WO2007113866A1

WO2007113866A1 - Device and method for the thermal ablation of tumors by means of high-frequency electromagnetic energy

Info

Publication number: WO2007113866A1
Application number: PCT/IT2006/000210
Authority: WO
Inventors: Giberto Garbagnati
Original assignee: Breval S.R.L.
Priority date: 2006-03-31
Filing date: 2006-03-31
Publication date: 2007-10-11

Abstract

A device for the thermal ablation (TA) of tumors by means of electromagnetic energy at high frequency comprising a thin hollow element (1), one or more electrodes (1, 8) connected to an electromagnetic energy generator at high frequency, e.g. radiofrequencies or microwaves, said element (1) being suitable for injecting a substance (4) into a tumoral mass, through one or more openings (3) provided in proximity of the tip (2) of the same hollow element (1). The substance (4) is biocompatible, dehydrates or boils at higher temperatures than the boiling temperature of the tissue liquids, has a higher viscosity than that of the blood and has an electrical conductivity comprised between one tenth and one hundred times that of the tissue liquids. The invention also relates to a method using the above-mentioned device for the thermal ablation.

Description

DEVICE AND METHOD FOR THE THERMAL ABLATION OF TUMORS BY MEANS OF HIGH-FREQUENCY ELECTROMAGNETIC ENERGY

The present invention relates to a device and a method for the treatment of tumors by means of thermal ablation (TA) induced by electromagnetic energy, for instance in the radiofrequencies (RF) or in the microwaves (MW) range, and in particular to a device and a method for the TA which allow to obtain large-volume thermal lesions having a controlled shape by using a substance capable of keeping ' constant the hydration conditions of the tissues and/or keeping a low coupling impedance between the active part of the electrode and the surrounding tissues even at high temperatures.

It is known that the procedure of TA induced by electromagnetic energy essentially consists of inserting in a tumoral mass an electrode that, being supplied with electromagnetic energy at a suitable frequency, leads to the generation of heat in the tumoral tissues surrounding the electrode, thus determining their coagulative necrosis. The electrode, being generally placed at the end of a needle or a catheter, is percutaneously inserted in the mass of the tumor and guided by means of echography or another known visualization technique. This procedure has proved to be effective for the ablation of tumors of the liver and has recently been suggested for the ablation of tumors of lung, kidney and other parenchymal organs. One of the major problems of this kind of procedure resides in the difficulty of destroying tumoral masses having a diameter that is larger than 3 cm. The main reason is that the energy delivered through the electrode inserted in the tumoral mass cannot be indefinitely increased. In fact, if on one hand the delivery of high power allows to increase the size of the thermal lesion, on the other hand it causes a rapid dehydration of the tissue being closest to the electrode. This causes a rapid increase in the electrical impedance, resulting in the impossibility of delivering further energy to said surrounding tissue.

Devices and methods are already known in order to delay the dehydration of the tissues adjacent to the electrode. For instance, in patent US 6.210.411 a device is disclosed being provided with an electrode which is partially permeable to liquids, through which water or another saline solution is injected into the tissues surrounding the same electrode. The end of the electrode is made of a porous sintered material that allows to uniformly inject the liquid into the tissues in order to prevent their dehydration in the proximity of the same electrode. However, this device exhibits the drawback of not allowing to control the real distribution of the injected liquid through the tissues and, in addition, requires the continuous liquid injection for the whole duration of the treatment.

Devices and methods are also known in order to increase the volume of the thermal lesion in the tumoral mass, consisting of the infusion of a conductive liquid therein, which transmits energy around due to its electrical conductivity. Patent US 6.911.019 discloses a catheter being provided with an helicoidal needle which is inserted into the tumoral mass in order to create an helicoidal cavity that is infused with a conductive liquid. The object is to create a channel with a prescribed shape in order to control the size of the thermal lesion. However, this method has the drawback of generating a thermal lesion having an irregular shape and a size being difficult to predict due to the uncontrollable distribution of the conductive liquid through the tissues.

In patent application US 20040006336 a device is disclosed showing a hollow electrode that allows to improve the infusion of the conductive liquid into the tissue. Also this device exhibits the drawback of not allowing the control of the distribution of the conductive liquid through the tissues, that is the size of the zone being subject to the TA.

In patent application WO 9428809 a device is disclosed being provided with one electrode that is cooled by means of a cooling system based on the circulation of a fluid. The cooled electrode delays the dehydration of the tissues surrounding it being caused by the high temperatures, thus allowing to generate thermal lesions having a larger volume with respect to those obtainable without cooling. However, even in a longer time, the dehydration of the tissues anyway occurs with such a device, but only thermal lesions having a limited volume can be achieved due to interruption of the energy delivery caused by the sudden increase of the impedance.

Object of the present invention is thus to provide a device and a method for the TA being free from the above-mentioned drawbacks, being suitable for increasing the volume of the thermal lesion to the utmost and for giving it a controllable shape, preferably as round as possible. Such an object is achieved with the device for the TA according to the present invention, whose characteristics are specified in claim 1. Further characteristics of such a device are specified in the dependent claims, hi the subsequent claims the characteristics of the method for the TA according to the present invention are specified. According to the present invention, the temperature being needed in order to dehydrate the tissues surrounding the active portion of the electrode and/or in order to increase the coupling impedance between the same tissues and the active portion of the electrode is much higher with respect to the known devices and therefore it is possible to deliver an adequate power level to the tumoral tissue wherein the electrode is inserted for a much longer time, without reaching the limit due to the dehydration of the tissues surrounding the electrode. Delivering high powers for a longer time allows to obtain the coagulative necrosis in regions being farther from the electrode and thereby thermal lesions having a much larger volume.

One advantage provided by the device and the method for the TA according to the present invention is that the injected substance allows to keep hydrated the region surrounding the electrode, even at very high temperatures.

Another advantage of the device and the method for the TA according to the present invention is that the impedance of the tissues being subject to the generated electric field is kept at suitably low values in a constant and controllable way. A further advantage of the device and the method for the TA according to the present invention is that they allow to predict the volume of the thermal lesion by establishing a suitable time-profile of the power delivery, due to the fact that the impedance is constantly kept at low values and the tissues are constantly kept hydrated.

This and other advantages of the device for the TA according to the present invention will be evident to those skilled in the art from the following detailed description of some embodiments thereof with reference to the annexed drawings wherein:

Figure 1 shows a detailed sectional view of the end of the device for the TA according to one embodiment; Figure 2 shows an example of a thermogravimetric curve of a hydrogel;

Figure 3 shows a detailed sectional view of the end of the device for the TA according to another embodiment;

Figure 4 shows a detailed sectional view of the end of the device for the TA according to still another embodiment;

Figure 5 shows a detailed sectional view of the end of the device for the TA according to a further embodiment; and

Figure 6 shows a detailed sectional view of the end of the device for the TA according to still a further embodiment.

Fig. 1 shows that the device for the TA according to the present invention is made of a thin hollow element 1 provided with a closed tip 2 and with one or more openings 3 circumferentially arranged in proximity of said tip 2. The diameter of the hollow element 1 is preferably comprised between about 0,9 mm and about 5 mm, on the basis of the type of operation and of the size of the zone to be treated. Once the hollow element 1 has been inserted into the mass of the tumor, an injection system injects a substance 4 through the one or more openings 3 of the hollow element 1 into the surrounding tissues. As the tip 2 of the hollow element 1 is closed, the substance 4 radially outflows from the openings 3 formed thereon, thus spreading in a substantially spherical zone in the tissues adjacent to the element 1. In this particular embodiment, the hollow element 1 is made of a conductive material and connected to a radiofrequency energy generator; thus the hollow element 1 forms the active electrode of the TA device.

The conductive exposed portion of the element 1 is preferably comprised between about 1 mm and about 100 mm, on the basis of the type and size of the thermal lesion desired to be produced. The portion of the element 1 being not exposed can be covered by an insulating material, such as for example an insulating paint or an insulating sheath 5. For instance, by using an insulating sheath 5 it is possible to remove a portion thereof, having the desired dimensions, at the beginning of the operation procedure in order to adjust the size of the conductive exposed portion of the element 1 and thereby the energy being delivered.

Then the radiofrequency energy generator supplies the device, thus causing ionic turbulence in the zone surrounding the element 1 and thereby generating resistive heat.

All tissues being comprised between the electrode and the 60°C isotherm undergo to a non-reversible coagulative necrosis. Non-reversible damages are associated to temperatures comprised between 46°C and 60⁰C, whose entity is proportional to the time of exposure.

The substance 4 must be biocompatible and capable of maintaining even at high temperatures a low coupling impedance between the active portion of the element 1 and the surrounding tissues and/or keeping the hydration conditions of the tissues even at temperatures being higher than the boiling temperature of the tissue liquids. In this way a continuous energy delivery is granted from the device to the surrounding tissues. In fact, due to the presence of the substance .4, the dehydration of the tissues does not occur, which would lead to a sudden increase of the impedance preventing any further delivery of energy. In addition, the substance 4 must have a high viscosity, that is at least higher than that of the blood, in order to remain enclosed in a limited region close to the active portion of the element 1 when it is injected in the area to be subject to the TA. Thanks to its viscosity, the substance 4 being injected into the tumor occupies a zone having shape and volume easily predictable and controllable, which allow to generate thermal lesions being predictable and controllable as well. Finally, especially in radiofrequency applications it is necessary that the substance 4 is also electrically conductive. Suitable conductivity values of the substance 4 are comprised between one tenth and one hundred times the electrical conductivity of the tissues liquids. The substance 4 can be, for example, a ionic aqueous solution having a boiling temperature much higher than that of the tissue liquids, and having viscosity and conductivity as described above. The properties of this viscous solution can be adjusted according to the type of the solute and to its the concentration. Alternatively, the substance 4 can also be a suspension having viscosity and conductivity as described above, with size of the suspended particles being comprised between about 1 and about 1000 μm.

In a preferred embodiment, the substance 4 is a hydrogel having such water complexation features that its dehydration occurs only at temperatures being higher than the boiling temperature of the tissue liquids, e.g. higher than 18O⁰C. Many articles have been published on the features of such a kind of substance 4, as for instance the article "Thermodynamic Study of Bone Composites", DV Rai and R. Singh, Trends Biomater. Artif. Organs, VoI 19(1), pp 33-38 (2005).

In Fig. 2 there is shown an example of a thermogravimetric curve related to a generic hydrogel. It is noted that in order to dehydrate a hydrogel it is necessary to bring the free water contained therein to boiling, release the water adsorbed therein and break the bonds of the water being chemically bonded. In order to dehydrate a hydrogel is thus necessary to provide large amounts of energy, in order to keep low the impedance of the hydrogel-tissues ensemble even at high temperatures for the whole duration of the procedure. Ionic substances can be dissolved in the gel in case, in order to improve its electric conductivity. A substance 4 being particularly suitable due to its characteristics of electrical conductivity, viscosity and hydration of the region to be subject to the TA is the gel obtained with the haemostatic absorbable powder. This substance is available in trade with the name Spongostan^®, by Ferrosan A/S (Denmark). Other substances being particularly suitable are the biological gels such as, for example, the ialuronic acid. It is also possible the use of a mixture of one or- more substances among the above- mentioned ones.

Still referring to Figure 1, it is noted that the opening 3 have such dimensions to allow an easy outflow of the substance 4, which has a high viscosity, to be injected in the region surrounding the active portion of the element 1. In order to grant an easy injection of substances 4 having a viscosity being higher than that of the blood, openings having a minimum width of about 0,2 mm are needed. The presence of a plurality of openings 3 being circumferentially arranged in proximity of the tip 2 of the element 1 allows to distribute the injected substance uniformly in more directions, thus allowing to generate thermal lesions having a spherical shape resembling as much as possible the shape and size of the mass of the tumor being treated.

In the known TA procedures, the impedance of the tissues surrounding the element 1 initially decreases in time starting from an initial value (initial impedance) till a minimum value (minimum impedance) at which the largest amount of energy is delivered. This minimum value is nearly constant in time until the tissue liquids come to boiling, which then lasts until the complete dehydration of the tissues being followed by a sudden increase in the impedance and by the impossibility of delivering further energy to the tissue. On the contrary, the use of the device and the method according to the present invention allows to continue to deliver energy even at temperatures being close to or higher than the normal boiling temperature of the tissue liquids, as the substance 4 allows to avoid the dehydration around the active portion of the element 1, thus granting a continuous energy delivery therefrom to the tissues to be subject to the TA.

Thanks to the device and the method according to the present invention, it is possible to deliver to the tissues energy amounts being much larger than those allowed with the known devices and methods. For example, in the case of the described devices for the TA with RF, the injection of a substance 4 capable of steadily and constantly keeping the impedance at low values, e.g. lower than 50 Ohm, always leads to an extension of the duration of the procedure for any power level and any area of the active surface of the element 1, as well as to a consequent increase in the volume of the obtained thermal lesion.

In Fig. 3 there is shown an alternative embodiment of the TA device with RF according to the present invention, wherein the hollow element 1, which is also the electrode, is cooled by means of a cooling system 6 based for instance on the circulation of a cooling fluid 7. The circulation can, for example, take place within a stylet, containing a cooling circuit, inserted into the element 1 once the substance 4 has been injected in the zone to be subject to the TA. In Fig. 4 there is shown another embodiment of the device for TA with RF according to the present invention being provided with at least two symmetrical openings 3 in proximity of the tip 2 of the hollow element 1. The openings 3 have such a size to allow the injection of very viscous substances and to allow the use of one or more filiform electrodes 8 being extractable therefrom. The extractable filiform electrodes 8 enter the tissues surrounding the element 1 and are inserted in more directions thus delivering energy in more points in the tumoral mass. The extractable filiform electrodes 8 may be linear or may have other shapes suitable for further enlarging the energy delivery zone, as for example spiral shapes.

In Fig. 5 there is shown a further embodiment of a device for the TA with RF being of a bipolar type. The end of the hollow element 1 is divided into an upper zone 9 and a lower zone 10 by interposing a ring 11 being made of an insulating material and having diameter and thickness equal to the element 1. The two upper 9 and lower 10 zones are connected to the two poles of the circuit, thus forming the active electrode and the counter electrode, respectively. During a TA procedure, the substance 4 is injected through the openings 3 of the hollow element 1 as previously described. When switching on the radiofrequency energy generator, field lines are generated going from one electrode to the other one and crossing the substance 4, and causing, as in the previous cases, ionic turbulence and consequent resistive heat.

In Fig. 6 there is shown an embodiment of the device for the TA according to the present invention being of a microwaves type, wherein, similarly to the previous embodiments, the hollow element 1 is provided with a closed tip 2 and with openings 3 being circumferentially arranged in proximity of the tip 2 for the injection of the substance 4. Inside the hollow element 1 a coaxial cable 12 is arranged delivering electromagnetic energy in the microwaves range. In this case the hollow element 1 is made of materials being transparent to the microwaves in order not to interfere with propagation thereof through the tissues.

By means of the above-described devices it is possible to perform the method for the TA according to the present invention comprising the steps of: a. inserting into a tumoral mass a device being provided with one hollow element 1; b. injecting a biocompatible substance 4 through one or more openings 3 of the hollow element 1; and c. delivering high frequency electromagnetic energy to the tumoral mass till the coagulative necrosis of the tissues.

In the method according to the present invention, the substance 4 to be injected into the tumoral mass is biocompatible, dehydrates or boils at temperatures being higher than the boiling temperature of the tissue liquids, has a viscosity being higher than that of the blood and has an electrical conductivity being comprised between one tenth and one hundred times the electrical conductivity of the tissue liquids.

Claims

1. A device for the TA comprising a thin hollow element (1), one or more electrodes (1, 8) connected to a generator of high frequency electromagnetic energy, said hollow element (1) being suitable for injecting a substance (4) into a tumoral mass, characterized in that said substance (4) is biocompatible, dehydrates or boils at higher temperatures than the boiling temperature of the tissue liquids, has a higher viscosity than that of blood and has an electrical conductivity comprised between one tenth and one hundred times that of the tissue liquids.

2. A device for the TA according to claim 1, characterized in that the substance

(4) is a gel.

3. A device for the TA according to claim 2, characterized in that the substance (4) is a hydrogel.

4. A device for the TA according to claim 3, characterized in that the substance (4) is a thixotropic hydrogel.

5. A device for the TA according to claim 1, characterized in that the substance (4) is an aqueous ionic solution.

6. A device for the TA according to claim 1, characterized in that the substance (4) is a suspension having a suspended particles size being comprised between about 1 μm and about 1000 μm.

7. A device for the TA according to claim 1, characterized in that the substance (4) is a mixture of the substances (4) according to claims 2, 3, 4, 5 and/or 6.

8. A device for the TA according to claim 1, characterized in that the tip (2) of the hollow element (1) is closed.

9. A device for the TA according to claim 1, characterized in that one or more openings (3) are provided on the hollow element (1), being circumferentially arranged in proximity of its tip (2).

10. A device for the TA according to claim 1, characterized in that the hollow element (1) is the active electrode.

11. A device for the TA according to claim 1, characterized by being provided with a cooling system (6) wherein a cooling fluid (7) circulates.

12. A device for the TA according to claim 1, characterized in that the element (1) is provided with one or more filiform electrodes (8) and the openings (3) are suitable for allowing the extraction of said filiform electrodes (8).

13. A device for the TA according to claim 1, characterized by being bipolar and in that the end of the hollow element (1) is divided into an upper zone (9) and a lower zone (10) by interposing a ring (11) being made of an insulating material and having diameter and thickness equal to the hollow element (1), said zones being respectively connected to the two poles of the circuit, thus forming the two electrodes.

14. A device for the TA according to claim 1, characterized by comprising a coaxial cable (12) for microwaves, being inserted into the hollow element (1).

15. Method for the TA comprising the steps of: a. inserting a device being provided with a hollow element (1) into a tumoral mass to be subject to TA; b. injecting a biocompatible substance (4) through one or more openings (3) of the hollow element (1); and c. delivering high frequency electromagnetic energy to the tumoral mass till the coagulative necrosis of the tissues; characterized in that said substance (4) is biocompatible, dehydrates or boils at higher temperatures than the boiling temperature of the tissue liquids, has a higher viscosity than that of the blood and has an electrical conductivity comprised between one tenth and one hundred times that of the tissue liquids.

16. Method for the TA according to claim 15, characterized in that the substance (4) is a substance according to any claim from 2 to 7.

17. Method for the TA according to claim 15, characterized in that the device inserted into the tumoral mass is the device for the TA of claim 1, 8, 9, 10, 11, 12, 13 and/or 14.