METHOD FOR NON-INVASIVE MONITORING OF FLUORESCENT TRACER AGENT WITH DIFFUSE REFLEX CORRECTIONS

Abstract

A method for monitoring a time-varying fluorescence signal emitted from a fluorescent agent within a medium with time-varying optical properties is provided and includes providing a measurement dataset comprising a plurality of measurement inputs, including at least two measurements obtained from a patient before and after administration of the fluorescent agent. The measurements may include one or more of: a DRex signal detected by an unfiltered light detector during illumination by excitation wavelength light of the first region adjacent to the diffuse reflecting medium; an Flr signal detected by a filtered light detector during illumination by excitation wavelength light; and a DRem signal detected by the unfiltered light detector during illumination by emission wavelength light.The method also includes identifying a post-agent administration portion of the measurement data set; and transforming each Flr signal into an IF signal that represents a detected fluorescence intensity emitted solely by the fluorescent agent.

Description

METHOD FOR NON-INVASIVE MONITORING OF FLUORESCENT TRACING AGENT WITH DIFFUSE REFLECTION CORRECTIONS QAOznn / eznz / E / YiAi Field of Invention The present description generally refers to methods for non-invasive monitoring of a fluorescent tracer agent within a medium characterized by scattering and / or absorption of light. More particularly, the present disclosure relates to methods for non-invasive assessment of renal function by monitoring the elimination of an exogenous fluorescent tracer within the tissues of a patient in vivo. Background of the Invention Dynamic monitoring of renal function in patients at the bedside in real time is highly desirable in order to minimize the risk of acute renal failure caused by various clinical, physiological and pathological conditions. It is particularly important in the case of critically ill or injured patients because a large percentage of these patients face the risk of multiple organ failure (MOF) incited by one or more severe dysfunctions, such as: acute lung injury (ALI), adult respiratory distress syndrome (ARDS), hypermetabolism, hypotension, persistent inflammation, and / or sepsis. Kidney function may also be affected due to kidney damage associated with the administration of nephrotoxic drugs as part of a procedure such as angiography, diabetes, autoimmune disease, and other dysfunctions and / or injuries casually linked to kidney damage. In order to evaluate a patient's status and monitor the severity and / or progress of renal function over extended periods, there is considerable interest in developing a simple, accurate, and continuous method for determining renal failure, preferably through non-invasive procedures. Serum creatinine concentration, an endogenous marker of kidney function, is typically measured from a blood sample and used, in combination with patient demographic factors such as weight, age, and / or ethnicity to estimate filtration rate. glomerular (GFR), a measure of kidney function. However, creatinine-based assessments of renal function may be prone to inaccuracies due to many potential factors, including: age, hydration status, renal perfusion, muscle mass, dietary intake, and many other anthropometric and clinical variables. To begin these variations, a series of creatinine-based equations (more recently extended to cystatin C) have been developed to incorporate factors such as sex, race and QAOznn / eznz / E / YiAi other factors relevant to the estimation of glomerular filtration rate (eGFR) based on serum creatinine measurements. However, these eGFR equations are not provided with any means to compensate for most of the above sources of variation, and therefore have relatively poor precision. Additionally, the eGFR method typically generates results that lag the true GFR by up to 72 hours. Exogenous marker compounds, such as inulin, iothalamate, 53Cr-EDTA, Gd-DTPA and 99mTc-DTPA have been used in existing methods to measure GFR. Other endogenous markers, such as o-iodoipurate labeled with 123I and 125I or 99mTc-MAG3 have been used in other existing methods to evaluate the tubular secretion process. However, the use of typical exogenous tracer compounds may be accompanied by several undesirable effects including the introduction of radioactive materials and / or ionizing radiation into the patient, and laborious ex vivo handling of blood and urine samples, presenting existing methods. using these exogenous markers inadequate for real-time monitoring of renal function at the patient's bedside. The availability of a real-time, accurate, repeatable measurement of renal excretion rate using exogenous markers under specific patient circumstances. QAOznn / eznz / E / YiAi patient, but even potentially changing would represent a substantial improvement over any currently practiced method. Furthermore, a method that relies solely on renal clearance of an exogenous chemical entity would provide a direct and continuous pharmacokinetic measurement that requires less subjective interpretation based on age, muscle mass, blood pressure, etc. Brief Description of the Figures The patent or application file contains at least one figure executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. The description will be better understood, and features, aspects and advantages other than those set forth above will be apparent when consideration is given to the following detailed description thereof. Such detailed description refers to the following figures, where: Figure 1 is a schematic illustration of a single wavelength renal monitoring device in one aspect; Figure 2 is a schematic illustration of a dual wavelength renal monitoring system in a QAOznn / eznz / E / YiAi aspect; Figure 3 is a graph summarizing the absorption, transmission, and emission spectra of various devices, materials, and compounds associated with the noninvasive monitoring of an exogenous fluorescent agent in vivo defined over light wavelengths ranging from approximately 430 nm at approximately 650 nm; Figure 4 is a graph summarizing the absorption spectra of oxyhemoglobin (HbCq) and oxyhemoglobin (Hb) defined over wavelengths of light ranging from about 200 nm to about 650 nm; Figure 5 is a schematic illustration of the timing of light pulse cycles associated with data acquisition by a dual wavelength renal monitoring system in one aspect, in which each light pulse cycle includes light pulses produced in the excitation wavelength and emission wavelength in sequence; Figure 6 is a side view of a sensor head of a kidney function monitoring system in one aspect; Figure 7 is a bottom view of the sensor head of Figure 6; Figure 8 is a top interior view of the sensor head of Figure 6 illustrating an arrangement of various electrical components within a housing of QAOznn / eznz / E / YiAi a sensor head of a kidney function monitoring system in one aspect; Figure 9 is an enlargement of the interior view of Figure 8; Figure 10 is a schematic illustration of apertures formed within a contact surface of a sensor head of a kidney function monitoring system in one aspect; Figure 11 is a schematic illustration of synchronous light detection by a light detector of a sensor head in one aspect; Figure 12 is a schematic illustration of light signal modulation and demodulation by the sensor head in one aspect; Figure 13 is a block diagram illustrating the subunits of a processing unit in a first and second aspect; Figure 14A is a flow chart illustrating the steps of a global error assignment method for determining the parameters of a diffuse reflectance correction equation in one aspect; Figure 14B is a flow chart illustrating the steps of a global error assignment method for determining the parameters of a diffuse reflectance correction equation in a second aspect; Figure 15A is a graph of measurements of QAOznn / eznz / E / YiAi Representative intrinsic fluorescence of the fluorescent agent (IFagent) detected by a renal monitoring device obtained before and after injection of an exogenous fluorescent agent. A subset of the data selected for analysis to determine correction errors is highlighted in orange. Figure 15B is a graph of representative intrinsic fluorescence measurements of the fluorescent agent (IFagent) detected by a renal monitoring device obtained before and after injection of an exogenous fluorescent agent. A subset of the data selected for analysis when fitting IFagent to a plasma-derived IFagent to determine correction factors are highlighted in orange. Figure 16 is a graph comparing the log-transformed individual exponential curve fit of the corrected fluorescence signal measurements (log[Fits], black dashed line) and the corrected fluorescence signal measurements of Figures 15A and 15B ( IFagent, red line) over a portion of the selected analysis region of Figures 15A and 15B. Figure 17 is a map of a representative error surface summarizing normalized root mean square errors (RMSE, color scale) calculated for the difference between the linear fit and the QAOznn / eznz / E / YiAi log fluorescence and fluorescence signal measurements corrected for a range of kexy kem correction factors, filtered, with a minimal RSME region identified by a white arrow superimposed on the map; Figure 18 is a graph comparing raw fluorescence signal measurements (F, blue line) and corrected fluorescence signal measurements (IF, red line) obtained before and after injection of an exogenous fluorescent agent. Figure 19 is a flow chart summarizing the steps of a linear regression model method for determining the parameters of a diffuse reflectance correction equation in an aspect; Figure 20 is a plot of a log-transformed raw fluorescence signal (Log(Flr)) showing regions of the data used as project fits for: a linear regression model used to develop a data correction algorithm (orange line), the response variable for the linear regression model (black dotted line), and the region of highly variable data used to train the linear regression model (blue line); Figure 21A is a graph of raw fluorescence signal measurements obtained before and after injection of an exogenous fluorescent agent. Measurements of QAOznn / eznz / E / YiAi raw fluorescence signals were obtained during exposure to various perturbations denoted as colored regions starting at approximately 13:50 h. The various perturbations included variations in blood oxygenation in the test subject, application and removal of pressure to the measured region, administration of blood pressure medication to the test subject, cooling of the measured region, and removal / replacement of the sensor head. Of the device; Figure 21B is a graph of corrected fluorescence signal measurements from Figure 21A; Figure 21C is a plot of diffuse reflector signal measurements measured simultaneously with the raw fluorescence signal measurements of Figure 21A. These signals are used in the correction of the raw fluorescence signal measurements of Figure 21A to produce the corrected signal shown in Figure 21B; Figure 22A is a block diagram illustrating a plurality of modules of a preprocessing subunit in one aspect; Figure 22B is a block diagram illustrating a plurality of modules of a preprocessing subunit in a second aspect; Figure 23 is an isometric view of a head QAOznn / eznz / E / YiAi sensor of a kidney function monitoring system in a second aspect; Figure 24 is a bottom view of the sensor head of a kidney function monitoring system illustrated in Figure 23; Figure 25 is an isometric view of the sensor head of a kidney function monitoring system illustrated in Figure 23 with the upper housing and various electrical components removed to expose an interior housing; and Figure 26 is an exploded view of the interior housing of the sensor head illustrated in Figure 25. This written description uses examples to describe the invention, including the best way, and also to enable any person skilled in the art to practice the invention, including making and using any of the devices or systems and performing any of the incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples occurring to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with differences. QAOznn / eznz / E / YiAi insubstantial from the literal languages ​​of the claims. Detailed description of the invention Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which the description pertains. Although any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of the present disclosure, preferred materials and methods are described below. A sample, as used herein, refers to a single discrete data value acquired from a signal and / or telemetry analog-to-digital converter (ADC) for an individual acquisition / telemetry channel. A measured value, as used herein, refers to a single, discrete data value created by demodulating or accumulating a sequence of samples from an acquisition channel. A measurement, as used herein, refers to a set comprising the in-phase demodulated, out-of-phase demodulated, and averaged measurement values ​​of a QAOznn / pznz / E / YiAi acquisition channel. A measurement subset, as used herein, refers to a set comprising all measurements for all acquisition channels during a single source LED illumination. For example, all measurements on an acquisition channel may include demodulated in-phase, demodulated out-of-phase, and averaged measurements. A metering assembly, as used herein, refers to an assembly comprising a metering subassembly for each source LED. An acquisition, as used here, refers to the general process by which a set of measurements is obtained. A measurement sequence, as used herein, refers to a sequence of one or more sets of measurements. A telemetry value, as used herein, refers to a single, discrete data value acquired from an individual channel of a telemetry ADC. A telemetry set, as used herein, refers to a set comprising a telemetry value from each telemetry channel. Figure 1 is a schematic illustration of a system 100, provided as a non-limiting example, in which fluorescence 102 is detected with an emission wavelength (Zem) of a region of interest of a patient 104 using a detector of light 110 configured to detect QAOznn / eznz / E / YiAi only those photons with an emission wavelength (Xem). Generally, exogenous fluorescent agent 112 produces fluorescence 102 in response to an excitation event including, but not limited to: illumination by light 106 at an excitation wavelength (λβχ), occurrence of an enzymatic reaction, changes in potential local electronic, and any other known excitation events associated with exogenous fluorescent agents. In one aspect, the system 100 may include a light source 108 configured to deliver light 106 at an excitation wavelength (λθχ) to the patient 104. In this aspect, fluorescence 102 occurs in response to illumination by light 106. Furthermore, the excitation wavelength (λθχ) of the light 106 and the emission wavelength (Xem) of the fluorescence 102 are spectrally distinct (i.e., Xe* sufficiently different from Xem so that the light detector 110 can be configured to selectively detect only fluorescence 102 by the inclusion of any optical wavelength separation device including, but not limited to, an optical filter. In some aspects, changes in fluorescence 102 may be monitored to obtain information regarding a function or physiological state of the patient. As a non-limiting example, the time-dependent decrease in fluorescence 102 measured after introduction of the QAOznn / eznz / E / YiAi exogenous fluorescent agent 112 in a circulatory vessel of patient 104 can be analyzed to obtain information regarding renal function of patient 104. In this non-limiting example, the rate of decrease in fluorescence 102 can be assumed to be proportional to the rate of removal of exogenous fluorescent agent 112 by the kidneys of patient 104, thereby providing a measure of renal function including, but not limited to: renal deterioration time constant (RDTC) and rate of glomerular filtration rate (GFR). Without being limited to any particular theory, the fluorescence intent 102 detected by the light detector 110 may be influenced by any one or more of numerous factors including, but not limited to: the intensity or energy of the light 106 at Xex supplied to the patient 104, the scattering and absorption of light 106 passing through intervention tissues 114 of the patient 104 between the light source 108 and the exogenous fluorescent agents 112, the concentration of exogenous fluorescent agents 112 illuminated by the light 106, and the scattering and absorption of fluorescence 102 in Xem passing through interventional tissues 114 of the patient 104 between the exogenous fluorescent agents 112 and the light detector 110. Existing methods typically assume that the optical properties within the intervening tissue 114 QAOznn / eznz / E / YiAi remain essentially unchanged during the period during which measurements are obtained by system 100. As a result, existing methods typically obtain initial measurements through the intervention tissue 114 of patient 104 prior to introduction of the agent. exogenous fluorescent agent 112, and these initial measurements are subtracted to correct all subsequent data obtained after introduction of the exogenous fluorescent agent 112. However, during long-term monitoring of the patient 104, changes in the optical properties of the intervention tissue 114 may occur. due to changes in at least one characteristic including, but not limited to: optical coupling efficiency of the light detector 110 to the patient 104; concentration of chromophores such as hemoglobin due to changes in blood volume caused by vascular dilation, constriction, or compression; changes in the optical properties of chromophores such as hemoglobin due to changes in oxygenation state; and changes in tissue structure such as changes related to edema. These dynamic changes in the optical properties of the intervention tissue 114 can introduce uncertainty in long-term measurements of fluorescence 102. As a non-limiting example, changes in the optical properties of the intervention tissue 114 can modulate the intensity or energy of the light 106. that illuminates the QAOznn / eznz / E / YiAi exogenous fluorescent agents 112, which causes a modulation of the fluorescence 102 produced by the exogenous fluorescent agents 112 that can be erroneously interpreted as a modulation in the concentration of the exogenous fluorescent agents 112. As another example Non-limiting, changes in the optical properties of the intervention tissue 114 can modulate the intensity or energy of the fluorescence 102 that reaches the light detector 110, which can also be erroneously interpreted as a modulation in the concentration of the exogenous fluorescent agents 112. Potential modulation of changes in the optical properties of the intervention tissue 114 may introduce uncertainty in fluorescence measurements 102, particularly those measurements associated with long-term monitoring of fluorescence 102 as described above. In various aspects, a method is provided for correcting real-time in vivo measurements of fluorescence from an exogenous fluorescent agent to remove the effects of changes in optical properties within the patient's tissue. The inclusion of an additional measurement of light passing through the patient's tissue through the separate optical path (i.e., diffuse reflectance) from the optical path of the fluorescence measurements improved the quantification of changes in the QAOznn / eznz / E / YiAi optical properties of these tissues during prolonged monitoring of fluorescence from an exogenous fluorescent agent within a patient. The inclusion of this additional measurement in the correction method in several respects was found to significantly improve the fidelity of fluorescence measurements, even in the presence of substantial perturbations as described here below. Detailed descriptions of devices for monitoring the fluorescence of an exogenous fluorescent agent in vivo and methods for correcting fluorescence measurements to remove the effects of diffuse reflectance of light within patient tissue are provided below. Although the devices and methods are described herein below in the context of a non-invasive optical renal function monitor, it will be understood that the correction method described herein, with appropriate modification, can be applied to any compatible device configured to perform measurements by delivering radiation. of EM from an external source through any scattering medium and / or receiving EM radiation propagated through any scattering medium to an external detector. Non-limiting examples of EM radiation include visible light, near-IR light, IR light, UV radiation, and microwave radiation. The QAOznn / eznz / E / YiAi scattering media may include any living or non-living material capable of propagating EM radiation of at least one EM frequency without limitation. At least a portion of the dispersion medium may further include one or more substructures or compounds capable of reflecting and / or absorbing EM radiation. Non-limiting examples of dispersion media include: a tissue of a living or dead organism, such as a skin of a mammal; a gas such as air with or without additional particles such as dust, fluid droplets, or a solid particulate material; a fluid such as water with or without additional particles such as gas bubbles or a solid particulate material. Furthermore, the devices and methods described herein below are not limited to detection of renal function, but may be modified for use in detecting the function of other physiological systems including, but not limited to, hepatic systems, or gastrointestinal systems. System Description In various aspects, methods for correcting fluorescence measurements to remove the effects of variations in local skin properties can be incorporated into any fluorescence monitoring system including, but not limited to, a system for optically monitoring renal function in vivo and in real time by measuring changes in fluorescence of an agent Exogenous fluorescent QAOznn / eznz / E / YiAi injected into a patient as the agent is renally eliminated from the patient. Figure 2 is a block diagram of a system 200 for optically monitoring renal function of a patient 202 through measurements of the fluorescence of an exogenous fluorescent agent injected into the patient 202, in one aspect. The system 200 may include at least one sensor head 204 configured to deliver light at an excitation wavelength (λεχ) into a first region 206 of the patient 202. The system 200 is further configured to detect light at a wavelength of emission (Xem), in a second region 208 of the patient 202, and to detect light at the excitation wavelength (λεχ), and / or emission wavelength (Xem), in a third region 210 of the patient 202. The system 200 may further include a controller 202 operatively coupled to the at least one sensor head 204, an operation unit 214, and a display unit 216. In various aspects, the controller 202 is configured to control the operation of the at least one sensor head 204 as described in additional detail here below. The controller 212 is further configured to receive light measurements from the at least one sensor head 204. The controller 212 is further configured to correct light measurements that correspond to fluorescence from fluorescent agents. exogenous QAOznn / eznz / E / YiAi in accordance with a method including, but not limited to, the methods described for correcting fluorescence measurements when using diffuse light reflectance measurements. The controller 212 is further configured to transform the fluorescence measurements received from the at least one sensor head 204 into a summary parameter representative of the kidney function of the patient 202. Furthermore, the controller 212 is configured to receive at least one signal that represents user input from the operation unit 214 and to generate one or more forms for display on the display unit 216 including, but not limited to, a graphical user interface (GUI). A detailed description of the sensor head 204 and controller 212 is provided below. A. Sensor Head In various aspects, the sensor head 204 includes at least one light source and at least one light detector in a housing. Figure 6 is a side view of a housing 600 for the sensor head 204 in an aspect that includes an upper housing 602 and a lower housing 604 joined together to encompass two light sources and two light detectors. The bottom surface 608 of the bottom housing 604 further includes a contact surface 606 configured to be attached to the skin of a QAOznn / eznz / E / YiAi patient 202 when using a biocompatible adhesive material including, but not limited to, a surgical adhesive. In use, the surface of the adhesive material opposite the contact surface 606 may be attached to the skin of the patient 202. In various aspects, the adhesive material may be configured to transmit light through the light sources at the patient and to further transmit the patient's fluorescence to the light detectors. In one aspect, the adhesive material may be an optically transparent material. In another aspect, the adhesive material may be produced from a non-fluorescent material to prevent the production of confusing fluorescence by the adhesive material. In various other aspects, the upper housing 602 may further include one or more openings 806 configured to provide interior access for a cable including, but not limited to, a USB cable, and / or to provide a window for a display generated by the circuitry contained within the housing 600, such as an indicator LED. Figure 7 is a bottom view of the housing 600 illustrated in Figure 8. The contact surface 606 may include an aperture plate 702 that includes one or more apertures 704 configured to transmit light between the patient's skin and the light sources and light detectors contained within the housing 600. In one aspect, the QAOznn / eznz / E / YiAi opening plate 702 may be epoxy bonded to the lower housing 604 to prevent liquid from entering the interior of the housing 600. In various aspects, the dimensions, arrangement, and / or spacing of the one or more Apertures 704 may be selected to improve various aspects of the operation of system 200, as described in additional detail here below. In another aspect, the contact surface 606 may further include a temperature sensor aperture 706 configured to provide a thermal path from the patient's skin surface to an additional temperature sensor 228 configured to monitor the temperature at the skin surface. of the patient. Figure 8 is a schematic diagram illustrating the arrangement of electrical components within the housing 600. Referring to Figure 8, the upper housing 602 and the lower housing 604 can be fixed together with screws 802, and the screw holes at the interface between the two housing pieces may be filled with a waterproof filler material 804 including, but not limited to, a silicone material, such as room temperature vulcanizing (RTV) silicone. to inhibit liquid entry into the housing QAOznn / eznz / E / YiAi 600. In one aspect, the housing 600 may further include a cable opening 806 formed through the upper housing 602. The cable opening 806 may be configured to provide interior access for an electrical cable including, but not limited to, a cable USB. In one aspect, the cable may provide power supply to the light sources, light detectors, and indicator lights, and associated electrical devices and circuits described herein below. In another aspect, the cable may further permit communication of control signals within the housing to permit operation of electrical components within housing 600, and the cable may further permit communication of data signals encoding measurements obtained by one of more of the sensor devices contained within the housing 600 including, but not limited to: the first light detector 222, the second light detector 224, any additional light detectors, such as a first monitor photodiode 904 and a second monitor photodiode 906, and any of the additional temperature sensors 228 (see Figure 9). In one aspect, the cable may be attached to the cable opening 806 and adjacent upper housing 606 with a light-absorbing adhesive including, but not limited to, black epoxy and may further be sealed against water incursion by using a filler material. waterproof including, QAOznn / eznz / E / YiAi but not limited to, RTV. In a further aspect, the housing 600 may further include at least one viewing opening 808 formed through the upper housing 602. In one aspect, each viewing opening 808 may be configured to provide a viewing window generated by the circuitry contained within. of the housing 600, such as an indicator LED 810. In one aspect, each indicator LED 810 may be placed on a circuit board 812. In one aspect, a light pipe 814 may be bonded with epoxy within the viewing opening 808 within of the upper housing 602 over each indicator LED 810. Each light pipe 814 can be filled with a water resistant filler material such as RTV for liquid weight protection. In various aspects, the at least one indicator LED 810 may illuminate in a predetermined pattern to allow a user of the system 200 to monitor the operating status of the sensor head 204. Figure 9 is a close-up view of the interior optical region of sensor head 204 showing the arrangement of light sources 218 / 220 and detectors 222 / 224 within housing 600 in one aspect. In one aspect, the light sources 218 / 220 are separate from the light detectors 222 / 224, and the first light detector 222 is separate from the second light detector 224 which are QAOznn / eznz / E / YiAi separated from each other by a sensor mount 912 secured to the aperture plate 702. In one aspect, the sensor mount 912 ensures that light from the light sources 218 / 220 does not reach the light detectors. 222 / 224 without coupling through the skin of the patient 202. The separation between the first light detector 222 within the first detection well 908 and the second light detector 224 within the second detection well 910 ensures that the fluorescence signal produced by the exogenous fluorescent agent within the patient's tissues 202 can be distinguished from the excitation or filtered light introduced by the first light source 218. Referring again to Figure 9, the sensor mount 912 can be aligned with a circuit board (not shown) containing the light sources 218 / 220 and light detectors 222 / 224 by using alignment pins 914 and by being held in place by using screws 916. In one aspect, the sensor mount 912 can be secured to the circuit board containing the light sources 218 / 220 and light detectors 222 / 224 using a light-absorbing adhesive that includes, but not limited to, black epoxy. In this aspect, the light resistant bond between the circuit board and the sensor mount 912 inhibits light leak between the light sources 218 / 222 and the detectors of the 222 / 224, and further inhibits light leak between the first light detector 222 and the second light detector 224. The openings 704 QAOznn / pznz / E / YiAi configured to transmit light to and from the skin under the contact surface 606 of the sensor head 204 are formed through a plate of structurally separated apertures 302 (see Figure 7) to provide precise alignment of the openings 704 to corresponding light sources 218 / 220 and light detectors 222 / 224, described in additional detail hereinbelow. In various aspects, the sensor mount 912 may further provide electrical shielding for any of the sensitive electrical devices within the sensor head 204 including, but not limited to, the light detectors 222 / 224. In one aspect, the sensor mount 912 may be constructed of an electrically conductive material including, but not limited to: aluminum and aluminum alloy. In this aspect, the sensor mount 912 may be electrically coupled to the circuit board ground by using conductive screws 916. Additionally, any of the glass windows positioned within the source well 902 and / or detector wells 908 / 910 adjacent to the aperture plate 702 including, but not limited to, an optical filter 244 and transparent glass 246 as described below (see Figure 2) may further include an electrically conductive coating. Non-limiting examples of electrically conductive coatings suitable for sensor mount glass windows QAOznn / eznz / E / YiAi include a conductive indium tin oxide (ITO) coating and any other suitable transparent and electrically conductive coating. Without being limited to any particular theory, the conductive material of the sensor mount 912 provides a partial Faraday box to provide the electrically sensitive detectors 222 / 224 for electrical noise generated by or conducted through the patient's body. The partial Faraday cage provided by the sensor mount 912 may be completed with conductive ITO coating on the glass windows within the source well 902 and / or detector wells 908 / 910. In one aspect, the electrically conductive coating on the glass windows, such as an ITO coating, are sufficiently conductive to provide electrical shielding while remaining sufficiently transparent for light transmission to and from the skin surface of the patient 202. In In another aspect, the ITO liner of each glass window may be grounded to an electrically conductive sensor mount 912 using any known electrical grounding method, including, but not limited to: a wire connecting the ITO liner. glass to the 912 sensor mount which is attached at both cable ends with conductive epoxy or bond coated glass QAOznn / eznz / E / YiAi directly to a glass accessory such as a shelf or frame formed within each of the source well 902 and / or detector wells 908 / 910 using an electrically conductive epoxy. In various aspects, the contact surface 606 of the housing 600 can be attached to the skin of the patient by using a biocompatible material and an adhesive 610 including, but not limited to, a transparent double-sided medical grade adhesive, as illustrated in Figure 6, and Figure 7. Any adhesive material selected to be optically transmissive at the excitation and emission wavelengths used by system 100 as described herein. The adhesive material 610 may be positioned on the contact surface 606 such that the adhesive material covers the openings 704, but exposes the temperature sensor opening 706 to ensure sufficient thermal contact with the skin of the patient 202. In one aspect, the Sensor head 204 may further be secured to patient 202 as necessary by using one or more biocompatible medical restraint devices including, but not limited to: Tegaderm bandages, medical tape, or any other suitable biocompatible medical restraint device. In one aspect, the contact surface 606 may be located near the front edge of the sensor head 204 to provide precise positioning of the QAOznn / cznz / E / YiAi contact surface 606 on a selected region of the patient's skin. In another aspect, the apertures 704 may be positioned toward the center of the contact surface 606 to reduce ambient light entry. Without being limited to any particular theory, ambient light may enter one or more of the openings 704 due to incomplete adhesion of the contact surface 606 to the patient's skin and / or due to propagation of ambient light passing through. the exposed skin of the patient located just outside the space of the contact surface 606 within the openings 704. Referring again to Figure 6, the bottom surface 608 of the sensor head 204 is curved away from the plane of the contact surface 606 to allow attachment of the sensor head 204 to various body types and locations. For attachment of the sensor head 204 to relatively flat or concave surfaces, any gap 612 between the bottom surface 608 and the skin surface of the patient 202 may be filled with a biocompatible foam to ensure consistent contact with the patient 202. i) Light Sources In various aspects, each sensor head 204 includes a first light source 218 and a second light source 220 configured to supply light to a first region 206 of a patient 202. The first light source 218 QAOznn / eznz / E / YiAi is configured to supply light at the excitation wavelength and the second light source 220 is configured to supply light at the emission wavelength. In one aspect, the excitation wavelength can be selected to fall within a spectral range in which the exogenous fluorescent agent exhibits relatively high absorbance. In another aspect, the emission wavelength can be selected to fall within a spectral range in which the exogenous fluorescent agent exhibits relatively high emission. The exogenous fluorescent agent may be selected for enhanced contrast relative to other chromophores within the patient's tissues 202 including, but not limited to, hemoglobin with red blood cells and / or melanin within melanocytes. In various aspects, the exogenous fluorescent agent may be selected to conduct measurements within spectral ranges with lower variation in absorption by other chromophores such as hemoglobin within the patient's tissues 202 during use. Without being limited to any particular theory, hemoglobin (Hb) is an absorber of visible light in the tissues of patient 202, and has the potential to interfere with fluorescence measurements of the exogenous fluorescent agent if the absorbance of Hb varies during the period of measurement system 200. Because hemoglobin (Hb) QAOznn / eznz / E / YiAi allows gas exchange within virtually all tissues that contain circulatory vessels, virtually all tissues are vulnerable to interference with system 200 fluorescence measurements due to fluctuations in hemoglobin concentration. Within most tissues, externally applied pressure can cause blood pooling that can be manifested as an apparent drop in fluorescence measured at the skin surface. The periodic opening and closing of blood vessels (vasomotion) near the skin surface can also cause fluctuations in hemoglobin concentration that can introduce additional noise into fluorescence measurements of the exogenous fluorescent agent by system 200. Additionally, in some patients 202 , such as those with lung disorders, variation in Hb oxygenation status may also be observed, leading to additional potential variations in background skin absorbance due to differences in oxyhemoglobin (Hb) and oxyhemoglobin absorption spectra. (HbCb), illustrated in Figure 3. In one aspect, the excitation and emission wavelengths for the exogenous fluorescent agent can be selected to coincide with a pair of HbCb / Hb isosbestic points, each isosbestic point defined herein as a wavelength characterized by absorbance of QAOznn / eznz / E / YiAi approximately equal light for HbC>2 and Hb. Without being limited to any particular theory, fluorescence measurements conducted at each isosbestic wavelength are less sensitive to variation due to changes in hemoglobin oxygenation, as long as the combined concentration of HbCt and Hb remains relatively stable during measurements. of fluorescence by system 200. Non-limiting examples of isosbestic wavelengths of HbCh / Hb include: about 390 nm, about 422 nm, about 452 nm, about 500 nm, about 530 nm, about 538 nm, about 545 nm, about 570 nm, approximately 584 nm, approximately 617 nm, approximately 621 nm, approximately 653 nm, and approximately 805 nm. In various aspects, the excitation and emission wavelengths can be selected based on the absorption and emission wavelengths of the selected exogenous fluorescent agent of the system 200. In one aspect, the excitation wavelength can be a length of isosbestic wave of HbCh / Hb and simultaneously can be a wavelength within a high absorbance spectral range of the exogenous fluorescent agent. In another aspect, the emission wavelength may be an isosbestic wavelength of HbCt / Hb and simultaneously may be a wavelength within a spectral range of emission by the exogenous fluorescent agent. Table 1 provides a summary of HbCg / Hb isosbestic wavelengths within the spectral range of 200 nm to approximately 1000 nm. Figure 4 is a plot of the absorption spectra used to identify the HbCt / Hb isosbestic wavelengths from Table 1. Table 1. Isosbestic Wavelengths of Hb02 / Hb λ = 200 1000 nm Excitation wavelength (nm) Molar Extinction Coefficient of Hb (M-1 cm1) HbO2 dA / dX (M 1 cnr1 nm1) Hb dA / dX (M 1 cm 1 nm1) 260 1.2x105 1.8x103 6.3 x102 288 1.1x105 -2.9x103 -3.4x103 298 7.0x104 -3.3x103 -3.2x103 314 6.5x104 1.6x103 1.5x103 324 8.2x104 1.9x103 1.8x103 340 1x105 6.5x102 1.6x103 390 1.7x105 1.0x104 5.1x103 422 4.3x105 -2.6x104 1.3x104 452 6.3x104 -2.3x103 -1.7x104 500 2.1x104 -1.7x102 4.8x102 Wavelength HbO2 coefficient dA / dX M-1 cm-1 nm1) (nm) Hb (M 1 cm 1) 530 3.9x104 2.0x103 7.2x102 545 5.1x104 -1.3x103 7.0x102 570 4.5x104 2.2x103 -9.0x102 584 3.4x104 -4.1x1o3 -7.1x 102 738 1.1x103 6.8x10° 3.5x10° 796 8.8x102 8.8x10° 1.1x101 QAOznn / eznz / E / YiAi As an illustrative example, Figure 3 is a graph summarizing the absorption spectra for HbC>2 and Hb, as well as the absorption and emission spectra of frequency spectra of MB-102, an exogenous fluorescent agent in one aspect. . Emission spectra for a blue LED light source and a green LED light source are also shown overlaid on the other aspects of Figure 3. In this aspect, the system 200 may include a blue LED as the first light source 218, and the excitation wavelength for system 200 may be the isosbestic wavelength of approximately 450 nm. As listed in Table 1 and shown in Figure 3, the Hb absorbance spectra lean strongly at the isosbestic wavelengths from about 420 nm to about 450 nm (see columns 3 and 4 of Table 1), which indicate that the relative absorbance of HbCb and Hb at the isosbestic wavelength of approximately 450 nm is sensitive to small changes in excitation wavelength. However, at wavelengths above about 500 nm, the HbCg / Hb spectra are less steeply skewed, and a broader band light source including, but not limited to, an LED with a filter of bandpass may be sufficient to be used as a first light source 218. In another aspect, the excitation wavelength may be selected to enhance the contrast in light absorbance between the exogenous fluorescent agent and the chromophores within the patient's tissues 202. By way of non-limiting example, as shown in Figure 3 at the isosbestic wavelength of 452 nm, the light absorption of MB-102 is more than three times higher than the light absorption of HbCh and Hb. Without being limited to any particular theory, a higher proportion of light illuminating patient tissue 202 at a wavelength of approximately 450 nm will be absorbed by MB-102 relative to HbCh and Hb, thereby improving efficiency. absorption by MB-102 and reducing the light intensity at the excitation wavelength necessary to obtain a detectable fluorescence signal. In various aspects, a second isosbestic wavelength may also be selected as the emission wavelength for the system 200. By way of non-limiting example, Figure 3 shows an emission spectrum of the QAOznn / eznz / E / YiAi MB-102 exogenous contrast agent characterized by an emission peak at a wavelength of approximately 550 nm. In this non-limiting example, the isosbestic wavelength of 570 nm may be selected as the emission wavelength to be detected by first and second detectors 222 / 224. In various other aspects, the emission wavelength of the system 200 may be selected to fall within a spectral range characterized by relatively low absorbance of the chromophores within the tissues of the patient 202. Without being limited to any particular theory, the low absorbance of chromophores at the selected emission wavelength can reduce the light losses emitted by the exogenous fluorescent agent and improve the fluorescence detection efficiency. In various aspects, the first light source 218 and the second light source 220 may be any light source configured to supply light at the excitation wavelength and at the emission wavelength. Typically, the first light source 218 supplies light at an intensity that is sufficient to penetrate the tissues of the patient 202 to the exogenous fluorescent agent with sufficient intensity remaining to induce the emission of light at the emission wavelength by the exogenous fluorescent agent. . Typically, the first light source 218 supplies light at an intensity that is sufficient to QAOznn / eznz / E / YiAi penetrate the patient's tissues 202 to the exogenous fluorescent agent with sufficient intensity that remains after scattering and / or absorption to induce fluorescence at the wavelength of emission by the exogenous fluorescent agent. However, light intensity supplied by the first light source 218 is limited to a higher value to prevent adverse effects such as tissue burning, cell damage, and / or photobleaching of the exogenous fluorescent agent and / or endogenous chromophores. on the skin (auto-fluorescence). Similarly, the second light source 220 supplies light at the emission wavelength of the exogenous fluorescent agent at an intensity configured to provide sufficient energy to propagate with scattering and absorption through the first region 206 of the patient and out of the second region. 208 and third region 210 with sufficient remaining intensity for detection by the first light detector 222 and the second light detector 224, respectively. As with the first light source 218, the light intensity produced by the second light source 220 is limited to a higher value to prevent adverse effects such as tissue injury or photobleaching described previously. In various aspects, the first light source 218 and the second light source 220 can be any light source. QAOznn / eznz / E / YiAi light suitable for use with fluorescent medical imaging systems and devices. Non-limiting examples of suitable light sources include: LEDs, diode lasers, pulsed lasers, continuously oscillating lasers, xenon arc lamps or mercury vapor lamps with an excitation filter, lasers, and supercontinuous sources. In one aspect, the first light source 218 and / or the second light source 220 can produce light in a narrow spectral bandwidth suitable for monitoring the concentration of the exogenous fluorescent agent when using the method described herein. In another aspect, the first light source 218 and the second light source 220 can produce light at a relatively wide spectral bandwidth. In one aspect, the selection of light intensity produced by the first light source 218 and the second light source 220 by the system 200 may be influenced by any one or more of at least several factors including, but not limited to. a, the maximum permissible exposure (MPE) for skin exposure to a laser beam in accordance with applicable regulatory standards such as ANSI Standard Z136.1. In another aspect, the light intensity by system 200 may be selected to reduce the possibility of photobleaching of the exogenous fluorescent source and / or other chromophores within patient tissues 202 including, but not limited to: QAOznn / eznz / E / YiAi collagen, keratin, elastin, hemoglobin within red blood cell cells and / or melanin within melanocytes. In yet another aspect, the light intensity for the system 200 may be selected in order to obtain a detectable fluorescence signal from the exogenous fluorescent source within the patient tissues 202 and the first light detector 222 and / or second light detector. light. In yet another aspect, the light intensity for the system 200 can be selected to provide suitably high light energy while reducing power consumption, which inhibits heating / overheating of the first light source 218 and the second light source 220, and / or reducing the exposure time of the patient's skin to light from the first light detector 222 and / or second light detector. 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 the concentration of chromophores within of patient 202, such as variations in skin pigmentation. In various other aspects, the detection gain of light detectors can be modulated to similarly compensate for variation in individual differences in skin properties. In one aspect, the variation in skin pigmentation may be between two different QAOznn / eznz / E / YiAi individual patients 202, or between two different positions in the same patient 202. In another aspect, light modulation can compensate for variation in the optical path taken by light through the tissues of the patient 202. Optical path may vary due to any one or more of at least several factors including, but not limited to: variation in separation distances between light sources and light detectors of system 200; variation in secure attachment of sensor head 204 to patient skin 202; variation in light output of light sources due to exposure of light sources to environmental factors such as heat and humidity; variation in the sensitivity of light detectors due to exposure of light detectors to environmental factors such as heat and humidity; modulation of illumination duration by light sources, and any other relevant operational parameters. In various aspects, the first light source 218 and the second light source 220 may be configured to modulate the intensity of the light produced as necessary in accordance with any one or more of the factors described herein above. In one aspect, if the first light source 218 and the second light source 220 are devices configured to continuously vary output fluence as necessary, for example, LED light sources, the QAOznn / eznz / E / YiAi light intensity may be modulated electronically by using methods including, but not limited to, modulation of the electrical potential, current, and / or energy supplied to the first light source 218 and / or the second source of light 220. In another aspect, the intensity of the light can be modulated by using optical methods including, but not limited to: partially or completely obstructing the light left by the first light source 218 and the second light source 220 by using an optical device including, but not limited to: an iris, a shutter, and / or one or more filters; divert the light path left by the first light source 218 and the second light source 220 away from the first region 206 of the patient using an optical device including, but not limited to a lens, a mirror, and / or a prism In various aspects, the intensity of light produced by the first light source 218 and the second light source 220 can be modulated through control of laser fluence, here defined as the rate of energy within the light beam produced. In one aspect, laser fluence may be limited to ranges defined by safety standards including, but not limited to, ANSI standard for exposure to laser energy such as ANSI Z136.1. Without being limited to any particular subject, the maximum fluence of light delivered to a patient 202 may be influenced by a variety of factors including, QAOznn / eznz / E / YiAi but not limited to the wavelength of the light supplied and the duration of light exposure. In various aspects, the maximum light fluence can vary from about 0.003 J / cm2 for light delivered at wavelengths of less than about 302 nm to about 1 J / cm2 for light delivered at wavelengths ranging from about 1500 nm to approximately 1800 nm for a duration of up to approximately 10 seconds. For light delivered at wavelengths ranging from about 400 nm to about 1400 nm (visible / NIR light) the maximum fluence may be about 0.6 J / cm2 for a duration of up to about 10 seconds, and up to about 0.2 J / cm2 for a duration varying from approximately 10 seconds to approximately 30,000 seconds. For extended exposures, the light supplied is limited to a maximum power density (W / cm2) in accordance with ANSI standards: visible / NIR light is limited to 0.2 W / cm2 and far IR light is limited to approximately 0.1 W / cm2 . Without being limited to a particular theory, extended exposure to light delivered at UV wavelengths is typically not recommended in accordance with ANSI standards. In another aspect, the fluence of light at the excitation wavelength produced by the first light source 218 can be modulated in order to provide energy QAOznn / eznz / E / YiAi sufficient to spread through the skin in the first region 206 of patient 202 to the exogenous fluorescent agent without photobleaching, and to illuminate the exogenous fluorescent agent with sufficient energy to induce detectable fluorescence in the first detector light source 222 and / or the second light detector 224. In a further aspect, the fluence of light at the emission wavelength produced by the second light source 220 can be modulated in order to provide sufficient energy to propagate to through the skin in the first region 206 of the patient 202 and through the skin of the second region 208 and the third region 210 without photobleaching to emerge as light detectable in the first light detector 222 and the second light detector 224 , respectively. As a non-limiting example, the light fluence produced by a light source at 450 nm or 500 nm can be limited to 1.5 and 5 mW / cm2, respectively, to prevent photobleaching. In various aspects, the fluence of light produced by the first light source 218 and the second light source 220 can be modulated by any of the suitable systems and / or devices without limitation as described herein above. This modulation may allow for individual timing during operation of the system 200, and as a result, the fluence of light produced by each of the first light source 218 and the second light source 220. QAOznn / pznz / E / YiAi may be relatively constant throughout the operation of system 200. In another aspect, light modulation may be permitted at discrete times for the duration of operation of system 200, or light modulation may be permitted continuously. for the duration of operation of system 200. In one aspect, light fluence can be modulated through manual adjustment of any of the light source configurations and / or optical device configurations as described above when the system 200 is configured in an Engineering Mode. In another aspect, light fluence may be automatically modulated through one or more control schemes encoded in the light source control unit of the controller 212 as described herein below. In this aspect, the degree of modulation may be specified at least in part based on feedback measurements obtained by various sensors provided in the sensor head 204 of the system 200 including, but not limited to, additional light detectors 226 and temperature sensors 228 as described in additional detail here below. In various aspects, light produced by the first light source 218 and the second light source 220 are further characterized by a pulse width, defined here as the QAOznn / eznz / E / YiAi duration of light produced. Although pulse width is typically used to characterize the performance of a light source that produces light in discrete pulses, such as a pulsed laser, it should be understood that the term light pulse, as used herein, refers to any burst of light. discrete light produced by a single light source at a single wavelength to enable the acquisition of a single fluorescence measurement by system 200. Similarly, the term pulse width, as used herein, refers to the duration of a individual light pulse produced by a single light source. The pulse width is typically selected based on one or more of at least several factors including, but not limited to: supplying sufficient light energy to obtain detectable fluorescence from the exogenous fluorescent agent without photobleaching of the exogenous fluorescent agent or other chromophores within patient tissues 202; compliance with safety standards for light supply to patients such as ANSI standards; light delivery at a rate high enough to allow data acquisition at a rate compatible with real-time monitoring of renal function; performance capabilities of selected light sources, light detectors, and other devices of system 200; conservation of the useful life of light sources, light detectors, and other devices related to producing and detecting energy from QAOznn / cznz / E / YiAi 6 light; and any other relevant factors. In various aspects, the pulse width of the light produced by the first light source 218 and the second light source 220 can be independently selected to be of a duration ranging from about 0.0001 seconds to about 0.5 seconds. In various other aspects, the pulse width of the light produced by the first light source 218 and the second light source 220 can be independently selected to be of a duration ranging from about 0.0001 seconds to about 0.001 seconds, to about 0.0005 seconds. to about 0.005 seconds, from about 0.001 seconds to about 0.010 seconds, from about 0.005 seconds to about 0.05 seconds, from about 0.01 seconds to about 0.1 seconds, from about 0.05 seconds to about 0.15 seconds, from about 0.1 seconds to about 0.2 seconds, from about 0.15 seconds to about 0.25 seconds, from about 0.2 seconds to about 0.3 seconds, from about 0.25 seconds to about 0.35 seconds, from about 0.3 seconds to about 0.4 seconds, from about 0.35 seconds to about 0.45 seconds, and from about 0.4 seconds to approximately 0.5 seconds. In one aspect, the QAOznn / eznz / E / YiAi pulse widths of the light produced by the first light source 218 and the second light source 220 are both approximately 0.1 second, as schematically illustrated in Figure 5. In another aspect, the light produced by the first light source 218 and the second light source 220 may further be characterized by a pulse sequence, defined here as the number of pulses produced by a light source per second. Although pulse frequency is typically used to characterize the performance of a light source that produces light in discrete pulses, such as a pulsed laser, the term pulse frequency, as used herein, will be understood to refer to the rate of production of a discrete light source by a single light source at a single wavelength in association with the acquisition of fluorescence measurements by system 200. In various aspects, the pulse frequency may be selected based on one or more of at least several factors including, but not limited to: compliance with safety standards for light delivery to patients such as ANSI standards; the performance capabilities of the selected light sources, light detectors, and other devices of system 200; light delivery rates compatible with data acquisition rates fast enough for real-time monitoring of kidney function; what preserves the QAOznn / eznz / E / YiAi the operational life of light sources, light detectors, and other devices related to producing and detecting light energy; and any other relevant factors. In various aspects, the light sources are configured to deliver light into the patient tissues 202 at an individual position such as a first region 206, illustrated schematically in Figure 2. In one aspect, the delivery of light both along the length of excitation wave as well as the emission wavelength to the same first region 206 allows both pulses to share at least a portion of the optical path displaced through the patient's tissues 202 between the entry point of the first region 206 and the detection point of the second region 208 and the third region 210. As discussed in detail below, this arrangement of optical paths improves the quality of data produced by the system 200. In one aspect, the first light source 218 and the second light source 220 may be operatively coupled to a common light supply means. In one aspect (not shown) the first light source 218 and the second light source 220 may each be operatively coupled to a first optical fiber and a second optical fiber, respectively, and the first and second optical fibers may be attached to a third optical fiber QAOznn / eznz / E / YiAi configured to direct light from the first optical fiber and / or the second optical fiber into the first region 206 of the patient 202. In another aspect, the first light source 218 and the second light source 220 can be operatively coupled to a common optical fiber or other objective assembly configured to direct light from the first light source 218 and / or the second light source 220 at the first region 206 of the patient 202. In this aspect, the light produced by The first light source 218 and the second light source 220 may be directed in an alternating pattern on the common optical fiber or other optical assembly using an adjustable optical device including, but not limited to, a dichroic mirror or a rotating mirror. In one aspect, system 200 may include sensor head 204 provided with a sensor mount 912 configured with one or more wells within which light sources 218 / 220 and light detectors 222 / 224 may be attached in a predetermined arrangement. . In one aspect, illustrated in Figure 9 and Figure 10, the first light source 218 and the second light source 220 may be located within a source well 902 of the sensor mount 912 positioned within the sensor head 204 ( see Figure 9). In one aspect, the source well 902 may contain a first LED light source 918 that produces light at the excitation wavelength and a second LED light source 220 that produces QAOznn / eznz / E / YiAi light at the emission wavelength operatively coupled to an individual light supply aperture 1002 (see Figure 10) formed through the aperture plate 702, which ensures that both wavelengths of light (i.e., excitation and emission) enter the skin of the patient 202 at approximately the same location including, but not limited to, a first region 206 as schematically illustrated in Figure 2. In one aspect, the source well 902 further contains a first monitor photodiode 904 and a second monitor photodiode 906, which are used to correct for variations in output power of the LED light sources as described in further detail here below. . In one aspect, only a fraction of the light energy produced by the LED light sources is delivered to the skin of the patient 202 through the individual light supply aperture 1002. In one aspect, the skin of the patient 202 receives approximately 1% of the light energy produced by LED light sources. In various other aspects, the skin of patient 202 receives about 2%, about 3%, about 4%, about 5%, about 7.5%, about 10%, about 20%, and about 50% of the light energy produced by LED light sources. Without being limited to any particular theory, the fraction of light produced by light sources QAOznn / eznz / E / YiAi LED light delivered to the patient's skin 202 may be increased by the incorporation of additional optical elements configured to focus and / or direct light from each LED light source to the light delivery aperture 1002. In Another aspect, a diffuser can be used to mix the output of the light sources so that the light energy appears homogeneous on the surface of the patient's skin. ii) Light Detectors Referring again to Figure 2, system 200 further includes a first light detector 222 and a second light detector 224 in various aspects. In aspect, the first light detector 222 is configured to measure unfiltered light emitted from the patient tissue 202 in the second region 208, and the second light detector 224 is configured to measure filtered light emitted from the patient tissue 202 in the third region 210. In this aspect, the second light detector 224 further comprises an optical filter 244 configured to block light at the excitation wavelength. As a result, the first light detector 222 is configured to measure received light at both the excitation and emission wavelengths and the second light detector 224 is configured to detect received light at the emission wavelength only. Combined with illumination of the patient's tissues 202 QAOznn / eznz / E / YiAi with light at the excitation wavelength only and at the emission wavelength only in an alternating series (see Figure 5) measurements from the first light detector 222 and a second light detector 224 They can be analyzed as described herein below to measure the fluorescence of an exogenous fluorescence agent and to correct the fluorescence measurements by removing the effects of diffuse reflectance of light in accordance with the correction methods described here below. In various aspects, the second region 208 and third region 210 within the patient tissues 202, from which light is detected by the first light detector 222 and a second light detector 224, respectively, are each separated by a distance nominal separation distance from the first region 206 to which light produced by the first light source 218 and the second light source 220 is supplied. This nominal separation distance can be selected to balance two or more effects that can impact the quality of data detected by light detectors. Without being limited to any particular theory, as the nominal separation distance increases, the total detected signal from the light detectors may decrease due to light scattering along the longest optical path between light source and detector. light. This effect can be mitigated by the choice of emission wavelength, which QAOznn / eznz / E / YiAi may result in a less pronounced decrease in the detected fluorescence signal (i.e., light at the emission wavelength) relative to the signals associated with light detected at the custom excitation wavelengths. which increases the nominal separation distance. Longer nominal separation distances result in higher sensitivity to signal changes due to changing tissue optical properties. In one aspect, the nominal separation distance may vary from 0 mm (i.e., placement of light sources and light detectors) to approximately 10 mm. In various other aspects, the nominal separation distance can range from about 1 mm to about 8 mm, from about 2 mm to about 5 mm, and from about 3 mm to about 5 mm. In various additional aspects, the nominal separation distance may be 0 mm, about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, and about 10 mm. In one aspect, the nominal separation distance may be about 4 mm to balance these competing effects of log signal drop and reduced size of the background signal relative to the exogenous fluorescent agent signal. Referring again to Figure 9, the QAOznn / eznz / E / YiAi first light detector 222 may be placed within a first detection well 908 of the sensor mount 912 and the second light detector 224 may be placed within a second detection well 910 of the sensor mount 912 within the sensor head 204. The first light detector 222 and the second light detector 224 can receive light from patient tissue 202 through a first detector aperture 1004 and second detector aperture 1006, respectively. In one aspect, the first detector aperture 1004, the second detector aperture 1006, and the light supply aperture 1002 are mutually separated from each other by the nominal separation distance described herein above which includes, but is not limited to, a distance nominal separation of 4 mm. In one aspect, the first detection well 908, second detection well 910, and light source well 902 of the sensor mount 912 can be optically isolated from each other to ensure that light from the light sources 218 / 220 does not reach the detectors. of light 222 / 224 without coupling through the skin of the patient 202. The separation between the two detection wells 908 / 910 ensures that the fluorescence signal detected from the exogenous fluorescent agent can be distinguished from unfiltered excitation light, such as It was described here in detail below. In one aspect, the three openings 704 of the plate QAOznn / eznz / E / YiAi aperture 702 (see Figure 7) are circular with a diameter ranging from approximately 0.5 mm to approximately 5 mm. In various other aspects, the diameters of the apertures can range from about 0.5 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2.5 mm to about 3.5 mm, approximately 3 mm to approximately 4 mm, approximately 3.5 mm to approximately 4.5 mm, and approximately 4 mm to approximately 5 mm. In one aspect, the three apertures 704 of the aperture plate 702 are circular apertures with a diameter of approximately 1 mm in diameter. This finite width of apertures can result in an effective source-detector separation of less than the nominal separation distance due to the log signal drop with increasing separation distance of the light sources at the skin interconnect of the imaging head. sensor 204. In various aspects, the light detectors 222 / 224 of system 200 may be any suitable light detection device without limitation. Non-limiting examples of suitable light detection devices include: photoemission detectors such as photomultiplier tubes, phototubes, and plate detectors. QAOznn / eznz / E / YiAi microchannel; photoelectric detectors such as reverse biased LEDs to act as photodiodes, photoresistors, photodiodes, phototransistors; and any other suitable detection device. In aspect, the light detectors 222 / 224 are sensitive enough to detect fluorescence emitted by exogenous fluorescent agents within patient tissues 202 that include melanin ranging from about 1% to about 40% melanin in the epidermis and volume. of blood that varies from approximately 0.5% to approximately 2% of the skin volume. In one aspect, the light detectors 222 / 224 may be silicon photomultiplier (SPM) devices. In one aspect, the first light detector 222 may be configured to detect light at both the excitation frequency and the emission frequency, and the second light detector 224 may be configured to detect light at the emission frequency only. In one aspect, the second light detector 224 may respond only to light of the emission wavelength as a result of the design and materials of the sensor elements of the second light detector 224. In another aspect, the second light detector 224 can respond to a broader range of light wavelengths, but an optical filter configured to pass only QAOznn / eznz / E / YiAi the portion of incoming light with the emission wavelength and further configured to block the passage of light wavelengths outside the emission wavelength. Any suitable optical filter can be selected for use with the second light detector 224 to selectively detect light at the emission wavelength. Non-limiting examples of suitable optical filters include absorbing filters and interference / dichroic filters. Without being limited to any particular theory, the performance of an absorption filter does not vary significantly with the angle of incident light, while the performance of an interference / dichroic filter is sensitive to the angle of incident light and may require additional collimation optics for Effectively filter the Lambertian light distribution representative of light emitted from the skin of patient 202. In one aspect, the second light detector 224 may be positioned downstream of an absorbing long pass filter configured to pass light above a predetermined wavelength to the second light detector 224. By way of non-limiting example, the second detector Light filter 224 may be placed downstream of an OG530 long-pass filter configured to pass light with wavelengths above approximately 530 nm. Other non-limiting examples of suitable filters include a Hoya 054 filter and QAOznn / pznz / E / YiAi a Hoya CM500 filter. In various aspects, an absorption filter 244 configured to absorb excitation wavelength light may be placed within the second detection well 910 between the second light detector 224 and the second detector aperture 1006. In one aspect, the absorption filter 244 absorption 244 can be constructed of OG530 glass. The thickness of the absorption filter 244 can be selected to allow an optical density sufficient to filter the excitation light by approximately three orders of magnitude. In one aspect, the thickness of absorption filter 244 can vary from about 1 mm to about 10 mm. In various other aspects, the thickness of the absorption filter 244 can vary from about 1 mm to about 8 mm, from about 2 mm to about 6 mm, and from about 3 mm to about 5 mm. In various additional aspects, the thickness of the absorption filter 244 may be about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm , and approximately 10 mm. In one aspect, the absorption filter 244 is a 3 mm thick filter constructed of OG530 Schott glass. In a further aspect, an optical diffuser can QAOznn / eznz / E / YiAi be provided within the light source well 902. In this aspect, the optical diffuser allows mixing of the light entering the light source well 902 from the first and second light sources 218 / 220. . By mixing light from the first and second light sources 218 / 220 using the optical diffuser prior to illumination of the first region 206 of the patient 202, the similarity of the optical paths taken by emission wavelength light and light from excitation wavelength through the patient's tissues is improved relative to the corresponding optical paths taken by unmixed light, thereby reducing a potential source of variation. In one aspect, a transparent material configured to pass light of both excitation and emission wavelengths may be placed within the first detection well 908 between the first light detector 222 and the first detector aperture 1004. In this aspect, The transparent material may be any material with optical properties similar to the absorption filter material 244 including, but not limited to, thickness and refractive index. In one aspect, the transparent material within the first detection well 908 may be fused silica glass of the same thickness as the absorption filter 244. As a non-limiting example, the transition spectrum of the OG 530 filter is provided in Figure 3. QAOznn / eznz / E / YiAi As illustrated in Figure 3, the transmission spectrum of the OG filter 530 overlaps when the emission spectrum of the exogenous fluorescent agent MB-102 and the emission spectrum of a green LED used as a second light source 220 (length of emission wave). Furthermore, the transmission spectrum of the OG filter 530 excludes the emission spectrum of the blue LED used as a first light source 218 and the absorbance spectrum of the exogenous fluorescent agent MB-102 (excitation wavelength). In one aspect, the transparent material such as glass 246 and the absorption filter 244 may be secured to shelves formed within the first detection well 908 and the second detection well 910, respectively. The transparent material such as glass 246 and the optical filter 244 can be secured in place by using an opaque and / or light absorbing adhesive including, but not limited to, black epoxy to ensure that all light received through the first detector aperture 1004 and the second detector aperture 1006 travels through the optical filter 244 glass 246 before detection by the first and second light detectors 222 / 224. In another aspect, the sides of the optical filter 244 or glass 246 may be painted black with a light absorbing coating including, but not limited to, India ink to ensure that light does not reach the first and second light detectors 222 / 224. without going to QAOznn / eznz / E / YiAi through 244 optical filter or 246 glass. In one aspect, the height of the detection wells 908 / 910, combined with the diameter of the detector apertures 1004 / 1006 can limit the fraction of light emitted from the second region 208 and third region 210 of the patient's skin that reaches the active areas of the 222 / 224 light detectors due to the Lambertian distribution of the angle of the light leaving the patient's skin. In aspect, the fraction of light emitted from the second region 208 and third region 210 of the patient's skin received by the light detectors 222 / 224 can vary from about 5% to about 90%. In various other aspects, the light fraction can vary from about 5% to about 15%, from about 10% to about 20%, from about 15% to about 25%, from about 20% to about 30%, from about 25%. % to about 35%, from about 30% to about 40%, from about 35% to about 45%, from about 40% to about 60%, from about 50% to about 70%, and from about 60% to about 90 %. In one aspect, for the sensor head 204 illustrated in Figure 6 and Figure 7 with 1 mm diameter apertures 1002 / 1004 / 1006, approximately 10% of the light emitted from the patient's skin surface can be QAOznn / eznz / E / YiAi reach the active area of ​​the light detectors 222 / 224 to be detected. In various aspects, the sensor head 204 may further include additional optical elements including, but not limited to, lenses and / or prisms configured to compensate for the Lambertian distribution of light angles in order to improve the fraction of light emitted from the skin of the patient that is directed to the active area of ​​the light detectors 222 / 224. iii) Temperature Sensors Referring to Figure 2, the sensor head 204 may further include one or more additional temperature sensors 228 configured to reflect temperatures from various regions within the sensor head 204 and in the vicinity of the sensor head 204. Non-limiting examples Suitable regions for which temperature may be monitored by the one or more additional temperature sensors 228 include: temperature at the skin surface of the patient 202; temperature in the vicinity of the first light source 218 and / or second light source 220; ambient temperature outside the sensor head 204; housing temperature 600 of sensor head 204; and any other suitable region. In one aspect, additional temperature sensors 228 may be configured to monitor the temperature in the vicinity of temperature-sensitive electrical components that QAOznn / eznz / E / YiAi include, but are not limited to: light sources 218 / 222 such as LEDs, light detectors 222 / 224 such as silicon photomultipliers (SPM), and any other electrical components sensitive to head temperature sensor 204. In some aspects, one or more temperatures measured by one or more additional temperature sensors 228 may be used as feedbacks in a control method for one or more of the temperature-sensitive devices of system 200 as described herein. continuation. By way of non-limiting example, a temperature measurement may be used to monitor the amount of light energy produced by an LED used as a first or second light source 218 / 220. In this example, LED temperatures measured by a second temperature sensor 1108 (see Figure 11) can be used in a control scheme to modulate the amount of power supplied to an LED light source to compensate for the effect of LED temperature on the output. of LED light. In another aspect, additional temperature sensors 228 may monitor the temperatures of LED light sources 218 / 220 to monitor and / or compensate for temperature variations of the LEDs as well as monitor and / or compensate for temperature-dependent transmission of the optical filters to maintain output wavelengths QAOznn / eznz / E / YiAi relatively constant. As another non-limiting example, an additional temperature sensor 228 may be included in the sensor head 204 in the form of a thermistor 816 (see Figure 8) configured to monitor the temperature of the housing 600 in the vicinity of the contact surface. 606 of the sensor head 204. Referring to Figures 7, 8 and 9, the thermistor 816 can be epoxy glued into the temperature sensor opening 606 in the temperature plate 702 in one aspect. In this aspect, the space 918 between the circuit board (not shown) and the lower housing 604 can be filled with a thermally conductive putty to ensure good conduction and thermal dissipation. In this example, the measured housing temperature can be used to modulate the light output of the sensor head 204 to prevent overheating of the skin of the patient 202 during use. In another aspect, additional temperature sensors 228 may monitor the temperatures of LED light sources 218 / 220 to monitor and / or compensate for temperature variations of the LEDs to allow maintenance of relatively constant output wavelengths by the LED light sources. 218 / 220. In a further aspect, temperatures measured by one or more additional temperature sensors 228 may provide subject safety by disabling one or more QAOznn / eznz / E / YiAi electrical devices including light sources 218 / 220 and / or light detectors 222 / 224 if an excessive temperature condition is detected. In one aspect, an overtemperature condition may be indicated if the case temperature detected by the thermistor 816 is greater than about 40°C. In various aspects, an overtemperature condition may be detected if the case temperature is greater than about 40.5°C or greater than about 41.0°C. B. Controller Referring again to Figure 2, the system 200 in various aspects may include a controller 212 configured to operate the light sources 818 / 200 and light detectors 222 / 224 in a coordinated condition to obtain a plurality of measurements used to obtain the fluorescence of the exogenous fluorescent agent within the tissues of patient 202, to correct the fluorescence data to remove the effects of diffuse light reflectance as described herein below, and to transform the fluorescence measurements into a parameter representative of renal function of patient 202. Figure 11 is a schematic diagram of an electronic circuit 1100 illustrating the arrangement of various electrical components that allow operation of system 200 in one aspect. In appearance, the controller 212 may be QAOznn / eznz / E / YiAi a computing device further including an operation unit 214 and a display unit 216. i) Light Source Control Unit Referring again to Figure 2, the controller 212 may include a light source control unit 230 configured to operate the first light source 218 and the second light source 220 to produce light at the excitation wavelength. and emission wavelength, respectively in a coordinated manner to produce a repetition pulse sequence as schematically illustrated in Figure 5. In various aspects, the light source control unit 230 can produce a plurality of control signals of light that encode one or more light control parameters including, but not limited to: activation or deactivation of each light source; relative activation and deactivation time of each light source to allow for light pulse width, pulse repetition rate, electrical energy supplied to the light source or other parameter associated with light pulse influence or light pulse energy; other light source-specific parameters that control the light output of the light source; and any other relevant light control parameters. In one aspect, the light source control unit 230 may receive one or more feedback measurements used to modulate the plurality of QAOznn / eznz / E / YiAi control signals to compensate for variations in performance of light sources in order to maintain a relatively stable light output of the light sources. Non-limiting examples of feedback measurements used by the light source control unit 230 include: light output of the light sources 218 / 220 measured within the source well 902 by the first monitor photodiode 904 and the second monitor photodiode monitor 906, respectively, temperatures of the light sources 218 / 220, and any other feedback measurements relevant to monitoring the performance of the light sources 218 / 220. By way of non-limiting example, the light source control unit 230 may be configured to operate LED light sources 218 / 220. In this example, the light output of the LED light sources 218 / 220 can control the magnitude of current provided to each LED. In one aspect, the light source control unit 230 may include at least one waveform generator 1122 including, but not limited to, a field programmable array assembly (FPGA) with a DAC. 16-bit 1124 operatively coupled to an LED current source 1126, as illustrated in Figure 11. In one aspect, waveforms generated by the at least one waveform generator 1122 including, but not limited to, waves square, you can control the output of the power supply QAOznn / eznz / E / YiAi LED current 1126. In one aspect, the magnitude of the current supplied to the LED light sources 218 / 220 can be adjustable based on the waveform signals provided by the shape generator. wave / FPGA 1122. Referring to Figure 5, in one aspect, each light pulse sequence 500 includes an emission wavelength light pulse 502 and an excitation wavelength light pulse 504 which are both formed from a plurality of square waves 506 produced by the first and second LED light sources 218 / 220. Referring to Figure 11, square waves generated by the waveform generator 1122 are received by the LED current source 1126. The current generated by the LED current source includes a square waveform similar to the waveform generated by the waveform generator 1122. Without being limited to any particular theory, because the intensity of light produced by the LED light sources 218 / 220 is proportional to the magnitude of the current received, the light produced by the LED light sources 218 / 220 also include the square waveform as illustrated in Figure 5. In another aspect, discussed in additional detail below, the square waves produced by the waveform generator 1122 can also be used by the 234 acquisition unit in a synchronous detection method to reduce the effects of various factors QAOznn / eznz / E / YiAi including, but not limited to, ambient light detection of detector signals generated by light detectors 222 / 224 during illumination of patient tissues at emission wavelengths and excitation by the first and second light sources 218 / 220, respectively. In various other aspects, a variety of alternating LED pulse modulation schemes may be equivalently employed without limitation. In one aspect, the excitation and emission pulses are delivered in an alternating series interspersed with a dark period after each pulse. In another aspect, the first and second LED light sources 218 / 220 are each modulated with a 50% duty cycle but different modulation frequencies, allowing the signals associated with the excitation and emission pulses to be separated by frequency filtration. Without being limited to any particular theory, the total optical energy delivered to the patient's skin can be limited by at least two factors: photobleaching of the exogenous fluorescent agent and / or endogenous chromophores, as well as overheating of patient tissues illuminated by the system 200. In one aspect, tissue heating may impose an absolute limit of approximately 9 mW on the optical power that can be delivered to the skin, based on safety standards that include, but QAOznn / eznz / E / YiAi not limited to, ANSI / IESNA RP-27. In another aspect, photobleaching of skin auto-fluorescence associated with endogenous chromophores including, but not limited to, collagen, hemoglobin, and melanin may contribute a background signal to the measured fluorescence that remains relatively constant as long as no self-bleaching occurs. of the chromophores. This constant auto-fluorescence background can be subtracted from the raw fluorescence signal, but if the auto-fluorescence varies with time due to photobleaching, this background correction can interfere with the kinetic calculation of the decay time constant. kidney (RDTC). In one aspect, the light output energy of the first light source 218 and / or second light source 220 may be limited to levels below energy thresholds associated with chromophore photo-bleaching. Referring again to Figure 9, the light output of the light sources 218 / 220 can be measured when using monitor photo diodes 904 / 906 in various aspects. Because the light intensity reaching these monitor photodiodes 904 / 906 is typically much stronger than the light intensity reaching the light detectors 222 / 224, through the patient's skin, fewer light detection devices Sensitive devices including, but not limited to, PIN photodiodes can be used to monitor the output of QAOznn / eznz / E / YiAi light sources 218 / 220. In various aspects, the system 200 may be configured to operate over a range of skin tones observed in the human population. Without being limited to any particular theory, variations in skin tones between different patients 202 can result in variations in the detected fluorescence signals that vary over approximately three orders of magnitude. Furthermore, variations in exogenous fluorescent agent concentrations within each patient 202 can vary over a range of approximately two orders of magnitude due to renal clearance of the agent over time. In various aspects, system 200 may be configured to detect fluorescence from the endogenous fluorescent agent over an intensity range of more than five orders of magnitude. In these various aspects, the system 200 may be configured by modulation of at least one operating parameter including, but not limited to: magnitude of light output by the light sources 218 / 220 and sensitivity of light detectors 222 / 224 that correspond to detector gains. In one aspect, the intensity of the light output by the light sources 218 / 220 can be set manually by a user through the operation unit 214. In QAOznn / eznz / E / YiAi Another aspect, the light source control unit 230 can be configured to modulate the intensity of light produced by the light sources 218 / 220 automatically. In one aspect, the light source control unit 230 may be configured to control the light intensity produced by the LED light sources 218 / 220 within a range of normalized output intensities from 0 (off) to 1 (full power). ). In one aspect, the intensity of the light sources 218 / 220 may be set by the light source control unit 230 in coordination with the gains of the light detectors 222 / 224 set by the light detector control unit 232. , as described here below. In one aspect, signals obtained during the first 10 detection cycles obtained by the system 200 after initiation of data acquisition, but before injection of the exogenous fluorescent agent, can be used by the light source control unit 230 to adjust automatically the intensity of those produced by the LED light sources 218 / 220, as well as the gain of the light detectors 222 / 224. In this example, the initial detection cycle can be obtained with the LED light sources 218 / 220 set at approximately 10% maximum LED intensity (corresponding to a normalized output intensity of 0.1) with a low gain setting for the detectors. light 222 / 224. Based on the intensity of detected light received at the light detectors 222 / 224 in the QAOznn / eznz / E / YiAi excitation and emission wavelengths for one detection cycle, the corresponding LED intensities can be modulated to allow the analog signals produced by the light detectors 222 / 224 to correspond to approximately 1 / 4 of the full range of each analog-to-digital converter (ADC) detector at the low detector gain setting. If the signals produced by the light detectors 222 / 224 in response to the light produced by the second LED light 220 at the emission wavelength do not agree, the larger signal may be produced to modulate the power configuration of the second LED light source 220. If the method described above results in modulation to an LED intensity setting greater than the maximum intensity (corresponding to a normalized output intensity of 0.1), the LED intensity setting is set to the maximum setting . Without being limited to any particular theory, the focused levels of signals produced by the light detectors 222 / 224 (i.e., 1 / 4 of the ADC range) are selected to reserve additional light detection capacity to detect signals that result from variations in optical properties of patient 202's tissues during the study due to any one or more of a plurality of factors including, but not limited to, QAOznn / pznz / E / YiAi the introduction of patient exogenous fluorescent agent 202. In a previous aspect, once the LED intensities are set by the light source control unit 230 in coordination with the detector gains of the light detectors 222 / 224 set by the light detector control unit 232 During the first 10 sensing cycles, 10 additional sensing cycles are obtained to confirm the suitability of these settings for operation of the system 200 given the tissue properties of the particular patient 202, followed by a recalculation of the LED intensity settings and detector gains as described here. If the newly calculated LED intensity is within a factor of two of the previously default settings, the detector gains do not change; the previously determined settings are maintained for subsequent data acquisition cycles used to determine renal function. Otherwise, the configurations are updated using the same method described here and another 10 cycles of data acquisition conducted to confirm the stability of the configurations. This process is repeated until either configuration is determined to be acceptably stable or 10 data acquisition cycles are conducted to obtain the configurations, in which case the most recent configurations are used. QAOznn / eznz / E / YiAi determined for all subsequent data acquisitions, and the user may be notified through the display unit 216 that the settings may not be optimal. ii) Light Detector Control Unit Referring again to Figure 2, the controller 212 may include a light detector control unit 232 configured to operate the first light detector 222 and the second light detector 224 to allow detection of light over the length of emission wave and unfiltered light at all wavelengths, respectively. In various aspects, the light detector control unit 232 may produce a plurality of detector control signals that encode one or more detector control parameters including, but not limited to, detector gains. In various other aspects, the light detector control unit 232 can produce a plurality of light measurement signals that encode the intensity of those detected by the detectors 222 / 224 including, but not limited to detector signals without process that can be received by an analog to digital converter (ADC) 1102 (see Figure 11) in several aspects. In another aspect, detector gains and / or other detector control signals can be set manually by a user's detector gains when system 200 is configured QAOznn / eznz / E / YiAi in an Engineering Mode. In various other aspects, the amount of light received by the light detectors 222 / 224 may vary due to any one or more of at least several factors including, but not limited to: variation in skin tones observed between individual patients 202 , variations in exogenous fluorescent agent concentrations within each patient 202, and any other relevant parameters. In one aspect, gains of the first light detector 222 and the second light detector 224 can be set by a user through the operation unit 214. In another aspect, the light detector control unit 232 can be configured to modulate the gain of the light detectors 222 / 224 automatically through a bias voltage gain of the bias voltage generator 1112 (see Figure 11). In one aspect, signals obtained during the first 10 detection cycles obtained by the system 200 after initiation of data acquisition, but before injection of the exogenous fluorescent agent, can be used by the light detector control unit 232 to adjust automatically the gains of the light detectors 222 / 224, as well as the output intensities of the light sources 218 / 220. As described here previously, the initial detection cycle can be obtained with the sources QAOznn / eznz / E / YiAi of 218 / 220 LED lights set at approximately 10% maximum LED intensity (corresponding to a normalized output intensity of 0.1) and with a low gain setting for the 222 / 224 light detectors and the LED intensities may be modulated to allow the analog signals produced by the light detectors 222 / 224 to correspond to approximately 1 / 4 of the full range of each detector analog-to-digital converter (ADC) in the low detector gain setting. . In this aspect, if the intensity of the first LED light source 218 (which produces the LED light at the excitation wavelength) is set to the maximum of the LED power range, a high detector gain for the second detector can be considered. of light 224 that corresponds to measurements filtered from the excitation wavelength only. In various aspects, the high detector gain can be 10 times greater than the corresponding low detector gain for a given light detector. Without being limited to any particular theory, the expected peak detected fluorescence signal from the exogenous fluorescence agent during the course of injection and renal elimination is typically expected to be approximately 10% of the magnitude of the signal received during illumination at the wavelength excitation by the first light source 218, which assumes that the excitation agent QAOznn / eznz / E / YiAi exogenous fluorescence is introduced by MB-102 in patient 202 at a dose level of approximately 4 pmol / kg of the patient's weight. In one aspect, if the expected detector signal received during illumination at the maximum LED intensity and with the detector gain set to the high setting remains below 10% of the range of the detector ADC, the detector gain for that measurement increases by 10 times. In another aspect, the saturation condition may persist for a predefined period of time including, but not limited to, a 30 second period after adjustments are made to the detector gain or LED power to avoid reacting to spurious signal spikes. In another aspect, the light detector control unit 232 may adjust the detector gain to a lower gain level if the detected light signals from one of the light detectors 222 / 224 exceed a threshold percentage of the ADC range. maximum to avoid signal saturation. Although the highest threshold percentage of the maximum ADC range associated with signal saturation is 100%, the onset of severe detector nonlinearity occurs at threshold percentages of approximately 40% or greater, and mild detector nonlinearity. occurs at threshold percentages that exceed approximately 15%. In various aspects, the maximum ADC interval threshold percentage may be 40%, 35%, 30%, 25%, 20%, 18%, 17%, 16%, 15%, 14%, 13%, 12% , QAOznn / eznz / E / YiAi 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the maximum ADC range. In one aspect, if the detected light signals from one of the light detectors 222 / 224 exceeds approximately 8% of the maximum ADC range, the gain setting will be adjusted. As a non-limiting example, if the detector gain on the near-saturated signal is high, it will be set to low. If the current detector gain is set to low and the corresponding detected light signal remains above the threshold percentage of the maximum ADC range, the output power setting of the corresponding LED light source will be reduced by ten times. In one aspect, the light detector control unit 232 may receive one or more feedback measurements used to modulate the plurality of detector signals to compensate for variations in the performance of the light detectors due to variations in temperature and / or output. of light source. Non-limiting examples of feedback measurements used by the light detector control unit 232 include: light output of the light sources 218 / 220 measured within the source well 902 by the first monitor photodiode 904 and the second monitor photodiode monitor 906, respectively (see Figure 11), temperatures of the light detectors 222 / 224 measured by a first temperature sensor 1106, LED temperatures measured by a second temperature sensor 1108, QAOznn / eznz / E / YiAi temperature of the sensor head housing measured by a third temperature sensor 1118, supply current of the LED current source 1126, and any other feedback measurements relevant to monitoring the performance of light detectors 222 / 224. In various aspects, the light detectors 222 / 224 may be silicon photon multiplier (SPM) detectors that may include low noise internal amplifications, and may operate in lower light ranges relative to other light sensor devices such as as PIN photodiodes. The detector signal generated by the SPM detectors 222 / 224 can be modified by using transimpedance amplifiers 1120 / 1118, respectively (see Figure 11) to translate a current generated by each light detector of SMP 222 / 224 into a detector voltage measurable. The transimpedance amplifier 1118 in the second SPM light detector 224 (i.e., detects filtered lights at the excitation wavelength only) may include a switchable detector gain that may select a low gain configured to detect a larger dynamic range. large for fluorescence measurements when the first LED light source 218 is activated to produce light at the emission wavelength. Switchable detector gain that can also select a high gain setting for the second detector QAOznn / cznz / E / YiAi of light from SPM 224 when the second light source 222 is inactive to improve the sensitivity of the second light detector from SPM 224 during the phase of the detection cycle when light at the emission wavelength produced by the exogenous fluorescent agent within the patient's tissues 212 detects, to ensure that the expected dark current from the second SPM light detector 224 occupies less than 1 / 4 of the total ADC output range. In one aspect, the second transimpedance amplifier of the second SPM light detector 224 may include a low detector gain configured to provide a transimpedance gain of approximately 4 kQ corresponding to approximately twice the value of the transimpedance resistor due to differential operation, and may further include a high detector gain configured to provide a transimpedance gain of approximately 40 <Ω. In another aspect, the first transimpedance amplifier of the first SPM light detector 222 may include a fixed detector gain configured to provide a transimpedance gain of about 2 kQ. iii) Acquisition Unit Referring again to Figure 2, the controller 212 may further include an acquisition unit 234 in various aspects. The acquisition unit 234 may be configured to receive a plurality of QAOznn / eznz / E / YiAi signals from the light sources 218 / 220, light detectors 222 / 224, and additional light detectors 226 and additional temperature sensors 228 and process the plurality of signals to produce one or more raw signals including, but not limited to, raw fluorescence signals that encode the fluorescence intensity detected by the second light detector 224 during illumination at the excitation wavelength, and raw internal reflectance signals that correspond to the intensity of light at the excitation wavelength detected by the first light detector 222 during illumination at the station wavelength as well as the intensity of light at the emission wavelength detected by both of the light detectors 222 / 224 during illumination at the emission wavelength. The plurality of signals received from the various sensors and devices described herein above are typically analog signals including, but not limited to, electrical voltages and currents. In various aspects, the acquisition unit 234 may allow transmission of the analog signals to one or more analog to digital converters (ADC) to convert the analog signals into digital signals for subsequent processing by the processing unit 236. Figure 11 is a schematic diagram of a circuit 1100 illustrating the QAOznn / eznz / E / YiAi arrangement of various electrical devices and components of the sensor head 204. In one aspect, analog signals encoding the intensity of light detected by the first light detector 222 and the second light detector 224 can be received for a first ADC 1102. In various aspects, the analog signals produced by the light detectors 222 / 224 and various monitor sensors can be digitized by using at least one 24-bit Sigma-Delta ADC. Referring again to Figure 11, analog signals encoding time-sensitive sensor measurements can be digitized using a high-speed 24-bit Sigma-Delta ADC 1102 in one aspect. In this aspect, time-sensitive sensors include sensors associated with the production and detection of light pulses characterized by potentially rapidly changing signals. Non-limiting examples of time-sensitive sensors of system 200 include: first and second light detectors 1118 / 1120, and first and second monitor photodiodes 904 / 906. In another aspect, analog signals that encode measurements from less time-sensitive sensors can be digitized using a low-speed 24-bit Sigma-Delta ADC 1104. In this other aspect, less time-sensitive sensors include sensors associated with conditions. of monitoring systems characterized by typically changing signals Slow QAOznn / eznz / E / YiAi including, but not limited to, temperatures of various components and / or system regions. Non-limiting examples of less time-sensitive sensors of system 200 include: a first and second thermistor 1106 / 1108 configured to monitor the temperatures of light sensors 222 / 224 and light sources 218 / 220, respectively, and a third temperature sensor. temperature 1128 configured to monitor a temperature of the housing 600 of the sensor head 204. In various aspects, the acquisition unit 234 may further be configured to allow synchronous detection of light by detectors 222 / 224. Without being limited to any particular theory, synchronous detection methods are intended to reject noise from detector signals associated with the detection of light produced by the 118 / 120 light sources and fluorescence produced by exogenous fluorescent agents within tissue tissues. patient 202 by distinguishing detector signals from noise associated with the detection of ambient light or other sources of interference. Figure 12 is a schematic illustration of a synchronous detection method in one aspect. Referring to Figure 11 and Figure 12, the FPA / waveform generator 1122 can generate a digital square wave 1202 that is received by the DAC 1124, and the converted square wave QAOznn / eznz / E / YiAi The resulting analog current is received by the LED current source 1126. The resulting current produced by the LED current source 1126 is also characterized by a waveform proportional to the square wave converted to analog. which drives 218 / 220 LED light sources. The light produced by the LED light sources 218 / 220, after passing through the patient's tissues 202, is detected, along with the fluorescence produced by the endogenous flowering agent, by the light detectors 222 / 224 and digitized by the 1102 high-speed ADC. Referring again to Figure 11 and Figure 12, the digital square wave 1202 generated by the waveform generator / FPA 1122 can also be converted by a DAC 1110 (see Figure 11) to an in-phase reference sine wave 1210 and an out-of-phase / quadrature reference cosine wave 1212. In one aspect, the digitized detector signals from the ADC 1102 and the in-phase reference sine wave 1210 may be sampled and subjected to signed multiplication to a first multiplier 1214. to generate a plurality of phase modulated signals. Additionally, the digitized detector signals and the quadrature reference cosine wave 1212 may be sampled and subjected to signature multiplication in a second multiplier 1216 to generate a plurality of quadrature modulated (out-of-phase) signals. In this regard, the unit of QAOznn / eznz / E / YiAi acquisition 234 may delay the samples of the reference waves 1210 / 1214 by an amount equivalent to the relative delay between the DAC 1124 that generates the reference waves 1210 / 1214 and the ADC 1102 that digitizes the signals. detector to synchronize the reference waves 1210 / 1214 to the detector data being acquired. Referring again to Figure 12, the phase modulated signals can be summed in a first accumulator 1218 to generate a phase intensity signal 1224. Similarly, the quadrature modulated signals can be summed in a third accumulator 1222 to generate a signal quadrature intensity signal 1228. The raw digitized detector signal may also be summed in a second accumulator 1220 to generate an average intensity signal 1226. Additionally, the in-phase intensity signal 1224 and the quadrature intensity signal 1228 may be the square root of the sum to generate a signal of magnitude 1230. Without being limited to any particular theory, the integration interval of the accumulators 1218 / 1220 / 1222 may correspond to an integer number of modulation cycles (corresponding to cycles of the digital square wave 1202) to avoid polarization in the measured signal. . The 1218 / 1220 / 1222 phase accumulators used to control synchronous detection operate on integers, but the sample clock frequency and modulation frequency QAOznn / eznz / E / YiAi are not divisible by an integer, so the number of cycles is not exactly an integer. However, the error associated with this mismatch can be minimized by adjusting the actual modulation frequency to match as closely as possible the sampling intervals that can be achieved and assigning an appropriate number of bits to the phase accumulator. In one aspect, the error associated with the mismatch between the modulation frequency and the sampling intervals may be on the order of about one part in 106. In one aspect, the digital square wave 1202 used to modulate the LED light sources 218 / 220 and to enable synchronous detection method as described herein above occurs at a frequency of approximately 1 kHz. Without being limited to any particular theory, a square wave was selected as the modulation waveform to allow for an improvement in signal-to-noise ratio (SNR) compared to a pure sine wave as the modulation waveform. of modulation wave for the same peak energy level. In another aspect, the acquisition unit 234 may further be configured to allow demodulation in the in-phase intensity signal 1224, average intensity signal 1226, and quadrature intensity signal 1228. In one aspect, the acquisition unit 234 may choose each QAOznn / eznz / E / YiAi component of the fundamental harmonic, which is characterized by an amplitude that is (4 / π) times larger than the amplitude of the square wave 1202 used to modulate the intensity signals 1224 / 1226 / 1228. In various aspects, to reject 50 / 60 Hz electrical noise generated by alternating current electrical power sources, and corresponding 100 / 120 Hz optical noise generated by ambient light sources powered by those electrical power sources, the integration of accumulators 1218 / 1220 / 1222 can be selected to be a multiple of 100 ms. In these various aspects, this selected integration period ensures that integration by the accumulators 1218 / 1220 / 1222 occurs over an integer number of cycles for the 50, 60, and 120 Hz signals. iv) Processing Unit Referring again to Figure 2, the controller 212 may further include a processing unit 236 configured to apply corrections to the demodulated detector signals and to transform a selected portion of the corrected detector signals into a renal function measurement in various aspects. Figure 3 is a block diagram illustrating the processing unit subunits 236 in one aspect. Referring to Figure 13, the processing unit 1236 may include a subprocessing unit 1302 configured QAOznn / eznz / E / YiAi to determine and correct detector signals to remove signal artifacts associated with a variety of confounding effects including, but not limited to, physiologically induced signal variations, variations in energy supplied to light sources 218 / 220, nonlinearities in response to detector, variation in ambient temperature, and tissue heterogeneity. The processing unit 236 may further include a reference subtraction subunit 1304 configured to remove the portion of the detector signals attributable to extraneous factors such as tissue auto-fluorescence and / or light leakage at the excitation wavelength. through the optical filter 244 of the second light detector 224. The processing unit 236 may additionally include a diffuse reflectance correction subunit 1306 configured to allow a method of applying a diffuse reflectance correction method to remove the effects of diffuse reflectance. of light within the tissues of the patient 202. The processing unit 236 may further include a post-equilibration selection subunit 1308 configured to select a portion of the detector data associated with the post-agent administration period for subsequent analysis to determine patient's kidney function. The processing unit 236 may further include an RDTC calculation subunit 1310. QAOznn / eznz / E / YiAi configured to transform detector signals obtained during the post-agent administration period to produce a renal deterioration time constant indicative of the patient's renal function. The processing unit 236 may also include a fault detection subunit 1312 configured to monitor the magnitudes of the detector signals to detect any system malfunctions. a) Pre-processing subunit In one aspect, raw signals corresponding to light intensity detected by light detectors 222 / 224 corresponding to illumination by the first light source 218 and the second light source 220 at the excitation and emission wavelength , respectively, are pre-processed by using various modules of the pre-processing subunit 1302 to remove the effects of a plurality of confounding factors from the raw signals, resulting in signals that more accurately reflect the underlying specific signals of interest. By way of several non-limiting examples, the intensity of light produced by a light source may be due to one or more of a plurality of factors including, but not limited to: fluctuations in the electrical current supplied to the light source and variations in the ambient temperature of the light source. Characterized light QAOznn / eznz / E / YiAi for two or more wavelengths emanating from the same sensor head source aperture may not share the same path to the same detector. Detectors may have thermally dependent sensitivity and gain. Additionally, the optical filter associated with the second light detector 224 may have temperature dependent transmission properties. In one aspect, the pre-processing subunit 1302 is configured to process the raw signals corresponding to light intensities detected by the first and second light detectors 222 / 224 in order to remove one or more of the measurement errors. associated with the devices and elements of system 200 and patient-specific factors including, but not limited to, the plurality of factors described above. Figure 22A is a block diagram illustrating the modules of the pre-processing subunit 1302 in one aspect. Figure 22B is a block diagram illustrating the modules of the pre-processing subunit 1302a in a second aspect. In one aspect, illustrated in Figure 22A, the pre-processing subunit 1302 1) resamples the signals by using the methods of the resampling module 2202 as described below, 2) removes saturated detector signals by using the methods of the module detection and QAOznn / eznz / E / YiAi detector output saturation removal 2204 as described below, 3) correct temperature dependent detector gain by using the methods of the detector temperature correction module 2206 described below, 4) correct the signals for instrument light directionality by using the methods of the light directionality correction module 2208 described below, 5) correct the signals for filter performance and temperature-dependent variation of fluorescence light by using the methods of the light directionality correction module 2208 described below, filter performance (emission) temperature correction 2212 described below, 6) corrects tissue heterogeneity by using the methods of the tissue heterogeneity correction module 2216 described below, 7) corrects signals for filter performance and dependent variation of temperature for excitation light and signal decomposition by using the Filter Performance Temperature Correction Module (Excitation) and Signal Decomposition Module 2214 methods as described below, Fractional Photon Normalization Module 2218 methods as described below. In one aspect, illustrated in Figure 22B, the pre-processing subunit 1302a calculates signal magnitudes by using the methods of the detector temperature correction module 2206a as described QAOznn / eznz / E / YiAi then resamples the signals by using the methods of the resampling module 2202a as described below, removes saturated samples by using the methods of the detector output saturation removal and detection module 2204a as described below. Next, correct the signals for temperature-dependent detector gain by using the methods of the detector temperature correction module 2206a described below, correct the signals for optical power variation by using the methods of the fractional photon normalization module 2218a as described below. described below, correct excitation light leakage on the measured fluorescence signal by using the filter performance (excitation) temperature correction module and signal decomposition module 2214a as described below, and correct light leakage of fluorescence on the excitation diffuse reflectance signal measured by using the filter performance (emission) temperature correction module 2212a as described below. Resampling Module Referring to Figures 12A and 22B, the pre-processing subunit 1302 / 1302a in various aspects includes a resampling module 2202 / 2202a configured to reduce signal variations associated with physiological processes of the patient 202 including, but not limited to, heart rate and breathing. Typically, a sequence of QAOznn / cznz / E / YiAi acquisition is characterized by alternating illumination intervals in excitation and emission separated by non-illumination intervals (i.e. dark intervals). Although both illumination intervals (excitation / emission) are timestamped with the same timestamp value as described above, the dark interval between the excitation and emission illumination intervals results in a separation interval between the illumination intervals. excitation and emission lighting. Without being limited to any particular theory, if the separation interval associated with an acquisition sequence is on the order of a separation interval between physiological events, such as heart rhythms or respiration, physiological noise can be introduced to the signals. In several aspects, this physiological noise can be reduced by resampling the signals associated with excitation and emission illumination to overlap before subsequent signal processing. By way of non-limiting example, a sample sequence may include a 100 ms dark interval, a 100 ms bright interval at the excitation wavelength, a second 100 ms dark interval, and a 100 ms bright interval. of 100 ms at the emission wavelength. Each sample packet is recorded with an individual timestamp, and each sample packet QAOznn / eznz / E / YiAi is separated by an interval of 400 ms. Because physiological signal variations, such as from cardiac rhythms, occur on this same time scale, the 200 ms difference between signal acquisition associated with the excitation and emission wavelengths becomes evident in the signals. . This physiological signal noise can be reduced by using pre-processing subunit 1302 by first resampling the signals associated with illumination at the excitation and emission wavelength illumination to overlap before performing any additional signal processing as described below. . In this non-limiting example, signals associated with illumination at the excitation wavelength may shift forward by 100 ms and signals associated with illumination at the emission wavelength may shift backward by 100 ms, resulting in an overlap of signals. In various aspects, the resampling module 2202 performs mastering as described above on signals detected by both the first and second detectors 222 / 224. In one aspect, the resampling module 2202 functions as a form of low pass filter. Detector Output Saturation Detection and Removal Module Referring again to Figures 22A and QAOznn / eznz / E / YiAi 22Β, the pre-processing subunit 1302 / 1302a in various aspects includes a detector output saturation detection and removal module 2204 / 2204a configured to detect and remove signal values ​​that fall outside the detection range of the light detectors 222 / 224. In one aspect, the pre-processing subunit 1302 compares the detected signals with the maximum ADC signal. If any signal falls within the threshold range of the maximum ADC signal when using the average or peak signal value, the detector output saturation detection and removal module 2204 identifies and removes that value from further processing. Detector Temperature Correction Module Figures 22A and 22B, the preprocessing subunit 1302 / 1302a in various aspects includes a detector temperature correction module 2206 / 2206a configured to allow a temperature correction to compensate for the thermal sensitivity of the light detectors 222 / 224. In one aspect, the intrinsic detector gain for a silicon photomultiplier (SPM) device typically used as a light detector is proportional to the difference between the device breakdown voltage and the bias voltage applied by the voltage generator. polarization 1112 (see Figure 11), referred to here as QAOznn / eznz / E / YiAi a surge. In this regard, the breakdown voltage varies with temperature in a well-characterized manner. In one aspect, the temperature correction takes into account both this internal detector gain variation and additionally temperature-related variation in photon detection efficiency. In one aspect, the temperature correction may be a scaling correction applied to detector measurements in which the scaling correction is based on a measured detector temperature. In one aspect, the measured light detector signals can be divided by the calculated gain G(t) to remove the temperature dependence. The scaling correction G(t) can be calculated according to Equation (2): G (T) = Cv * Vpolarization ~ Vbreak (1 + Ct)TEquation (2) In Equation (2), the monitor temperature T is obtained from a first temperature sensor 1106 (see Figure 11) configured to monitor the temperature of the sensors 222 / 224. The bias voltage (Vpoiarization') can be measured by the bias voltage generator 1112. The breakdown voltage (Vbreak) and the reference temperature (To) are constants specific to the particular light detecting device included in the system 200. By way of non-limiting example, if the light detectors 222 / 224 are silicon photomultiplier devices QAOznn / eznz / E / YiAi (SPM), Vbreak may be 24.5 V and To may be 21 degrees C. In another aspect, the coefficients Cv and Ct used in Equation (2) can be derived empirically based on measurements obtained by using a constant phantom over an ambient temperature varying from approximately 18 degrees C to approximately 26 degrees C. In another aspect, the temperature portion of the gain correction is determined by Equations (3)(5). —C. T7, . .. —17 11 -l- (W7measure ~To Equation (3) ^Use case ~vpolarizationme¿i(javrupture v-1) ^nominal=' Vpolarizationminal~ ^break (1 + Cp)Tnuminal^Equation (4) r· , _GCusecase ^correction ~Gnom¡nalEquation (5) This gain correction may be applied to each of the signal magnitudes as measured by the first and second light detectors 222 / 224 as follows: QAOznn / eznz / E / YiAirnl, + ,ι SPMmaqnitude SPMmagmtudcorregi(¡a=---------Gcorrection Equation (6) In one aspect, the magnitudes of the corrected temperature measurements of each detector and monitor photodiode are calculated from the sum square roots of the in-phase intensity signals 1224 (T) and quadrature intensity signals 1228 (Q) according to with Equation (1): Μ = l2+ Q2Equation (1) The signal magnitudes of the light detectors 222 / 224 calculated using Equation (1) are normalized by the monitor photodiode magnitude for each measurement set that corresponds to the measurements obtained during illumination by one of the LED light sources 218 / 220 at either excitation or emission wavelength. In one aspect, if a photodiode is placed in source well 902, the individual photodiode magnitude of the corresponding measurement array is used for this normalization. In another aspect, if two monitor photodiodes 904 / 906 are placed in the same source well 902 as both LED light sources 218 / 220 (see Figure 9), the average of the two monitor photodiode magnitudes of the measurement set corresponding is used for this normalization. In one aspect, the in-phase intensity signal 1224, quadrature intensity signal 1228, and average intensity signal 1226 (see Figure 12) are further processed for the number of accumulated samples and ADC scaling so that the intensity signals 1224 / 1226 / 1228 are returned as a fraction of the full range of the high-speed ADC 1102 (i.e., ranging from a minimum of 0 to a maximum of 1). Measurements from the 904 / 906 monitor photodiodes (see Figure 19) are similarly scaled as a fraction of the QAOznn / eznz / E / YiAi 100 full range of low speed ADC 1104. In one aspect, Gcorrection may incorporate a power correction to correct the effects of fluctuations in the LED power supply. In this aspect, the signals of the first monitor photodiode 904 and the second monitor photodiode 906 are calibrated by measuring optical output energy with an energy meter as the light intensities of the light sources 218 / 220 are varied. The calibration coefficients of each 218 / 220 light source, Cfuentei and Cfuente2, are calculated as milliwatts measured per detector per recorded monitor photodiode signal value Cfuentei and CfUente2 are used to determine the absolute light output in tissue at each length cool. Referring again to Figure 22B, the detection temperature correction module 2206a corrects signal magnitudes for the variable intensity of the LEDs by normalizing the corrected temperature detected signals by using the LED output signal PDmagnitude measured by the first monitor photodiode 904 and / or the second monitor photodiode 90 6. In this case, the variable Gcorrection for each light source 218 / 220 of the above is amended as follows: c _GCosodeuso nr> \ ^correctionr* ' ^magnitude Equation ( / ) Light Directionality Correction Module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes QAOznn / eznz / E / YiAi 101 a light directionality correction module 2208 configured to allow a correction to variations in the detected signals associated with differences in the scattering and absorption of light of different wavelengths through the tissues of the patient 202 during data acquisition. In aspect, the correction term for light directionality can be measured by acquiring data from one or more homogeneous tissue phantoms and using a sensor configuration in which no emission filters are present. The ratio of the signals detected by the first light detector 222 (Detl) and the signals detected by the second light detector 224 (Det2) measured are used to determine a Gex or Gem coefficient for signals obtained in association with light illumination in the excitation and emission wavelengths, respectively. The coefficients are used to modify the signal detected by the first light detector 222. In one aspect, the correction of the signals acquired in a homogeneous medium by the first light detector 222 when using the coefficients Gex or Gem consider the signals read by the first and second detectors 222 / 224, as equivalent to within 20% of each other. In other aspects, the correction of the signals acquired in a homogeneous medium by the first light detector 222 when using the Gex or Gem coefficients considers the signals measured by the first and second detectors 222 / 224 as equivalent to within QAOznn / cznz / E / YiAi 102 approximately 10%, to be within approximately 5%, to be within approximately 2%, and to be within approximately 1%. Detector Non-Linear Response Correction Module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes a detector non-linear response correction module 2210 configured to allow a correction to variations in the detected signals associated with non-linear response of the detectors. In this regard, a calibration curve based on average data can be used to scale the magnitude data obtained by the detectors 222 / 224. Filter Performance (Emission) Temperature Correction Module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes a filter performance (emission) temperature correction module 2212 configured to allow a correction to variations in detected signals associated with optical properties. temperature dependent optical filter 244 associated with the second light detector 2224 during emission wavelength illumination. In this aspect, the Det2 signals detected by the second light detector 224 can be corrected in accordance with the QAOznn / eznz / E / YiAi 103 Equation (8): „ _ Det2-Det2(cemF,.inclination τ(Τ~Τηοτη)) Det2 = ------------------------------- ,tc.. CemF.nom Equation (8) In various aspects, the signal Det2 measured by the second light detector 224 can be monitored while cycling the ambient temperature over a range that includes the operating temperature range or a sufficiently large subset of the range to adequately determine the temperature dependence of the filter. issue. These data are acquired with the optical filter 244 installed in the second light detector 224 of a homogeneous, non-fluorescent phantom. Additionally, simultaneous measurements of the first light detector 222 are monitored, and a ratio of the Det2 / Detl measurements is determined. The nominal filter coefficient, CemF,nom is calculated as the nominal Det2 / Detl ratio obtained at a nominal operating temperature Tnom. In this aspect, the coefficient CemF,inciinationT is obtained from the slope of Det2 / Detl obtained over a range of ambient temperatures during emission wavelength illumination of the homogeneous, non-fluorescent phantom. Tissue Homogeneity Correction Module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes a tissue heterogeneity correction module 2216 configured to allow a correction to variations in the QAOznn / eznz / E / YiAi 104 detected signals associated with heterogeneity of the tissues that intervene between the first region 206 illuminated by light sources 218 / 220 and second and third regions 208 / 210 in which the light detectors 222 / 224 are placed. In this aspect, the signal Detl corrected for light directionality by the light directionality correction module 2208 and the signal Det2 corrected for filter effects by the filter performance (emission) temperature correction module 2212 are used to calculate Chetero, a coefficient to correct for tissue heterogeneity, in accordance with Equation (9): Chetero = Det2 / Detl Equation (9) Filter element temperature correction (excitation) and signal decomposition module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes a filter performance (excitation) temperature correction module and signal decomposition module 2214 configured to allow a correction to variations in the detected signals associated with temperature-dependent optical properties of the optical filter 244 associated with the second light detector 224 during excitation wavelength illumination. In this regard, because the emission filter is configured to block light at the excitation wavelength, the emission correction module QAOznn / eznz / E / YiAi 105 filter performance (excitation) temperature and signal decomposition module 2214 performs a correction to the variation in the amount of excitation light leakage due to temperature-related changes in the optical properties of the optical filter 244. Additionally, the module Filter performance temperature correction (excitation) and signal decomposition module 2214 allows corrections to the signals measured by the first light detector 222 during excitation wavelength illumination due to the presence of fluorescence induced by the illumination of excitation wavelength superimposed over the portion of the signal associated with the illumination excitation wavelength. In this aspect, the temperature-dependent variation effects on excitation wavelength leakage through the optical filter 244 are calculated as expressed in Equation (10): CexLT=CexLT,nom + CexLT, inclinationT (T~Tnom) Equation (10) In this regard, CexLT,nom is calculated from the ratio of Detl and Det2 signals measured from a homogeneous, non-fluorescent phantom at the nominal operating temperature Tnom during excitation wavelength illumination, CexLT,tiltT is calculated as the tilt of the measured Det2 signal of a homogeneous, non-fluorescent phantom at a range of operating temperatures T during QAOznn / eznz / E / YiAi 106 excitation wavelength illumination. In this aspect, the filter element temperature correction module (excitation) and signal decomposition module 2214 further performs signal extraction to isolate portions of the detected signals associated with diffuse illumination reflectance and wavelength fluorescence. of excitement. DRex2, which is the impact amount of excitation light on the second light detector 224 in the absence of an optical filter 244, is not measurable, due to the presence of the optical filter 244. Furthermore, the signal Detl measured by the first light detector 222 is a signal composed of both diffuse reflectance of the DRexi excitation wavelength illumination and Flrl fluorescence. Cnetero is obtained by using the 2216 tissue heterogeneity correction module as described above. The underlying signals are extracted by using the following system of equations: Det2 = CexLTDRex2 + Flr2 Equation (11) Deti = DRexi + Flri Equation (12) Flr2 = CneteroFlri Equation (13) DRex2 = CneteroDRexi Equation (14) In this aspect, Flr2 is determined by solving the previous system of equations using only medium signals Detl and Det2 as shown below: Det2 = CexLTCneteroDRexi t Flr2 Equation (15) QAOznn / eznz / E / YiAi 107 Det2 = CexLTCnetero {Deti - Fin) + Fin Equation (16) Det2 = CexLTCneteroDeti - CexLTCneteroFlri + Fin Equation (17) Det2 - CexLTÜHeteroDeti = Fln(l- CexLT) Equation (18) ε·ι„ _ Det2- CexLT^Hetero^>e^l — i-cexLTEquation (19) In this regard, once Flr2 is obtained as described above, the other signals Fin, DRexi, and DRex2 can be easily obtained through insertion into the system of equations (Equations (11)-(14)) presented above. Fractional Photon Normalization Module Referring again to Figure 22A, the pre-processing subunit 1302 in this aspect includes a fractional photon normalization module 2218 configured to detect the detector signals, after pre-processing as described above, in units of fractional photons for use in subsequent background subtraction and intrinsic fluorescence correction algorithms as described here. In this aspect, the detector signals can be converted to photocurrent by reversing the scaling associated with the ADC and the transimpedance amplifier used to acquire the detected signals to obtain the signals in photo units. QAOznn / eznz / E / YiAi 108 currents. Once the photocurrent is obtained, a detector receptivity supplied by the light detector manufacturer is used to convert the detector photocurrents to units of watts. The detector signals in watts are then proportional to the source power in watts as measured by additional light detectors 226 used to monitor the output of the light sources 218 / 220 to obtain the number of fractional photons detected. Optical power correction module Referring again to Figures 22A and 22B, the pre-processing subunit 1302 / 1302a in this aspect includes a fractional photon normalization module 2218 / 2218a configured to convert the detector signals, after pre-processing as follows. described above, in units of fractional photons for use in subsequent background subtraction and intrinsic fluorescence correction algorithms as described here. In this aspect, the detector signals can be converted to photocurrent by reversing the scaling associated with the ADC and the transimpedance amplifier used to acquire the detected signals to obtain the signals in photocurrent units. Once photocurrent is obtained, a detector receptivity supplied by the QAOznn / eznz / E / YiAi 109 light detector is used to convert detector photocurrents to units of watts. The detector signals in watts are then proportional to the power source in watts as measured by additional light detectors 226 used to monitor the output of the light sources 218 / 220 to obtain the number of fractional photons detected. Excitation Light Leakage Subtraction Module Referring again to Figure 22B, the pre-processing subunit 1302a in this aspect includes a fractional photon normalization module 2222 configured to perform an excitation leakage subtraction on the Flrmedi signal. To arrive at a fluorescence signal due to fluorescent photons (F1 rphotons), excitation leakage subtraction is performed. To remove the excitation light contribution, the excitation leakage is taken to be a fraction of the diffuse reflectance excitation signal ^^exme¿¡, where the universal calibration factor, Cexlt, measures in the fraction of the signal to subtract from the Flrmedí as expressed below: ExLT = CExLT* DReXmedien where Cexlt is a calibration factor that is QAOznn / eznz / E / YiAi 110 obtained by calculating the ratio between the excitation light detected by both detectors in a non-fluorescent optical phantom as described below: „ _ F^medi EXLT Γ) Γ) LZ lí j. c*meai This signal is then subtracted from the Flrmedi to provide a fluorescence signal due solely to fluorescent photons as expressed below: Flrphotons=Fljfmedi ~ ExLT Fluorescence light leak subtraction module Referring again to Figure 22B, the pre-processing subunit 1302a in this aspect includes a fluorescence light leak subtraction module 2224a configured to perform a fluorescence leak subtraction on the Flrmedi signal. To obtain the diffuse reflectance, here defined as the excitation signal due solely to excitation photons (DRexphotons), a fluorescence leakage subtraction is performed. To remove fluorescence leakage, a calibration factor, CpirLT, was determined based on the relationship between the amount of fluorescence leakage observed in a human subject database and tissue heterogeneity as measured by the relationship between the reflectance DRemFilt diffuse, broadcast signals ( ) . This relationship is a UKSiTl QAOznn / eznz / E / YiAi 111 linear relationship as expressed below: / DRemCFlrLT = P1 * [DRemFUten where pl and p2 are approximately 0.61 and 0.01, respectively, in one aspect, as determined by the relationship mentioned above. In another aspect, pl and p2 may assume any other value without limitation as defined by the above relationship. The DRexphoton signal is then calculated by subtracting that measured fluorescence fraction from the diffuse reflective excitation signal, as follows: DRexphotons ~ DR ex medi ~ * ^FlrLT b) reference subtraction subunit Referring again to Figure 13, the processing unit 236 further includes a reference subtraction subunit 1304. In one aspect, the reference subtraction unit 1304 subtracts a reference signal from the light detector measurements to correct auto-fluorescence and light leak effects. The reference period, as used herein, refers to a time period of measurements obtained before injection of the exogenous fluorescent agent. During the baseline period, the fluorescence signal measured by system 200 can be assumed to be associated with tissue auto-fluorescence. 112 and / or excitation light from the LED light sources 218 / 220 leaking through the absorption filter 244 of the second light detector 224. In one aspect, the average signal measured during the reference period, referred to herein as a reference signal, can be subtracted from subsequent fluorescence measurements to generate a measurement associated solely with the fluorescence produced by the exogenous fluorescent agent within the patient's tissues. In another aspect, corrections for excitation light leakage and auto-fluorescence can be implemented separately. For this other aspect, a subtraction of the excitation light leakage effects can be performed before the diffuse reflectance correction described here below, and a subtraction of the autofluorescence effects can be performed after the diffuse reflectance correction. c) Diffuse reflectance correction subunit Referring again to Figure 13, the processing unit 236 further includes a diffuse reflectance correction subunit 1306. In one aspect, the diffuse reflectance correction subunit 1306 can correct the measured fluorescence data to remove the effects of changes to the optical properties (absorption and scattering) of patient 202's tissues during renal extraction monitoring of an exogenous fluorescent agent within QAOznn / eznz / E / YiAi 113 of a patient's tissues. As described here previously, the optical properties of tissues can change due to any one or more factors including, but not limited to: vasodilation, vasoconstriction, oxygen saturation, hydration, edema, and any other suitable factor within the region of interest monitored by the system, associated with changes in the concentrations of endogenous chromophores such as hemoglobin and melanin. Without being limited to any particular theory, the fluorescence measurements obtained by system 200 that are used to determine renal function include emission wavelength photons that are detected by the second (filtered) light detector 224. These wavelength photons Emission waveforms are emitted by the exogenous fluorescence agent introduced into the patient's tissues in response to illumination by excitation wavelength photons. The emission wavelength photons travel from the fluorescence source (i.e., the exogenous fluorescence agent) to the second (filtered) light detector 224 through the third region 210 of the patient's skin. However, the emission wavelength light that is detected by the second (filtered) light detector 224 may also include auto-fluorescence emitted by endogenous fluorophores such as keratin and collagen within the tissues of the QAOznn / cznz / E / YiAi 114 patient, as well as leakage of excitation wavelength light through the optical filter 244 of the second light detector 224. The excitation wavelength photons that induce fluorescence from the exogenous fluorescent agent are produced by the first source of light 218 and are directed at the first region 206 of the patient's skin. If the optical properties of the patient's skin (dispersion and / or absorption) vary with the time in which the detector data used to determine renal function are acquired (i.e. from a few hours to approximately 24 hours or more), the accuracy of Fluorescence measurements may be impacted, as previously discussed above. During each measurement cycle in one aspect, the system 200 may direct light into the first region 206 of the patient's skin with an emission wavelength light pulse and an excitation wavelength light pulse in a alternate series and can detect all of the light emerging from the second region of the patients' skin by using the first (unfiltered) light detector 222 and a portion of the light emerging from the third region of the patient's skin 210 using the second (filtered) light detector 224. The light intensity detected by each combination of excitation and emission wavelength illumination of the first region 206 and detection by the unfiltered / filtered light detectors 222 / 224 contain QAOznn / eznz / E / YiAi 115 information not only about the concentration of the exogenous fluorescent agent in the patient's tissues, but also information about the optical properties of the patient's skin. QAOznn / eznz / E / YiAi Table 2: Light detector measurements after temperature and power fluctuation corrections Illumination wavelength First Light Detector (Reference) Unfiltered Second Light Detector (Primary) Filtered Excitation wavelength El Z'medi El I?medi Emission wavelength DRem DRem, filtered The primary fluorescence measurement is Flrmedi, the fluorescent light intensity measured at the filtered detector. The Flrmedi diffuse reflectance measurement represents the propagation of photons to the unfiltered arm and is mainly composed of excitation photons. DRem and DRem, futrated represents the propagation of emission-only photons. Referring to Table 2, the light intensity measured by the second (filtered) light detector 224 during illumination by light of wavelength 116 excitation captures the raw light intensity emitted by exogenous fluorescent agents (Flrmecu) before any correction of tissue optical properties in several aspects. After baseline subtraction corrections as described here previously, the emission wavelength light contained in Flrmedi is assumed to originate predominantly from the exogenous fluorescent agent, with only minor contributions due to autofluorescence by endogenous chromophores, and therefore It is called Flragent. In one aspect, if no change in the optical networks of the patient's skin is assumed, all auto-fluorescence contributions would be subtracted during the reference correction described herein above. However, if the optical properties of the patient's skin change during data acquisition, slightly more or less auto-fluorescence may emerge from the patient's skin at the emission wavelength, thereby introducing uncertainty within the accuracy of the background subtraction correction made previously. Furthermore, varying skin optical properties can further alter the intensity of light at the excitation wavelength that reaches the exogenous fluorescent agent, thereby altering the amount of energy absorbed. QAOznn / eznz / E / YiAi 117 by the exogenous fluorescent agent and the induced fluorescence intensity of the exogenous fluorescent emitted in response to illumination by the excitation wavelength light. In various aspects, the remaining three light measurements allow monitoring of the optical properties of the patient's skin and provide data that can be used to adjust for any changes in the optical properties of the patient's skin. Referring again to Table 2, the represented signals DRexmedi and Flrmedi, which have been corrected for variations in temperature and optical output are further processed to signals attributed solely to photons of the desired wavelength before applying a reflectance correction. diffuse. The number of photons due to either diffuse reflectance, excitation or fluorescence in any detector depends on light directionality and the gain of the detector at the detected wavelength, as shown below: DRSXmedi=Al * DRSXphotons t Bf ★ Fljfphotons Fllfmedi=Al * DRCX photons + B2 * Fllffotons where the coefficients Al, A2, Bl, B2 are composed of a directionality gain factor, for example, Ai = c1450spmi * Gspmi@45o Isolation of signals arising from fluorescence emission and excitation wavelength photons QAOznn / eznz / E / YiAi 118 diffuse reflectance is performed as below: / A 2 \¿4 2Flrf°tones = Flr™d‘ ~A^DRexmedi / A1BT\B 42(---]DRexr. = DRex,Flr>\A2B2) fotonesexmedt B2medl Since the kidney function monitor measures rate, which is independent of magnitude, the terms in front of the photon signals (e.g.) are not necessary, as demonstrated below. IF = C0+ C.e-F^ log( / F) = log / CJ - | AB As such, the terms — (or CExLT) and — (or CFirLT) can 41b be determined experimentally to isolate Flrphotons and DRexphotons, respectively. The table below represents the names of the signals used to represent each of the four signals measured in the development of diffuse reflectance correction. Note that any of the pre-processing paths described can be followed to arrive at signals that can be used to develop the correction. Table 3: Detector and Light Measurements Used for Obtain Fluorescence Measurements Corrected for Variable Tissue Optical Properties Generic signal name Pre-processed signals for use DRex DRexphotons ° DRex2 119 Flr F1 rphotons O F1112 DRem DRem DRem, filtering DRem, filtering wherein any of the excitation wavelength signals can be used as alternate methods to obtain a diffuse reflectance correction with any of the pre-processing methods described. Again referring to Table 2, light intensity measured by the first light detector (unfiltered reference) 222 during illumination by excitation wavelength light captures a measure of the wavelength light reflectance. of excitation propagated through the patient's skin (DReXmau). Although the first light detector 222 is configured to detect both excitation wavelength and emission wavelength light, the intensity of the excitation wavelength light is orders of magnitude higher than the intensity. of light emission wavelength as a result of the lower efficiency to produce light through fluorescence. In several respects, the emission wavelength light ratio within DRexmedi is assumed to be imperceptible. In other aspects, the proportion of emission wavelength light within DRexmed¡ is estimated and subtracted. Without being limited to any particular theory, because the The intensity of the excitation wavelength light directed at the patient's skin is assumed to be relatively constant with imperceptible losses due to absorption by the exogenous fluorescent agent, and is subject to energy corrections as described here previously, serving as a baseline measurement to evaluate changes in the optical networks of the patient's skin with respect to excitation wavelength light. Light intensity measured by the first light detector (unfiltered reference) 222 during illumination by emission wavelength light captures a measure of the diffuse reflectance of emission wavelength light propagated through the patient's skin ( DRem). Without being limited to any particular theory, because the exogenous fluorescent agent is not induced to emit emission wavelength light due to the absence of excitation wavelength illumination during this phase of the data acquisition cycle, and Due to the intensity of the emission wavelength light directed at the patient's skin being relatively constant and subject to energy corrections as described here previously, DRem silVG COIRO a reference measurement to evaluate changes in the optical properties of the patient's skin with respect to the emission wavelength light. Light intensity measured by the second detector QAOznn / eznz / E / YiAi 121 light (filtered) 224 during illumination by emission wavelength light captures a second measurement of the diffuse reflectance of emission wavelength light propagated through the patient's skin DRem, futrated}. In one aspect, DRem,futrado is subject to the same assumptions as DRem as described here above. Additionally, DRem,futrado provides a means to assess heterogeneity of tissue optical properties. Because DRem, futrate is measured by the second light detector 224 configured to detect light emerging from the patient's skin in the third region 210 (see Figure 2), the light intensity measured in DRem, futrate has spread to along an optical path through the patient's skin that is different from the optical path displaced by light measured in DRem. Without being limited to any particular theory, since the distances of the first detector aperture 1004 and second light aperture 2006 through which light is supplied to the first and second light detectors 222 / 224, respectively, are designed to be equidistant from the light supply aperture 1002 (see Figure 10), any difference between DRem, filtering and DRem is assumed to be a result of heterogeneity in the optical properties of the skin traversed by the two different optical paths. In one aspect, the intrinsic fluorescence (IF), defined here as the fluorescence measured in the length of QAOznn / eznz / E / YiAi 122 emission wave attributable solely to emissions by the exogenous fluorescent agent, can be calculated in accordance with Equation (20): QAOznn / eznz / E / YiAi jp __________Fmedi__________ DRkeexxDRke^DR^l£l^ra,doEquation (20) ex em em,p[trado The factors IF, Flr, DRex, DRem, and DRem, futrado are defined here above. As expressed in Equation (20), each of the factors of the diffuse reflectance correction measurement signals DRex, DRem, and DRem,futrado are raised to the energies kex, kem, and kem,futrado respectively. In one aspect, each measurement in Table 2 is subjected to the energy / temperature corrections and background subtraction corrections as described herein previously (see Figures 22A and 22B) before applying the diffuse reflectance correction of Equation (20 ). In several respects, the values ​​of kex, kem, and kem, futrado can be determined empirically. Non-limiting examples of suitable empirical methods for determining appropriate values ​​of kex, kem, and kem,futrado include a global error map method and a linear regression method, both described in detail here below. In one aspect, once the values ​​for each of the energies (kex, kem, kem, futrado) are identified, the same set of exponents can be reused for subsequent intrinsic fluorescence measurements. Examples 123 non-limiting applications of the systems and methods described herein in which a set of selected exponents can be reused includes: repeated measurements on the same patient using the same sensor head 204, repeated measurements using the same sensor head on different patients of the same species; repeated measurements by using different sensor heads with the same design in patients of the same species; repeated measurements by using different sensor heads with different designs in patients of the same species; repeated measurements by using different sensor heads with the different designs in patients of the different species; and any other suitable application of the systems and methods described herein. In another aspect, exponents can be updated with repeated use of the systems and methods described herein. In this further aspect, new exponent sets may be determined for each use of the systems and methods, and the stored exponent sets may be evaluated periodically or continuously to evaluate whether an updated exponent selection is indicated. By way of non-limiting example, if an analysis of multiple exponent sets determined that the exponents did not vary outside a threshold range in previous uses of the system, the system can be used to conduct measurements using the previous exponent set, an average / average of all QAOznn / cznz / E / YiAi 124 prior exponent sets, or any other suitable exponent estimates based on prior exponent values. In this non-limiting example, if an analysis of multiple previous exponent sets determined that the exponents varied outside of a threshold range, re-exponent selection using one of the methods described herein below may be indicated. Global Error Map Method In one aspect, the values ​​of the energies used in Equation (20) above are determined empirically by using a global error surface method. A flow chart illustrating the various steps of a global error surface method 1400 is illustrated in Figures 14A and 14B. The method in this aspect includes selecting ranges of values ​​of each of the energies (áex, kemr kem, filtering) for each of the diffuse reflectance signals (DRSX, DRem, DRem, filtering) that are selected by a user in the step 1402. In various aspects, the ranges of values ​​for each of the energies may be influenced by any one or more of a variety of factors including, but not limited to: the design of the system 200, which includes the design of the head sensor 204; the properties of the selected exogenous fluorescent agent such as excitation / emission wavelengths, absorption efficiency, emission efficiency, and dose concentration QAOznn / eznz / E / YiAi 125 initial in patient tissues; patient 202 species and corresponding concentrations of endogenous chromophores; the position of the sensor head 204 of the patient 202; and any other relevant factors. In one aspect, the method may include choosing a large array for each coefficient (kex, kem, kem, filtering) and conducting a broad search. The error surfaces from this broad search can be analyzed to locate wells on the error surface and the associated intervals for each of the coefficients. The method in this regard includes adapting the ranges of each coefficient to include the regions of the broad search within which QAOznn / eznz / E / YiAi pits were observed on the error surface and repeat the analysis. This method can be repeated until a suitably fine resolution is achieved that is capable of accurately capturing the minimum error. In a non-limiting example, for a human patient, the selected ranges of potential factors may be [0,2] for kex, [0,4] for kem, and [—4,0] kem, filtered. Referring again to Figures 14A and 14B, step sizes can be selected at 1404 for the ranges of values ​​selected at 1402 for each energy kex, kem, kem, filtered. In one aspect, the step size for each factor may be selected based on any one or more of at least several factors including, but not limited to. 126 a: the anticipated sensitivity of the IF values ​​calculated by Equation (20) to change in each factor; an adequate total number of energy combinations used to calculate factors considered by IF that include available computational resources, acceptable data processing times, or any other relevant factors; and any other appropriate criteria for step size. In several respects step sizes can be QAOznn / eznz / E / YiAi the same value for all kex, kem, kem, futrado energies. As a non-limiting example, the step size for all energies can be 0.5. In various other aspects, the step sizes may be constant for all values ​​of a single energy kex, kem, kem, futrado, but the step sizes selected for each energy may be different between different energies. As a non-limiting example, the selected step size for kex may be 0.01 and the selected step size for kem, and kem,futrado may be 0.6. In various additional aspects, the step size within one or more of the energies may vary within the range of values ​​for each energy. As a non-limiting example, the step sizes selected for kex may be distributed non-linearly around the average value. In this non-limiting example, the vector of potential values ​​for kex can be [0 0.5 0.75 0.9 1 1.1 127 1.25 1.5 2]. In these various additional aspects, the step size can be reduced within subranges of values ​​for an energy for which the IF calculated by Equation (20) is predicted to be more sensitive to small changes in that energy. Non-limiting examples of suitable variable step sizes within a range of values ​​for an individual energy include: different step sizes selected by a user, random step sizes, a linear increase and / or decrease in step size, a non-limiting distribution. linear in different step sizes such as a logarithmic distribution, an exponential distribution, or any other suitable nonlinear distribution of step sizes. Referring again to Figures 14A and 14B, the exponent ranges selected at 1402, along with the step sizes selected at 1404, can be used to form vectors of exponential values ​​of kex, kem, kem, filtered at 1406. As a non-limiting example, assuming selected ranges of potential exponents of [0,2] for kex, [0,4] for kem, and [—4,0] kem,futrado, and assuming a constant step size of 0.5 for all energies, the vectors created in 1406 are: kex = [0.0 0.5 1.0 1.5 2.5] (5 values) kem = [0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0] (9 QAOznn / eznz / E / YiAi values) 128 kem, filtered = [“4.0 “3.5 “3.0 “2.5 “2.0 “1.5 -1.0 -0.5 -0.0] (9 values) Referring again to Figures 14A and 14B, for each combination of exponents among all vectors formed at 1406, IF is calculated from the measurements Flr, DRex, DRerr., and DRem, filtered at 1408 by using Equation (twenty). For each combination of exponents, a plurality of IF values ​​are calculated at 1408 where each IF value corresponds to one of the data acquisition cycles (i.e., a single sequence of emission wavelength illumination followed by illumination of wavelength excitation waveform as illustrated in Figure 5). By way of non-limiting example, using the potential exponent vectors listed here above, a total of 405 (5*9*9) pluralities of IF signals would be calculated. In one aspect, the plurality of potential exponent combinations can be evaluated to select a combination of exponents from the plurality to be assigned for use in subsequent diffuse reflectance corrections calculated using Equation (20). Referring again to Figures 14A and 14B, an error estimate of the corrected Flr signal data (i.e., IF signal data calculated using Equation (20)) can be calculated at 1410. An error estimate can be calculated in 1410 that QAOznn / eznz / E / YiAi 129 includes, but is not limited to, a quantity related to residuals of the IF signal data in relation to a curve fit of the IF signal data. Any type of known curve fitting method can be used to curve fit the IF signal data including, but not limited to, a single exponential curve fit. Without being limited to any particular task, the clearance rate of an exogenous fluorescent agent, such as MB102, from the kidneys is expected to be an exponential decay constant characterized by the renal decay time constant RDTC. In one aspect, a subset of the Flr signals corresponding to the post-agent administration period 1508 / 1510 can be selected to estimate an error for each combination of exponents used to calculate the IF signals by using Equation (20) against a reference curve, including, but not limited to, a curve obtained by using plasma measurements. By way of non-limiting example, if the exogenous fluorescent agent is introduced into the patient's tissues by way of intravenous injection, the post-agent administration period includes a period after injection in which the exogenous fluorescent agent has been subjected to sufficient diffusion of blood into the extracellular fluid space throughout the patient so that the fluorescence decay is representative of the QAOznn / eznz / E / YiAi 130 elimination of the agent by the kidneys. In various aspects, the post-agent administration period 1508 / 1510 of the Flr measurements can be selected by any suitable method without limitation. Non-limiting examples of suitable methods for identifying a post-agent administration period include: selection through inspection by a user and an automated selection method such as the balance detection method permitted by the balance selection subunit 1308 as It is written in detail here below. Figures 15A and 15B are a graph of fluorescence measurements obtained from a patient during a period of approximately 10 hours after injection of an exogenous fluorescence agent (MB-102) after a pre-injection period of approximately 3 hours. Referring to Figures 15A and 15B, the preinjection / baseline period 1502 is characterized by a relatively low and stable level of fluorescence, probably due to the absence of endogenous fluorescent agent in the patient's blood. Following injection 1503 of the exogenous fluorescence agent, fluorescence measurements exhibit a marked increase 1504 to a peak concentration 1506, followed by a relatively uniform exponential decrease 1508 back to background fluorescence levels as the kidneys clear the agent of QAOznn / eznz / E / YiAi 131 exogenous fluorescence from the patient's blood. Without being limited to any particular theory, it was thought that the injected exogenous fluorescence agent is likely to be equilibrated throughout the extracellular space once the fluorescence decay is well described by a linear fit (or a line or graph plot). semi-logarithm). Figure 16 is an enlargement of the graph of Figures 15A and 15B showing a comparison of the fluorescence data measured at a linear curve fit 1604 to the logarithm of the IF signal within a portion of the post-equilibration period 1510, which demonstrates the close fit of the single exponential curve fit to the IF signal data. In one aspect, the logarithm of the calculated IF signal value can be fitted with a line and curve fitting error relative to the individual IF values ​​that can be compared to the calculated IF signals using Equation (20) for each of the plurality of exponent combinations to calculate the error at 1410. Any statistical summary parameters suitable for quantifying the error of the individual exponent curve fitting and the corresponding IF signal values ​​may be used without limitation including, but not limited to: root mean square error (RMS), mean absolute deviation, mean signed deviation, squared deviation QAOznn / eznz / E / YiAi 132 average, and any other appropriate statistical summary parameters. In one aspect, the error calculated at 1410 may be normalized RMS error from the linear fit of the log(JF) signals. In this aspect, the normalized RMS error calculated at 1410 into a single numerical quantity to facilitate subsequent selection of an individual combination of exponents from the plurality of combinations identified at 1406. Referring again to Figures 14A and 14B, method 1400 includes selecting an individual combination of exponents at 1412 from the plurality of combinations for which IF was calculated at 1408. Without being limited to any particular theory, it is assumed that The combination of exponents associated with a calculated IF signal that minimizes the calculated error in 1410 is best suited to correct the measured Flr signals to remove the effects of variation in the optical properties of the patient's skin during data acquisition within the period of post-agent administration 1508 / 1510. In various aspects, any known method for identifying exponent combinations can be used without limitation including, but not limited to, selecting individual exponent combinations from a map of all error values ​​corresponding to all exponent combinations. QAOznn / cznz / E / YiAi 133 In various aspects, the plurality of error values ​​corresponding to the plurality of exponent combinations can be transformed into an error map comprising a three-dimensional volume in which each of the three dimensions corresponds to the energies used in Equation (20 ): kex, kem, and kem, futrado, respectively. In these various aspects, each error value corresponding to one of the combinations of exponents is assigned to a coordinate (kexi, kemi, and kem,futradoi) within the three-dimensional volume, where kexi, kemi, and kem,futradoi are the numerical values ​​for a combination of exponents. In various aspects, each of the error values ​​can be assigned to the three-dimensional volume in any known format including, but not limited to: a number, a color, a grayscale value, and any other suitable format. In one aspect, the three-dimensional map of error values ​​described above can be transformed into a plurality of error surfaces corresponding to a planar map of the error values ​​associated with an individual value of one of the energies kex, kem, and kem, futrated, with the full numerical range of the remaining two exponents acting as a horizontal axis and a vertical axis of the error map. Figure 17 is an error map of the normalized RMS errors of the exponential curve fits QAOznn / eznz / E / YiAi of the calculated IF signals that assign the 134 full intervals of kem, futrado (horizontal axis) and kex (vertical axis) at a constant value of kem in which the normalized RMS errors are represented as colors in the error map. In one aspect, the normalized RMS value calculated for each coefficient may be normalized in accordance with Equation (21). RMSECV= QAOznn / eznz / E / YiAi -1 Fggent Fggent)2- • fit (JFagent) Equation (21) where IFagent is the calculated IF signal, and fit (IFagent} is the corresponding value of the individual coefficient curve fitting equation. In one aspect, the method of global error map to determine the energies to be used in correcting for variation in optical properties of the skin when analyzing an individual measurement set as described above. In another aspect, the global error map method can analyze. and combining multiple sets of measurement data for multiple individuals obtained by using the same system and / or sensor head. In yet another aspect, the global error map method can analyze multiple sets of measurement data from multiple individuals obtained by using. multiple systems and sensor heads. In one aspect, the energies to be used in the correction according to Equation (20) can be determined for each measurement of each individual. In other respects, the energies that leave 135 to be used can be obtained by using at least several different measurement data sets and the energies thus obtained can be stored for subsequent use for measurement data sets obtained from a new individual and / or obtained by using a system and / or sensor different. In various aspects, projections through each of the error surfaces (a projection of kem, futrado-kex, a projection of kem, futrado-kem, and a projection of kem-kex) can be inspected to determine whether the intervals of energy defined in 1402 were adequate. In one aspect, the error surface can be inspected to confirm that the map includes a clearly defined minimum value. In one aspect, if inspection of the error map does not identify a minimum value, the ranges of one or more energy values ​​may be revised and method 1400 may be repeated. In one aspect, an evaluation of the optical properties of the patient's skin (e.g., melanin absorbance, blood content, and / or scattering coefficient) can be used to classify the patient so that an appropriate set of coefficients can be selected. for that category. In one aspect, the combination of exponents kex, kem, and kem, futrated can be stored and used for subsequent measurements conducted by the system 200. Figure 18 is a graph comparing the raw fluorescence signal (blue line) with the signal Calculated IF (red line) QAOznn / eznz / E / YiAi 136 for a measurement data set. In a further aspect, a global correction can be calculated by combining measurements obtained using a plurality of different systems and / or sensor heads and identifying the combination of exponents that correspond to an overall minimum error value. Linear Regression Method In one aspect, the energy coefficient values ​​used in Equation (20) above are determined empirically by using the linear regression method. A flow chart illustrating the various steps of the linear regression method to obtain a correction in the form of a regression equation with predictor viables (DRex, DRem, and DRem,filtered) is provided in Figure 19. Referring to Figure 19, method 1900 may include logarithm transforming Flr to log(Flr) to prepare raw fluorescence measurements Flr for analysis in 1902. Figure 20 is a plot of log(Flr) produced in 1902 Referring again to Figure 19, the method 1900 may further include selecting a region of stable optical properties 2002 (see Figure 20) in one aspect. In this aspect, regions of stable optical properties 2002 typically correspond to linear segments on the log (Flr) plot as shown in Figure 20. In this aspect, the method 1900 further includes QAOznn / eznz / E / YiAi 137 obtain a linear regression model 2004 within the region of stable optical properties 2002 in 1906. The linear regression model 2004 can be obtained by using any regression method without limitation including, but not limited to, a regression modeling method multivariable linear. Referring again to Figure 19, the method 1900 may further include extending the linear regression model 2004 obtained within the region of stable optical properties 2002 to produce an extended linear regression 2008 that extends into a region of varying optical properties. 2010 in 1908. In one aspect, the region of variable optical properties 2010 is characterized by a non-linear profile within the log(Flr) plot as illustrated in Figure 20. Referring again to Figure 19, the method 1900 may further include obtaining a linear regression model 2004 with predictor variables of Flr, DRex, DRem, and DRem, filtered at 1910 and linear curve fitting 2004 as the response planned. The extension of the 2008 linear regression produced in 1908 can be used to train the linear regression model obtained in 1910. The linear regression model can be developed by using a set of measurement data obtained from an individual individual and / or an individual system and measurement head. QAOznn / eznz / E / YiAi 138 sensor in one aspect. In another aspect, the linear regression model may be developed using multiple sets of measurement data obtained from multiple individuals and / or multiple systems and sensor heads. In some aspects, a linear regression model can be developed anew for each new set of measurement data obtained for an individual. In at least some other aspects, the constants and parameters that characterize a linear regression model developed as described herein above can be stored for subsequent use instead of developing a linear regression model again for each set of measurement data obtained as described. described here above. d) Fault detection subunit 13, the processing unit 236 of the controller 212 may further include a fault detection subunit 1312 configured to monitor the function of the light sources 218 / 220 and light detectors 222 / 224 and to inform the user of any irregularity of any fault detected within the system 200 through the display unit 216. In various aspects, the fault detection subunit 1312 may allow basic identification of fault states and notification by examining the levels signal received from light sources 218 / 220 and light detectors 222 / 224 and QAOznn / eznz / E / YiAi 139 associated additional temperature sensors 228 and additional light detectors 226 of the sensor head 204 (see Figure 2). In various aspects, signal magnitudes (see Equation (1)) and average signals can be used to determine the peak and nadir modulation levels of the LED light sources 218 / 220. The signal nadir, defined here as the signal averaged minus half the peak-to-peak signal, can be used to monitor ambient light levels in one aspect. Without being limited to any particular theory, additional combinations of the nadir levels of the modulated signals, such as amplifier DC offset, can be ignored since it is small and constant relative to the ambient light leak contributions. In one aspect, if the detected ambient light levels register in excess of about one-quarter of the range of high-speed ADC 1102 at low detector amplifier gain, an ambient light notification is issued to the user through the control unit. visualization 216. In various other aspects, detector saturation of the light detectors 222 / 224 may also be monitored by the fault detection subunit 1312. In these other aspects, saturation may be monitored by calculating the peak value of the signal, defined herein as the signal value averaged over half of the signal QAOznn / eznz / E / YiAi 140 peak to peak. If the peak value of the signal falls within 5% saturation of the ADC range, the fault detection subunit 1312 may issue a saturation notification to the user through the display unit 216. If saturation event is detected by the fault detection subunit 1312, the ambient light level can then be performed to determine whether the saturation event is associated with ambient light saturation, defined here as a saturation event that occurs concurrently with an ambient light notification as described here previously. If an ambient light saturation event is detected, the fault detection subunit 1312 issues an ambient light saturation notification to the user through the display unit 216, and data acquisition by the acquisition unit 234 continues at this time. notification status to allow the user to resolve the condition. If a saturation event is detected that is not associated with excess ambient light, the fault detection unit may signal the light detector control unit 2232 to perform a detector gain adjustment and / or may signal the light source control unit 230 to make an adjustment to the LED current source 1126 to adjust LED intensity. In QAOznn / eznz / E / YiAi various aspects, the fault detection unit issues a 141 notification to the user through the display unit to report either the ambient light saturation event, or the saturation event not associated with excess ambient light. In some aspects, if a clipping event is detected, but automatic gain adjustment has been disabled by a user when the system 200 is configured in the Engineering Model as described herein above, the user is also notified via the display unit. e) Post-agent administration selection subunit Referring again to Figure 13, the processing unit 234 may further include a post-agent management selection subunit 1308 configured to automatically identify the portion of the measurement data set that corresponds to the post-agent management period. agent 1508 / 1110 (see Figures 15A and 15B). Referring against Figures 15A and 15B, as described herein above, after an exogenous fluorescent agent is subjected to a period of equilibration of blood flow diffusion into the rest of the patient's extracellular tissues. After injection of agent 1503, the temporal profile of the Flr fluorescence signal can be characterized as a biQAOznn / eznz / E / YiAi signal profile 142 exponential described by Equation (22): IFpre-equilibrium ~ G) + ^ie+ ^2e t^2Equation (22) where Co is the reference signal that is typically removed by reference subtraction as described here previously. Referring again to Figures 15A and 15B, once the diffusion of the exogenous fluorescent agent in the extracellular tissues of the patient reaches a quasi-steady state condition, the post-equilibrium period 1510 is achieved and the fluorescence signal can be characterized. as a linear deterioration. Without being limited to any particular theory, the post-equilibrium region of the measurement data set is assumed to be characterized as a region of the temporal profile of IF that, when log-transformed, is well described by a linear equation. In one aspect, the post-equilibrium region also described by Equation (23): IFpos-equilibrium =Co + (\ε~ί / τEquation (23) In one aspect, the post-agent management selection subunit 1308 may identify the post-agent management period 1510 automatically by performing individual exponent curve fitting on different portions of the IF data set by analyzing fit errors. associated curve of each of the large portions. In several aspects, the subunit of QAOznn / eznz / E / YiAi 143 post-agent management selection 1308 may select the first-occurring portion of the IF data set where the curve fitting error associated with the individual exponent curve fitting falls below a threshold value as the post-agent management portion -initial IF data set agent suitable for data correction and analysis as described here previously. Any suitable analysis method for purchasing association of curve fitting errors with individual exponential curve fits of different portions of the IF data set may be used in the post-agent management selection subunit 1308 including, but not limited to, linear curve fitting portions of the IF data set that fall within overlapping or non-overlapping data windows and compare the curve fitting errors of the corresponding data windows. In one aspect, the post-agent management selection subunit 1308 may produce at least one signal configured to signal the time interval within the IF data set that corresponds to the post-agent management period 1508 / 1510 to the correction subunit. of diffuse reflectance 1306 and / or RDTC calculation subunit 1310 to allow selection of an appropriate portion of the IF data set to correct and analyze as described herein. In another aspect, a linear fit and a biQAOznn / eznz / E / YiAi fit 144 exponential to the IF data can be compared. In another aspect, equilibrium can be identified as complete once the fit error is equivalent (corrected for the extra degrees of freedom in the bi-exponential fit). f) RDTC calculation subunit In various aspects, the system 200 is configured to transform the various measurements for the light detectors 222 / 224 and associated light sources 218 / 220 and other thermal and light sensors into a corrected intrinsic fluorescent (IF) signal that corresponds to the Detected fluorescence attributable solely to fluorescence emission by exogenous fluorescent individuals at the emission wavelength in response to illumination by light of the excitation wavelength. In several aspects, the exponential decay of IF signals during the post-agent administration portion of the IF data set can be analyzed to monitor and quantify renal function. In one aspect, the exponential decrease in IF signals during the post-agent administration portion of the IF data set can be transformed into a glomerular filtration rate (GFR) to quantify renal function. In another aspect, the exponential decay of IF signals during the post-equilibrium portion of the IF data set can be transformed into a renal deterioration time constant (RDTC), also configured to quantify function. QAOznn / eznz / E / YiAi 145 kidney. In another aspect, the exponential decay of IF signals during the post-equilibrium portion of the IF data set can be transformed into a kidney deterioration rate, also configured to quantify kidney function. Referring again to Figure 13, the processing unit 236 may further include an RDTC calculation subunit 1310 configured to automatically transform the IF signals into a renal deterioration time constant (RDTC). As used herein, the renal decay time constant (RDTC) is defined as the time constant associated with the post-equilibrium individual exponential decay described in Equation (23) hereinbefore. In one aspect, the precise reference subtraction by the reference subtraction subunit 1304, the renal deterioration time constant τ can be calculated by performing a linear regression of the log-transformed IF signal data (log(IF)}, as was described in Equation (24) log( / F) = logCCj - Equation (24) In various aspects, the RDTC calculation subunit 1310 may produce signals configured to produce a display of the calculated RDTC using the display unit 216. The display of the calculated RDTC may be provided to the display unit 216 in any suitable format that includes, but not limited to: QAOznn / eznz / E / YiAi 146 a graph of RDTC as a function of time, individual discrete RDTC value, a table of RDTC values ​​as a function of time, a color-coded display or other graphical representation configured to specify whether the calculated RDTC can be classified as normal classification / healthy, abnormal, high, short, and / or any other appropriate. In various other aspects, any of the graphical formats described above may be updated continuously or non-continuously as additional data is obtained and analyzed. In one aspect, the RDTC calculation subunit 1310 may calculate RDTC as described herein above within non-overlapping and / or overlapping windows within the IF data set. In another aspect, the RDTC calculation subunit 1310 can convert RDTC to glomerular filtration rate (GFR) using known methods. In this aspect, RDTC can be inverted and multiplied by a slope, resulting in cGFR, a prediction of GFR that can be corrected for body size (e.g., body surface area, or volume of distribution). v) Memory Referring again to Figure 2, the controller 212 of the system 200 may further include a memory 242 configured to facilitate data storage in the system 200. In some embodiments, the memory QAOznn / eznz / E / YiAi 147 242 includes a plurality of storage components such as, but not limited to, a hard disk drive, flash memory, random access memory, and a magnetic or optical disk. Alternatively or additionally, memory 242 may include remote storage such as a server in communication with controller 212. Memory 242 stores at least one computer program that, when received by the at least one processor, causes the at least one processor performs any of the functions of controller 212 described above. In one implementation, memory 242 may be or contain a computer-readable medium, such as a floppy disk device, a hard disk device, an optical disk device, or a tape device, flash memory, or other storage device. solid state memory or similar, or a set of devices, including devices in a storage area network or other configurations. A computer program producer can be tangibly represented in an information carrier. The computer program product may also contain instructions that, when executed, perform one or more functions, such as those described herein. The information carrier may be a non-transitory computer-readable or machine-readable medium, such as memory 242 or memory in processor 238. QAOznn / cznz / E / YiAi 148 In various aspects, the system 200 may record raw measurements and processed data to a series of files. Each file can contain a header, which contains information about the trader, instrument and session. Each experimental session records a set of files in a separate folder for each sensor head used at that station. The raw data file may contain in-phase, quadrature, and average measurements from the detectors and monitors during active periods of both the excitation wavelength and emission wavelength LEDs, along with the gain settings. the LEDs and detectors at the time of data acquisition. In various other aspects, the processed data file may contain diffuse reflective and fluorescence measurements after magnitude calculation and correction for the monitor readings, along with the gain settings of the LEDs and detectors. The intrinsic fluorescence data file may contain intrinsic fluorescence measurements that result from diffuse reflectance correction of the raw fluorescence signals. The GFR file may contain the GFR calculated as a function of time, classified to indicate whether post-equilibration has occurred, along with confidence limits. The telemetry file may contain temperature and voltage measurements. The file of QAOznn / eznz / E / YiAi 149 event log can contain both user and automatically generated event logs. vi) GUI Unit Referring again to Figure 2, the controller 212 may include a GUI unit 240 configured to receive a plurality of signals that encode various measured and transformed data from other units of the system in various aspects. Furthermore, the GUI unit and may be configured to produce signals configured to operate the display unit 216 in order to display data, charts, shapes, and / or other information communications between the user and the system 200. vii) Processor Referring again to Figure 2, the controller 212 may further include a processor 238. The processor 238 may include any type of processor, microprocessor, or conventional processing logic that interprets and executes instructions. The processor 238 may be configured to process instructions for execution within the controller 212, including instructions stored in memory 242 for displaying graphical information for a GUI on an external input / output device, such as a display unit 216 coupled to an interface. Of high speed. In other implementations, multiple processors and / or multiple buses may be used, QAOznn / eznz / E / YiAi 150 as appropriate, along with multiple memories and memory types. Also, multiple controllers 212 may be connected, with each device providing portions of the operations necessary to enable the functions of the system 200. In some embodiments, the processor 238 may include the acquisition unit 234, the light detector control unit 232, the light source control unit 230, and / or the processing unit 236. As used herein, a processor such as processor 238 may include any programmable system including systems using microcontrollers, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC, for its acronym in English), logic circuits, and any other circuit or processor capable of executing the functions described here. The above examples are examples only, and are not intended to limit in any way the definition and / or meaning of the term processor. As described here, computing devices and computing systems include a processor and memory. However, any processor in a computing device herein may also refer to one or more processors wherein the processor may be in a computing device or a plurality of computing devices acting in parallel. Additionally, any QAOznn / eznz / E / YiAi 151 memory in a computing device herein may also refer to one or more memories where the memories may be in a computing device or a plurality of computing devices acting in parallel. C. Operation Unit The operation unit 214 may be configured to allow a user to interface (e.g., visual, audio, touch, button presses, stylus taps, etc.) with the controller 212 to control the operation of the system 200. In some In embodiments, the operation unit 214 may further be coupled to each sensor head 204 to control the operation of each sensor head 204. D. Display Unit Referring again to Figure 2, the system 200 may further include a display unit 216 configured to allow a user to view data and control information from the system 200. The display unit 216 may further be coupled to other components of the system. 200 such as the sensor head 204. The display unit 216 may include a visual representation such as a cathode ray tube (CRT) display, liquid crystal display (LCD). English), light-emitting diode (LED) display, or e-ink display. In some embodiments, the QAOznn / eznz / E / YiAi 152 display unit 216 may be configured to represent a graphical user interface (e.g., a web browser and / or a client application) to the user. A graphical user interface may include, for example, a display for GFR values ​​as described herein above as produced by system 200, and operational data from system 200. Exogenous Markers Without being limited to any particular theory, molecules that are highly hydrophilic and small (creatinine, molecular weight = 113) and moderately mentioned (inulin, molecular weight ~5500) are known to be rapidly eliminated from the systemic circulation by glomerular filtration. In addition to these properties, an ideal GFR agent would not be reabsorbed or secreted by the renal tubule, exhibiting imperceptible binding to plasma proteins, and would have very low toxicity. In order to design optical probes to satisfy all these requirements on a balance between photophysical properties, molecular size and hydrophilicity of the fluorophore. For example, while hydrophobic cyanine and indocyanine dyes optionally absorb and emit within the near-infrared (NIR) biological window (700-900 nm), the hydrophilicity is not high enough to function as agents. of pure GFR. Molecules of QAOznn / eznz / E / YiAi 153 Smaller dyes can be more easily converted to the extremely hydrophilic species required for renal elimination, but the limited π systems that result from these lower molecular weight compounds generally allow photon excitation and emission in the ultraviolet (UV). To solve pharmacokinetic problems in conjunction with improving photophysical properties, simple derivatives of 2,5-diaminopyrazine-3,6-dicarboxylic acid act as very low molecular weight fluorescent scaffold systems with bright emission in the yellow to red region of the spectrum. electromagnetic. SAR studies have been carried out using amine-linked variants of these derivatives for simultaneous optimization of pharmacokinetic and photophysical properties of GFR. A variety of hydrophilic functionalities to allow rapid renal clearance of this class of pyrazine fluorophores including carbohydrate, alcohol, amino acid, and various PEG-based linker strategies can be employed. PEG substitution can be used to increase hydrophilicity and solubility, reduce toxicity, and modulate aggregation of the resulting pyrazine derivatives. Variations in molecular weight and architecture (and thus hydrodynamic volume) in a series of moderately sized PEG pyrazine derivatives may also be suitable for QAOznn / eznz / E / YiAi 154 be used as endogenous fluorescent agents. In one aspect, the endogenous fluorescent agent is MB-102. EXAMPLES The following example illustrates several aspects of the systems and methods described. Example 1: Disturbance Analysis To demonstrate the effectiveness of the diffuse reflectance data correction method described here above, the following experiments were conducted. A system similar to system 200 described here above was used to monitor fluorescence produced during renal elimination of an exogenous fluorescent agent, MB-102, using the methods described here above, in particular the diffuse reflectance data correction method. Figure 21A is a graph summarizing the changes in the magnitude of the raw fluorescence signal (Flr). Just before injection of MB-102 fluorescent agent into a pig for approximately 6 hours post-injection. During the post-equilibration portion, which corresponds to a time of approximately 13:45 in Figure 21A, the pig was subjected to a series of perturbations selected to vary the optical properties of the pig's skin and / or underlying tissues: administration of QAOznn / eznz / E / YiAi 155 blood pressure medications to induce vasodilation / vasorestriction 2102, application of pressure to compress tissue 2104, lateral movement of sensor head 2106, decrease in SpOj 2108, decrease in SpO? 2110, remove / replace sensor head 2112 / 2114, and skin cooling 2116. Figure 21B is a graph summarizing the corrected intrinsic fluorescence (IF) signal corrected as described herein above without reference subtraction. At time points later than 2 hours after agent injection, the time course of the IF signal was characterized by the expected individual exponential decay of the signal, with attenuated variation due to the applied perturbations. Table 4 summarizes the specific effects of the diffuse reflectance data correction method on the Flr data with each individual perturbation: Table 4. Effect of Data Correction Diffuse Reflectance DISTURBANCE CORRECTION EFFECT Pressure Application Decreased data excursions / outliers Lateral Sensor Movement Decreased data excursions / outliers Decreased SpC>2 Improved IF signal decay slope 156 Increased SpCt Improved IF signal decrease slope Remove / Replace Sensor Head Decreased data excursions / outliers Cooling No noticeable impact Figure 21C is a graph that summarizes the signals QAOznn / eznz / E / YiAi detected diffuse reflectance DRem, futrated DRem, and DRex substituted into Equation (20) to determine the diffuse reflectance correction of the raw Flr signal as described here previously. As illustrated in Figure 21C, the DRem, futrated signal was the most sensitive to the various perturbations. DRem, and DRex signals exhibited the most modest variation in response to perturbations. The results of these experiments demonstrated that diffuse reflectance data correction was able to correct the raw fluorescent signal data to compensate for the effects of a variety of perturbations that induced a variety of changes in the optical properties of the skin. Example 2: Sensor head with widened housing Figure 23 is a perspective view of a sensor head 204a in another aspect. In this further aspect, the sensor head 204a includes a housing 600a formed of an upper housing 602a and an enlarged lower housing 604a. The surface area of ​​the housing 157 bottom 604a expands to form an enlarged bottom surface 608a. The housing 600a further includes a cable opening 806a formed through the upper housing 602a. Figure 24 is a bottom view of the sensor head 804a showing the bottom surface 608a of the housing 600a. The bottom surface 608a may include an aperture plate 702a that includes one or more apertures 704a configured to transmit light between the patient's skin and the light sources and light detectors contained within the housing 600. As illustrated in Figure 24, The apertures 704a include a light supply aperture 1002a configured to supply illumination produced by the first and second light sources 218 / 220 to tissues of the patient 202, as well as first and second detector apertures 1004 / 1006 configured to receive light from the patient tissues 202. In one aspect, the bottom surface 608a allows positioning of the openings 704a under a relatively large area obscured from ambient light conditions by the bottom surface 608a. This reduction of scattered ambient light entering the first and second detector apertures 1004 / 1006 reduces noise introduced into the light intensity measurements obtained by the first and second light detectors. QAOznn / eznz / E / YiAi 158 222 / 224. In various aspects, the bottom surface 608a of the housing 600a can be attached to the skin of the patient by using a biocompatible and transparent adhesive material 610a including, but not limited to, transparent double-sided medical grade adhesive, as illustrated in the Figure 24. The transparent adhesive material 610a can be placed on the bottom surface 608a so that the adhesive material 610a covers the openings 704a. Figure 25 is an isometric view of the sensor head 204a with the upper housing 602a and various electrical components removed to expose an inner housing 2502. Figure 26 is an exploded view of the inner housing 2502 and associated electrical components illustrated in Figure 25. Referring to Figure 25 and Figure 26, the inner housing 2502 is contained within the housing 600a and is mounted to the lower housing 608a. The inner housing 2502 contains a sensor mount 912 with a first detection well 908, a second detection well 910, and a light source well 902 formed therethrough. The first light detector 222 is mounted within the first detection well 908 and the second light detector 224 is mounted within the second detection well 910. The first and second light sources 218 / 220 are QAOznn / eznz / E / YiAi 159 mounted within the light source well 902. In one aspect, the first detection well 908, second detection well 910, and light source well 902 of the sensor mount 912 are optically isolated from each other to ensure that the Light from the light sources 218 / 220 does not reach the light detectors 222 / 224 without coupling through the skin of the patient 202. The separation between the two detection steps 908 / 910 ensures that the detected fluorescence signal from the fluorescent agent exogenous can be distinguished from unfiltered excitation light, as described in detail above. Referring to Figure 26, the interior housing 2502 includes a first detection aperture 2602, second detection aperture 2604, and light source aperture 2606. The sensor mount 912 is coupled to the interior housing 2502 such that the first Detection aperture 2602, second detection aperture 2604, and light source aperture 2606 are aligned with the first detection well 908, second detection well 910, and light source well 902 of the sensor mount 912, respectively. In one aspect, optically transparent windows 2610, 2612, and 2614 are coupled within the first detection aperture 2602, second detection aperture 2604, and light source aperture 2606, respectively, QAOznn / eznz / E / YiAi 160 to seal the openings while also providing optically transparent passages between the tissues and the interior of the sensor head 204a. Additionally, diffusers 2616, 2618, and 2620 are coupled onto optically transparent windows 2610, 2612, and 2614, respectively. Diffusers 2616, 2618, and 2620 are provided to spatially homogenize light supplied to tissues by sources 218 / 220 and to spatially homogenize light detected by light detectors 222 / 224. In one aspect, the absorption filter 244 is coupled to the diffuser 2616. In one aspect, an optically clear adhesive is used to couple the absorption filter 244 which is coupled to the diffuser 2616. In view of the above, it will be seen that the various advantages of the description are achieved and other advantageous results are obtained. Since various changes could be made to the above methods and systems without departing from the scope of the description, it is intended that all matter contained in the above description and shown in the accompanying figures be construed as illustrative and not in a limiting sense. When elements of this description are introduced from the various versions, modality(s) or aspects thereof, the articles a, one / an, the / the / the / thes and such / such are intended to mean that there are QAOznn / cznz / E / YiAi 161 one or more of the elements. The terms comprising, including and having are intended to be inclusive and to mean that there may be additional elements other than those elements listed. It is stated that, in relation to this date, the best method known to the applicant to put the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A sensor head, characterized in that it comprises: a housing configured to attach to a patient's body surface and comprising a lower surface; at least two light sources configured to supply light to a first region of the patient comprising a first blue LED light source and a second green LED light source, wherein the first blue LED light source supplies light at an excitation wavelength; and at least one light detector configured to detect light at an emission wavelength in a second region of the patient; wherein the housing encompasses the at least two light sources and the at least one light detector.

2. The sensor head according to claim 1, characterized in that the sensor head further comprises a contact surface on the lower surface of the housing. 163 3. The sensor head according to claim 2, characterized in that the contact surface is configured to bond to the body surface of a patient with a biocompatible adhesive material.

4. The sensor head according to claim 3, characterized in that the adhesive material is configured to transmit light through the at least two light sources in the patient and from the patient to the light detectors.

5. The sensor head according to claim 3, characterized in that the adhesive material is an optically transparent material.

6. The sensor head according to claim 3, characterized in that the adhesive material is produced from a non-fluorescent material.

7. The sensor head according to claim 2, characterized in that the contact surface comprises an aperture plate including one or more apertures configured to transmit light between the patient's skin and the at least two light sources and the at least one light detector.

8. The sensor head according to claim 2, characterized in that the contact surface comprises a temperature sensor opening QAOznn / eznz / E / YiAi 164 configured to provide a thermal path from the patient's skin surface to a temperature sensor within the housing.

9. The sensor head according to claim 7, characterized in that the aperture plate comprises a sensor mount configured to inhibit light leakage between the at least one light source and the at least one light detector.

10. The sensor head according to claim 9, characterized in that the conductive material is composed of a conductive material.

11. The sensor head according to claim 7, characterized in that the openings are positioned towards the center of the contact surface.

12. The sensor head according to claim 1, characterized in that the lower surface of the housing is configured to widen in order to provide a larger surface area to come into contact with the patient's body surface.

13. The sensor head according to claim 12, characterized in that the contact surface is configured to bond to a patient's body surface with a transparent adhesive material. QAOznn / eznz / E / YiAi 14. The sensor head according to claim 13, characterized in that the transparent adhesive material is placed on the lower surface so that the adhesive material covers the openings.

15. A sensor head, characterized in that it comprises a housing configured to attach to a patient's body surface, the housing comprising: (i) an inner housing having a sensor mount; (ii) at least two light sources configured to supply light to a first region of the patient, wherein at least one light source supplies light at an excitation wavelength; and (iii) at least two light detectors configured to detect light at an emission wavelength in a second region of the patient, wherein the housing encompasses the at least two light sources and the at least two light detectors, wherein the sensor mount comprises: a first detection well having a first light detector mounted thereon; a second detection well having a second light detector mounted thereon;and a light source well having a first light source and a second light source mounted thereon, and QAOznn / eznz / E / YiAi 166 wherein the first detection well, the second detection well and the light source well are configured to be optically isolated from each other to ensure that light from the light sources does not reach the uncoupled light detectors through the patient's body surface.

16. The sensor head according to claim 15, characterized in that the inner housing further comprises: a first detection opening configured to align with the first detection well; a second detection opening configured to align with the second detection well; and a light source opening configured to align with the light source well.

17. The sensor head according to claim 16, characterized in that the inner housing further comprises optically transparent windows configured to fit within the first detection aperture, the second detection aperture, and the light source aperture.

18. The sensor head according to claim 17, characterized in that the inner housing further comprises diffusers configured to fit over the optically transparent windows. QAOznn / eznz / E / YiAi 167 19. The sensor head according to claim 15, characterized in that the first light source comprises a blue LED and the second light source comprises a green LED, and wherein the first light source 5 blue LED supplies light at the excitation wavelength.

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