RU2510248C2 - Method for removing cerebral tumours with fluorescence diagnostics detection of tumour in combination with coagulation and aspiration and device for implementing it - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. A device comprises a sapphire probe with longitudinal canals accommodating optical fibres; some of them are applicable for supplying a radiation exciting fluorescence and coagulating the radiation into tissue destruction from attached radiation sources; the others are applicable for supplying the fluorescence radiation onto a radiation detector. The sapphire probe also has an open aspiration canal connected to an aspirator by means of a hose. The relative position of the canals enables detecting fluorescence from an area matched with the tissue coagulation and aspiration area. A flat end of a point may be presented at a right angle to a probe axis and/or may have inclined refractive edges. The other open canal comprises metal contacts attached to an electrocoagulator. Implementing the method requires measuring fluorescence in a small neighbourhood of the sapphire probe. If certain threshold fluorescence has been exceeded, a laser coagulation and/or electric coagulation and aspiration of the coagulated and tumour tissue through the same sapphire probe is conducted.

EFFECT: group of inventions enables increasing an accuracy of tumour delimitation with using a fluorescent diagnostics, reducing a time required for the complete tumour removal and enables removing the difficult tumours.

8 cl, 8 dwg, 1 ex

Description

The claimed invention relates to medicine, namely to Oncology, and can be used to remove malignant tumors by laser coagulation and tissue aspiration with continuous fluorescence diagnosis of tumor borders.

The principle of fluorescence diagnostics is the ability of photosensitizers, selectively accumulating in malignant tissue, to emit fluorescence when irradiated with a laser of the appropriate wavelength. Spectrometric analysis of such fluorescence allows us to draw conclusions about the presence of cancer cells in the tissue.

The use of fluorescence diagnostics provides significant advantages in the removal of tumors located in the brain. This is due to the fact that damage to the blood-brain barrier in tumor cells allows the photosensitizer to penetrate into the tumor cells, while healthy cells do not accumulate it. This leads to a high contrast (up to 40: 1) fluorescence of the tumor tissue to the fluorescence observed in areas of healthy tissue. The use of fluorescence diagnostics for the removal of brain tumors allows to double the 6-month survival rate of patients.

A known method of removing brain tumors with the allocation of the boundaries of the tumor using fluorescence diagnostics. The method consists in the fact that to highlight the boundaries of the tumor, it is contrasted with a photosensitizer. The fluorescence of a photosensitizer (or substances secreted by cells in the presence of a photosensitizer), an excess concentration of which is created in tumor cells, is observed on a video monitor or in a fluorescent channel of a neurosurgical microscope when the surgical field is illuminated with radiation of a certain spectral range (Stummer W., Pichlmeier U. et al. ALA. Glioma Study Group, Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomized controlled multicentre phase III trial // Lancet Oncol. 2006. V.7, p. 392-401). According to the observed fluorescence pattern, the boundaries of the tumor are specified. Detected pathological tissue under visual control is removed by coagulation (for example, electrocoagulation) and aspiration with standard surgical instruments or non-contact evaporation (ablation) when exposed to high-energy laser radiation.

This method of removing brain tumors with the allocation of tumor boundaries using fluorescence diagnostics has the following disadvantages.

It has low accuracy, since the surgical field, which is not flat, is almost impossible to uniformly illuminate, which leads to different fluorescence intensities from areas with an equal concentration of photosensitizer. A significant drawback is the probability of transmission of tumor areas that do not fall into the direct field of view due to overhanging edges, which makes it impossible to use this method to remove deep-lying tumors through a small access channel. The disadvantage is the inability to quantify the level of fluorescence in the diagnosed areas, which reduces the accuracy of determining the boundaries of the tumor.

This method is carried out using a known device (M. Noguchi, E. Aoki, D. Yoshida, Etsuko Kobayashi, S. Omori, Y. Muragaki, H. Isski, K. Nakamura, and I. Sakuma "A Novel Robotic Laser Ablation System for Precision Neurosurgery with Intraoperative 5-ALA-lnduced PplX Fluorescence Detection ”/ R. Larsen, M. Nielsen, and J. Sporring (Eds.): MICCAI 2006, LNCS 4190, pp.543-550, 2006). The device includes a video camera with filters, with which images of the surgical field with fluorescent areas are obtained. A unit containing an additional measuring probe and a microlaser, which can be driven in a coordinated movement using the mechanism of the scanning system, is rigidly fixed to the video camera. A personal computer is used to process and store fluorescence images, as well as to control a unit containing a measuring probe and a microlaser.

This system has a number of significant drawbacks. Since diagnostics and laser ablation are performed by the nodes of the system at a certain distance from the tumor tissue, this excludes the possibility of fluorescence diagnosis and destruction of areas of the tumor that do not fall into the direct field of vision. It is also impossible to remove the tumor through the small access channels and the removal of interstitial tumor nodes. Due to the small depth of penetration of the laser radiation used for ablation and, accordingly, the small thickness of the removed tissue layer, as well as to reduce the likelihood of errors in diagnosis, a large number of cycles are required, including the mandatory layer-by-layer acquisition of fluorescence images and laser ablation, which greatly increases the time required to remove the entire tumor volume.

Closest to the proposed invention relating to a method for removing brain tumors by isolating tumor boundaries by fluorescence diagnostics is the method described in the publication (N. Haj-Hosseini, J. Richter, S. Andersson-Engels, and K. Wardell Optical Touch Pointer for Fluorescence Guided Glioblastoma Resection Using 5-Aminolevulinic Acid / Lasers in Surgery and Medicine 42: 9-14 (2010)). This method consists in selective excitation and quantitative measurement of fluorescence in the vicinity of the working end of the contact fiber optic probe and the subsequent removal of the diagnosed tumor tissue using standard surgical instruments. The advantage of this method is the high accuracy of distinguishing between tumor and healthy tissue at the border of the tumor due to quantitative measurements of fluorescence. The diagnostic depth has also been increased due to the possibility of taking fluorescence measurements with a probe immersed in tissue.

The disadvantage of this method is that the fluorescence diagnosis and removal of the diagnosed tumor tissue is carried out by different tools. Errors resulting from this lead to an increase in the probability of missing sections of the tumor and unreasonable removal of healthy tissue. For the same reason, using this method, it is impossible to perform operations to remove deep-lying tumors through a small access channel.

A known device related to systems for removing tumors with the allocation of tumor boundaries using fluorescence diagnostics and closest to the present invention is a system for resection of biological tissues with a sapphire blade with simultaneous fluorescence diagnostics of their malignancy (Pat. RF No. 2372873 C1, publ. 20.11. 2009). The device contains a sapphire blade-fiber with longitudinal channels in which optical fibers are placed, some of the fibers are designed to supply radiation that excites fluorescence to the tissue incision zone from the attached radiation sources, other fibers are used to transmit fluorescence radiation to the means that records this radiation. In addition, part of the fibers can be used to supply high-energy laser radiation, which is additionally concentrated by the light-conducting edge of the blade to coagulate tissues and blood vessels in the incision region to stop bleeding.

However, surgery of brain tumors (and other interstitial tumors) with this device has a limited scope, since the tumor tissue (including coagulated) is only cut off with a blade and an additional device is required to remove fragments of the tumor, coagulated tissue, blood, etc. from the operating area . Thus, there are significant drawbacks: simultaneous exposure to two devices is necessary, which complicates the work of the surgeon, limits the use of the device for deep-lying tumors, access to which is difficult, etc. At the same time, the structure of brain tissues (and other homogeneous tissues) allows removal of malignant tissue by local coagulation (by various physical methods) and aspiration of coagulated tissue. Thus, tissue dissection by the device is not required.

The present invention aims to achieve a technical result, which consists in increasing the accuracy of removal of brain tumors using fluorescence diagnostics, in reducing the time required for complete removal of the tumor, in the ability to remove hard-to-reach tumors.

The technical result indicated by the applicant is achieved due to the fact that the method of removing brain tumors by highlighting the boundaries of the tumor by fluorescence diagnostics with simultaneous coagulation and aspiration includes, if a threshold value measured in a small vicinity of the end of the sapphire probe exceeds a certain threshold value, local laser coagulation and / or electrocoagulation of this volume and aspiration of coagulated and tumor tissue through a sapphire probe.

The technical result indicated by the applicant is achieved due to the fact that the device for removing brain tumors with the allocation of tumor boundaries by fluorescence diagnostics with simultaneous coagulation and aspiration contains a sapphire probe with longitudinal channels in which optical fibers are placed. Some of the fibers are designed to supply radiation to the tissue to excite fluorescence and coagulation, while the other fibers are designed to transmit fluorescence radiation to a means that registers this radiation. The sapphire probe has open channels, one of which is connected to the aspirator via a hose, while the distal ends of the optical fibers are at a minimum distance from the end of the sapphire element, and their relative position provides the possibility of detecting fluorescence radiation from the area coinciding with the coagulation and aspiration of tissues. The end face of the sapphire probe can be made at right angles to the axis of the probe and / or have inclined refracting faces. In another open channel there are metal contacts attached to the electrocoagulator, or on the outer surface of the sapphire probe there are metal contacts attached to the electrocoagulator.

In addition, in the particular case of the invention, the sapphire probe, which provides the introduction of optical fibers from its side surface (for example, a groove is made on the side surface, opening channels for fibers and other instruments and not affecting the suction channel), has a lightweight probe assembly consisting in the introduction of fibers (as well as other elements) into the channels intended for them, as well as the replacement of fibers / tools directly during the operation without shutting down the aspirator.

In addition, in the particular case of the invention, the sapphire probe has a cylindrical shape with the axis of the suction channel coinciding with the axis of the sapphire probe; channels containing fibers intended for supplying fluorescence exciting radiation and channels containing fibers intended for transmitting fluorescence radiation, as well as channels containing fibers intended for supplying coagulating radiation, are arranged in a circle in the wall of the sapphire probe.

In addition, in the particular case of the invention, a conical narrowing is made on the outer surface of the sapphire probe, and the narrowing surface and the inner cylindrical surface of the suction channel form a circular knife.

In addition, in the particular case of the invention, a surface is coated on the surface of the sapphire probe in the distal part, absorbing and / or partially absorbing electromagnetic radiation coating (light filter).

In addition, in the particular case of the invention, a sterile sleeve is worn on the sapphire probe.

In addition, in the particular case of the invention, the means for detecting fluorescence radiation is configured to provide an audio signal when the fluorescence parameter exceeds a specified level, and / or there is at least one LED that can be placed in the channel of the sapphire probe, which turns on when the parameter is exceeded fluorescence of an established level.

The implementation of the invention

Figure 1 - a device for removing brain tumors with the allocation of the boundaries of the tumor by fluorescence diagnostics with simultaneous coagulation and aspiration;

Figure 2 - sapphire probe;

Figure 3 - options for the location of the channels in the sapphire probe;

Figure 4 - the distal end of the sapphire probe with refractive faces;

Figure 5 - the distal end of the sapphire probe having a narrowing and a circular "knife";

6 - the distal end of the sapphire probe with the electrode of the electrocoagulator in the channel;

7 - the distal end of the sapphire probe with a soldered electrode of the electrocoagulator;

Fig - fluorescence spectra obtained by the movement of the sapphire probe in the channel of access to the tumor.

A device for removing brain tumors with the allocation of tumor borders by fluorescence diagnostics with simultaneous coagulation and aspiration (Figure 1) contains a sapphire probe 1, a radiation source 2, for example a laser or LED radiation source connected to an optical fiber 4b, fluorescence recording means 5 connected to optical fiber 4a, an aspirator 3 connected to a hose 4c, a sterile sleeve 6.

A device for removing brain tumors by laser coagulation and aspiration with the allocation of the boundaries of the tumor probe fluorescence diagnostics works as follows.

To fluorescently contrast the tumor, a patient is injected with a fluorescent drug, for example, ALASENS based on 5-ALA (5-aminolevulinic acid) at a dosage of 20 mg / kg 4-6 hours before surgery. Due to the fact that the blood-brain barrier in the tumor cells is damaged, by the time the operation begins, a high concentration of protoporphyrin-IX, synthesized by 5-ALA, which has penetrated into the tumor cells, is created in the tumor cells.

At the stage of forming the channel of access to the tumor, removal of the tumor, and control after removal of the tumor, a spectrophotometric assessment of the concentration of protoporphyrin-IX in the brain tissue is performed using fluorescence radiation registration means 5 with delivery of exciting radiation and fluorescence radiation through optical fibers 4b and 4a, respectively, to the distal end of the sapphire probe 1. To quantify the concentration of protoporphyrin-IX using a calibration curve obtained using prepared samples in with a known concentration of fluorophore. During the operation, the fluorescence of healthy tissue is measured, and then the contrast of tissue fluorescence in the vicinity of the probe to the fluorescence of healthy tissues is monitored. When the contrast exceeds the established fluorescence level, the means 5 shows the excess on the computer screen either in the form of an audio signal, or by applying a light signal to the surgeon's field of vision, for example, by glowing LEDs in one of the channels of the sapphire probe.

The radiation from the laser source 2 with the help of fibers 4b is delivered to the distal end of the sapphire probe 1 and, leaving the probe, is absorbed into the tissue, which leads to its coagulation with sufficient radiation power. The radiation wavelength is chosen so as not to fall into the absorption bands of the diagnostic fluorescent drug to prevent burnout, as well as to have an optimal penetration depth and size of the laser coagulation zone for neurosurgery. An aspirator 3 with a hose 4 s attached to a sapphire probe removes brain tissue degradation products from the area diagnosed as tumor tissue.

Sapphire probe 1 has a channel for aspiration 7, open from the distal end, channels 10 for delivery of fibers of the diagnostic system and coagulating fibers 5 (Figure 2). The channels for optical fibers are impassable from the distal end and are “opened” by a groove 9, so that the suction channel is not affected, and the optical fibers 4a are introduced through the groove into the corresponding channels. The distal end of the suction hose 8 covers the sapphire probe behind the groove 9. The sterile sleeve 6, worn on the sapphire probe, isolates the fibers and the suction hose 4c from the sterile area. Thus, the fibers that are during the work of the destructor in the channels of the sapphire element do not require sterilization.

Figure 3 shows the options for the shape and placement of the suction channels 7 and channels for accommodating optical fibers 10 in the volume of the sapphire probe. To increase the cross-sectional area of the suction channel, its configuration may differ from cylindrical.

For the spatial combination of the diagnostic, coagulation and aspiration zones on the end of the sapphire probe opposite the channels, faces 11 can be made (Fig. 4), which refract the course of the optical rays.

In the particular case of the invention, the distal part of the sapphire probe is made in the form of an annular “knife” (Figure 5): at the distal end of the sapphire probe with the axial location of the suction channel, narrowing is made, so the inner cylindrical surface of the suction channel 14 and the conical surface of the narrowing form an annular wedge 12 In this configuration, the device works like a sapphire blade in a prototype device: a beam of light emerging from the optical fiber, passing the air-sapphire interface, falls on a plane STI annular wedge near its edge; Having undergone several complete internal reflections at the sapphire-biological tissue interface, the radiation partially leaves sapphire and, with each re-reflection, increases the fraction of energy leaving the probe. Thus, at the distal end of the sapphire probe, an annular zone 13 with a high radiation energy density is formed (Figure 5).

In some embodiments of the invention, the number of channels for the fibers 10 can be increased. So, for example, the number of fibers detecting fluorescence can be increased when performing fluorescence spectroscopy at several wavelengths and / or the number of emitting fibers can be increased to form the optimal shape of the laser diagnostic and coagulation zone. Some channels can also be made open from the distal end of the probe and used for biopsy, as well as for placement of the electrodes of coagulators 15 (Fig.6). Also, coagulation can be used contacts 16, deposited on the surface of the sapphire probe by spraying, welding, etc. (Fig.7).

The work of the invention is illustrated by the following example.

Patient V. (44) has a clinically defined focal lesion of the right parietal-temporal region with pyramidal insufficiency corresponding to the lesion. On CG and MRI of the brain with contrast enhancement, an intracerebral tumor of the right parietal-temporal region was revealed.

Based on the examination on the neuronavigation system, planning was performed and surgical treatment was performed. For intraoperative fluorescence diagnostics, the drug 5-ALA was used (Alasens 20 mg / kg 6 hours before surgery). Under the control of the navigation system, osteoplastic craniotomy and access planning were performed. As the access channel was formed and approached the tumor tissue, fluorescence analysis was continuously performed on the luminescence of induced protoporphyrin-IX using the invention. At the position of the distal end of the sapphire probe on the border of the tumor (according to CT, MRI), an increase in the fluorescence contrast in relation to healthy tissues was recorded up to 6–7 (Fig. 8) and when the instrument was in the center of the tumor up to 20 or more times, which allowed with high probability to testify to the correct implementation of access. Then, total removal of tumor tissue by traditional methods was performed.

After the operation, neurological symptoms did not increase. The patient is activated. Glioblastoma (G4) was histologically verified. After 2 weeks, radiation therapy was performed according to standard protocols.

The method of removing brain tumors with the allocation of tumor boundaries by fluorescence diagnostics with simultaneous laser coagulation and aspiration and a device for its implementation based on a sapphire probe allow us to differentiate the boundaries of the tumor process of brain tissue directly at the time of tumor removal at the tissue level.

The claimed invention can be implemented using known means and methods, which allows us to conclude that the invention meets the patentability criterion of "industrial applicability".

Claims (8)

1. A method for removing brain tumors with the allocation of tumor borders by fluorescence diagnostics with simultaneous coagulation and aspiration, including measuring fluorescence, coagulation and aspiration of tumor tissue, characterized in that when a certain threshold fluorescence threshold value is measured in a small neighborhood of the end of the sapphire probe, laser coagulation is performed and / or electrocoagulation of this tissue region and aspiration of coagulated and tumor tissue through the same sapphire probe. 2. A device for removing brain tumors with the allocation of tumor boundaries by fluorescence diagnostics with simultaneous coagulation and aspiration, containing a sapphire probe with longitudinal channels in which optical fibers are placed, one of the fibers is designed to supply fluorescence stimulating radiation and coagulating radiation to the tissue destruction zone from attached radiation sources, other fibers are designed to transmit fluorescence radiation to a means that registers this radiation, characterized in that the probe probe has open channels, one of which is connected to the aspirator via a hose, while the relative position of the suction channel and the channels into which the fibers are placed makes it possible to register fluorescence radiation from the zone coinciding with the coagulation and tissue aspiration zone in the region of the working end of the probe , the end of which can be made at right angles to the axis of the probe and / or have inclined refracting faces, in another open channel there are metal contacts attached to the electrocoagulum py, or on the outer surface of the sapphire probe has metal contacts attached to electrocautery. 3. The device according to claim 2, characterized in that the introduction of optical fibers from its side surface is provided in the sapphire probe. 4. The device according to claim 2, characterized in that the sapphire probe has a cylindrical shape with the axis of the suction channel coinciding with the axis of the sapphire probe; channels containing fibers intended for supplying fluorescence exciting radiation and channels containing fibers intended for transmitting fluorescence radiation, as well as channels containing fibers intended for supplying coagulating radiation, are arranged in a circle in the wall of the sapphire probe. 5. The device according to claim 2, characterized in that the conical narrowing is made on the outer surface of the sapphire probe and the narrowing surface and the inner cylindrical surface of the suction channel form a circular knife. 6. The device according to claim 2, characterized in that on the surface of the sapphire probe in the distal part is coated, absorbing and / or partially absorbing electromagnetic radiation coating (light filter). 7. The device according to claim 2, characterized in that the sapphire probe wears a sterile sleeve. 8. The device according to claim 2, characterized in that the means for detecting fluorescence radiation is configured to provide an audio signal when the fluorescence parameter exceeds a specified level and / or there is at least one LED that can be placed in the channel of the sapphire probe turning on when the fluorescence parameter exceeds the set level.

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