Intracorporeally introducible suspension of ferromagnetic...

Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation

Reexamination Certificate

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C424S009300

Reexamination Certificate

active

06280384

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to a method for spatially resolved temperature monitoring in a living examination subject, as well as to a suspension of ferromagnetic microparticles usable in the method.
2. Description of the Prior Art
In the field of medicine, it is necessary to detect the temperature in a living organism as precisely as possible in a spatially resolved manner. This is true for hyperthermia treatment, for example. Treatments with hyperthermia are conducted with LITT (Laser Induced Thermotherapy) or with regionally deep hyperthermia, for example, the latter method being used to treat tumors located deep in the body with HF radiation.
Particularly in hyperthermia, the temperature measurement must be highly accurate. It must be guaranteed that the tumor tissue is heated sufficiently intensely in order for the treatment to be effective, but burning of the patient (surrounding tissue) must be precluded. The temperature in the treated region must thus be kept within narrow limits, about 42.5° C. for hyperthermia, for example. This temperature is the same in all experiments, so that temperature detection need only be exact in this region.
With current methods, the temperature in the body can only be determined at individual points or along a hollow catheter. This is unsatisfactory for the above purpose, however, since a maintenance of the desired temperature over the entire treatment region cannot be guaranteed in this manner.
There are known applications of MR imaging for obtaining the temperature in the interior of a body in a spatially resolved manner. To the extent that these methods are based on proton nuclear spin resonance, the following parameters have been relevant references for the tissue temperature: chemical shift of the water peak, the T
1
relaxation time of the protons, the total magnetization of the water, and the diffusion coefficient of water protons in the tissue. A non-invasive and spatially resolved monitoring of the body temperature is also possible at points far from the surface. Larger regions of the body can be simultaneously monitored. Nevertheless, these kinds of methods are not exact enough for the aforementioned purpose and are often too sensitive to external disturbances.
In the articles “Encapsulated Liquid Crystals as Probes for Remote Thermometry,” (Franklin, K. J. et al;
International Journal Hyperthermia;
Vol 8(2); 1992:253-262) and “Sonochemically Produced Fluorocarbon Micropsheres: A New Class of Magnetic Resonance Imaging Agent,” (
Journal of Magnetic Resonance;
6, 1996:675-683), it is suggested that the phase transition of crystals be employed for thermometry by means of magnetic resonance. It has been established that certain substances have a considerably lower intensity of the MR signal in the solid phase than in the liquid phase. In the latter reference, a fluorocarbon-hydrocarbon mixture is suggested, which mixture changes from the solid phase into the liquid phase at a specific temperature. When this mixture is introduced into a body, it can be determined by the differences in the signal intensity of the allocated MR signal whether the prescribed temperature is exceeded. Liquid crystals were suggested in the first reference for a similar effect. In order to prevent the employed substances from being metabolized by the body and acting toxically, it is provided that these substances are enclosed in a non-toxic encapsulation which is not dissolved in the body (i.e. a body-inert encapsulation).
A common feature of all the above methods for temperature monitoring by means of MR on the basis of changes of the signal intensity in the phase transition is that a nuclear resonance measurement must be conducted with respect to this substance, e.g. fluorine. While this does not pose a problem in MR spectrometers, imaging MR devices are available practically only for proton resonance. In addition, fluorine, for instance, is present in the body only in very low concentrations, so that the body tissue could be imaged only with an extremely low signal-noise ratio. Imaging of the body tissue is a necessity for the localization of the temperature monitoring in the tissue. The above methods could be carried out, if at all, only with devices which are constructed specifically for this purpose, so that these methods are only of academic interest, at least at the present time.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a method with which an accurate and reliable localized temperature monitoring is possible.
The above object is achieved in accordance with the principles of the present invention in a method for spatially resolved temperature measuring in a living body including the steps of intracorporeally introducing a ferromagnetic substance into the body, the substance having a Curie temperature which corresponds to a desired temperature limit value, and obtaining a spatially resolved representation of the body by obtaining magnetic resonance data from the body and forming an image of the body from the data, the image containing artifacts caused by the substance being in the ferromagnetic state, and using these artifacts as a criterion for determining that the temperature limit value has not yet been reached.
If the MR measurement is related to protons, conventional MR imaging devices can be employed, which ordinarily function by means of nuclear spin resonance of protons. The ferromagnetic substance can be intracorporally introduced in the form of an implant or as an injectable suspension on encapsulated ferromagnetic microparticies.
Another object of the Invention is to provide a contrast agent which is suitable for monitoring temperature by means of the effect of magnetic resonance, and the utilization of such a substance for that purpose.
This object is achieved in accordance with the principles of the present invention in a suspension of firm magnetic microparticles which have a Curie temperature in a range between an overcooled body temperature and an overheated body temperature of a living examination subject, the microparticles being encapsulated so as to be inert to metabolization by the living body.


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