JP2573774B2 - Laser generator for medical equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a laser generator for a medical device mainly used for a cancer diagnostic / treatment device.

[0002]

2. Description of the Related Art For diagnosis and treatment of cancer, a fluorescent substance having high affinity for cancer, such as HpD, is previously absorbed in a lesion, and the fluorescent substance and the laser light when this part is irradiated with laser light are used. There has been proposed a method and apparatus for diagnosing and treating cancer by selectively necroticizing only cancer cells by utilizing the photochemical reaction described above.
This is described in JP-A-59-40830 and JP-A-59-4.
0869.

Further, there has been proposed an apparatus for monitoring a treatment state by detecting infrared light (wavelength 1.27 μm) of a specific wavelength generated from active oxygen generated in a tissue during treatment. This is described in JP-A-1-151436.

Japanese Patent Application Laid-Open No. 3-159661 discloses an Hp
A technology relating to a laser treatment apparatus capable of changing the oscillation wavelength of a therapeutic laser beam in accordance with the absorption wavelength of a photochemical treatment agent to be used so as to be able to cope with not only D but also other photochemical treatment agents Is described.

[0005]

However, in the conventional cancer diagnosis and treatment apparatus, only the amount of active oxygen is monitored. The absorption wavelength of the photosensitizer is shifted to a longer wavelength side than the absorption wavelength originally possessed by the photosensitizer by binding to the biological tissue. Since this shift varies depending on the tissue, it is considered that the optimal treatment laser beam wavelength varies depending on the patient or the affected area.

An object of the present invention is to solve the above-mentioned problems, and an object of the present invention is to provide a laser generator for a medical device which is used as a cancer diagnostic / treatment device with a higher treatment effect.

[0007]

Means for Solving the Problems In order to solve the above problems, a diagnostic laser is irradiated around the treatment site to determine the treatment site, and the determined treatment site is irradiated with the therapeutic laser beam to perform a photochemical reaction. In a laser generator for a medical device that necroses cells at a treatment site, the treatment laser light is output from a wavelength variable laser generation means capable of changing the wavelength, and the active oxygen of the treatment site generated by the treatment laser light is generated. Monitoring means for monitoring the generation amount by light from the treatment site, and wavelength setting means for setting the wavelength of the treatment laser light to a wavelength at which the generation amount increases in accordance with information from the monitoring means. Features.

Further, the wavelength tunable laser generating means includes N
d-YAG laser generator, second and third harmonic generators for obtaining second and third harmonics from laser light generated therefrom, and third harmonic An optical parametric oscillator having a nonlinear optical crystal that obtains a different wavelength from the wavelength of the therapeutic laser light is set to a desired wavelength by changing the angle of the nonlinear optical crystal by wavelength setting means. May be a feature.

The monitoring means may detect a specific wavelength emitted by the active oxygen, or may detect a specific wavelength of chemiluminescence generated by the active oxygen and a specific reagent.

[0010]

A photosensitizer having a high affinity for a tumor or the like is administered, and the photosensitizer is absorbed in a desired lesion area in advance. Then, when a diagnostic laser beam is irradiated at the time of diagnosis, fluorescence having a specific peak wavelength is generated by the photosensitizer, so that the position of the lesion and its range can be specified. In addition, the irradiation of the therapeutic laser light causes a photochemical reaction between the laser light and the photosensitizer, so that only the area where the photosensitizer is absorbed, that is, only the cells in the lesion can be necrotic. .

Here, when the therapeutic laser beam is applied to the lesion, the amount of active oxygen generated by the photochemical reaction between the therapeutic laser beam and the photosensitizer is monitored.
The progress of the treatment can be grasped from the amount of active oxygen generated. Further, by irradiating the therapeutic laser light to the lesion while changing the wavelength within a predetermined range, and monitoring the amount of the active oxygen generated, the amount of the active laser is increased so as to increase the amount of the active oxygen generated. The wavelength can be set.

[0012]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be specifically described below with reference to the drawings.

FIG. 1 shows a configuration example of an embodiment of the present invention. First, the main configuration and operation in an example in which HpD is used as a photosensitizer will be described with reference to FIG.

The laser light source 1 has a diagnostic laser beam (405n).
m) and therapeutic laser light (around 630 nm). The irradiation of the laser beam and the reception of the fluorescence are performed via the light guide 2. Then, the fluorescence received by the spectroscope 3 is discriminated by wavelength, and 600 to 7 out of the discriminated light.
The light of 00 nm is amplified by the amplifier 4. The data of the amplification device 4 is analyzed by the analysis circuit 5 and the result is displayed on the display device 6. Further, the light of 1270 nm of the light discriminated by the spectroscope 3 is detected by the detection device 7, and the optimum wavelength of the therapeutic laser light generated by the laser light source 1 is selected and set by the wavelength setting circuit 8 based on this data. These devices are controlled by a timing signal of a timing control circuit 9.

Next, the configuration and operation of each device of the embodiment will be described in detail separately for diagnosis and treatment.

At the time of diagnosis, 4
A pulse laser beam of 05 nm is irradiated through the light guide 21 for irradiation. The lesion part C is previously absorbed with an appropriate amount of a photosensitizer such as HpD. As a result, fluorescence is generated from the lesion C and is guided to the spectroscope 3 through the light receiving light guide 22.

The fluorescence emitted from the emission end of the light guide 22 in the spectroscope 3 diverges, is reflected by the primary reflecting mirror 31, and
The light enters the diffraction grating 32. The light having a wavelength of 600 to 700 nm is split by the diffraction grating 32 for each wavelength and enters the amplifier 4. The light of about 1.27 μm indicating the amount of singlet oxygen generated during treatment (described later) is reflected by the secondary reflector 33,
The light enters the detection circuit 7.

600 to 700 nm incident on the amplifier 4
Is the photocathode 42 of the image intensifier tube 43
An image is formed thereon, and a fluorescence spectrum image of the fluorescence is obtained at this position. Since the fluorescence spectrum image is weak, it is multiplied by the image intensifier tube 43, and the multiplied fluorescence spectrum image is formed on the phosphor screen 44. This spectral spectrum image is converted into a high-sensitivity camera 46 by an imaging lens 45.
, And a spectral spectrum image is captured with low loss.

The output video signal of the spectrum image photographed by the high-sensitivity camera 46 is signal-processed by the analysis circuit 5 and then spectrum-displayed as a waveform A on a TV monitor 61 which is a display device 6. If the spectral spectrum image obtained by the TV monitor 61 is specific to a photosensitizer such as HpD, it is understood that the lesion C contains a photosensitizer such as HpD. Since a photosensitizer such as HpD has a strong affinity for cancer, it can be estimated that the lesion C is likely to be cancerous.

The shutter 41 is provided to protect the photocathode 42 of the image intensifier tube 43 from irradiation of strong light, and is used in an open state at the time of diagnosis, and a strong laser for treatment at the time of treatment. Used in a closed state because light enters.

The image intensifier tube driving circuit 47 is a power supply circuit for supplying a voltage for operating the image intensifier tube 43 and switching between an ON / OFF state by a gate signal of the timing control circuit 9. Actually, in an endoscopic diagnostic system (see FIG. 2) for visually confirming a lesion during treatment, white light is irradiated to observe the lesion C. The white light and the 405 nm laser light irradiate the lesion part alternately with time. Since the reflected light from the focus of the white light is strong, the supply of the applied voltage to the image intensifier tube 43 is stopped during the irradiation of the white light, and the image intensifier tube 43 is stopped.
Has stopped working.

At the time of treatment, the wavelength from the laser light source 1 is switched from the diagnostic laser light to the therapeutic laser light, and the pulse laser light of this wavelength is applied to the lesion C through the irradiation light guide 21. A photochemical reaction occurs between the treatment laser beam and HpD contained in the lesion C, and HpD fluorescence, which is 1.27 μm light from singlet oxygen, is emitted, thereby treating the lesion tissue. The 1.27 μm light is guided to the spectroscope 3 through the light receiving light guide 22, is diffracted by the diffraction grating 32, is reflected by the secondary reflecting mirror 33, and enters the detection device 7.

In the detection device 7, 1.27 μm light is detected by the photodetector 71 whose gate time is set by the gate circuit 74. The output signal from the photodetector 71 is amplified by the amplifier 72, and the output is
3 is read. Here, the gate time is set so that the photodetector 71 operates only when the light of 1.27 μm is emitted by the treatment. The output signal of the amplifier 72 is sent to the analysis circuit 5, where the signal is processed and the TV monitor 61
The intensity is displayed on the upper side as shown by the waveform B, and the progress of the treatment is determined.

When setting the wavelength of the therapeutic laser beam, the output signal of the amplifier 72 is sent to the wavelength setting circuit 8. The wavelength setting circuit 8 scans the wavelength of the therapeutic laser beam in a predetermined range, and outputs the amplifier 72 having an intensity of 1.27 μm.
The wavelength at which the output signal of the above becomes the maximum value is obtained. And 1.
The wavelength of the therapeutic laser light of the laser light source 1 is set to a wavelength at which the intensity of the light of 27 μm becomes the maximum, that is, the maximum therapeutic effect can be obtained.

The details of the wavelength setting circuit 8 when HpD is used as the photosensitizer will be described with reference to FIG.

After the diagnosis is completed and the affected part is specified, the wavelength of the therapeutic laser light is varied between 600 and 700 nm, and light derived from the amount of singlet oxygen at each wavelength is detected by the detector 71.
Receive at Then, it is sent to the memory circuit 81 in the wavelength setting circuit 8 via the amplifier 72, and the amount of singlet oxygen at each wavelength of 600 to 700 nm is stored. The stored data is analyzed by a wavelength analysis circuit 82, a wavelength at which the amount of singlet oxygen is maximized is selected, a stepping motor 84 is driven by a stepping motor driving circuit 83, and the nonlinear optical The crystal 15c is rotated to set the selected wavelength.

In practice, the wavelength setting of the therapeutic laser beam is performed before and during the treatment. Thereafter, the diagnosis and treatment, the wavelength setting and the treatment are repeated to treat the lesion.

Next, FIG. 3 shows a timing chart of the device of the present invention employed at the time of diagnosis, and the operation of the timing control circuit 9 will be described.

In FIG. 3, the pulse width 1 for triggering the laser light source from the timing control circuit 9 is shown.
A laser trigger signal (FIG. 3A) with 0 μs, a voltage of 5 V, and a repetition frequency of 0 to 120 Hz is output. Approximately 1 μs later, a diagnostic 405 nm laser beam (FIG. 3B) having a width of approximately 5 ns is generated. The fluorescence of a photosensitizer such as HpD is obtained at substantially the same time as the laser light.

The observation white light pulse for observing the lesion (FIG. 3C) is located at the middle of the repeated laser pulse, and is related to the 1.27 μm light detection at the time of treatment as shown in FIG. It is defined by such time conditions. The gate signal of the image intensifier tube 43 operates the image intensifier tube 43 only when fluorescence of a photosensitizer such as HpD is detected (ON state), and emits the image intensifier tube 43 at the time of white light pulse irradiation. This is to stop the operation (OFF state) to protect the device.

Laser light for treatment and Hp contained in lesion C
A photochemical reaction occurs with D to treat the lesion tissue, and HpD fluorescence (FIG. 3D) is released from the lesion during irradiation of the therapeutic 630 nm laser light.

Next, a timing chart of the apparatus during treatment is shown in FIG. 5 and will be described.

The same therapeutic laser light as that at the time of diagnosis is generated about 1 μs later than the laser trigger (FIG. 5B). White light for observation is 10ms, 5ms behind the laser trigger
Light is emitted as a white light pulse having a width (FIG. 5C). Hp
Infrared fluorescence from the living tissue D and the lesion C is emitted at approximately the same time as the laser light (FIG. 5 (d)). The photodetector gate is turned on at the time when the emission of the infrared fluorescent light ends, and turned off before the emission of the white light pulse (FIG. 5E).

The reason for providing this photodetector gate is as follows.
This is for appropriately detecting 27 μm light. That is,
The light near the wavelength of 1.27 μm includes, in addition to the relaxation light from singlet oxygen, strong infrared fluorescence from HpD or from the living body of a lesion as shown in FIG. This infrared fluorescence is generated at about the same time as the laser light, while the relaxation light from singlet oxygen is generated by following a complicated process as shown in FIG. (FIG. 5F). For details, see “Yusuke Kuroda: Basic Research on Laser Photochemotherapy.
[4] p. 27 (1986) ". Therefore, in order to accurately detect 1.27 μm light emitted from singlet oxygen, the photodetector 71 needs to detect 1.27 μm light from this singlet oxygen.
It is necessary to set the gate time to operate only when emitting m light.

FIG. 5 shows an example in which the photodetector gate is turned on 0.5 ms after the laser trigger and is maintained for 2 ms. However, the gate time is expected to slightly vary the emission start time of 1.27 μm light from singlet oxygen depending on the target lesion C. Therefore, it is desirable that the gate time can be variably adjusted depending on the target.

It is necessary that the gate ON time can be varied within a range where the white light pulse and the infrared fluorescent light emission time do not overlap. This is because if the emission time of the white light pulse overlaps, the infrared light from the lesion C due to this overlaps with the detection of 1.27 μm light from singlet oxygen. For this reason, 1.27 μm light from singlet oxygen is detected within the gate time.

This is an example of the laser light source 1 in FIG.
FIG. 6 shows an example of a pulse light source capable of switching between diagnostic and therapeutic use.

A laser beam having a wavelength of 1064 nm from an Nd-YAG laser generator 10 which is a solid-state laser generator is switched via a switching device 11 to a fundamental wave generator 12 and a second harmonic generation comprising a KDP crystal and the like. Apparatus 1
3. When the light enters the third harmonic generator 14 and has a wavelength of 10
Laser beams of 64 nm, 532 nm, and 355 nm are obtained, respectively. The laser light of 355 nm is further incident on the optical parametric oscillating unit 15 and has a wavelength of
A laser beam of 00 nm is obtained. The optical parametric oscillator 15 includes a collimator lens 15a and two mirrors 15a.
b, 15d, and a non-linear optical crystal 15c such as β-BaB ₂ O ₄ between them.
By rotating c to change the incident angle of the laser beam, a laser beam having the above-mentioned wavelength is obtained.

405 nm, 600-710 nm and 710
The laser light of ２０００2000 nm is separated by the filter 16. Then, the laser light, the fundamental wave, and the second harmonic are condensed by the condensing lens 17 and incident on the irradiation light guide 21. Of these laser beams, 405 nm or 5
Diagnosis laser light of 32 nm laser light, 600 to 200
A laser beam of 0 nm is used as a therapeutic laser beam.

The present invention is not limited to the above-described embodiment, but can be variously modified.

Generally, 1.27 μm is used as the photodetector 71.
A germanium detector with high sensitivity at m is used,
In some cases, a cooling medium to increase the S / N ratio,
For example, a germanium photodetector cooled with liquid nitrogen may be used.

As another method for monitoring the amount of singlet oxygen, a chemiluminescent reagent is absorbed in a lesion, and the detector 71 receives chemiluminescent light due to the reaction between the singlet oxygen and the chemiluminescent reagent. You may do it. At this time, the detector 71 may be sensitive to visible light in some cases.

Further, a diagnostic laser beam and a therapeutic laser beam may be simultaneously or temporally alternately applied to a lesion.

Further, FIG. 1 shows a method of displaying spectra obtained at the time of diagnosis and treatment on two monitors, respectively. The spectrum at the time of diagnosis and treatment is displayed on one monitor by signal processing by the analysis circuit 5. It is also possible.

The wavelengths of the diagnostic laser beam and the therapeutic laser beam are not limited to around 405 and 630 nm. The photosensitizer used is not limited to HpD, but may be DHE, PH-11.
26, NPe6, phthalocyanine, ALA, ATX-S
10, pheophorbide a or the like may be used.

[0046]

As described above, according to the present invention, the lesion is irradiated with the therapeutic laser beam while changing the wavelength within a predetermined range, and the photochemical reaction between the therapeutic laser beam and the photosensitizer is performed. By monitoring the amount of active oxygen generated by the reaction, the wavelength of the therapeutic laser beam can be set so that the amount of active oxygen generated increases. Generally, the greater the amount of active oxygen generated, the greater the effect of necrosis of the cells at the lesion.
That is, by setting the wavelength of the treatment laser light so that the amount of generation increases, the treatment can be performed more effectively.

This also means that the wavelength can be changed according to the type of photosensitizer and the like. Furthermore, it is possible to cope with a difference in the optimum wavelength of the treatment laser light due to a difference between individuals and a difference in a tissue and a position of a lesion.

Therefore, by selecting the most suitable treatment laser beam for the medicine to be used and the lesion to be treated, the treatment effect can be maximized and the treatment time can be shortened.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram of an embodiment of the present invention.

FIG. 2 is a schematic diagram of an endoscope diagnosis system and a photochemical reaction diagnosis / treatment system according to an embodiment of the present invention.

FIG. 3 is a diagram showing timing at the time of diagnosis according to the embodiment of the present invention.

FIG. 4 is a diagram showing generation and emission of singlet oxygen according to an example of the present invention.

FIG. 5 is a diagram showing timing at the time of treatment according to the embodiment of the present invention.

FIG. 6 is a schematic view of a laser light source according to an embodiment of the present invention.

FIG. 7 is a schematic diagram of a wavelength setting circuit according to an embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Laser light source, 2 ... Light guide, 3 ... Spectroscope, 4 ...
Amplification device, 5: analysis circuit, 6: display device, 7: detection device, 8: wavelength setting circuit, 9: timing control circuit.

Claims (4)

(57) [Claims] 1. A medical treatment for irradiating a diagnostic laser beam around a treatment site to determine a treatment site, irradiating the determined treatment region with a treatment laser beam, and necroticizing cells at the treatment site by a photochemical reaction. In the apparatus laser generator, the treatment laser light is output from a wavelength-variable laser generation means capable of changing a wavelength, and the amount of active oxygen generated at the treatment site generated by the treatment laser light is calculated as the treatment site. Medical equipment comprising: monitoring means for monitoring with light from the apparatus; and wavelength setting means for setting the wavelength of the therapeutic laser light to a wavelength at which the generation amount increases in accordance with information from the monitoring means. Laser generator. 2. The tunable laser generating means according to claim 1, wherein
A YAG laser generator, a second harmonic generator and a third harmonic generator for obtaining a second harmonic and a third harmonic from laser light generated by the Nd-YAG laser generator, A parametric oscillator having a non-linear optical crystal that obtains a different wavelength from the third harmonic, wherein the wavelength of the therapeutic laser light is a desired wavelength by changing an angle of the non-linear optical crystal by the wavelength setting means. The laser generator for a medical device according to claim 1, wherein the laser generator is set to: 3. The laser generator according to claim 1, wherein the monitor detects a specific wavelength emitted by the active oxygen. 4. The laser generator according to claim 1, wherein said monitor detects a specific wavelength of chemiluminescence generated by said active oxygen and a specific reagent.