DE19539829A1 - Determining blood flow and vitality of organs - Google Patents

Abstract

After an intravenous injection with the fluorescent substance, monochromatic light is generated. The light is deflected into a body cavity of a patient and to the region (9) under examination by means of a first flexible optical waveguide (6) to which a light probe (7) is connected. A second flexible optical waveguide (8) is connected to the probe. Light reflected from the region (9) is fed via the probe (7) and second waveguide (8) via a photomultiplier (11) to a computer (13). The computer (13) compares the fluorescence intensity of the reflected light with that of a healthy reference region (9a) and/or with the known pharma-kinetics of the substance in healthy tissue. The comparison result is shown on a screen and/or printed and/or represented by an optical and/or acoustic signal.

Description

The invention relates to a method and Device for determining deficient blood flow and Vitalities of organs by means of an injection of Fluorescein and a fluorometer.

Fluorometry is a process chemical analysis, in which from the Fluorescence intensity on the amount of to be determined Substance in a solution, usually in a test tube, is closed when the dependence of fluorescence of concentration is known. With this procedure is mainly used to determine fluorometry Protein, alkaloids, vitamins, hormones and the like applied.

Such a fluorometer is described, for example, in EP 0 207 485 B1.

Furthermore, DE 39 15 692 describes a method for Determination of rapidly changing fluorescence processes biological samples by excitation with a switchable laser described, the Fluorescent light from the sample with a detector system  is detected. This procedure is therefore for the not suitable because the human body Fluorescence excitation due to a laser beam its radiation intensity with an irradiation time in Minute range can lead to physical damage. Furthermore, fluorescence without laser excitation and a correspondingly high level without a light source Fluorescence concentration ahead, which is also the case with human body must be avoided. And finally goes from the introduction to this Pre-publication shows that so far Fluorescence method for the measurement of intact Plant leaves have been used. At a there were limits to such an application because the distinction between irradiated and non-irradiated Leaf areas is unclear and also due to the density the chloroplast excitation light is absorbed and through the absorption and the re-emission spectrum Intensity of the fluorescent light can be influenced.

After two essays by David G. Silverman, "JOURNAL OF SURGICAL RESEARCH" VOL. 34, 1983, pp. 179-186 and "SURGERY" February 1985, pp. 185-193, are on open abdominal cavities of rats and dogs Blood flow to a strangulated intestine using a relatively high dose of injected fluorescein and one Fluorometer examined. Since this investigation is on open abdominal cavities could have an impact fluorescence from daylight or  Artificial light cannot be prevented. In this respect, these are Investigations with corresponding uncertainty factors afflicted. For example, the interpretation of the colored pattern subjectively under ultraviolet light and on the concentration of fluorescein above that visible threshold is limited. An objective measurement was found therefore not instead.

Furthermore, according to the essay by Kurt Lange ("THE DERMOFLUOROMETER" the Journal of Laboratory and Clinical Medicine 1943, pp. 1746-1750) skin examinations using a fluorometer carried out, the patient concerned 10 cm³ 5% fluorescein solution was injected intravenously and different in a darkened room Body test points examined with a fluorometer were. This method and also the device have the disadvantage of a subjective - because visual - Comparative affairs require relatively high ones Fluorescein doses and can be examined of blood vessels within a human body in a preoperative phase.

For example, in the past 30 years intestinal ischemia gained importance and was observed increasingly frequently. This is partly the case with increasing life expectancy for an increased incidence attributed. It is essential to recognize that intestinal disorder in many diseases  Blood flow is a common etiology. The Symptoms are uncharacteristic and deliver because of little subjective complaints and little striking examination findings are often deceptive Picture. Determination of serum lactate, leukocytosis and the clinical course can be trend-setting. To date, there is a laboratory test that shows intestinal ischemia with sufficient sensitivity and specificity, not known. The invasive X-ray diagnosis can be done by the detection of mesenteric vascular breaks at the selective catheter angiography find application. For Assessment of gut vitality must currently be immediate exploratory laparotomy. Despite the Improvements in surgical, vascular reconstructive Measures and despite improving the intensive medical techniques will increase the lethality of the Disease indicated with 80% to 90%. For belittling this high lethality stands alongside the early one Diagnosis especially the safe assessment of the Intestinal vitality in the foreground. This is where the invention comes in a.

This is based on the task of making it possible of short-term repeat exams lowest possible dosage of dye on fluorescein differentiated quantitative and qualitative statements of the Fluorescein concentration and the associated Fluorescence intensity within unlit  Body cavities to assess the quality of Blood circulation and cell vitality.

This task becomes procedural solved according to the invention in that after a intravenous injection with fluorescein monochromatic Generated light and using a first flexible Light guide and a light probe connected to it into a human body cavity on the Examination area is directed and over the same Light probe and a second connected flexible light guide from the examination area reflected light over a photomultiplier Computer that is routed through a The target-actual value comparison is the fluorescence intensity of this reflected light with the fluorescence intensity a healthy reference range and / or with the known pharmacokinetics of fluorescein in healthy Tissue compares and these comparative values on one Displays, prints out and / or through a screen visual and / or acoustic signal clarified.

Depending on the size, duration and type of Let fluorescence intensity of the reflected light the following quantitative statements meet:

• a) With a steep rise and a further fall in the Fluorescence intensity of the yellow-green emitted light from the examined body part, e.g. B. the intestinal part  this is due to good circulation and vitality of the Close the examination area because that over the Blood flow of the blood vessels in the examination area fluorescein got this steep rise and also whose drop is caused by the removal of the fluorescein and thus clarifies.
• b) In the case of a steep increase, then about to same level of remaining fluorescence intensity of the reflected light leaves this on a Blood flow to the examination area concerned, e.g. B. the intestine, but close to a lack Vitality, since it is obvious that the Fluoresceins due to, for example, a deposit in the Intermediate cell space did not occur due to cell damage.
• c) One versus a healthy reference range significantly reduced fluorescence intensity of the reflected light indicates insufficient blood flow to the Close the examination area because of lack of blood flow is only a correspondingly low one Proportion of fluorescein for the relevant measuring range, for example, due to an embolism or thrombosis is.

By transmitting the reflected light is not via a photomultiplier to a computer just an objective one, but also a quick quantitative one Statement about the blood circulation and / or vitality of the Examination area possible. Furthermore, these Investigations using the flexible light guide and  one attached to it, either rigid or equally flexible, light-guiding probe in a closed body cavity, e.g. B. human Abdominal cavity, before any that may be required Operation can be carried out, for example at the mesenteric ischemia due to the unremarkable Examination findings with the one already described deceptive image without a significant burden on the Patient can be made. Because of the computerized target-actual value comparison of the Fluorescence intensity can also have slight differences be recorded, so that even short-term Repeat exams at low Dye dosing on fluorescein can be performed can a differentiated quantitative and qualitative statement of the fluorescence concentration, the associated fluorescence intensity and the Assessment of blood flow and cell vitality allow inside unlit body cavities.

To the examining surgeon immediately through endoscopic visual inspection to enable the investigation will be made after a particularly advantageous development of the invention the examination area light with a wavelength of which neither the excitation nor the Fluorescence intensity of the reflected light Interference, reflection or absorption can be influenced can. The excitation of the Fluorescence light with a wavelength of 482 nm to 494 nm and to inspect the  Examination area light with a wavelength of found larger than 540 nm.

The light reflected from the examination area becomes advantageous in a range from 517 nm to 533 nm Photomultiplier fed. By the in the aforementioned Areas occurring light intensity peaks of the Fluorescence stimulating and that of the examination area reflected light will be even at low Dosages of fluorescein are clearly qualitative and quantitative statements of blood circulation and vitality of the examination areas despite the low dosage Fluorescein enables. In all cases the light kicks in for lighting and thus for the visual perception of the Examination area with a wavelength of at least 540 nm not negative in appearance.

In terms of device, that of the invention underlying task solved in that by means of one of a power supply and an ignition circuit excited xenon light source to split off light Light of a certain wavelength to the light input of a Excitation device can be fed, by the Light output the split light in a first flexible light guide with the light probe is conductive, with which is a second flexible light guide for derivation of the light reflected from the examination area to Light entrance of an emission device in connection stands, the light output with a photomultiplier which is connected to a computer interface and a Computers are subordinate. With the light probe it can  split off from the xenon light source monochromatic light laparoscopically on the Examined area and then through the same light probe the reflected light in the second Light guide of the emission device with the Photomultiplier are fed. Thereby exists a first embodiment, which is already in the test has proven the excitation facility from one Excitation monochromator and the emission device from an emission monochromator. This device can replaced by a second embodiment that the excitation facility by one Excitation filter and the emission device from one Emission filters are formed.

According to an advantageous development of the invention the first and second light guides consist of either a quartz light guide or one Liquid light guide. The quartz light guide has this the preference for spectral transmission Light transmission lengths of 1000 mm and 4000 mm with a transmission between 50% and 60% in one Wavelength range above 400 nm. In contrast is the spectral transmittance of flexible Liquid light guides with light transmission lengths of 1000 mm, 2000 mm and 4000 mm at wavelengths between 400 nm and 550 nm for a transmission of over 70%. This high transmission of the on Examination area of striking light and of it reflected light can also be minor  Differences in fluorescence recorded objectively and even low fluorescein doses in short-term Repeat examinations exact qualitative and quantitative statements about the blood circulation and Vitality state of the examination area hit will.

It is between the excitation and Emission filter advantageously a dichroic mirror arranged the one hand from the excitation filter to first light guide to guide light almost completely reflected and on the other hand that from the examination area reflected light almost completely through this Dichroic mirror passes through to the emission filter.

The sensitivity of the photomultiplier is advantageous over the size of its anode voltage adjustable, being the relative light intensity of the light reflected from the examination area in Dependence on a basic calibration measures. As Basic calibration will change the sensitivity of the Photomultipliers at an anode voltage between 690 volts and 790 volts at about 1000 Dye Fluorescence Units (DFU) adjusted, whereby the light probe in a black - not absolutely black - body without any incidence of light.

Several devices according to the invention as well with these feasible inventive methods  are described below with reference to the drawings. Show:

Fig. 1 shows a schematic arrangement of a device with Exzitations monochromator emission monochromator, photomultiplier, computer interface, and computer,

Fig. 2 shows a second embodiment with an arranged behind the xenon excitation light source excitation filter with a dichroic mirror and an emission filter,

Fig. 3 is a schematic representation of the light generation and filtering of the light of a fluorometer, and a lamp for laparoscopy before and after their impact with the tissue of the examination zone,

Fig. 4 shows the transmission in% of the spectral transmittance of two different lengths quartz optical fiber to the wavelength of the guided light of them,

Fig. 5 shows the transmission in% of the spectral transmittance of three different lengths of flexible liquid light guides to the wavelength of the guided light of them,

Fig. 6 shows the relative light intensity of the exzitierten from the xenon light source and light emitted by the examination area light over the wavelength in nm and

Fig. 7 shows the relative light intensity of the xenon light source to the wavelength of the individual light fields.

According to a first embodiment according to FIG. 1, the device 1 for determining deficient blood flow and vitality of human organs consists of a xenon light source 4 excited by a power supply unit 2 and an ignition circuit 3 , the light of which for splitting off light of a certain wavelength reaches the light input 5 a an excitation device 5 is supplied, the light output 5 b of which is connected via a first light guide 6 to the light probe 7 , with which a second light guide 8 for deriving the light reflected from the examination area 9 (see FIG. 3) to the light input 10 a one Emission device 10 is coupled, the light output 10 b is connected to a photomultiplier 11, which is followed by a computer interface 12 and a computer 13 . In the case shown, the excitation device 5 consists of an excitation monochromator and the emission device 10 consists of an emission monochromator. Both monochromators are driven by a common motor drive 14 , which is coupled to the computer interface 12 via a control line 15 .

FIG. 2 shows a second exemplary embodiment of a device 16 for determining insufficient blood flow and vitality of human organs in a block diagram. 1 thereby matching parts with FIG. Designated by like reference numerals. Here too, spectral light is generated by means of a xenon light source 4 excited by a power supply unit 2 and an ignition circuit 3 , which is guided through an excitation filter 17, which is followed by a dichroic mirror 18 , to filter out monochrome light of a certain wavelength. From the dichroic mirror 18 , the monochrome light filtered out by the excitation filter 17 , the beam path of which is indicated here by the solid line, is directed to the input 19 of the light guide 6 , through which it is directed by the light probe 7 onto the examination area 9 . The light reflected by the examination area 9 is then guided via the same light probe 7 with a second light guide 8 accommodated in the same line and via 19 to the dichroic mirror 18 , which almost completely transmits this reflected light, the beam path of which is shown in broken lines, to an emission filter 20 , which are followed by the photomultiplier 11 , the computer interface 12 and the computer 13 . The photomultiplier 11 essentially consists of a photon counter which measures the size of the fluorescence intensity of the reflected light and communicates it to the computer 13 via the computer interface 12 .

The embodiment according to FIG. 1 essentially differs from the embodiment according to FIG. 2 in that the excitation monochromator 5 and the emission monochromator 10 are replaced by the excitation filter 17 and the emission filter 20 and by a dichroic mirror 18 arranged between them .

The first and second light guides 6 , 8 can either consist of a quartz light guide or a liquid light guide. The light probe 7 is either rigid or flexible like the first and second light guides 6 , 8 .

The sensitivity of the photomultiplier 11 can be adjusted via the size of its anode voltage, wherein it measures the relative light intensity of the light reflected by the examination area 9 as a function of a basic calibration. As a basic calibration, the sensitivity of the photomultiplier 11 is set to approximately 1000 dye fluorescence units (DFU), for example at an anode voltage between 690 volts and 790 volts, the light probe 7 being located in a black body without any incidence of light.

The method for determining deficient blood flow and vitality of human organs is illustrated most clearly in FIG. 3. In this schematic illustration, parts that correspond to FIG. 2 are designated by the same reference numbers. In addition to the device 1 from FIG. 1 and the device 16 from FIG. 2, a further laparoscopic lamp 21 and an optical filter 22 are provided in FIG. 3 for endoscopic inspection of the examination area 9 :

Light of different wavelengths is generated by the xenon lamp 4 of the device 16 from FIG. 2, the letters in FIG. 3 meaning the English abbreviations as follows:

Uv = ultraviolet,
V = violet,
B = blue,
G = Green,
Y = Yellow,
O = orange,
R = Red.

The excitation filter 17 transmits the light of all other wavelengths than the violet light beam V with a wavelength of 488 nm ± 6 nm. This light beam 23 strikes the examination area 9 and excites the amount of fluorescein present there for fluorescence, as a result of which light in the yellow-green area is emitted, for example with the light beams 25 , and strikes the emission filter 20 together with the partly also reflected violet light beam 24 . However, this emission filter 20 only allows single-color light according to the light beam 25 with a wavelength of 526 nm ± 8 nm, which then strikes the photomultiplier 11 . The fluorescence intensity is measured by this 11 and communicated to the computer 13 via the computer interface 12 . The computer 13 compares the fluorescence intensity of this emitted light according to the light beam 25 with the fluorescence intensity of a healthy reference area, for example a reference area 9 a, and / or with the known pharmacokinetics of fluorescein in healthy tissue and by means of a target / actual value comparison shows these comparison values either on a screen 13 a according to FIG. 1 or prints them out using a printer (not shown) or clarifies an alarming clinical picture either by means of an optical and / or acoustic signal.

So that the surgeon can correctly guide the light probe 7, for example in the abdominal cavity of a person, by inspecting the examination area 9 , the examination area 9 must be illuminated by a further xenon lamp 21 for laparoscopy. All of the light generated by this second laparoscopic lamp 21 is passed through an optical filter 22 which only transmits light with a wavelength of more than 540 nm. This light, for example in the yellow, orange or red area, also strikes the examination area 9 and is reflected by it, but is no longer transmitted by the emission filter 20 , but is completely filtered out. Since the light striking the examination area 9 from the laparoscopic lamp 21 has a wavelength of at least 540 nm, it can neither according to the light transmitted by the excitation filter 17 according to the light beam 23 with a wavelength of 488 nm + 6 nm nor the light reflected from the examination area 9 influence the light beam 25 with a wavelength of 526 nm ± 8 nm by interference, reflection or absorption. As a result, the photomultiplier 11 objectively counts, depending on the amount of fluorescein present in the examination area 9 , the light intensity of the reflected light according to the light beam 25 , after which the computer 13 in fractions of a second this fluorescence intensity with the fluorescence intensity of a healthy reference area 9 a and / or compares with the known pharmacokinetics of the fluorescein in healthy tissue and represents the result visually on the screen 13 a clear or by an expression or by an optical and / or acoustic signal. As a result, the surgeon receives an objective report on the blood flow and vitality state of the examination area 9 in the shortest possible time, so that he can make the qualitative and quantitative assessments described in the introduction to the description before a complete opening of the body cavity that may become necessary. After this, he can decide whether, for example, an intestine has to be resected or a vascular reconstruction has to be carried out in case of other vascular damage.

In all investigations, the higher the transmission (in%) of the light through the first and second light guides 6 , 8 , the greater the accuracy of the measurements of the photomultiplier 11 . This spectral transmission is of different conductor lengths in FIG. 4 for a quartz light guide once with a length of 1000 mm and again with a length of 4000 mm and in FIG. 5 for three liquid light guides with lengths of 1000 mm, 2000 mm and 4000 mm shown.

As has already been described above, the devices 1 , 16 according to the invention are oriented such that excitated light with a wavelength of 482 nm to 494 nm is guided via the light guide 6 . For these wavelengths with a length of 1000 mm the transmission is approx. 60% for a quartz light guide and approx. 90% for a liquid light guide. Due to this high transmission, even with low injected fluorescein doses, the fluorescein that has reached the examination area 9 via the bloodstream can experience considerable fluorescence excitation and, with a correspondingly high transmission, the emitted light can be guided to the photomultiplier 11 via the emission filter 20 or the emission monochromator 10 .

As shown in FIGS. 6 and 7, according to the invention, from the total light generated of all wavelengths of the xenon lamp 4, exactly the two wavelengths with clear peaks are used once for excitation and another time for emission, which are well above their relative intensity the neighboring light wavelengths, in particular far above the light intensity of the laparoscopic lamp 21 and the light filtered by the optical filter 22 with a wavelength of over 540 nm. Through this deliberate selection of the excited light according to the light beam 23 to the examination area 9 , the deliberate selection of the emitted light from the examination area 9 according to the light beam 25 to the photomultiplier 11 and also the high transmission associated therewith, in particular if a liquid for directing the light If light guides 6 , 8 are selected, objectively accurate qualitative and quantitative statements about the blood flow and vitality state of the examination area 9 can be made even with low doses of fluorescein. Because of the low fluorescein doses, repeat examinations are possible without any significant physiological stress on the patient concerned.

Reference list

1 , 16 devices
2 power supply
3 ignition circuit
4 xenon light source
5 excitation facility
5 a light input of the excitation device 5
5 b light output of the excitation device 5
6 , 8 light guides
7 light probe
9 Examination area
9 a Reference range
10 emission device
10 a light input of the emission device 10
10 b light output of the emission device 10
11 photomultiplier
12 computer interface
13 computers
13 a screen
14 motor drive
15 control line
17 excitation filter
18 dichroic mirror
19 input of the light guide 6
20 emission filters
21 laparoscopic lamp
22 optical filter
23 , 24 , 25 light rays

Claims (14)

1. A method for determining insufficient blood flow and vitality of organs by means of an injection of fluorescein and a fluorometer, characterized in that monochromatic light is generated after an intravenous injection with fluorescein and by means of a first flexible light guide ( 6 ) and a light probe ( 7 ) connected to it. is directed into the examination area ( 9 ) in a human body cavity and the light reflected from the examination area ( 9 ) is transmitted to a computer ( 13 ) via a photomultiplier ( 11 ) via the same light probe ( 7 ) and a second flexible light guide ( 8 ) connected to it. which compares the fluorescence intensity of this reflected light with the fluorescence intensity of a healthy reference area ( 9 a) and / or with the known pharmacokinetics of fluorescein in healthy tissue and compares these comparison values on a screen ( 13 a) display gt, printed out and / or illustrated by an optical and / or acoustic signal. 2. The method according to claim 1, characterized in that for endoscopic inspection of the examination area ( 9 ) is directed to this light with a wavelength from which neither the excitation nor the fluorescence intensity of the emitted light is influenced by interference, reflection or absorption. 3. The method according to claim 1 and 2, characterized in that for exciting the fluorescence light with a wavelength of 482 nm to 494 nm and that for inspection of the examination area ( 9 ) and for illuminating light with a wavelength of at least 540 nm is used . 4. The method according to one or more of claims 1 to 3, characterized in that the light reflected from the examination area ( 9 ) in a range from 517 nm to 533 nm is fed to the photomultiplier ( 11 ). 5. The method according to one or more of claims 1 to 4, characterized in that depending on the increase, decrease and other course of the fluorescence intensity of the light emitted by the examination area ( 9 ) in comparison with a healthy reference area ( 9 a) and / or the known pharmacokinetics of fluorescein in healthy tissue is used to infer the quality of the blood circulation and vitality of the examination area ( 9 ). 6. Device for performing the method according to claims 1 to 6, characterized in that by means of a power supply ( 2 ) and an ignition circuit ( 3 ) excited xenon light source ( 4 ) light for splitting off light of a certain wavelength, the light input ( 5th a) an excitation device ( 5 ) can be fed, from whose light output ( 5 b) the split-off light can be guided into a first flexible light guide ( 6 ) with the light probe ( 7 ), with which a second flexible light guide ( 8 ) can be derived of the light reflected from the examination area ( 9 ) is connected to the light input ( 10 a) of an emission device ( 10 ), the light output ( 10 b) of which is connected to a photomultiplier ( 11 ) which has a computer interface ( 12 ) and a Computers ( 13 ) are subordinate. 7. The device according to claim 6, characterized in that the excitation device ( 5 ) consists of an excitation monochromator and the emission device ( 10 ) consists of an emission monochromator. 8. The device according to claim 7, characterized in that the excitation monochromator and the emission monochromator have a common motor drive ( 14 ). 9. The device according to claim 6, characterized in that the excitation device ( 5 ) by an excitation filter ( 17 ) and the emission device ( 10 ) are formed by an emission filter ( 20 ). 10. The device according to one or more of claims 6 to 9, characterized in that the first and second light guides ( 6 , 8 ) consist of either a quartz light guide or a liquid light guide. 11. The device according to one or more of claims 6 to 10, characterized in that the light probe ( 7 ) is either rigid or also flexible. 12. The device according to one or more of claims 6 to 11, characterized in that between the excitation and the emission filter ( 17 , 20 ) a dichroic mirror ( 18 ) is arranged, which on the one hand that from the excitation filter ( 17 ) to the first light guide ( 6 ) light to be guided is almost completely reflected and, on the other hand, the light reflected from the examination area ( 9 ) passes almost completely through this dichroic mirror ( 18 ) to the emission filter ( 20 ). 13. The device according to one or more of claims 6 to 12, characterized in that the sensitivity of the photomultiplier ( 11 ) is adjustable via the size of its anode voltage and it measures the relative light intensity of the light reflected from the examination area ( 9 ) as a function of a basic calibration . 14. The apparatus according to claim 13, characterized in that the basic calibration, the sensitivity of the photomultiplier ( 11 ) at an anode voltage between 690 volts and 790 volts is set to about 1000 dye fluorescence units (DFU), the light probe ( 7 ) in one black body is located without any incidence of light.