JP4504207B2 - Fluorescent agent integrated concentration measuring apparatus and fluorescent agent integrated concentration measuring method - Google Patents

Description

The present invention relates to a fluorescent agent integrated concentration measuring apparatus and a fluorescent agent integrated concentration measuring method for measuring the integrated concentration of a fluorescent agent integrated in a living tissue.

  In recent years, autofluorescence from a living body and fluorescence of a drug injected into a living body are detected as a two-dimensional image, and a disease state (for example, disease type or infiltration range) such as degeneration of a living tissue or cancer is diagnosed from the fluorescence image. Techniques are shown in US Pat. No. 4,556,057 and US Pat. No. 5,042,494.

  When light is irradiated onto a living tissue, fluorescence having a wavelength longer than that of the excitation light is generated. Examples of fluorescent substances in vivo include NADH (nicotinamide adenine nucleotide), FMN (flavin mononucleotide), pyridine nucleotide, and the like. Recently, the correlation between these endogenous substances and diseases is becoming clearer. .

  In addition, fluorescent agents such as HpD (hematoporphyrin), Photofrin, and ALA (δ-amino levulinic acid) have the ability to accumulate in cancer. By injecting these fluorescent agents into a living body, fluorescence observation is performed. A disease site can be diagnosed.

As a technique for diagnosing a lesion part from the above fluorescence transendoscopically, for example, there is a fluorescence observation endoscope apparatus such as JP-A-8-224208.
US Pat. No. 4,556,057 US Pat. No. 5,042,494 JP-A-8-224208

However, in order to appropriately detect abnormal tissues such as cancer by fluorescence observation, the time when the concentration of the fluorescent agent in the living tissue reaches a peak is important.
Since the concentration of the fluorescent agent injected into the living body into the living tissue varies depending on individual differences, conventionally, a patient who has been injected with the fluorescent agent into the living body needs to stay in the hospital until the concentration of the fluorescent agent reaches a peak.

  The patient may be required to be hospitalized for several days because the time at which the accumulated concentration reaches a peak may be several hours or several tens of hours, for example. In addition, when it is not possible to appropriately determine when the accumulated concentration reaches a peak, there is a problem that it is difficult to effectively perform fluorescence observation with a fluorescence observation endoscope.

The present invention has been made in view of the above circumstances, and provides a fluorescent agent integrated concentration measuring apparatus and a fluorescent agent integrated concentration measuring method capable of appropriately calculating the peak timing of the concentration of the fluorescent agent accumulated in a living tissue. The purpose is to do.

The fluorescent agent integrated concentration measuring device of the present invention is
An excitation light source that irradiates a sample solution containing a body fluid collected from a living body into which a medicine containing a fluorescent dye is injected with excitation light that excites fluorescence with respect to the fluorescent dye;
Fluorescence detection means for detecting the fluorescence;
A fluorescent dye concentration calculating means for calculating the concentration of the fluorescent dye in the living body based on a detection signal from the fluorescent detecting means ,
The fluorescent dye concentration calculating means is configured to determine the concentration of the drug containing the fluorescent dye in the tissue in the living body based on the elapsed time of injection of the drug containing the fluorescent dye into the living body and the calculated concentration of the fluorescent dye. There is a peak time estimation means for estimating the peak time.
The fluorescent agent accumulation concentration measuring method of the present invention is:
An excitation light irradiation step of irradiating a sample solution containing a body fluid collected from a living body into which a medicine containing a fluorescent dye is injected with excitation light that excites fluorescence with respect to the fluorescent dye;
A fluorescence detection step for detecting the fluorescence;
A fluorescent dye concentration calculating step for calculating the concentration of the fluorescent dye in the living body based on the detection signal detected in the fluorescent detection step;
With
In the fluorescent dye concentration calculating step, the concentration of the medicine containing the fluorescent dye in the tissue in the living body based on the elapsed time of injection of the medicine containing the fluorescent dye into the living body and the calculated concentration of the fluorescent dye. There is a peak time estimation step for estimating the peak time.

  According to the present invention, there is an effect that it is possible to appropriately calculate the peak timing of the concentration of the fluorescent agent in the living tissue.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIGS. 1 to 11 relate to Embodiment 1 of the present invention, FIG. 1 is an external view showing the external appearance of the fluorescent agent integrated concentration measuring device, and FIG. 2 is a diagram showing a first display example of the display unit in FIG. 3 is a block diagram showing the configuration of the fluorescent agent integrated concentration measuring device of FIG. 1, FIG. 4 is a diagram showing the light absorption and emission characteristics of the sample in the test bottle of FIG. 2, and FIG. 5 is the transmission of the barrier filter of FIG. FIG. 6 is a block diagram showing a configuration of a modified example of the fluorescent agent integrated concentration measuring device of FIG. 1, FIG. 7 is a diagram showing transmission characteristics of the excitation light filter of FIG. 6, and FIG. 8 is a fluorescence diagram of FIG. FIG. 9 is a diagram illustrating an example of an analysis pattern group consisting of a plurality of analysis patterns reflecting individual differences for each fluorescent agent stored in the pattern storage unit of FIG. FIG. 10 explains the matching process with each analysis pattern of the analysis pattern group of FIG. Figure 11 is a diagram showing a second display example of the display unit of FIG.

  As shown in FIG. 1, the accumulated concentration measuring device 1 of the present embodiment is portable and can be lent to a patient, and the accumulated concentration of a fluorescent agent injected into a living tissue by a patient at home or the like. This is a device that measures the patient himself.

  The fluorescent agent integrated concentration measuring device 1 has a loading unit 3 for detachably loading a test bottle 2 containing a sample containing a patient's saliva, urine fluid, blood, etc., on the upper surface of the loading unit 3. A light-shielding lid 4 is provided for shielding external light when the test bottle 2 is loaded inside.

  On the front surface of the fluorescent agent integrated concentration measuring apparatus 1, a display unit 11 such as an LCD for displaying various data and an input switch unit 12 for inputting various data are provided. The input switch unit 12 includes, for example, a date setting switch 13 for specifying a date, a patient ID setting switch 14 for specifying a patient ID, a fluorescent agent setting switch 15 for specifying a fluorescent agent injected into the patient, and a measurement start And a keyboard portion 18 or the like capable of inputting a character string such as numerals or alphabets.

  As shown in FIG. 2, in addition to the date data, patient ID, fluorescent agent name, and the like input using the input switch unit 12, the display unit 11 displays the number of times the patient himself / herself has been examined under these conditions and the examination result. It has come to be.

  In detail, as shown in FIG. 3, the fluorescent agent integrated concentration measuring apparatus 1 includes a single wavelength LED (single wavelength laser light source) 21 that irradiates excitation light to a test bottle 2 loaded therein, and A barrier filter (optical filter) 22 that transmits only fluorescence, a light receiving element 23 that receives fluorescence through the barrier filter 22 and outputs an electrical signal, and processes the electrical signal from the light receiving element 23 to detect fluorescence intensity To calculate the tissue integrated concentration peak time of the sample in the test bottle 2 by comparing the detection processing circuit 24 that performs detection and the detection result from the detection processing circuit 24 with an analysis pattern (described later) stored in the pattern storage unit 25. The circuit 26 includes a control circuit 27 that controls the circuits, the display unit 11, and the input switch unit 12.

  As shown in FIG. 4, the sample in the test bottle 2 absorbs excitation light having a wavelength shorter than the wavelength λ with a predetermined wavelength λ as a boundary, and generates fluorescence having a wavelength longer than the wavelength λ excited by the excitation light. .

  Therefore, by irradiating the sample in the test bottle 2 from the single wavelength LED 21 with excitation light having a single wavelength shorter than the wavelength λ, the light receiving element 23 receives the light through a barrier filter 22 having transmission characteristics as shown in FIG. Only the fluorescence from the sample in the test bottle 2 is detected by the light receiving element 23.

  As shown in FIG. 6, it is possible to use a white lamp (for example, a xenon lamp) 31 as a white light source instead of the single wavelength LED 21, but in this case, between the white lamp 31 and the test bottle 2. 7, by providing an excitation light filter (transmission filter) 32 having transmission characteristics as shown in FIG. 7, only the light having a wavelength shorter than the wavelength λ is irradiated on the test bottle 2, and the light receiving element 23 passes through the barrier filter 22. You may comprise so that fluorescence may be received.

  The operation of this embodiment configured as described above will be described.

  When a fluorescent agent is administered into a living body in a hospital or the like, the patient is lent the fluorescent agent integrated concentration measuring device 1 of this embodiment from the hospital or the like, and this fluorescent agent integrated concentration measuring device 1 is installed at home or the like. Install. At this time, a predetermined reagent for mixing with the test bottle 2 and a sample such as saliva, urine fluid or blood is supplied to the patient from a hospital or the like together with the fluorescent agent integrated concentration measuring device 1.

  When the examination time instructed in advance by the hospital or the like is reached using the fluorescent agent integrated concentration measuring apparatus 1 installed at home or the like in this manner, as shown in FIG. Alternatively, a sample such as blood is collected, and the sample and the supplied predetermined reagent are mixed and stored in the test bottle 2 in step S2. When the fluorescent agent in the sample is a fluorescent agent having a PeT (Photo-induced Electron Transfer) mechanism, the predetermined reagent is an agent that activates the fluorescent agent in the sample.

  In step S3, the test bottle 2 containing the sample is loaded into the loading unit 3 of the fluorescent agent integrated concentration measuring device 1 and the light shielding lid 4 is closed, so that the test bottle 2 is shielded from external light and is fluorescent. It is installed inside the integrated concentration measuring device 1.

  Next, in step S4, using the input switch unit 12 (date setting switch 13, patient ID setting switch 14, fluorescent agent setting switch 15 and keyboard unit 18), various data such as date data, patient ID, and fluorescent agent name are stored. input.

  Although not shown, for example, an RF-ID tag or the like in which a patient ID, a fluorescent agent name, etc. are recorded is provided in the test bottle 2, and an RF-ID communication means is provided in the fluorescent agent integrated concentration measuring device 1. Thus, the patient ID and the fluorescent agent name recorded on the RF-ID tag may be taken into the fluorescent agent integrated concentration measuring device 1 wirelessly.

  In step S5, the start switch 16 of the input switch unit 12 is pressed to start the inspection of the concentration of the fluorescent agent in the sample in the test bottle 2.

  When the inspection is started, first, excitation light is irradiated to the test bottle 2 from the single wavelength LED 21. Then, fluorescence generated from the excited sample in the test bottle 2 is received by the light receiving element 23 through the barrier filter 22. Then, an electrical signal from the light receiving element 23 is output to the detection processing circuit 24.

  In step S6, the arithmetic circuit 26 collates the fluorescence intensity and the inspection time from the excited sample in the test bottle 2 with the analysis pattern stored in the pattern storage unit 25.

  As shown in FIG. 9, the in-vivo concentration of the fluorescent agent is not only different for each type of fluorescent agent, but also varies depending on individual differences in the same fluorescent agent. An analysis pattern group composed of a plurality of analysis patterns reflecting the difference is stored, and collation with a sample is performed using these analysis pattern groups. As an example, FIG. 9 shows two sets of analysis pattern groups each including three analysis patterns of individual differences in the fluorescent agent A (solid line) and the fluorescent agent B (broken line).

  Thus, since the in-vivo concentration of the fluorescent agent varies depending not only on the type of the fluorescent agent administered to the patient but also on individual differences among patients, the time at which the in-vivo concentration of the fluorescent agent peaks differs. In FIG. 9, the peak point of the fluorescent agent A (solid line) is indicated by ●, and the peak point of the fluorescent agent B (broken line) is indicated by ▲.

  Therefore, in the verification with the analysis pattern in step S6, an analysis pattern group to be verified is selected based on the type of fluorescent agent (fluorescent agent name), and as shown in FIG. Result) and each analysis pattern of the analysis pattern group are collated.

  By performing such collation a plurality of times, for example, three times, the peak time of the accumulated concentration of the fluorescent agent is estimated. Therefore, in step S7, it is determined whether the number of inspections has reached a predetermined number. If not, the next inspection time is displayed on the display unit 11 as the inspection result in step S8 as shown in FIG. The process ends. When the number of examinations reaches the predetermined number and the peak time of the accumulated concentration of the fluorescent agent is estimated, the date and time of visit are displayed as the examination result in step S9 as shown in FIG.

  Here, estimation of the peak time of the accumulated concentration of the fluorescent agent will be described in detail. Although the examination time varies depending on the type of the fluorescent agent, the first examination time from the administration of the fluorescent agent is instructed by a hospital or the like. Further, the next inspection time is a time having a predetermined time interval from the first inspection time.

  When a certain fluorescent agent is administered, the fluorescence intensity from the sample at a plurality of inspection times (inspection) is verified by performing a plurality of inspections at a predetermined time interval, for example, three times at an interval of 6 hours from the administration time of the fluorescent agent. It can be seen on which analysis pattern the result is). The peak of the corresponding analysis pattern is estimated as the peak time of the accumulated concentration of the fluorescent agent.

  FIG. 10 is an example in which it is estimated that the peak time of the concentration of accumulated fluorescent agent is, for example, three times at intervals of 6 hours from the administration time of the fluorescent agent, and the time when 15 hours have elapsed from the final time.

  As described above, in this embodiment, the fluorescent agent integrated concentration measuring device 1 can be carried and lent to the patient. Therefore, the patient needs to be in the hospital until the concentration of the fluorescent agent in the living tissue reaches a peak. Disappear. As a result, the peak time of the concentration of the fluorescent agent in the living tissue can be estimated simply by measuring the concentration of the fluorescent agent in the sample such as saliva or blood by the fluorescent agent integrated concentration measuring device 1 at a predetermined time interval at home or the like. By notifying the patient of this peak time, the patient can be urged to visit the hospital.

  FIG. 12 is a block diagram showing a configuration of a fluorescent agent integrated concentration measuring apparatus according to Embodiment 2 of the present invention.

  Since the second embodiment is almost the same as the first embodiment, only different points will be described, and the same components are denoted by the same reference numerals and description thereof will be omitted.

  As shown in FIG. 12, in this embodiment, a communication I / F 101 capable of communicating with a wide area network such as the Internet 100 is provided in the fluorescent agent integrated concentration measuring apparatus 1, and the pattern storage unit 25 is connected to the Internet 100. It is provided and configured in the hospital server 102 in the hospital. Other configurations and operations are the same as those in the first embodiment.

  In the case of the present embodiment, since it is not necessary to provide the pattern storage unit 25 in the fluorescent agent integrated concentration measuring device 1, the configuration is more excellent in portability. In addition, since the fluorescence intensity (test result) information from the patient sample can be stored in the in-hospital server 102, more various analysis patterns based on the fluorescence intensity (test result) information are generated and the pattern storage unit 25 can be stored. Note that the arithmetic circuit 26 can be omitted by providing the hospital server 102 with the arithmetic function of the arithmetic circuit 26.

  The present invention is not limited to the above-described embodiments, and various changes and modifications can be made without departing from the scope of the present invention.

1 is an external view showing the external appearance of a fluorescent agent integrated concentration measuring device according to Embodiment 1 of the present invention. The figure which shows the 1st example of a display of the display part of FIG. The block diagram which shows the structure of the fluorescent agent integrated density | concentration measuring apparatus of FIG. The figure which shows the light absorption and light emission characteristic of the sample in the test bottle of FIG. The figure which shows the transmission characteristic of the barrier filter of FIG. The block diagram which shows the structure of the modification of the fluorescent agent integrated concentration measuring apparatus of FIG. The figure which shows the transmission characteristic of the excitation light filter of FIG. The flowchart explaining the effect | action of the fluorescent agent integrated concentration measuring apparatus of FIG. The figure which shows an example of the analysis pattern group which consists of a several analysis pattern which reflected individual difference for every fluorescent agent stored in the pattern storage part of FIG. The figure explaining the collation process with each analysis pattern of the analysis pattern group of FIG. The figure which shows the 2nd example of a display of the display part of FIG. The block diagram which shows the structure of the fluorescent agent integrated concentration measuring apparatus which concerns on Example 2 of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Fluorescent agent integrated density | concentration measuring apparatus 2 ... Test bottle 3 ... Loading part 4 ... Light shielding cover 11 ... Display part 12 ... Input switch part 21 ... Single wavelength LED (single wavelength laser light source)
22: Barrier filter (optical filter)
DESCRIPTION OF SYMBOLS 23 ... Light receiving element 24 ... Detection processing circuit 25 ... Pattern storage part 26 ... Arithmetic circuit 27 ... Control circuit 31 ... White lamp (white light source)
32. Excitation light filter (transmission filter)
Attorney Susumu Ito

Claims (14)

An excitation light source that irradiates a sample solution containing a body fluid collected from a living body into which a medicine containing a fluorescent dye is injected with excitation light that excites fluorescence with respect to the fluorescent dye;
Fluorescence detection means for detecting the fluorescence;
A fluorescent dye concentration calculating means for calculating the concentration of the fluorescent dye in the living body based on a detection signal from the fluorescent detecting means ,
The fluorescent dye concentration calculating means is configured to determine the concentration of the drug containing the fluorescent dye in the tissue in the living body based on the elapsed time of injection of the drug containing the fluorescent dye into the living body and the calculated concentration of the fluorescent dye. A concentration measuring apparatus for concentration of fluorescent agent, characterized in that it has a peak time estimating means for estimating the peak time of the fluorescent agent. An optical filter that cuts the excitation light and transmits the fluorescence;
The fluorescent agent integrated concentration measuring apparatus according to claim 1, wherein the fluorescence detection unit detects the fluorescence via the optical filter. The fluorescent agent integrated concentration measuring device according to claim 1 or 2, wherein the body fluid is saliva, urine fluid, or blood. The fluorescent agent integrated concentration measuring apparatus according to claim 1, 2 or 3, wherein the excitation light source is a single wavelength laser light source. The said excitation light source consists of a white light source which light-emits white light, and a permeation | transmission filter which permeate | transmits only the wavelength range | band of the said excitation light among the said white light. Fluorescent agent integrated concentration measuring device. The fluorescent agent integrated concentration measuring apparatus according to claim 1, 2 or 3, further comprising container loading means for detachably placing a container containing the sample solution on an optical path of the excitation light. The fluorescent agent integrated concentration measuring apparatus according to claim 6, further comprising a light shielding unit configured to shield external light from the container loaded in the container loading unit. 2. The fluorescent agent integrated concentration measuring apparatus according to claim 1, wherein the peak time estimating unit estimates the peak time based on a plurality of different times and the fluorescent dye concentration calculated at the plurality of times. . 9. The fluorescent agent integrated concentration measuring apparatus according to claim 8, further comprising curve data storage means storing concentration-time curve data used for collation with the fluorescent dye concentrations calculated at the plurality of times . It has a communication means to send and receive data with an external server connected to the network,
The fluorescent agent integrated concentration measuring apparatus according to claim 9, wherein at least the curve data storage means is provided in the external server . An excitation light irradiation step of irradiating a sample solution containing a body fluid collected from a living body into which a medicine containing a fluorescent dye is injected with excitation light that excites fluorescence with respect to the fluorescent dye;
A fluorescence detection step for detecting the fluorescence;
A fluorescent dye concentration calculating step for calculating the concentration of the fluorescent dye in the living body based on the detection signal detected in the fluorescent detection step;
With
In the fluorescent dye concentration calculating step, the concentration of the medicine containing the fluorescent dye in the tissue in the living body based on the elapsed time of injection of the medicine containing the fluorescent dye into the living body and the calculated concentration of the fluorescent dye. A peak time estimation step for estimating the peak time of
A method for measuring concentration of accumulated fluorescent agent. The peak time estimating step estimates the peak time based on a plurality of different times and the fluorescent dye concentration calculated at the plurality of times.
The fluorescent agent accumulation concentration measuring method according to claim 11. A curve data storage step of storing, in a data storage means, density-time curve data used for collation with the fluorescent dye concentrations calculated at the plurality of times;
The fluorescent agent accumulation concentration measuring method according to claim 12. Having a communication step of sending and receiving data to and from an external server connected to the net;
At least the data storage means is provided in the external server
The fluorescent agent accumulation concentration measuring method according to claim 13.

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