Patent Application
20180132932
The present invention relates to devices and methods for heat treatment of tissue of the living human or animal body. With certain kinds of conditions caused by diseases involving unnatural growths in tissues, treatment with heat gives a good result after treatment. The tissue is heated to the degree that it dies. Examples of disease conditions of this kind are certain types of cancer and benign prostate hyperplasia, BPH. With treatment certain parts of the tissue are heated so that death of the tissue occurs, while other parts of the tissue must or should be protected. The conditions of disease which are primarily focused on here are those which occur in tissue surrounding cavities in the body. As examples, in addition to those mentioned above, cancer of the esophagus, trachea, urethra, and intestine can also be mentioned.
Corresponding conditions of disease can also occur in animals, where similar treatment can be applied. Among these, treatment of domestic animals such as for example dogs, probably would be of most interest,
In order to produce heat, different devices can be employed. Laser, microwave, and radio frequency antennas are usually used. A method using the insertion of a container with liquid into the bodily cavity is also known. The liquid expands the container so that good contact against the surrounding tissue is achieved. The liquid is then heated either by supplying warm liquid through a circulating system or by supplying energy to a heating device within the container from which heat is transferred in some way to the liquid and then to the tissue.
Since the volume of the tissue which will be treated varies as well as the ability to absorb heat in this tissue and adjacent tissue, which will not be treated, it is appropriate that continuous monitoring occur during treatment. When treatment is in progress, the heating of tissue occurs. The heating should occur within certain temperature ranges for the best result of the treatment. At too high a temperature unnecessarily great damage occurs in the tissue and at too low a temperature the desired result of treatment does not occur.
It is common that the device for heating incorporates some form of temperature sensor that is arrayed on the element inducing heating in order to monitor the temperature in adjacent tissue. A disadvantage of this design is that the temperature sensor gives information more on the temperature of the element than on the temperature of the tissue.
An example of this type of heating device is shown and described in EPO 370 890. The device encompasses a catheter contained in a microwave antenna that is embodied to emit radio energy to the tissue surrounding the antenna. The catheter is also provided with a cooling channel for cooling the tissue that is located closest to the catheter. In the catheter a temperature transducer is located for reading the temperature of the catheter. The detected temperature is thus not in agreement with the temperature of the tissue that is being treated.
A more developed method of temperature detection is shown and described in PCT/SE96/00649. In order to be able to register the rise of temperature directly in the tissue to be treated, a first temperature detection instrument according to PCT/SE96/00649 is connected with a first temperature transducer carrier. The carrier is led through a channel in the catheter and is devised to be extendable through an opening in the catheter. In the opening of the catheter a mechanical guide for the carrier is appropriately aligned in such a manner that the carrier is directed into the tissue at a desired angle in relation to the longitudinal axis of the catheter. The carrier carries three spaced apart temperature transducers. The treatment carried out with the above-mentioned microwave device is often called TUMT (Trans Urethral Microwave Thermotherapy).
Either the carrier or the temperature detection instrument is equipped with a tip that facilitates penetration into the tissue. The temperature detection instrument can be conventionally embodied as a resistive transducer or a semiconductor. The cabling required for transducers of this type is done via channels in the catheter. If a transducer of the optical type is used, a fiber-optic guide is provided through a channel in the catheter.
According to the devices described above and according to other known techniques, the attending physician normally determines the duration and temperature of treatment. In spite of the possibility to conduct continuous temperature detection, there could be problems relating to the positioning of the temperature transducer carrier, and thus of the temperature transducers themselves.
An object of the invention is to provide a device for supply of heat to body tissue, whereby the disadvantages mentioned above are essentially eliminated. This object is achieved according to the invention by the features indicated in the patent claims 1 through 10.
According to the invention there is also the possibility of adjusting the supply of heat beforehand in different ways and to predict the result better. A device according to the invention is used in order to calculate the temperature distribution in the whole prostate based on temperature information from certain intra-prostatic measurement points and based on information on the distribution of energy absorption in the body tissue concerned, when subjected to an energy or heat source. The temperature distribution is determined on the basis of the relation between the temperature in the tissue and absorbed energy, tissue blood flow, i.e. perfusion, and heat conduction. Through continuous measurement of the temperature and the time during which heat is applied, and with continuous monitoring of the temperature distribution in relation to theoretical and/or experimental information on the survival of cells undergoing thermal exposure, the amount of tissue destroyed at certain points in time during the exposure is determined.
In a preferred embodiment the temperature distribution as well as the amount of destructed tissue is continuously presented graphically and/or with the aid of text on a display, so that the attending physician can constantly be informed on current conditions. Heat is supplied to the tissue until a portion of the tissue has been destroyed. The size of the portion can be adjusted. Further advantages and special features of the invention can be seen by the following description, drawings, and dependent patent claims.
The invention will now be described in more detail with the aid of examples of embodiments with reference to the attached drawings, illustrating embodiments and together with the description, serve to explain the principles of the methods and systems. In the drawings
A catheter 10 for the treatment of benign prostate hyperplasia (BPH) is inserted into the urethra according to
In order to be able to follow the temperature development in the tissue during heat treatment a first temperature transducer 20 is located on a carrier 22 also known as a probe 22. Carrier 22 is designed to be advanced through a channel or conduit 24 (c.f.
The carrier 22 of the catheter 10 for treatment can also be provided with a second temperature transducer 30, arranged a first distance from the tip of the carrier. The first distance is chosen such that when the carrier is advanced to the satisfaction of the treating physician, the second temperature transducer becomes located just outside the catheter. Information on the temperature close to catheter 10 for treatment is thus obtained from the second temperature transducer 30. In the embodiment shown in
A liquid channel 28 is also incorporated in the catheter for treatment. It opens into balloon 16 and through it liquid can be directed for expansion of balloon 16 when the catheter for treatment is in place. Liquid channel 28 is also used to empty balloon 16 at the conclusion of treatment and before the catheter for treatment is withdrawn from the urethra. A conventional syringe or similar is preferably used for insertion of liquid and for emptying balloon 16.
A feed cable 32, by means of which heating means 26 is supplied with energy, is also, as a side effect, warmed as a result of energy loss within the feed cable. In order to avoid injury of tissue beyond the area of treatment, for example, on the sphincter that surrounds the urethra outside the prostate, feed cable 32 is cooled. This is done by providing cooling channels (not shown) in catheter for treatment 10, preferably around feed cable 32. In an embodiment according to the invention the cooling channels have a limiting wall at which the cooling liquid circulating in the cooling channels returns. In this manner cooling of heating means 26 itself is avoided, which in turn means that the power, which needs to be supplied from an energy supply unit 27, can be less. With lower levels of power the risk of injury to healthy tissue is reduced.
At high temperatures in the range of 90-150° C. the tissue also hardens and forms a crust. The crust can prevent or lessen problems that can occur if the prostate gland swells in connection with the treatment. During treatment a high temperature is reached in tissue closest to catheter 10 and the portion of the urethra that passes through the prostate at the area of treatment will be affected to a high degree and injured. This portion of the urethra, however, restores itself relatively quickly.
In a preferred embodiment heating means 26 comprises a microwave antenna. Since the urethra is completely filled by catheter 10 in the area of treatment and no free space remains, the fit of the microwave antenna against the tissue will also be very good. The adjustment of impedance between the antenna and the tissue is very good, which simplifies dimensioning of the antenna and energy supply unit and facilitates the setting of microwave power.
When treatment is finished, the energy supply to heating means 26 is terminated. It is not suitable to remove the catheter for treatment as long as any part of the catheter has a temperature such that injuries could occur with the passage of the catheter through the body. Cooling water supply is maintained and when it is judged that catheter can be removed without risk, the carrier or probe 22 is first retracted into catheter, and then catheter may be removed from patient.
In cases of treatment involving the prostate or urine bladder, whereby catheter 10 having a rounded tip is introduced into urine bladder 14, drainage of urine and possibly of other liquid from the urine bladder can occur through a drainage channel 36 provided in catheter 10. The drainage channel runs through the full length of catheter 10 and ends with opening 38 near the tip of catheter 10. With certain types of treatment, it can be suitable to leave catheter 10 in place for a certain time after treatment. It is the function of the drainage channel to drain the urine bladder even during this time.
Rotational orientation of the catheter 10 is important for extending and positioning the carrier 22 in a favorable direction. An orientation meter 23 is arranged on the catheter 10 for obtaining information about the present orientation of the catheter. Suitably there is provided a visual marking on the outer surface of the catheter and extending in the longitudinal direction of the catheter to show to the treating physician in what direction the carrier or probe 22 will be deployed. Together with the torsional rigidity of the catheter the marking will provide information to physician. However, since effect of torsional rigidity depends on catheter material and length of catheter there could be differences between estimated and actual position of probe 22. An improvement in this regard is the provision of the orientation meter 23, which preferably senses the orientation of the catheter relative to an absolute reference such as the gravitational force. The orientation meter 23 may be embodied as a 3-axis accelerometer and/or a 3-axis gyroscope. Preferably the orientation meter is connected to an indicator or display using thin wires extending through the catheter. The orientation meter is arranged with its reference direction being zero or a known offset value relative to opening in catheter for probe or carrier 22.
The treated and dead tissue is reabsorbed or rejected and eliminated with urine. A cavity in the prostate caused by the removal of tissue ensures the unconstructed correct passage of urine. The cavity at first has a shape that corresponds to the volume heated the most during treatment.
As shown in
One difficulty that may arise is that both angle a (approximately 30 degrees) and c (approximately 180 degrees) of probe or carrier 22 as shown in 4a. The reason for this is the anatomical conditions in the area. The curvature of urethra gives rise to this effect. The urethra curves with a concave shape towards the front/abdominal side of the body, and convex shape towards the back side of the body. Because the urethra curves towards abdominal side or “upwards” as closer to the bladder it gets, the tip of the temperature probe 22 will reach at an approximately 3 o'clock position, seen from a plane closest to the balloon. The temperature probe is normally deployed from the catheter approximately 30 mm behind the balloon. In the case that the temperature probe 22 exits at 12 o'clock the curvature of the urethra will cause the tip 20 to end up close to the urethra and cause the temperature curves of T, M, and B to be approximately the same. If, on the other hand, the temperature probe 22 instead exits at approximately 6 o'clock (angle “a”), the tip of temperature probe 22 would end up a much longer distance from the urethra, even outside the reach of the microwaves, which will result in temperature curve from tip (T) temperature transducer 20 being the lowest i.e. the coldest. See
Such angles as “a” and “c” therefore should, if possible, be avoided. Temperature curves of
Note that the angle b in the transversal plane as defined above is not to be confused with an angle α (alfa) between the longitudinal direction of the catheter and the portion of the carrier 22 or probe 22 extending outside the catheter 10. The opening for the probe 22 guides the probe in a fixed direction producing an angle alfa of preferable around 45 degrees.
The cross sectional view of
Conduit 24 extends through a third cavity formed between two wings 44 and the outer wall 46. A section of the carrier 22 with second temperature transducer 30 extends out through an opening in the outer wall 46 of catheter 10. Opening in the outer wall may initially be covered with penetrable membrane as disclosed above. In various embodiments different combinations of drainage channel 36, liquid channel 28 and conduit 24 are arranged in other cavities.
When heating means 26 is activated and produces heat to surrounding tissues the temperature will increase. A correct positioning and orientation of catheter 10, carrier 22 supporting said first temperature transducer 20, said second temperature transducer 30 and said third temperature transducer 34 will produce a desired increase of temperature in the surrounding tissue. In
However, should catheter 10 be rotated in either direction from a correct orientation “b” as indicated in
Different conditions such as supply of blood in different parts of the tissue will have an impact on the temperature development. However, should the temperature after a treatment period of tT deviate more than within an allowed interval, an indication of error or possible error is given.
The diagram of
The block diagram in
Said first temperature transducer 20, said second temperature transducer 30 and said third temperature transducer 34 all supported by the carrier 22 are operatively connected to a transducer interface 50. Temperature data from said temperature transducers are received in said transducer interface 50. Calculations, comparisons and control steps can be performed in said control unit 42 or said transducer interface 50 that is operatively connected thereto. A memory or memory unit 52 is operatively connected to the transducer interface 50, said input/output means 45 and said energy supply unit 27 to hold and store data relating to temperature, treatment process and physiological conditions. In various embodiments the orientation meter 23 is connected to the transducer interface to relay information regarding rotational angle of the catheter 10 to the display unit 48. The information on such rotational angle may also be transferred to the control unit 42 for use as a further basis for calculation of control signals to energy supply unit 27.
For treatment with TUMT and similar methods of treatment the temperature of the tissue is determined to the greatest degree by three different processes: i) generation of heat by absorption of microwave energy or another source of radiated energy, ii) heat distribution as a result of heat conduction in the tissue, and iii) heat loss as a result of the flow of blood (tissue perfusion). Parameter i) is determined by the current catheter for treatment being used, can be calculated, while iii) is dependent on the patient and is unknown. The relationship is given by a known equation for bio-heat:
The metabolic term Qm can be ignored in the context of heat treatment. The thermal characteristics of the prostate tissue have been calculated from its water content, which is assumed to be 80%. The equation or corresponding data can be stored in memory unit 52, so that it can be solved continuously during the application of heat.
Since it can be assumed that microwave absorption is symmetrical in the radial orientation, cylindrical geometry was used for the numerical solution of equation 1. The finite differential technique was used for the solution. The microwave absorption term Qs in equation 1 was determined by the specific absorption rate (SAR, W/kg) in a certain catheter for treatment 10. A practical way to determine the specific rate of absorption is to place a TUMT catheter in a tissue-like body, for example made of the material known as TX150, and measure the temperature distribution in the body after heating with a microwave output of 50 W for 60 seconds. One way to measure the specific absorption rate SAR is described in detail in the British Journal of Urology 78 (1996), pages 564-572.
In memory unit 52 known data as to the survival of cells at different cell temperatures during different durations of treatment are stored, for example in the form of suitable equations, data tables, or similar. Memory unit 52 is suitably configured so that stored data is complemented and, if necessary, corrected as new results of treatments are collected. Tissue damage caused by the treatment can be described mathematically by an Arrhenius equation according to the following:
Ω=A∫e−E
A suitable measure is that patient and result of treatment are followed up at certain intervals after treatment, for example, every month for a certain period. In memory unit 52, there are stored data on blood flow and on other factors that affect heat absorption and heat dispersion in the type of tissue undergoing treatment. With exact data it is possible to store information in memory unit 52 which enables creation of a model of the tissue with respect to the factors cited above that models heat distribution very close to the actual tissue. Preferably, these later data are continually complemented and corrected even after the treatment.
Before heat treatment of a patients prostate certain current physical factors are determined, for example, the size of the prostate, the degree of narrowing of prostatic urethra, and the distance between the prostate and the rectum. Such physical factors or conditions may be determined with the aid of an ultrasound examination. With information on these conditions a suitable type of catheter for treatment and suitable temperature for treatment are determined. Different types of catheters may differ in diameter, in overall length, in length and power of heating means 26, and/or in distance from heating means 26 to inflatable balloon 16. Instead of duration of treatment, which according to previous devices was a decisive factor, a weight value and/or a volume value is determined for the desired volume/weight of the tissue that is to be treated, so that it can be destroyed. The value is given so that it is available to control unit 42, for example, by feeding it via a keyboard 43 and input/output unit 45. A highest value for temperature, or mean value for the temperature of the treatment, or a temperature range are preferably also input. The device can also be provided with further memories for storage of suitable combinations of volume/weight and temperature of the treatment. In the latter case, a norm value is automatically selected for the temperature of the treatment.
Also orientation meter 23 is operatively connected to said control unit 42 With these inputs mentioned above, the control unit 42 can calculate and send a control signal to energy supply unit 27, which supplies energy to the heating means so that heating means 26 begins to emit energy for heating of the tissue. Energy supply unit preferably supplies electrical energy while heating means preferably emit microwave energy. First temperature transducer 20 and preferably also second temperature transducer 30 and third temperature transducer 34 provide continuous information regarding the current temperature of the surrounding tissue, both near heating means 26 and at a certain distance from it in the tissue under treatment, as disclosed above
Control unit 42 is operatively connected to temperature transducer 20 and preferably also to transducers 30 and 34 and can, depending on the current temperature in the area of treatment, govern energy supply unit 42, so that suitable output is directed to heating means 26. By this means, it is possible to raise the temperature strongly in the surrounding tissue, so that death of the tissue occurs in the desired way. Data on temperature from temperature transducers 20, 30 and 34 can also be shown continuously in display unit 48. With the aid of input/output means 45 it is also possible to indicate a suitable level of output power from heating means 26, or as it can be rated from energy supply unit 27. The output level affects the temperature that the tissue obtains and may in certain cases affect the level of pain experienced by the patient.
Control unit 42 is configured to, during treatment, to continuously compare data from temperature transducers 20, 30, and 34 with the data stored in memory unit 52, and control unit 42 can by this means continuously calculate how the temperature varies in the prostate tissue at various distances from catheter for treatment 10. It is also possible in this way for control unit 42 continuously to calculate the volume/weight of the tissue that has been treated in the desired manner and where the desired result of treatment (cell death) has been achieved in the tissue.
Control unit 42 is also configured such that information calculated in the above way is continuously sent to display 48, so that besides numerical data regarding the treated volume/weight, the attending physician has an image of how the treatment is proceeding. A suitable method is that a schematic image similar to that in
The temperature in different parts of the prostate tissue is continuously calculated by the control unit 42 on the basis of the measured temperatures, and the current temperature is shown in the image of the prostate, for example, by means of markings in different colors. At the same time different graphs and/or tables regarding temperatures, blood flows, and volume/weight of the tissue under treatment are shown. The attending physician can in this way follow the treatment and continuously receive indications on how much tissue has been treated and where in the prostate tissue death has occurred.
A timer (not shown), operatively connected with control unit 42, or being an integral part of the same, continuously sends information on the time, so that the measured data becomes related to the treatment timeline. When one of the values for the volume or weight of the tissue being treated, as calculated by control unit 42, is in agreement with the preset value, the treatment can automatically be interrupted. With the aid of the display unit 48 or another indication instrument it is possible instead to indicate when the value set has been reached, so that the attending physician can interrupt the supply of heat manually. Corresponding interruption or indication can also occur if the temperature measured or calculated in some part of the tissue exceeds a threshold value, or if other input data, such as, for example, the temperature in the rectum or in the bladder indicates a risk for the patient. In such embodiments means for measuring rectal and bladder temperature are arranged to be input to the transducer interface 50 or input/output unit 45.
It is also possible continuously to alter certain settings during treatment, for example the desired temperature of treatment or the microwave input, without affecting or needing to change the value set for volume/weight. Instead the duration of treatment is affected. The duration of treatment can vary quite significantly with the method described above, depending on physiological differences and does not control the treatment in any decisive manner in comparison with methods of treatment employed previously.
Below two particular control methods will be described in more detail. The control methods are called “A” and “B” respectively. The purpose of both methods is to achieve cell-death of the desired amount of tissue in spite of unintentional undesired placement of temperature probe 22.
The control method A comprises the following steps:
Clinical studies have shown that under these conditions the cell kill estimation algorithm performs excellent. As a rule intended cell kill (approx. 20%) is reached within 7 to 15 minutes of treatment. An end temperature is in most of these cases within interval of 50-70 degrees Celsius for temperature values of T and M and lower for B. The “Endpoint”, i.e. the criteria defining termination of treatment is in this case the reaching of estimated desired cell kill, typically 20% of size of prostate gland before treatment.
The control method B comprises the following steps:
If weight of prostate gland is 50 gram the treatment should be terminated after 25 kJ. In order to retain the highest degree of safety a limit is set at which treatment is terminated, in spite of a big gland, and this limit may as a suggestion be 50 kJ.
The inventive idea and rationale for using the point in time when microwave energy supplied to the tissue exceeds a certain amount has been derived from eq. 1; if you eliminate perfusion, the temperature of the prostate during treatment will only depend on supplied energy. The perfusion blood flow can easily be cut during treatment by, before treatment injecting adrenaline into the prostate, which will cause the blood vessels to constrict temporarily, lowering the perfusion of the gland to almost naught. As a secondary endpoint of treatment, it is therefore possible to use a level of total amount of supplied energy (kJ).
Further, temperatures exceeding predetermined values in any tissue outside of the treated area may be indicated by sounding of an alarm signal. Temperatures exceeding predetermined values in the tissue outside of the treated area may cause the control unit 42 to automatically interrupt the supply of heat.
It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the inventive concept. Other embodiments will be apparent to those skilled in the art from consideration of the specification and practice disclosed herein. It is intended that the specification and examples be considered as exemplary only.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1550217-2 | Feb 2015 | SE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/SE2016/050137 | 2/25/2016 | WO | 00 |
