Implantable hyperthermia device and system

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Malignant tumors and especially malignant brain tumors are one type of cancer that has a very poor cure rate. The available modalities of treatment, including surgery, radiation therapy, and chemotherapy, have not been of substantial success in most cases in the management of this disease. It is an established laboratory fact that altering the environment in which the tumor cells are developing can cause the death of the tumor, and modest increases in the temperature of the environment of tumor cells can lead to their destruction. It has also been proven by clinical research that a modest increase in the temperature of a tumor, known as hyperthermia technique, has led to regression, disappearance, and on some occasions, cure of malignant tumors. However, a system for delivering energy into the tumor environment to produce hyperthermia, especially for extended periods of time, is not presently available except for the use of radiation means which are damaging to the surrounding tissue and difficult to control. An ideal system for introducing hyperthermia should be efficient, accurate, reproducable, safe, programmable, and totally implantable or self contained under the skin of the patient for reasons that will become apparent.

The present invention teaches the construction and operation of a device and system that has all of the desirable characteristics mentioned above. For example, the present invention teaches the construction of an implantable probe connected electrically to an internal control unit (ICU), which probe and internal control unit and the connections therebetween are all implantable under the surface of the skin so that there is nothing that projects through or from the skin. In the present construction, the probe is an elongated member which includes one or more heater elements and one or more temperature sensors which are located on the probe at positions such that when the probe is implanted on the patient the heater and sensor elements will be positioned to heat and to respond to the tumor temperature at the locations desired to be treated. The heat sensors when properly located in relation to the tumor respond to and monitor the temperature of the tumor thereat, and the internal control unit is connected to the heater element or elements and to the sensors by wires which are preferably coil constructed and located under the skin so as to allow the patient normal body movement without discomfort and without the possibility for stretching or contracting the wires. It is also contemplated to use one or more probes each equipped with one or more heater elements and sensors all connected to be controlled by the same internal and external control means.

In the present construction, the internal or implanted control unit includes its own power supply which is implanted with the unit completely in the patient's body and under the skin. The power supply may include a battery or other energy source which is preferably rechargeable by external means that can be coupled to the internal means for this and other purposes. The power supply includes circuitry to deliver energy from the battery to the heater and sensor elements in the probe and also provides the energy for operating the internal control unit. The internal control unit controls the energizing and deenergizing of the heater element in response in part to the temperature sensed by the sensors and in part due to external and internal controls and programs and it includes means to control the amount of heat generated by the heater element and the frequency and duration that the heater element is energized. This is done under control of the sensors and other control and program means so that there is a careful and precise control over the amount of heat generated in the tumor according to a program established therefor. The device may include means for keeping an ongoing record of the operation for evaluation and reprogramming purposes and in some cases the same information may be used for diagnostic purposes. The internal control unit also contains means to store a program therefor, means to store responses of the sensors, and means for transmitting and receiving instructions to and from an external control unit and/or a computer so that information can be exchanged therebetween for evaluation and program updating. The information exchanged can be control information, information as to the amount of heat to be introduced into the tumor, information as to the temperature and changes in the temperature at specific locations in the tumor, information as to the charge remaining on the power supply, fail safe information, verification and assessment information, and information as to the frequency and duration of applied heat. This information can be stored in memory means which are included in the internal unit for transmission by internal transmission means through the skin to external receiver means which are part of the external control unit. The information thus exchanged can be used to program and reprogram the internal unit depending upon the amount and frequency of heat required to be generated taking into account the measured temperature of the tumor and the treatment requirements. The external control unit can also be used to control the recharging of the internal battery or power pack contained in the internal unit from time to time as required and to monitor the amount of power remaining in the power pack to assure continuity of operation of the internal unit and the safety of the patient. The external control unit, like the internal control unit, should also contain storage means for storing information it receives from the internal unit, and the external control unit should include computer means or means for coupling to a computer or other data processing device having the capability and software programs to evaluate the information it receives and to produce outputs for transmitting to and entering in the internal control unit as required. Such information can be used to reprogram the internal unit as by changing the amount and frequency of heat application to the tumor for some reason such as to achieve and maintain some desired tumor temperature. The computer to which the external unit is coupled should possess the software necessary to produce the functions described above.

So far as known there is no system in existence that has the features, benefits and capabilities of the present system including having means for predeterminately accurately generating heat in a tumor using a probe with a heater element thereon as distinguished from other forms of heat producing means such as radiation means which are known to often cause damage to tissue and organs adjacent to the area being treated when the radiation is applied to the tumor for therapeutic reasons. So far as known, there are no devices which include a self-contained implantable system for applying heat therapy to a tumor and which includes means to continuously monitor the temperature of the tumor in order to assess and verify the treatment and which are manually or automatically programmable to change or adjust the treatment. The present invention therefore represents a new, more accurate, and safer means for generating heat in a tumor or in some body organ without the use of medicines or radiation, for some therapeutic and/or other reason. The present invention allows for the internalization of a self contained control system which includes means programmable to control all of the functions thereof, and yet can be coupled to external control means for treatment evaluation, verification and assessment of past and present operational conditions and which can be programmed and reprogrammed to change the treatment as by selecting a different level of heat generation, a different schedule of treatment frequency and duration of heat application and which contains means for charging or trickle charging an internal power pack or battery to maintain and sustain the operating condition of the system and to substantially extend the life of the implanted system without surgical procedures. All of these and other functions can be performed on a continuing safe basis, for extended periods of time, and without having repeatedly to surgically remove portions of the implanted system.

The present system therefore represents an important advance in means for heat treating tumors and other body organs including particularly the treatment of brain tumors using carefully controlled and regulated hyperthermia means which do not produce any radiation which can cause damage to other body parts and functions, and the present system provides a useful additional medical option for use in treating such tumors. The present device also allows for prolonged periods of therapy under precisely controlled circumstances and with appropriate feedback and control systems which can be used to evaluate the results of the treatment and can be used to reprogram the system taking into account changes in the patient's condition and the condition of the tumor or other organ being treated. The present system also has fail-safe features which continuously monitor and, if necessary, update or abort the treatment so that the chances of putting the patient at risk are minimal.

It is an important advantage of the present invention that it provides a totally implantable hyperthermia system for the treatment of tumors and other internal organs and the like which substantially reduces the risk of infection even over prolonged periods of treatment by not having any parts of the implanted system pass through or extend from the skin. Also, since all of the operational components of the present system are implanted under the skin, a patient equipped with the implanted components may be ambulatory during treatment, and it is expected that at least some patients so equipped can be away from any external controls while treatment continues even for extended periods of time, often while carrying on other activities of daily living including possibly being involved in gainful employment. This is not usually possible with any other known hyperthermia or related treatment procedures. While the patient is moving about the treatment progresses under control of a program that is stored in the implanted system, and the program can be monitored and revised or changed from time to time as required by coupling the internal control unit to the external control means and if necessary to a central computer. As explained the power supply or battery that is incorporated into the implanted system is selected because it is small in size and rechargeable from external means as by trickle charging it by means which couple the internal and external units. The degree of flexibility and control available with the present system is non-existant in any known device at the present time. The present system therefore represents an important technical advance and a modality of management especially useful for the care and treatment of cancerous tumors which is not otherwise available on the market.

It is therefore a principal object of the present invention to provide an important alternative means for treating cancerous tumors.

Another object is to teach the construction and operation of an implantable system for controlling and monitoring the application of heat to an internal region of the body including into a cancerous tumor.

Another object is to provide means to control and program an implanted heat producing system by means which couple the implanted system to an external control system.

Another object is to provide a self contained implantable treatment system for use in generating heat in a cancerous tumor or other location inside the body to predeterminately raise and maintain a desired temperature in the tumor.

Another object is to provide the possibility for making patients with cancerous tumors including cancerous brain tumors ambulatory during treatment thereof.

Another object is to provide means for recharging a power supply implantable under the skin by means which couple to the implanted power supply from an external source through the skin.

Another object is to provide relatively safer means for treating cancerous tumors.

Another object is to generate heat in a tumor by means of an electric heater element positioned in the tumor.

Another object is to locate a heater element at a location within the tissue or tumor to be treated so that heat generated thereby radiates outwardly into the surrounding treatment area.

Another object is to minimize the surgical procedures necessary in the treatment of cancerous tumors including cancerous tumors located in the brain.

Another object is to provide an implantable system for applying heat to tumorous areas including means for regulating the amount, frequency and duration of heat applied in response at least in part to temperatures sensed by heat sensors also located in the region where the heat is applied.

Another object is to teach the construction and operation of a novel probe assembly capable of being implanted extending into a cancerous tumor with minimum surgical procedure and damage to the patient.

Another object is to minimize the surgical procedures necessary to implant and maintain a heat generating device in a tumor.

Another object is to provide more information for evaluation purposes during the treatment of tumors using a hyperthermia technique.

Another object is to provide a probe for extending into a cancerous tumor that includes means for generating heat in the tumor and means for sensing the tumor temperature at one or more locations in the region where the heat is generated.

These and other objects and advantages of the present invention will become apparent after considering the following detailed specification covering preferred embodiments thereof in conjunction with the accompanying drawings, wherein:

FIG. 1 is a side view of the head and upper body portion of a person equipped with an implanted hyperthermia system constructed according to the teachings of the present invention;

FIGS. 2A and 2B together are a schematic diagram of a control circuit for an implantable hyperthermia system including an internal or implanted system portion and the external portion for coupling to the internal portion;

FIG. 3 is an enlarged cross-sectional view through a single element probe with a portion of cable attached thereto for use with the present device;

FIG. 4 is a cross-sectional view taken on line 4--4 of FIG. 3;

FIG. 5 is an enlarged cross-sectional view through a multiple element probe with a portion of cable attached thereto for use with the present device;

FIG. 6 is a side view of the probe and cable portion of FIG. 5 but shown in a non-linear configuration; and

FIGS. 7A and 7B together are a flow chart for the systems shown in FIGS. 2A and 2B.

Referring to the drawings more particularly by reference numbers, number 10 in FIG. 1 refers to the head and upper body portion of a patient equipped with an implantable system constructed according to the present invention. The system includes a probe 12 which is shown imbedded in the head of the patient in position to extend from the surface or cranium of the head inwardly into a tumor T to be treated. A cable 14 is connected between the probe 12 and the internal control unit 16. The probe 12, the cable 14, and the internal control unit 16 are all surgically implanted in the body of the patient beneath the surface of the skin so that there is no protruding portion of the system which extends through or pierces the skin surface. This is important to the prolonged functional operation of the system since having the internal portions of the system completely implanted substantially reduces or eliminates the chances for infection and it is therefore expected that the internal system can remain in place for an extended period of time without any further surgical procedure being required. The details of the probe 12 and the internal control unit 16 will be described more in detail in connection with FIGS. 2A and 3.

In FIGS. 2A and 2B, the skin 18 of the patient is shown positioned between the internal control unit 16 and an external control unit 22. The internal control unit 16 is shown coupled by leads 24, 26, 28, and 30 which are in the cable 14 to control elements located in the probe 12 including one or more heater elements 34 and one or more heat sensitive elements or thermistors 36. The probe 12, including the elements 34 and 36, and the internal control unit 16, are all surgically implanted under the skin of the patient so that nothing pierces or extends through the skin to cause infection or other problems. As stated, this is an important advantage of the present system. The internal control unit 16 includes means for controlling the application of electrical energy to the heater element or elements 34 according to some predetermined program or instructions established in the internal control unit and changed from time to time by the external unit 22 as will be described. The internal control unit 16 also has connections with the thermistor or thermistors 36 located on or adjacent to the probe at locations such that the thermistors are able to sense the temperature in the treatment area or tumor and provide outputs which can be used to evaluate and assess the effect of the treatment to enable modifying the treatment including the amount of heat generated by the heater element 34 as required to maintain some internal temperature condition for treatment purposes. For example, if the temperature of the tumor as sensed decreases then additional energy may need to be applied to the heater element 34 to maintain the temperature in the tumor at some desired level and for some desired time period or periods.

The heater elements 34 are preferably selected to be non-inductive, to have relatively low temperature coefficients and to be resistive type elements. The heaters should be able to increase the temperature of the surrounding tissue from normal body temperature of about 37.degree. C. to a maximum temperature adjacent thereto of about 45.degree. C. The heaters 34 should also be able to withstand repeated exposure to radiation without any degradation in performance characteristics such as degradation in resistance, temperature coefficient, heat capacity and/or heat dissipation constant. For a typical probe construction the heater elements should also be as small as practical, and a typical size is in the order of 2 millimeters in diameter and 6 millimeters in length. Such devices are available commercially.

Referring to FIG. 2A the internal control unit 16 includes a power supply 38, grounded at 40 and shown connected to a power pick-up trickle charge circuit 42 which in turn is connected to a power inductor coil 44. The inductor coil 44 is preferably located on the unit 16 as near as possible to the surface of the skin 18 so that external means can be closely coupled thereto when it is necessary to recharge or trickle charge the power supply 38. The power supply 38 may include a rechargeable battery or some other similar rechargeable energy source. The power supply 38 has an output connection 46 which is the main power lead used to supply energy for the internal control unit including for operating the heater and thermistor elements 34 and 36.

The internal control unit (ICU) 16 is the portion of the system that controls the temperature generated by the heater element 34 as programmed internally by means of the external control unit (ECU) 22. The internal control unit 16 also includes ultrasonic transmit/receive means (transceiver) 50 which include transmitting portion 52 used to transmit information for receipt by the external control unit 22, and a receiver portion 54 which receives information transmitted by the external control unit 22 for various purposes including programming and reprogramming the internal control unit and controlling the transmissions of information between the units. The internal control unit includes a digital to analogue converter (DAC) circuit 56 which converts 8-bit binary parallel words from the output of an internal microprocessor (uP) 58 to current outputs which are used to energize the heater 34 to produce the amount of heat that is desired. The output of the 8-bit DAC 56 is applied through a current driver circuit 60 which may be an emitter follower circuit that receives power from the power supply 38 by way of emergency power-off circuit 62 connected thereto, as shown. The output of the current driver circuit 60 is a voltage that is applied to the non-grounded side of the heater element 34 by leads 64 and 24. The same output applied to the heater 34 is also applied as an input to an analogue multiplexer (MUX) circuit 68. The analogue multiplexer 68, under control of the microprocessor 58, is constructed and connected so as to be able to select and monitor various conditions throughout the internal control unit including the voltage on the heater element 34, the voltage on the thermistor or heat sensor 36, as well as other circuit conditions, and it converts the signals or responses being monitored to a digital format by means of an 8-bit analogue to digital converter (ADC) 70 by way of amplifier circuit 72. The signals thus converted are applied to the data bus 73 for entry into the microprocessor 58 and other circuit components. The analogue multiplexer 68 has other input connections from various locations in the circuit including an input connection from the output of the 8-bit digital to analogue converter 56 on lead 74, an input from the output of the current driver 60 on leads 64 and 76, an input from the output of the emergency power-off component 62 on lead 78, an input from the non-grounded side of the thermistor 36 on leads 30 and 80, and inputs from a precision voltage source 82 on leads 84, 86 and 80. The precision voltage source 82 is used in connection with the calibration of the thermistor 36. The lead 86 from the source 82 includes a biasing resistor 88. The analogue multiplexer 68 also has a power input connection on lead 90 which is connected to output lead 92 on the power supply 38. The analogue multiplexer 68 is controlled from the microprocessor 58 and from other circuit connections by signals present on address bus 93 whereby the analogue multiplexer 68 can, among other things, maintain accuracy of the system even if some of the circuit parameters drift out of specification by automatically compensating for such errors. As a result the need for further surgery to manually adjust or replace implanted components is substantially reduced.

The microprocessor 58, as indicated, is the portion of the internal control unit 16 that controls all of the various functions thereof including also the functions of communicating with the external control unit 22. The microprocessor 58 has control and other connections including data and address connections to a 1024 bit random access memory (RAM) 94 which memory is programmable from the external control unit 22. When programmed the RAM 94 will enable a patient equipped with the subject internal control unit 16 to be able to undergo hyperthermia treatment while away from or out of communication with the external control unit 22. This is an important feature of the present device because it means that therapy can proceed continuously, reliably, safely, and in a precisely controllable manner for extended periods of time without constant attention thereby enabling the patient to maintain a fairly normal lifestyle even while undergoing treatment. The RAM 94 also converts data from the MUX 68 for subsequent transmittal to the external control unit.

Other portions of the internal control unit include a 2-K read only memory (ROM) 96 which is shown as part of the microprocessor 58 itself, an universal asynchronous receive/transmit circuit (UART) 98 which is provided to couple the microprocessor 58 as well as other portions of the internal control unit 16 to the ultrasonic transmit/receive circuit 50 which converts signals between the internal and external control units. The internal control unit 16 may include an emergency digital to analogue converter (DAC) 100 which can be connected to the ultrasonic transceiver 50 by lead 102 and connected to the power supply by way of the emergency power-off circuit 62. In addition, the internal control circuit 16 includes various circuit connections including the data bus 73 described above which has connections between the 8-bit DAC 56, the microprocessor 58, the 8-bit analogue to digital converter (ADC) 70, the RAM 94, and the UART 98. A second group of interconnections identified as the address bus 93 which provides other connections between the microprocessor 58, the analogue multi