein providing the GFR value comprises displaying the GFR value on a display screen. 17. The method of claim 1, wherein providing the GFR value comprises transmitting the GFR value to a remote device. 18. The method of claim 1, wherein generating the IF signal comprises generating the IF signal directly from measurement data. 19. The method of claim 1, wherein filtering the IF signal associated with the early fluorescence data comprises omitting a portion of the early fluorescence data when generating the IF signal. 20. The method of claim 1, wherein each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is a diffuse reflection signal detected by a filter detector in a region adjacent to the diffuse reflection medium during irradiation of the diffuse reflection medium with excitation wavelength light; wherein generating the IF signal includes combining the at least two measurement results according to a transformation relation comprising a mathematical equation for converting the Flr signal into the IF signal. 21. The method of claim 1, wherein each of the plurality of measurement entries includes at least one measurement result of a fluorescence emission (Flr) signal detected by a filter detector at the diffuse reflection medium during irradiation of the diffuse reflection medium with excitation wavelength light; wherein generating the IF signal includes transforming the at least one measurement result according to a transformation relation comprising a mathematical equation for converting the Flr signal into the IF signal. 22. The method of claim 21, wherein the excitation wavelength light includes the wavelength of the exogenous fluorescent agent.23. A method for determining biological parameters in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of the exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from the exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining the portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value. Claims 3 / 3 Page 4 CN 122139117 A Technical Field of Intrinsic Fluorescence Generation Using Exogenous Fluorescent Agents

[0001] This disclosure generally relates to operable intrinsic fluorescence signals, including modulation based on early fluorescence data. Background Art

[0002] Monitoring biological parameters in critically ill or injured patients is important. Organ function may be impaired due to organ damage, aging, underlying diseases, and others. Assessing organ function allows for the identification of organ damage and / or organ failure.

[0003] Details of one or more aspects of the subject matter described in this disclosure are set forth in the accompanying drawings and the following description. However, the drawings illustrate only some typical aspects of this disclosure and should therefore not be considered as limiting the scope of this disclosure. Other features, aspects, and advantages will become apparent from the description, drawings, and claims.

[0004] In order to describe the ways in which the foregoing enumerations and other advantages and features of this disclosure can be obtained, a more specific description of the principles briefly described above will be presented by reference to specific examples of this disclosure illustrated in the accompanying drawings.It should be understood that these figures depict only exemplary examples of this disclosure and should therefore not be considered as limiting the scope of this disclosure. The principles herein are described and explained with additional specificity and detail using the accompanying drawings, in which: Figure 1 is a schematic diagram of a single-source monitoring device in one aspect; Figure 2 illustrates irradiation from a light source and an exogenous fluorescent agent, and detection by a first detector and a second detector; Figure 3 illustrates irradiation from another light source, and detection by a first detector and a second detector; Figure 4 is a schematic diagram of a multi-source monitoring system in one aspect; Figure 5 illustrates an example of a sensor head having one or more sources and two detectors; Figure 6 is an exploded view of the inner housing of the sensor head shown in Figure 5; Figure 7 is a graph summarizing the absorption, transmission, and emission spectra of various devices, materials, and compounds associated with noninvasive monitoring of exogenous fluorescent agents in vivo, defined in the wavelength range of about 430 nm to about 650 nm; Figure 8 is a graph of representative intrinsic fluorescence signal measurements (IFagent) obtained before and after administration of an exogenous fluorescent agent, detected by a renal monitoring device; Figure 9 illustrates a flowchart corresponding to a method for determining glomerular filtration rate (GFR) using an exogenous fluorescent agent. Detailed Description

[0005] Various examples of this disclosure are discussed in detail below. While specific implementations are discussed, it should be understood that this is for illustrative purposes only. Those skilled in the art will recognize that other components and configurations can be used without departing from the spirit and scope of this disclosure. Therefore, the following description and figures are illustrative and should not be construed as limiting. Numerous specific details are described to provide a thorough understanding of this disclosure. However, in some cases, well-known or conventional details are not described to avoid obscuring the description. Reference to an example or an example in this disclosure may be a reference to the same example or any example; and such reference means at least one of the examples. Specification 1 / 17 pages 5 CN 122139117 A

[0006] A reference to “an example” or “an example” means that a particular feature, structure, or characteristic described in conjunction with that example is included in at least one example of this disclosure. The phrase "in one example" appearing throughout the specification does not necessarily refer to the same example in all instances, nor is it a separate or alternative example mutually exclusive with other examples. Furthermore, descriptions may depict various features that can be shown by some examples but not by others.

[0007] The terms used in this specification generally have their ordinary meaning in the field, in the context of this disclosure, and in the specific context in which each term is used. Alternative language and synonyms may be used for any one or more of the terms discussed herein, and should not be given a special meaning regardless of whether the term is elaborated or discussed in detail herein. In some cases, synonyms for certain terms are provided.The listing of one or more synonyms does not preclude the use of other synonyms. Examples used anywhere in this specification (including examples of any terms discussed herein) are merely illustrative and are not intended to further limit the scope and meaning of this disclosure or any of the example terms. Similarly, this disclosure is not limited to the various examples given in this specification.

[0008] Without limiting the scope of this disclosure, examples of instruments, apparatus, methods, and related results according to this disclosure are given below. It should be noted that the use of headings or subheadings in the examples may be for the convenience of the reader and should in no way limit the scope of this disclosure. Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In case of conflict, this document (including the definitions) shall prevail.

[0009] Additional features and advantages of this disclosure will be set forth in the following description and will be apparent in part from the description, or may be learned by practice of the disclosure herein. The features and advantages of this disclosure may be realized and obtained by means of the instruments and combinations specifically pointed out in the appended claims. These and other features of this disclosure will become more apparent from the following description and the appended claims, or may be learned by practice of the principles set forth herein. Additionally, unless specifically required, the order of one or more of the steps may be as described or may be rearranged.

[0010] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” or any other variation thereof are intended to cover non-exclusive inclusion. For example, a process, product, article, or apparatus that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to the process, article, or apparatus. Furthermore, unless expressly stated to the contrary, “or” means inclusive or, rather than exclusive, or. For example, any of the following conditions satisfy either A or B: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0011] As used herein, the term “substantially” is defined as substantially conforming to a particular size, shape, or other word modified by “substantially”, such that the part does not need to be precise. For example, “substantially cylindrical” means that the object resembles a cylinder but may have one or more deviations from a true cylinder.

[0012] The term “coupled” is defined as a connection, whether direct or indirect through an intermediary component, and is not necessarily limited to a physical connection. A connection can permanently or releasably connect objects.The term “comprising” means “including but not limited to”; specifically, it indicates members in an open-ended combination, group, series, etc.

[0013] The phrase “diffuse medium” refers to any material through which light propagates, including multiple portions, particles, or molecules that can scatter, reflect, and / or absorb light as it propagates. The distribution of the multiple portions, particles, and / or molecules may be uniform or non-uniform and may vary over time.

[0014] This disclosure provides non-invasive monitoring of biological parameters indicative of organ function in a patient based on intrinsic fluorescence (IF) signals. This disclosure utilizes a portion of the specification, page 2 / 17 of CN 122139117 A, which describes whether an IF signal includes early fluorescence data, by uniquely filtering the IF signal, and, after determining this portion of early fluorescence data, identifies a range of operable IF signals by filtering the IF signal associated with the early fluorescence data. The IF signal is based on the use of a suitable indicator administered to the patient. In one example, it may be administered to the patient by injection. In another example, it may be administered to the patient by ingestion. In one example, organ function is intestinal barrier function, wherein intestinal barrier function in a patient is assessed based on an IF signal. In at least one example, organ function is renal function. This disclosure improves the accuracy of calculating renal function in a patient based on an IF signal.

[0015] Suitable indicator substances for the methods and apparatus described herein are disclosed in U.S. Patent Nos. 8,155,000, 8,664,392, 8,697,033, 8,703,100, 8,722,685, 8,778,309, 9,005,581, 9,283,288, 9,376,399, RE47,413, RE47,255, 10,137,207, 10,525,149, and 11,590,244, the entire contents of which are incorporated herein by reference for all purposes. In some aspects, the indicator substance is eliminated from the patient's body by glomerular filtration. In some aspects, the indicator substance is eliminated from the patient's body solely by glomerular filtration. In some aspects, the indicator substance is a GFR agent.

[0016] Systems, apparatus, methods, computer-readable media, and circuits for monitoring biological parameters indicating organ function using exogenous fluorescent agents in a patient are disclosed.According to at least one example, the method includes: obtaining a measurement dataset comprising multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value. For example, the system obtains a measurement dataset comprising multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generates an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determines whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value.

[0017] In another example, a system is provided for determining biological parameters (e.g., glomerular filtration rate (GFR)) in a patient using an exogenous fluorescent agent. The system includes: a storage device (e.g., a memory configured to store data such as virtual content data, one or more images, etc.); and one or more processors (e.g., implemented in a circuit system), coupled to the memory and configured to execute instructions, and combined with various components (e.g., a network interface, a display, an output device, etc.) to cause the system to: obtain a measurement dataset comprising multiple measurement entries obtained before and after administration of the exogenous fluorescent agent; generate an intrinsic fluorescence (IF) signal representing the detected fluorescence intensity emitted from the exogenous fluorescent agent within a diffuse reflective medium; determine whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identify an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determine a biological parameter value (e.g., a glomerular filtration rate (GFR) value) in the patient based on the rate of change of the operable IF signal; and provide the biological parameter (e.g., GFR) value.

[0018] According to another example, a method for determining intestinal barrier function includes: obtaining a measurement dataset comprising multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from the exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining an intestinal barrier function value in the patient based on the rate of change of the operable IF signal; and providing the intestinal barrier function value.

[0019] In another example, the above-described system for determining biological parameters determines intestinal barrier function by determining the value of intestinal barrier function in the patient based on the rate of change of the operable IF signal, thereby providing an intestinal barrier function value to determine intestinal barrier function.

[0020] FIG1 is a schematic diagram of a system 100 for administering an exogenous fluorescent agent 112 to a patient. A light source 108 emits light 106 into the patient 104. Light 106 can be described as excitation light or an excitation source. Light 106 can also be controlled to be at one wavelength, multiple wavelengths that vary over time, or multiple wavelengths emitted simultaneously. Exogenous fluorescent agent 112 generates fluorescence 102 in response to excitation events, including: irradiation of light 106 at the excitation wavelength, occurrence of an enzymatic reaction, change in local potential, and any other known excitation event associated with the exogenous fluorescent agent. Light source 108 can be configured to deliver light 106 at the excitation wavelength (λex) to patient 104. Fluorescence 102 can be generated as described above. In at least one example, the excitation wavelength (λex) of light 106 and the emission wavelength (λem) of fluorescence 102 can be spectrally distinguishable (i.e., (λex) and (λem) are sufficiently different such that photodetector 110 can be configured to selectively detect only fluorescence 102 by means of any known optical wavelength separation device including optical filters).

[0021] Changes in fluorescence 102 can be analyzed to obtain information about organ function of patient 104. As described herein, two non-limiting examples of organ function may be either renal function and / or intestinal barrier function. In one example, the rate of decrease in fluorescence 102 may be proportional to the rate of clearance of exogenous fluorescent agent 112 by one or more organs of patient 104, thereby providing a biological parameter value. In another non-limiting example, the rate of decrease in fluorescence 102 may be proportional to the rate of clearance of exogenous fluorescent agent 112 by the kidneys of patient 104, thereby providing renal function measurements including renal decay time constant (RDTC) and / or glomerular filtration rate (GFR). Additionally, this disclosure may calculate permeability or leakage measurements when measuring intestinal function.

[0022] FIG2 illustrates the use of a light source 108 in the form of an excitation light-emitting diode (LED) 321 in the presence of an exogenous phosphor 112. The excitation LED 321 can emit light of one or more different excitation wavelengths. In one example, the excitation wavelength can be blue light. In other examples, the excitation wavelength can be both blue and green light. In other examples, the excitation wavelength can be selected based on a selected exogenous phosphor 112. The photodetector 110 can be in the form of a first photodetector 322 and a second photodetector 323. As shown, the first photodetector 322 can receive a first signal labeled SPM1, and the second photodetector 323 can receive a second signal labeled SPM2. In at least one example, the first photodetector 322 and the second photodetector 323 can be silicon photomultiplier tubes. While the photodetectors 322, 323 can take many different forms, silicon photomultiplier tubes and / or photodiodes can provide the desired characteristics for performing measurements to achieve the accuracy expected of those measurements.

[0023] Additionally, filter 324 can be configured to filter out light before the second detector 323 receives it. Filter 324 can be configured to substantially or completely block the excitation light wavelength. Additionally, filter 324 can be configured to allow light emitted from the exogenous phosphor to pass through substantially unimpeded. In the example shown, the excitation light wavelength can be a blue wavelength, and filter 324 can be configured to allow green light to pass through. As a result, the first detector 322 is configured to measure the light received at both the excitation and emission wavelengths, and the second detector 323 is configured to detect only the light received at the emission wavelength. By combining light irradiation of the patient 104's tissue 320 with light of the excitation wavelength only and light of the emission wavelength only in an alternating sequence, measurements from the first detector 322 and the second detector 323 can be analyzed, as described in U.S. Patent Nos. 10,548,521, 10,980,459, 10,952,656, 11,478,172, and 10,194,854, to measure the fluorescence of an exogenous fluorophore, and the fluorescence measurements are corrected by removing the effects of autofluorescence, excitation wavelength light leakage, and diffuse reflection of light according to the correction methods described therein. While the example shown includes only a single filter 324, in this example, additional filters can be configured to filter the light before the first photodetector 322. In other examples, a single filter can be positioned before the first photodetector 322 instead of the second photodetector 323, as described on page 4 / 17 of the specification, CN 122139117 A.

[0024] Excitation LED 321 (e.g., blue LED) can emit light 325 directed toward exogenous phosphor 112.Additionally, the light emitted from the excitation LED 321 can travel through the patient 104, causing the patient's tissue 320 to act as diffuse light. This diffuse light can be referred to as a diffuse reflection (DR) signal. Furthermore, the light 325 striking the exogenous fluorescent agent 112 and the fluorescence emission (Flr) signal 334 travel to detectors 322 and 323. As shown, the first detector 322 receives a DR signal 333 labeled DRex1 and an Flr signal 332 labeled Flr1, and the second detector 323 receives a DR signal 335 labeled DRex2 and an Flr signal 334 labeled Flr2. Flr signals 332 and 334 include contributions from the exogenous fluorescent agent 112 and tissue autofluorescence. These measurements are used to derive the intrinsic fluorescence (IF) signal of the fluorescent agent alone, as described herein.

[0025] Figure 3 illustrates the use of a light source 108 in the form of another light-emitting diode (LED) 341. In one example, the other LED 341 may be a green LED. In other examples, the other LED 341 may be another type of LED that provides light with a different wavelength than the excitation LED 321. In one example, the other LED 341 may be operable to emit light with a wavelength substantially the same as that emitted from the exogenous agent. In other examples, a single LED capable of emitting light of various wavelengths may be implemented. The light emitted from the other LED 341 may travel through the patient 104, causing the patient's tissue 320 to act as diffuse light. The diffuse light may be referred to as a DR signal, as described herein. As shown, the first detector 322 receives a DR signal 342 labeled DRem1, and the second detector 323 receives a DR signal 344 labeled DRem2. As shown in Figure 2, a filter 324 may be implemented. This filter may be the same as that in Figure 2. Although the other LED 341 and the excitation LED 321 are indicated to be separate from each other, the other LED 341 and the excitation LED 321 may be coupled to each other. Although the example shown includes only a single filter 324, in the example, additional filters may be configured to filter the light before the first detector 322. In other examples, a single filter may be deployed before the first detector 322 instead of the second detector 323.

[0026] FIG4 is an example schematic diagram of an organ monitoring system 200. The system may include a controller 212, which includes a processor 238 and a memory 242. The controller 212 may be coupled to one or more sensor heads 204. Each sensor head may include a first light source 218 and a second light source 220. The first light source 218 may be an excitation LED as indicated above. The second light source 220 may be another LED as indicated above. In other examples, the excitation LED may be the second light source 220, and the other LED may be the first light source 218.As shown, a first filter 246 and a second filter 244 are included. In other examples, only one of the first filter 246 and the second filter 244 may be implemented, as described with respect to Figures 2 and 3. The sensor head 204 may optionally include one or more temperature sensors 228. The one or more temperature sensors 228 may collect data while the first photodetector 222 and / or the second photodetector 224 collect data. The one or more temperature sensors 228 may be used to determine characteristics associated with the first photodetector 222 and / or the second photodetector 224. Additionally, the one or more temperature sensors 228 may be arranged to provide information about the patient 202. Although the example shown includes a controller 212 separate from the sensor head 204, in other examples, the controller 212 and the sensor head 204 may be part of a single unit without being wired or wirelessly coupled.

[0027] The first light source 218 and the second light source 220 may be configured to emit light into the patient 202. Light can diffuse within the patient's body, and a portion of the light is received at the first photodetector 222, and / or a portion of the light is received at the second photodetector 224. Data acquired by the first photodetector 222 and / or the second photodetector 224 can be transmitted to the controller 212. The data can be stored in the memory 242 or another storage device in which the controller communicates electronically.

[0028] The processor 238 may be operable to execute instructions according to one or more methods described herein. The processor 238 may be operable to calculate biological parameter values. In one example, the biological parameter value may be one or more of GFR and / or RDTC. In other examples, the biological parameter value may be a parameter describing intestinal wall permeability and / or leakage.

[0029] In various aspects, the first light source 218 and the second light source 220 may be any light source configured to deliver light with an excitation wavelength and an emission wavelength as described on page 5 / 17 of the specification, CN 122139117 A. Typically, the first light source 218 delivers light with an intensity sufficient to penetrate the patient's tissue 202 to reach the exogenous fluorophore, thereby ensuring that the remaining intensity is sufficient to induce fluorescence at the emission wavelength by the exogenous fluorophore. However, the intensity of the light delivered by the first light source 218 is limited to an upper limit to prevent adverse effects such as tissue burns, tissue tanning, cell damage, and / or photobleaching of exogenous fluorophores and / or endogenous chromophores (“autofluorescence”) in the skin.

[0030] Similarly, the second light source 220 is configured to deliver light of an emission wavelength sufficient to utilize the energy of the exogenous fluorophore that propagates through the first region of the patient and exits from the second and third regions, such that the remaining intensity is sufficient to be detected by the first photodetector 222 and the second photodetector 224, respectively. Like the first light source 218, the intensity of the light produced by the second light source 220 is limited to an upper limit to prevent adverse effects such as tissue burns, tissue tanning, cell damage, and / or photobleaching of exogenous fluorophores and / or endogenous chromophores (“autofluorescence”) in the skin.

[0031] In various aspects, the first light source 218 and the second light source 220 can be any light source suitable for use with fluorescence medical imaging systems and devices. Non-limiting examples of suitable light sources include: LEDs, diode lasers, pulsed lasers, continuous-wave lasers, xenon arc lamps or mercury vapor lamps with excitation filters, lasers, and supercontinuum light sources. In one aspect, the first light source 218 and / or the second light source 220 can produce light with a narrow spectral bandwidth suitable for monitoring the concentration of exogenous fluorescent agents using the methods described herein. In another aspect, the first light source 218 and the second light source 220 can produce light with a relatively wide spectral bandwidth.

[0032] In one aspect, the selection of the intensity of the light produced by the first light source 218 and the second light source 220 by the system 200 can be influenced by any one or more of at least several factors, including but not limited to the maximum permissible exposure (MPE) of the skin to a laser beam according to applicable regulatory standards such as ANSI Standard Z136.1. In another aspect, the light intensity for the system 200 can be selected to reduce the likelihood of photobleaching of other chromophores within the exogenous fluorescent source and / or tissues of the patient 202, including but not limited to: collagen, keratin, elastin, hemoglobin in red blood cells and / or melanin in melanocytes. In another aspect, the light intensity of system 200 can be selected to extract a detectable fluorescence signal from an exogenous fluorescence source within the tissue of patient 202 and from the first photodetector 222 and / or the second photodetector. In yet another aspect, the light intensity of system 200 can be selected to provide appropriately high light energy while reducing power consumption, suppressing heating / overheating of the first light source 218 and the second light source 220, and / or reducing the time the patient's skin is exposed to light from the first photodetector 222 and / or the second photodetector.

[0033] In various aspects, the intensity of the first light source 218 and the second light source 220 can be modulated to compensate for any one or more of at least several factors, including but not limited to: individual differences in chromophore concentration within patient 202, such as variations in skin pigmentation. In various other aspects, the detection gain of the photodetector can be modulated to similarly compensate for variations in individual differences in skin properties.In one aspect, variations in skin pigmentation may exist between two different individual patients 202 or between two different locations on the same patient 202. In one aspect, light modulation may compensate for variations in the optical path taken by light through the tissue of patient 202. The optical path may vary due to any one or more of at least several factors, including but not limited to: variations in the separation distance between the light source and the photodetector of system 200; variations in the firmness of the sensor head 204 and the skin of patient 202; variations in the light output of the light source due to exposure to environmental factors such as heat and moisture; variations in the sensitivity of the photodetector due to exposure to environmental factors such as heat and moisture; modulation of the duration of light irradiation; and any other relevant operating parameters.

[0034] In various aspects, the first light source 218 and the second light source 220 may be configured to modulate the intensity of light produced as required by any one or more of the factors described herein according to the above specification, page 6 / 17, 10 CN 122139117 A. In one aspect, if the first light source 218 and the second light source 220 are devices configured to continuously vary the output energy density as needed (e.g., LED light sources), the intensity of the light can be electronically modulated using methods including, but not limited to, modulating the potential, current, and / or power supplied to the first light source 218 and / or the second light source 220. In another aspect, the intensity of the light can be modulated using optical methods, including but not limited to: partially or completely blocking light leaving the first light source 218 and the second light source 220 using optical devices including but not limited to apertures, shutters, and / or one or more filters; and diverting the path of light leaving the first light source 218 and the second light source 220 away from a first region of the patient using optical devices including but not limited to lenses, mirrors, and / or prisms.

[0035] In various aspects, the intensity of the light produced by the first light source 218 and the second light source 220 can be modulated via control of the laser energy density, which is defined herein as the rate of energy within the produced beam. In one aspect, the laser energy density can be limited to a range defined by safety standards, including but not limited to ANSI standards for exposure to laser energy, such as ANSI Z136.1.

[0036] In various aspects, the pulse width of the light generated by the first light source 218 and the second light source 220 can be independently selected as a duration ranging from about 0.0001 seconds to about 0.5 seconds.

[0037] FIG5 illustrates an example of a sensor head having one or more light sources and two or more photodetectors. As shown, a single opening 531 formed in the sensor head 510 allows light from the first light source 218 and the second light source 220 to pass through it.The sensor head 510 also includes a first detector 530 and a second detector 532. A corresponding opening 531 may be formed in the sensor head 510 to allow light to reach the first detector 530 and / or the second detector 532. The second detector 532 is separated from one or more light sources 218, 220 by a distance 534. The sensor head 510 may also include a clamp receiver 520, which is designed to be coupled to one or more components not shown.

[0038] FIG6 is an exploded view of the inner housing 660 of the sensor head 510 shown in FIG5. FIG6 is an isometric view of the sensor head 604a with the upper housing and various electrical components removed, exposing the inner housing 660. The inner housing 660 is housed within a housing. The inner housing 660 includes a sensor support having a first detection recess 652, a second detection recess 650, and a light source recess 654 formed therethrough. A first photodetector 622 is mounted in the first detection recess 652, and a second photodetector 624 is mounted in the second detection recess 650. First and second light sources 618 / 620 are mounted within light source recesses 654. In one aspect, the first detection recess 652, the second detection recess 650, and the light source recess 654 of the sensor holder are optically isolated from each other to ensure that light from the light sources 618 / 620 does not reach the photodetectors 622 / 624 without being coupled through the patient's skin. The separation between the two detection recesses 652 / 650 ensures that the detected fluorescence signal from the exogenous fluorescent agent is distinguishable from the unfiltered excitation light, as described in detail above.

[0039] In one aspect, optically transparent windows 640, 642, and 644 are coupled within the first detection opening, the second detection opening, and the light source opening, respectively, to seal the openings while also providing an optically transparent channel between the tissue and the interior of the sensor head 604a. Additionally, diffusers 630 and 632 are coupled above the optically transparent windows 640, 642, and 644, respectively. Diffusers 630 and 632 are configured to spatially homogenize the light delivered to the tissue by light source 618 / 620 and to spatially homogenize the light detected by photodetectors 622 / 624. In one aspect, an absorption filter 602a is coupled to diffuser 630. In one aspect, an optically clear adhesive is used to couple absorption filter 602a to diffuser 630.

[0040] Figure 7 is a graph 1210 summarizing the absorption, transmission, and emission spectra of various devices, materials, and compounds associated with noninvasive monitoring of exogenous fluorescent agents in vivo, defined in the wavelength range of about 430 nm to about 650 nm.By way of illustrative example, Figure 7 is a graph summarizing the absorption spectra of (HbO2) and (Hb) in one aspect, as well as the absorption (1214) and emission spectra of the exogenous fluorescent agent relmapirazin (also known as MB-102) (1215). The emission spectra of the blue LED light source 1211 and the green LED light source 1212 are also shown superimposed on the other spectra in Figure 7. In this aspect, the system may include a blue LED as a first light source 218, and the excitation wavelength of the system may be an isoabsorbance wavelength of approximately 450 nm. As shown in Figure 7, the Hb absorption spectrum is strongly tilted from approximately 420 nm to approximately 450 nm, indicating that the relative absorbance of (HbO2) (1217) and (Hb) (1216) at an isoabsorbance wavelength of approximately 450 nm is sensitive to small changes in the excitation wavelength. However, at wavelengths above approximately 500 nm, the (HbO 2) / (Hb) spectrum slopes more gently, and wider-bandwidth light sources, including but not limited to LEDs with bandpass filters 1213, can be sufficient as the first light source.

[0041] In another aspect, the excitation wavelength can be selected to enhance the contrast in absorbance between the chromophore and the exogenous fluorescent agent within the patient tissue. By way of a non-limiting example, as shown in FIG7, at an isoabsorbance wavelength of 452 nm, the absorbance of remimapyrazine is more than three times higher than that of (HbO 2) and (Hb). Without being limited to any particular theory, a higher proportion of light irradiating the patient tissue at a wavelength of approximately 450 nm will be absorbed by remimapyrazine relative to (HbO 2) and (Hb), thus enhancing the absorption efficiency of remimapyrazine and reducing the intensity of light at the excitation wavelength required to elicit a detectable fluorescence signal.

[0042] In various aspects, a second isoabsorbance wavelength can also be selected as the emission wavelength of the system. By way of a non-limiting example, Figure 7 shows the emission spectrum of a remimapyrazine exogenous contrast agent (1215) characterized by an emission peak at a wavelength of approximately 550 nm. In this non-limiting example, an isoabsorbance wavelength of 570 nm can be selected as the emission wavelength to be detected by a first detector and a second detector. In various other aspects, the emission wavelength of the system can be selected to fall within a spectral range characterized by a relatively low absorbance of the chromophore within the tissue of patient 202. Without being limited to any particular theory, the low absorbance of the chromophore at the selected emission wavelength can reduce the loss of light emitted by the exogenous fluorescent agent and enhance the efficiency of fluorescence detection.

[0043] Figure 8 is a graph 1250 of representative intrinsic fluorescence signal measurements (IFagent) obtained before and after administration of the exogenous fluorescent agent, detected by a renal monitoring device.Figure 8 is a graph of fluorescence measurements obtained from the patient over a period of approximately 15 hours following the administration of an exogenous fluorophore (such as remimapyrazine) after a baseline time of approximately 1 hour (1252). The pre-administration / baseline time of 1252 is characterized by relatively low and stable fluorescence levels, possibly due to the absence of the exogenous fluorophore in the patient's blood. After administration of the exogenous fluorophore at 1253, fluorescence measurements show a sharp rise to a peak concentration of 1255, followed by a relatively smooth exponential decline back to background fluorescence levels as the kidneys clear the exogenous fluorophore from the patient's blood. Without being limited to any particular theory, it is assumed that the administered exogenous fluorophore, after an exponential decrease in concentration over a certain period of time, may homogenize. Following administration of an exogenous fluorophore (such as remimapyrazine), the exogenous fluorophore undergoes an equilibrium period of diffusion from the bloodstream to the remaining extracellular tissues of the patient. Once the exogenous fluorophore has diffused into the patient's extracellular tissues and reached quasi-steady-state conditions, post-equilibrium is achieved, and the fluorescence signal can be characterized as a single exponential decay. Without being limited to any particular theory, it is assumed that the pre-equilibrium region of the measurement dataset is characterized as the time region of the IF dataset.

[0044] As shown in FIG8, the post-application period includes a mixing and distributing portion 1254 and a renal clearance-dominant portion 1256. The region where the mixing and distributing portion 1254 contacts and / or overlaps with the renal clearance-dominant portion 1256 can be defined as the beginning of the region dominated by the single exponential decay 1257. To calculate the region dominated by the single exponential decay 1257, the system can implement the following methods and apparatus.

[0045] FIG9 illustrates a flowchart corresponding to Example Method 700. Although Example Method 700 depicts a particular sequence of operations, this sequence can be changed without departing from the scope of this disclosure. For example, some of the depicted operations can be performed in parallel or in different sequences that do not substantially affect the functionality of Method 700. In other examples, different components of the example apparatus or system implementing Method Specification 8 / 17 pages 12 CN 122139117 A 700 can perform functions at substantially the same time or in a particular sequence.

[0046] According to some examples, as depicted in FIG9, method 700 includes obtaining a measurement dataset at box 702, the measurement dataset including multiple measurement entries obtained before and after the application of an exogenous fluorescent agent. For example, the system and / or device shown in FIG4 can obtain a measurement dataset including multiple measurement entries obtained before and after the application of an exogenous fluorescent agent. For example, the system and / or device can be used to collect data from one or more sensor heads using one or more light sources and one or more detectors. The collection of data can be managed by a controller and / or processor. In at least one example, the controller and / or processor can store the data locally for processing. In another example, the data can be sent to a secure remote computer for processing.The system and / or device can be configured such that one or more sensor heads are close to or in contact with the patient whose data is being measured. The system and / or device can operate for a predetermined period of time prior to administration. An example of data collection and processing to provide results for renal function values ​​can be illustrated in Figure 8.

[0047] In at least one example, each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is detected by a filter detector in a region adjacent to the diffuse medium during irradiation of the diffuse medium with excitation wavelength light. In other examples, the filter detector may be configured such that a filter is positioned in front of the photodetector to optically filter the light based on a physical filter. In other examples, the light may be filtered by processing data from the photodetector.

[0048] In another example, each of the plurality of measurement entries includes at least one measurement result of an Flr signal detected by a filter detector in the diffuse medium during irradiation of the diffuse medium with excitation wavelength light, wherein generating the IF signal includes transforming the at least one measurement result according to a transformation relation comprising a mathematical equation that converts the Flr signal into an IF signal. In yet another example, each of the plurality of measurement entries includes at least one measurement signal detected by a filtered detector at the diffuse medium during illumination by light with a wavelength similar to or equal to that of the exogenous fluorophore.

[0049] According to some examples, the method includes generating an intrinsic fluorescence (IF) signal at block 704 representing the detected fluorescence intensity emitted from the exogenous fluorophore within the diffuse medium. For example, the processor of the system shown in FIG4 may generate an IF signal representing the detected fluorescence intensity emitted from the exogenous fluorophore within the diffuse medium. In at least one example, the diffuse medium is one or more portions of the patient under discussion having the properties associated with diffuse media described herein. In at least one example, the generation of the IF signal includes generating the IF signal directly from the measurement data. In some configurations of the system and / or device of FIG4, the IF signal may be measured directly. In other configurations, the system and / or device may perform calculations. In other examples presented herein, the IF signal may be generated by additional calculations. In other examples, generating an IF signal involves combining at least two measurements according to a transformation relation that includes a mathematical equation for converting a fluorescence emission (Flr) signal into an IF signal. Further examples of methods for generating IF signals are described in U.S. Patent Nos. 10,548,521, 10,980,459, 10,952,656, 11,478,172, 10,194,854, and 11,602,570.

[0050] According to some examples, the method includes determining at box 706 whether the IF signal includes a portion of early fluorescence data. For example, the processor of the system shown in FIG4 can determine whether the IF signal includes a portion of early fluorescence data. This can be considered as an example for determining renal function values ​​in FIG8. In at least one example, the method includes determining a falling segment of the IF signal at box 706 in FIG9. In other examples, when determining the falling segment of the IF signal, the method can identify a predetermined fitting window. A predetermined fitting window refers to a predetermined time window such that the window has a time length set to a predetermined length. The predetermined time window can be adjusted over time. In other examples, the predetermined time window has a fixed amount of time, but the window itself can move within the data. In one aspect, when determining the biological parameter values ​​of a patient's renal function, the method may further include performing a single exponential curve fitting of the IF signal according to the following formula: IFfit = C0 + C1 e (Page 9 / 17, CN 122139117 A - t / RDTC), where IFfit represents the fitting of a portion of the IF, C0 and C1 are curve fitting constants, t is time, and RDTC is a time parameter. Additionally, the method may calculate multiple RDTC values ​​in at least two segments of a predetermined minimum fitting window. In this example, RDTC is a parameter that can vary over time. Furthermore, the method may compare multiple RDTC values ​​from the at least two segments until all of the multiple RDTC values ​​correspond to positive values.

[0051] In at least one example for determining renal function values, when determining whether the IF signal includes a portion of early fluorescence data, the method may determine the preliminary GFR value (GFRprel) appearing at the preliminary GFR time (tGFRprel). In one example, determining GFRprel includes calculating the renal decay time constant (RDTC) by: performing an initial estimate of a single exponential curve fit for the IF signal across at least a sequential or overlapping portion of the IF signal, based on determining when the IF signal exceeds a quality threshold in a segment prior to tGFRprel. The method may further include determining a start time tstart, which represents a point in time before evaluating tGFRprel and during the determined IF signal decline segment; determining the start of a fitting interval for the single exponential curve fit, which is the sum of the start time tstart and a calculated value of a first constant multiplied by the exponent of the Euler number plus a second constant (ttoeq); and setting the fitting interval as a single exponential curve fit.In one example, once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus the time tinterpol, which is determined using GFRprel by linear interpolation between the following two: a low GFR boundary (GFRlow) with an associated time tolow and / or a high GFR boundary (GFRhigh) with an associated time tohigh.

[0052] In another example, the method may determine a start time (tstart), which represents a point in time before the single exponential curve fitting of the operable IF signal range and during the determined IF signal descent segment. In at least one example, the method sets the starting point (teq) of the single exponential curve fitting of the operable IF signal range, where teq = tstart + ttoeq, and = × - prel / + , where A, B, and C are constants. The method may also set teq based on determining when the single exponential curve fitting according to the IFfit equation exceeds a quality threshold. The quality threshold may be a fixed value based on previous measurements. In other examples, the quality threshold is a set value. In at least one example, the method can determine the peak of the IF signal using a recursive filter. The recursive filter can be a variety of different filters. Additionally, the method can exclude data from the fit within a predetermined time period after the peak of the IF signal. The amount of data excluded from the fit can be a predetermined fixed time period. In at least one example, the fixed time period can be between ten minutes and ten hours. In other examples, the fixed time period can be between twenty minutes and five hours. In other examples, the fixed time period can be between twenty minutes and one and a half hours. In other examples, the amount of data excluded can be determined using a variable time period to determine when the data stabilizes, thereby increasing the speed of the remainder of the process.

[0053] Furthermore, the method can determine an estimate of the single exponential curve fit during the determined IF signal descent phase when determining GFRprel, and wherein setting the starting point for the single exponential curve fit in the measurement dataset (which occurs when or after the initial estimation of the single exponential curve fit for the measurement dataset) includes performing a reverse-look component filter. In this process, a recursive or variable approach can be implemented to improve the accuracy of the overall result. A reverse-look component filter can be implemented to exclude portions of the dataset in a reverse-look manner. In other words, data initially excluded from the calculation can be included once it is determined to be above a threshold. For example, if the excluded data is stable, it can be included, thereby reducing the total time in the process. However, if the data does not maintain the same quality as the current data or data previously recorded for that dataset, the dataset is still excluded.

[0054] According to some examples, the method includes, at box 708 depicted in FIG9, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data after determining a portion of the early fluorescence data. For example, the processor of the system shown in FIG4 may identify an operable IF signal range by filtering the IF signal associated with the early fluorescence data after determining a portion of the early fluorescence data. In at least one example, filtering the IF signal associated with the early fluorescence data includes omitting a portion of the early fluorescence data when generating the IF signal. In other examples, filtering the IF signal may make calculations to modify the IF signal to more accurately represent the operable IF signal. In at least one example, filtering the IF signal associated with the early fluorescence data includes omitting a portion of the early fluorescence data when identifying the IF signal, such that this portion of the early fluorescence data is included in the IF signal and subsequently excluded from the operable IF signal.

[0055] According to some examples, the method includes, at box 710 depicted in FIG9, determining a biological parameter value in a patient based on the rate of change of the operable IF signal. For example, the processor of the system shown in Figure 4 can determine a biological parameter value in a patient based on the rate of change of the operable IF signal. In one example, the biological parameter value is the glomerular filtration rate (GFR). In another example, the biological parameter value is intestinal barrier function.

[0056] In at least one example, the method determines the GFR based on the rate of change of the operable IF signal after the start of a single exponential curve fitting of the operable IF signal. An example of single exponential curve fitting is explained herein. In another example, a method for determining GFR is disclosed in U.S. Patent No. 11,602,570. In at least one example, determining the GFR value includes calculating the renal decay time constant (RDTC) by performing a single exponential curve fitting of the operable IF signal across at least a sequential portion of the operable IF curve. A continuous portion of the operable IF curve refers to portions that are temporally adjacent or overlapping. In one example, single exponential curve fitting of the operable IF signal includes performing a logarithmic transformation on the operable IF signal and subsequently fitting a linear function to the logarithmically transformed operable IF signal.

[0057] The method may also begin determining the GFR value from the starting point of a single exponential curve fit of the operable IF signal (teq) identified in block 706. Alternatively, the method may determine the GFR based on the rate of change of the operable IF signal after the start of the single exponential curve fit of the operable IF signal.

[0058] According to some examples, the method includes providing a biological parameter value at block 712. For example, the processor of the system shown in FIG4 may provide biological parameter values.In at least one example, the bioparameter value is one of GFR and / or intestinal barrier function. In at least one example, providing the bioparameter value includes displaying the bioparameter value on a display screen. In another example, providing the bioparameter value includes transmitting the bioparameter value to a remote device. In other examples, the method may include transmitting the bioparameter value to a remote device and also displaying the bioparameter value on a local display screen. The local display screen may be included on the device shown in FIG. 4. The local display screen may be included together with the controller 212 of system 200 of FIG. 4.

[0059] Illustrative aspects of this disclosure include: Aspect 1. A method for determining glomerular filtration rate (GFR) in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change across the operable IF signal range; and providing the GFR value.

[0060] Aspect 2. The method of aspect 1, wherein determining whether the IF signal includes the portion of early fluorescence data includes determining a falling segment of the IF signal.

[0061] Aspect 3. The method according to aspect 2, wherein determining whether the IF signal includes early fluorescence data comprises: determining a preliminary GFR value (GFRprel) occurring at the preliminary GFR time (tGFRprel), wherein determining GFRprel comprises calculating the renal decay time constant (RDTC) by: performing an initial estimation of a single exponential curve fitting of the IF signal across at least the sequential or overlapping portion of the IF signal based on determining when the segment of the IF signal prior to tGFRprel exceeds a quality threshold.

[0062] Aspect 4. The method according to aspect 3, further comprising: determining a start time tstart, the start time representing a time point before estimating tGFRprel and during the determined IF signal decline segment; determining the start of a fitting interval for a single exponential curve fitting of the operable IF signal, the fitting interval being the sum of the start time tstart and a calculated value of a first constant multiplied by the exponent of the Euler number plus a second constant (ttoeq); setting the fitting interval as a single exponential curve fitting of the operable IF signal.

[0063] Aspect 5. The method according to aspect 4, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time tinterpol, which is determined using GFRprel by linear interpolation between the following two: a low GFR boundary (GFRlow) with associated time tlow and / or a high GFR boundary (GFRhigh) with associated time thigh.

[0064] Aspect 6. The method according to aspect 3, further comprising: determining a start time (tstart), which represents a point in time prior to the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; setting the starting point (teq) of the single exponential curve fitting of the operable IF signal range; wherein teq = tstart + ttoeq, and wherein A, B, and C are constants.

[0065] Aspect 7. The method according to aspect 3, wherein determining the falling segment of the IF signal comprises: identifying a predetermined fitting window; performing a single exponential curve fitting of the IF signal according to the following formula: IFfit = C0 + C1 e-t / RDTC, where IFfit represents the fitting of a portion of the IF, C0 and C1 are curve fitting constants, t is time, and RDTC is a time parameter; calculating RDTC values ​​in at least two segments of the predetermined fitting window; comparing RDTC values ​​from the at least two segments until all RDTC values ​​correspond to positive values.

[0066] Aspect 8. The method according to aspect 7, further comprising: determining a start time (tstart), the start time representing a point in time prior to the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; setting the starting point (teq) of the single exponential curve fitting of the operable IF signal; where teq = tstart + ttoeq, and where A, B, and C are constants.

[0067] Aspect 9. The method according to aspect 8, wherein teq is set based on determining when the single exponential curve fit according to the IFfit equation exceeds a quality threshold.

[0068] Aspect 10. The method according to aspect 8, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time (tinterpol), which is determined using GFRprel by linear interpolation between: a low GFR boundary (GFRlow) with associated time low and / or a high GFR boundary (GFRhigh) with associated time high.

[0069] Aspect 11. The method of aspect 3, wherein determining whether the IF signal includes a portion of early fluorescence data further includes performing a reverse look-through component filter.

[0070] Aspect 12. The method of any one of aspects 1 to 11, wherein determining the GFR value includes calculating the renal decay time constant (RDTC) by performing a single exponential curve fitting of the operable IF signal across at least a sequential or overlapping portion of the operable IF signal.

[0071] Aspect 13. The method of aspect 12, wherein the single exponential curve fitting of the operable IF signal includes performing a logarithmic transformation on the operable IF signal and subsequently fitting a linear function to the logarithmically transformed operable IF signal.

[0072] Aspect 14. The method of aspect 12, wherein the GFR value is determined starting at the start point (teq) of the single exponential curve fitting of the operable IF signal.

[0073] Aspect 15. The method of aspect 12, wherein the GFR value is determined based on the rate of change of the operable IF signal after the start of the single exponential curve fitting of the operable IF signal.

[0074] Aspect 16. The method according to any one of aspects 1 to 15, wherein providing the GFR value includes displaying the GFR value on a display screen.

[0075] Aspect 17. The method according to any one of aspects 1 to 16, wherein providing the GFR value includes transmitting the GFR value to a remote device.

[0076] Aspect 18. The method according to any one of aspects 1 to 17, wherein generating the IF signal includes generating the IF signal directly from the measurement data.

[0077] Aspect 19. The method according to any one of aspects 1 to 18, wherein filtering the IF signal associated with the early fluorescence data includes omitting a portion of the early fluorescence data when generating the IF signal.

[0078] Aspect 20. The method according to any one of aspects 1 to 19, wherein each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is a diffuse reflection signal detected by a filter detector in a region adjacent to the diffuse reflection medium during irradiation of the diffuse reflection medium with excitation wavelength light; wherein generating the IF signal includes combining the at least two measurement results according to a transformation relation comprising a mathematical equation that converts the Flr signal into an IF signal.

[0079] Aspect 21. The method according to any one of aspects 1 to 20, wherein each of the plurality of measurement entries includes at least one measurement of a fluorescence emission (Flr) signal detected by a filter detector at the diffuse medium during irradiation of the diffuse medium by excitation wavelength light, wherein generating the IF signal includes transforming the at least one measurement according to a transformation relation comprising a mathematical equation that converts the Flr signal into an IF signal.

[0080] Aspect 22. The method according to aspect 21, wherein the excitation wavelength light includes the wavelength of an exogenous fluorescent agent.

[0081] Aspect 23. A method for determining biological parameters in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value.

[0082] Aspect 24. A method for determining glomerular filtration rate (GFR) in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change across the operable IF signal range; and providing the GFR value.

[0083] Aspect 25. The method according to aspect 24, wherein determining whether the IF signal includes the portion of early fluorescence data includes determining a falling segment of the IF signal.

[0084] Aspect 26. The method according to aspect 25, wherein determining whether the IF signal includes the portion of early fluorescence data comprises: determining a preliminary GFR value (GFRprel) that appears at the preliminary GFR time (tGFRprel), wherein determining GFRprel comprises calculating the renal decay time constant (RDTC) by: performing an initial estimate on a single exponential curve fitting of the IF signal across at least the sequential or overlapping portions of the IF signal based on determining when the fragment of the IF signal before tGFRprel exceeds a quality threshold.

[0085] Aspect 27. The method according to aspect 26 further includes: determining a start time tstart, which represents a point in time before the evaluation of tGFRprel and during the determined falling segment of the IF signal; determining the start of a fitting interval for a single exponential curve fitting of the operable IF signal, the fitting interval being the sum of the start time tstart and a calculated value of a first constant multiplied by the exponent of the Euler number plus a second constant (ttoeq); setting the fitting interval as a single exponential curve fitting of the operable IF signal. Specification 13 / 17 pages 17 CN 122139117 A

[0086] Aspect 28. The method according to aspect 27, wherein tstart is determined once GFRprel is determined at tGFRprel, and tstart is tGFRprel minus the time tinterpol, which is determined using GFRprel by linear interpolation between: a low GFR boundary (GFRlow) with an associated time tolow and / or a high GFR boundary (GFRhigh) with an associated time tohigh.

[0087] Aspect 29. The method according to aspect 26 further includes: determining a start time (tstart), the start time representing a point in time prior to the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; setting a starting point (teq) for the single exponential curve fitting of the operable IF signal range; wherein teq = tstart t + ttoeq, and wherein A, B, and C are constants.

[0088] Aspect 30. The method according to aspect 26, wherein determining the falling segment of the IF signal includes: identifying a predetermined fitting window; performing a single exponential curve fitting of the IF signal according to the following formula: IFfit = C0 + C1 e-t / RDTC, where IFfit represents the fitting of a portion of the IF, C0 and C1 are curve fitting constants, t is time, and RDTC is a time parameter; calculating RDTC values ​​in at least two segments of the predetermined fitting window; comparing the RDTC values ​​from the at least two segments until all RDTC values ​​correspond to positive values.

[0089] Aspect 31. The method according to aspect 30 further includes: determining a start time (tstart), the start time representing a point in time prior to the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; setting a starting point (teq) for the single exponential curve fitting of the operable IF signal; wherein teq = tstart + ttoeq, and wherein A, B and C are constants.

[0090] Aspect 32. The method of aspect 31, wherein teq is set based on determining when a single exponential curve fit according to the IFfit equation exceeds a quality threshold.

[0091] Aspect 33. The method of aspect 31, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time (tinterpol), which is determined using GFRprel by linear interpolation between: a low GFR boundary (GFRlow) with associated time tlow and / or a high GFR boundary (GFRhigh) with associated time thigh.

[0092] Aspect 34. The method of aspect 26, wherein determining whether the IF signal includes a portion of early fluorescence data further includes performing a reverse look-through component filter.

[0093] Aspect 35. The method of any one of aspects 24 to 34, wherein determining the GFR value includes calculating the renal decay time constant (RDTC) by performing a single exponential curve fit of the operable IF signal across at least a sequential or overlapping portion of the operable IF signal.

[0094] Aspect 36. The method of aspect 35, wherein the single exponential curve fitting of the operable IF signal comprises performing a logarithmic transformation on the operable IF signal and subsequently fitting a linear function to the logarithmically transformed operable IF signal.

[0095] Aspect 37. The method of aspect 35, wherein the GFR value is determined to begin at the starting point (teq) of the single exponential curve fitting of the operable IF signal.

[0096] Aspect 38. The method of aspect 35, wherein the GFR value is determined based on the rate of change of the operable IF signal after the start of the single exponential curve fitting of the operable IF signal.

[0097] Aspect 39. The method of any one of aspects 24 to 38, wherein providing the GFR value comprises displaying the GFR value on a display screen.

[0098] Aspect 40. The method of any one of aspects 24 to 39, wherein providing the GFR value comprises transmitting the GFR value to a remote device. Specification 14 / 17 pages 18 CN 122139117 A

[0099] Aspect 41. The method according to any one of aspects 24 to 40, wherein generating the IF signal comprises generating the IF signal directly from the measurement data.

[0100] Aspect 42. The method according to any one of aspects 24 to 41, wherein filtering the IF signal associated with the early fluorescence data comprises omitting a portion of the early fluorescence data when generating the IF signal.

[0101] Aspect 43. The method according to any one of aspects 24 to 42, wherein each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is a diffuse reflection signal detected by a filter detector in a region adjacent to the diffuse reflection medium during irradiation of the diffuse reflection medium by excitation wavelength light; wherein generating an IF signal includes combining the at least two measurement results according to a transformation relation including a mathematical equation that converts the Flr signal into an IF signal.

[0102] Aspect 44. The method according to any one of aspects 24 to 43, wherein each of the plurality of measurement entries includes at least one measurement result of a fluorescence emission (Flr) signal detected by a filter detector in the diffuse reflection medium during irradiation of the diffuse reflection medium by excitation wavelength light, wherein generating an IF signal includes transforming the at least one measurement result according to a transformation relation including a mathematical equation that converts the Flr signal into an IF signal.

[0103] Aspect 45. The method according to aspect 44, wherein the excitation wavelength light includes the wavelength of an exogenous fluorescent agent.

[0104] Aspect 46. A method for determining biological parameters in a patient using an exogenous fluorescent agent, the method comprising: obtaining a measurement dataset including multiple measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value.

[0105] Aspect 47. A system for determining glomerular filtration rate (GFR) in a patient using an exogenous fluorescent agent, the system comprising: at least one storage device including a memory configured to store instructions; a processor configured to execute the instructions and cause the processor to perform the following steps: obtaining a measurement dataset including a plurality of measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a GFR value in the patient based on the rate of change across the operable IF signal range; and providing the GFR value.

[0106] Aspect 48. The system according to aspect 47, wherein determining whether the IF signal includes the portion of early fluorescence data includes determining a falling segment of the IF signal.

[0107] Aspect 49. The system according to aspect 48, wherein determining whether the IF signal includes the portion of early fluorescence data comprises: determining a preliminary GFR value (GFRprel) occurring at the preliminary GFR time (tGFRprel), wherein determining GFRprel comprises calculating the renal decay time constant (RDTC) by: performing an initial estimation of a single exponential curve fit for the IF signal across at least a sequential or overlapping portion of the IF signal based on determining when a segment of the IF signal prior to tGFRprel exceeds a quality threshold.

[0108] Aspect 50. The system according to aspect 49, wherein the processor is configured to: determine a start time tstart, which represents a point in time before the evaluation of tGFRprel and during the determined IF signal decline segment; determine the start of a fitting interval for a single exponential curve fit of the operable IF signal, the fitting interval being the sum of the start time tstart and a calculated value of a first constant multiplied by the exponent of the Euler number plus a second constant (ttoeq); and set the fitting interval as a single exponential curve fit of the operable IF signal.

[0109] Aspect 51. The system according to aspect 50, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time tinterpol, which is determined using GFRprel by linear interpolation between the following two: a low GFR boundary (GFRlow) with associated time tolow and / or a high GFR boundary (GFRhigh) with associated time tohigh.

[0110] Aspect 52. The system according to aspect 49, wherein the processor is configured to: determine a start time (tstart), which represents a point in time before the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; set the starting point (teq) of the single exponential curve fitting of the operable IF signal range; wherein teq = tstart + ttoeq, and wherein A, B, and C are constants.

[0111] Aspect 53. The system according to aspect 49, wherein determining the falling segment of the IF signal comprises: identifying a predetermined fitting window; performing a single exponential curve fitting of the IF signal according to the following formula: IFfit=C0+C1 e-t / RDTC, where IFfit represents the fitting of a portion of the IF, C0 and C1 are curve fitting constants, t is time, and RDTC is a time parameter; calculating RDTC values ​​in at least two segments of the predetermined fitting window; comparing the RDTC values ​​from at least two segments until all RDTC values ​​correspond to positive values.

[0112] Aspect 54. The system according to aspect 53, wherein the processor is configured to: determine a start time (tstart), which represents a point in time before the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; set the starting point (teq) of the single exponential curve fitting of the operable IF signal; wherein teq = tstart + ttoeq, and wherein A, B, and C are constants.

[0113] Aspect 55. The system according to aspect 54, wherein teq is set based on determining when the single exponential curve fitting according to the IFfit equation exceeds a quality threshold.

[0114] Aspect 56. The system of aspect 54, wherein once GFRprel is determined at tGFRprel, tstart is determined, and tstart is tGFRprel minus time tinterpol, which is determined using GFRprel by linear interpolation between a low GFR boundary (GFRlow) with an associated time tlow and / or a high GFR boundary (GFRhigh) with an associated time thigh.

[0115] Aspect 57. The system of aspect 49, wherein determining whether the IF signal includes a portion of early fluorescence data further includes performing a reverse look-through component filter.

[0116] Aspect 58. The system of any one of aspects 47 to 57, wherein determining the GFR value includes calculating the renal decay time constant (RDTC) by performing a single exponential curve fitting of the operable IF signal across at least a sequential or overlapping portion of the operable IF signal.

[0117] Aspect 59. The system according to aspect 58, wherein the single exponential curve fitting of the operable IF signal includes performing a logarithmic transformation on the operable IF signal and subsequently fitting a linear function to the logarithmically transformed operable IF signal.

[0118] Aspect 60. The system according to aspect 58, wherein the GFR value is determined at the starting point of the single exponential curve fitting of the operable IF signal (teq).

[0119] Aspect 61. The system according to aspect 58, wherein the GFR value is determined based on the rate of change of the operable IF signal after the start of the single exponential curve fitting of the operable IF signal.

[0120] Aspect 62. The system according to any one of aspects 47 to 61, wherein providing the GFR value includes displaying the GFR value on a display screen.

[0121] Aspect 63. The system according to any one of aspects 47 to 62, wherein providing the GFR value includes transmitting the GFR value to a remote device.

[0122] Aspect 64. The system according to any one of aspects 47 to 62, wherein generating the IF signal comprises directly generating the IF signal from the measurement data specification, page 16 / 17, 20 CN 122139117 A.

[0123] Aspect 65. The system according to any one of aspects 47 to 64, wherein filtering the IF signal associated with early fluorescence data includes omitting a portion of the early fluorescence data when generating the IF signal.

[0124] Aspect 66. The system according to any one of aspects 47 to 65, wherein each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is a diffuse reflection signal detected by a filter detector in a region adjacent to the diffuse reflection medium during irradiation of the diffuse reflection medium with excitation wavelength light; wherein generating the IF signal includes combining the at least two measurement results according to a transformation relationship including a mathematical equation that converts the Flr signal into an IF signal.

[0125] Aspect 67. The system according to any one of aspects 47 to 66, wherein each of the plurality of measurement entries includes at least one measurement of a fluorescence emission (Flr) signal detected by a filter detector at the diffuse medium during irradiation of the diffuse medium by excitation wavelength light, wherein generating the IF signal includes transforming the at least one measurement according to a transformation relation comprising a mathematical equation that converts the Flr signal into an IF signal.

[0126] Aspect 68. The system according to aspect 67, wherein the excitation wavelength light includes the wavelength of an exogenous fluorescent agent.

[0127] Aspect 69. A system for determining biological parameters in a patient using an exogenous fluorescent agent, the system comprising: at least one storage device including a memory configured to store instructions; a processor configured to execute the instructions and cause the processor to perform the following steps: obtaining a measurement dataset including a plurality of measurement entries obtained before and after administration of an exogenous fluorescent agent; generating an intrinsic fluorescence (IF) signal, the IF signal representing the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; determining whether the IF signal includes a portion of early fluorescence data; after determining this portion of the early fluorescence data, identifying an operable IF signal range by filtering the IF signal associated with the early fluorescence data; determining a biological parameter value in the patient based on the rate of change of the operable IF signal; and providing the biological parameter value.Instruction manual 17 / 17 page 21 CN 122139117 A Figure 1 Figure 2 Instruction manual drawing 1 / 8 page 22 CN 122139117 A Figure 3 Instruction manual drawing 2 / 8 page 23 CN 122139117 A Figure 4 Instruction manual drawing 3 / 8 page 24 CN 122139117 A Figure 5 Instruction manual drawing 4 / 8 page 25 CN 122139117 A Figure 6 Instruction manual drawing 5 / 8 page 26 CN 122139117 A Figure 7 Instruction manual drawing 6 / 8 page 27 CN 122139117 A Figure 8 Instruction manual drawing 7 / 8 page 28 CN 122139117 A Figure 9 Instruction manual drawing 8 / 8 page 29 CN 122139117 A.

Claims

1. A method for determining glomerular filtration rate (GFR) in a patient using an exogenous fluorescent agent, the method comprising: A measurement dataset is obtained, which includes multiple measurement entries obtained before and after the application of the exogenous fluorescent agent; Generate intrinsic fluorescence (IF) signal, which represents the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; Determine whether the IF signal includes a portion of early fluorescence data; After determining the portion of the early fluorescence data, the range of operable IF signals is identified by filtering the IF signal associated with the early fluorescence data; The GFR value in the patient is determined based on the rate of change across the range of the operable IF signal. Provide the GFR value.

2. The method according to claim 1, wherein, Determining whether the IF signal includes the portion of the early fluorescence data includes determining the falling segment of the IF signal.

3. The method according to claim 2, wherein, Determining whether the IF signal includes the portion of the early fluorescence data includes: Determining the occurrence at the initial GFR time (t) GFRprel Preliminary GFR value at ) prel ), among which, GFR is determined prel This includes calculating the renal decay time constant (RDTC) through the following steps: based on determining the IF signal at t GFRprel When the preceding segment exceeds the quality threshold, an initial estimate is performed on the single exponential curve fitting of the IF signal across at least the sequential or overlapping portions of the IF signal.

4. The method according to claim 3, further comprising: Determine the start time t start The start time refers to the time during the evaluation t. GFRprel Previously and during the determined falling segment of the IF signal; Determine the start of the fitting interval for the single exponential curve fitting of the operable IF signal, wherein the fitting interval is the start time t. start Multiply the first constant by the exponent of the Euler number and add the second constant (t) toeq The sum of the calculated values ​​of ). The fitting interval is set to fit the single exponential curve of the operable IF signal.

5. The method according to claim 4, wherein, Once in t GFRprel The location determined GFR prel , then determine t start , and t start It is t GFRprel Subtract time t interpol The time t interpol Is using GFR prel Determined by linear interpolation between the following two: having associated time t low Low GFR boundary (GFR low ) and / or with associated time t high High GFR boundary (GFR high ).

6. The method according to claim 3, further comprising: Determine the start time (t) start The start time refers to a point in time before the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; The starting point (t) of the single exponential curve fitting is set for the range of the operable IF signal. eq ); Among them, t eq =t start +t toeq ,and , where A, B and C are constants.

7. The method according to claim 3, wherein, Determining the falling segment of the IF signal includes: Identify the predefined fitting window; Perform a single-exponential curve fitting of the IF signal according to the following formula: IF fit = C0 + C1 e -t / RDTC , Where IF fit This represents the fitting of a portion of IF, where C0 and C1 are curve fitting constants, t is time, and RDTC is the time parameter; Calculate the RDTC values ​​in at least two segments of the predetermined fitting window; Compare the RDTC values ​​from the at least two segments until all RDTC values ​​correspond to positive values.

8. The method according to claim 7, further comprising: Determine the start time (t) start The start time refers to a point in time before the single exponential curve fitting of the operable IF signal and during the determined falling segment of the IF signal; Set the starting point (t) of the single exponential curve fitting of the operable IF signal. eq ); Among them, t eq =t start +t toeq ,and , where A, B and C are constants.

9. The method according to claim 8, wherein, Based on the determination according to the IF fit The equation's single-exponential curve fit is set to determine when t exceeds a quality threshold. eq .

10. The method according to claim 8, wherein, Once in t GFRprel The location determined GFR prel , then determine t start , and t start It is t GFRprel Subtract time (t) interpol The time mentioned is using GFR prel Determined by linear interpolation between the following two: having associated time t low Low GFR boundary (GFR low ) and / or with associated time t high High GFR boundary (GFR high ).

11. The method according to claim 3, wherein, Determining whether the IF signal includes the portion of the early fluorescence data also includes performing a reverse lookup component filter.

12. The method according to claim 1, wherein, Determining the GFR value involves calculating the renal decay time constant (RDTC) by performing a single exponential curve fitting of the operable IF signal across at least a sequential or overlapping portion of the operable IF signal.

13. The method according to claim 12, wherein, The single-exponential curve fitting of the operable IF signal includes performing a logarithmic transformation on the operable IF signal and then fitting a linear function to the logarithmically transformed operable IF signal.

14. The method according to claim 12, wherein, The GFR value is determined at the starting point (t) of the single exponential curve fitting of the operable IF signal. eq Start at ).

15. The method according to claim 12, wherein, The GFR value is determined based on the rate of change of the operable IF signal after the start of the single exponential curve fitting of the operable IF signal.

16. The method according to claim 1, wherein, Providing the GFR value includes displaying the GFR value on a display screen.

17. The method according to claim 1, wherein, Providing the GFR value includes transmitting the GFR value to a remote device.

18. The method according to claim 1, wherein, Generating the IF signal includes generating the IF signal directly from the measurement data.

19. The method according to claim 1, wherein, Filtering the IF signal associated with the early fluorescence data includes omitting a portion of the early fluorescence data when generating the IF signal.

20. The method according to claim 1, wherein, Each of the plurality of measurement entries includes at least two measurement results, one of which is a fluorescence emission (Flr) signal, and the second of which is a diffuse reflection signal detected by a filter detector in a region adjacent to the diffuse reflection medium during the period when the diffuse reflection medium is irradiated with excitation wavelength light; Generating the IF signal includes combining the at least two measurement results according to a transformation relationship comprising a mathematical equation that converts the Flr signal into the IF signal.

21. The method according to claim 1, wherein, Each of the plurality of measurement entries includes at least one measurement of a fluorescence emission (Flr) signal detected by a filter detector at the diffuse medium during the period when the diffuse medium is irradiated with excitation wavelength light; Generating the IF signal includes transforming the at least one measurement result according to a transformation relationship comprising a mathematical equation that converts the Flr signal into the IF signal.

22. The method according to claim 21, wherein, The excitation wavelength light includes the wavelength of the exogenous fluorescent agent.

23. A method for determining biological parameters in a patient using an exogenous fluorescent agent, the method comprising: A measurement dataset is obtained, which includes multiple measurement entries obtained before and after the application of the exogenous fluorescent agent; Generate intrinsic fluorescence (IF) signal, which represents the detected fluorescence intensity emitted from an exogenous fluorescent agent within a diffuse reflective medium; Determine whether the IF signal includes a portion of early fluorescence data; After determining the portion of the early fluorescence data, the range of operable IF signals is identified by filtering the IF signal associated with the early fluorescence data; The biological parameter values ​​in the patient's body are determined based on the rate of change of the operable IF signal; Provide the biological parameter values.

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