Patent Application
20140243701
This invention relates to the field of temperature measurement and more specifically to the measurement of temperature without contact with the object being measured.
Thermotherapeutic treatments of disease such as cancer function by causing the temperature of a target tissue to increase to a level which causes the target tissue to change physiologically or die. The effectiveness of the technique relies upon accurate measurement of temperature in the target tissue. Too small a temperature increase, and the treatment may not be effective. Too large a temperature increase, and the temperature of non-intended tissues may rise.
The accurate measurement of temperature is difficult, especially in tissues located deep within the body. Standard techniques such as infrared or other optical probes are limited substantially to accessible tissue surfaces of the body. What is needed is a method of accurately measuring temperature in a tissue located deep within the body without using invasive means.
The present invention addresses this need.
In one aspect, the invention relates to a method for measuring the change in temperature of a material being heated. In one embodiment, the method includes the steps of introducing particles having one or both of a magnetic susceptibility and an electrical conductivity into the material; heating the material and particles; measuring, using a circuit having a resonant frequency, the change in the resonant frequency of the circuit as the temperature of the particles changes; and correlating the change in resonant frequency to a change in material temperature. In another embodiment, the particles are nanoparticles. In still another embodiment, the nanoparticles are magnetic.
In yet another embodiment, the material is a tumor and the particles comprise a nanoparticle and an antibody or receptor. In still yet another embodiment, the circuit is a tank circuit in electrical communication with a variable alternating current source. In one embodiment, the variable alternating current source adjusts the frequency of the alternating current to track the resonant frequency as the resonant frequency changes. In another embodiment, the step of correlating comprises relating the change in resonant frequency to a temperature change using a calibration table or function by a computer. In yet another embodiment, the heating of the material and the measuring of the resonant frequency change is performed with the same circuit.
In another aspect, the invention relates to a method of measuring temperature in a tissue undergoing hyperthermia treatment. In one embodiment, the method includes the steps of: introducing magnetic and/or conductive particles to the tumor; measuring, using a circuit which has a coil in a tank circuit and a resonant frequency, the change in resonant frequency of the circuit during hyperthermia treatment; tracking a change in electromagnetic resonant frequency during hyperthermia treatment; and correlating the change in electromagnetic resonant frequency to a change in tissue temperature using a computing device monitoring the circuit. In another embodiment, the particles are nanoparticles. In still another embodiment, the nanoparticles are magnetic. In yet another embodiment, the particles include a nanoparticle and an antibody or receptor ligand. In still yet another embodiment, the tank circuit is in electrical communication with an alternating current variable frequency source.
In one embodiment, the alternating current variable frequency source adjusts the frequency of the alternating current to track the resonant frequency as the resonant frequency of the circuit changes. In another embodiment, the step of correlating comprises relating, using a computing device, the change in resonant frequency to a temperature change using a calibration table or function. In yet another embodiment, the hyperthermia treatment and the measuring of the resonant frequency change is performed with the same circuit.
In another aspect, the invention relates to a system for measuring the temperature change in a material. In one embodiment, the system includes a magnetic and/or conductive particle in contact with the material undergoing heating; a resonance circuit comprising: a tank circuit comprising inductance and capacitance and having a resonant frequency; an alternating current variable frequency source capable of tracking changes in the resonant frequency of the tank circuit to maintain the frequency of the alternating current at the then current resonant frequency of the tank circuit; and a processor in electrical communication with the alternating current variable frequency source for measuring the change in resonant frequency of the tank circuit in response over time. In one embodiment, the tank circuit generates an alternating magnetic field in response to current from the alternating current variable frequency source. In another embodiment, when the magnetic or conductive particles are within the alternating magnetic field, the resonant frequency of the tank circuit changes. In still yet another embodiment, the temperature of the magnetic or conductive particles causes the resonant frequency of the tank circuit to change. In one embodiment, the particles are nanoparticles. In another embodiment, the nanoparticles are bound to an antibody or receptor ligand.
This Summary is provided merely to introduce certain concepts and not to identify any key or essential features of the claimed subject matter.
The structure and function of the invention can be best understood from the description herein in conjunction with the figures. The figures are not necessarily to scale, emphasis instead generally being placed upon illustrative principles. The figures are to be considered illustrative in all aspects and are not intended to limit the invention, the scope of which is defined only by the claims.
a) is a highly schematic diagram of the embodiment of the system of
In brief overview and referring to
f=a{1/(LC)1/2}
where f is the resonant frequency and (a) is the constant of proportionality.
As the inductance (L) or the capacitance (C) changes, the resonant frequency will therefore change. By tracking the change in resonant frequency, one can track the change in the components of the circuit. When a magnetic or conductive material enters the field generated by the coil, the magnetic field changes and this in turn affects the self-inductance of the coil and hence the resonant frequency of the system, i.e. the combination of tank circuit and magnetic material. This change in the magnetic field generated by the coil is a result of the magnetization of the magnetic material or the flow of eddy currents in the conductive material.
The effect of the magnetic material on the inductance of the coil is a function of the material's magnetic susceptibility. The magnetic material's magnetic susceptibility varies with temperature. Thus, as the temperature of the material changes, the susceptibility changes, resulting in a change in the coil inductance and thus a change in the resonant frequency of the system.
In the case of a collection of magnetic nanoparticles of a single size, theory states that the magnetic susceptibility at low fields is inversely proportional to the absolute temperature. For instance, a 50K increase from room temperature in theory could result in a change in susceptibility of up to 17%. In real preparations, magnetic nanoparticles have a distribution of sizes which makes it necessary to calibrate the magnetic susceptibility against the temperature.
a) is a highly schematic diagram of the system of
Referring to
By tracking the change in resonant frequency, one can determine the change in the temperature of the magnetic or conductive material being measured.
The electronic control unit which provides the current to the tank circuit includes alternating current variable frequency source and a feedback loop and varies the frequency of the alternating current to compensate for the change in resonant frequency of the tank circuit. The output of the control unit is connected to the input of a processor and transmits the magnetic field strength and the alternating current frequency at which the field strength is measured.
The processor compares the frequency changes against a table of values listing the change in temperature against a change in frequency for a given type of magnetic or conductive particle to determine the effective temperature change. The resonance tracking circuit of the controller is of standard configuration and is well known to one skilled in the art. The coil is shown as a tube but the coil may in fact be any inductor regardless of shape, such as a flat or plate coil.
In use, the magnetic or conductive material, in one embodiment, is a magnetic nanoparticle of iron oxide coated with a dextran such as Ferucarbotran (Meito Sangyo Ltd, Nagoya, Japan). Generally these particles are used for the thermotherapeutic treatment of cancer. The magnetic nanoparticle is frequently coupled to antibodies or receptor ligands which will bind to an antigen or receptor in the cell membrane of the cancer cells. In one embodiment, the magnetic particles are conjugated using sodium periodate to sm3E, a single chain Fv antibody fragment which binds to human carcinoembryonic antigen (CEA4,5). In other embodiments, for example for use with glioblastoma, the magnetic particles are bound to Designed Ankyrin Repeat Proteins. When introduced into the body, the magnetic nanoparticle-antibody complex binds the magnetic nanoparticles to the cancer. The cancerous tumor then is heated by induction heating as described above.
Using the technique described, the shift in the resonant frequency of the system provides a measure of the change in temperature of the magnetic nanoparticles and hence the tumor to which they are bound. In this way, it is possible to assure that the temperature of the tumor has risen sufficiently to be damaged or killed.
The aspects, embodiments, features, and examples of the invention are to be considered illustrative in all respects and are not intended to limit the invention, the scope of which is defined only by the claims. Other embodiments, modifications, and usages will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.
It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present teachings remain operable. Moreover, two or more steps or actions may be conducted simultaneously.
Where a range or list of values is provided, each intervening value between the upper and lower limits of that range or list of values is individually contemplated and is encompassed within the invention as if each value were specifically enumerated herein. In addition, smaller ranges between and including the upper and lower limits of a given range are contemplated and encompassed within the invention. The listing of exemplary values or ranges is not a disclaimer of other values or ranges between and including the upper and lower limits of a given range.
This application claims priority to U.S. Provisional Application No. 61/768,020 filed on Feb. 22, 2013, the contents of which are herein incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61768020 | Feb 2013 | US |
