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Número de publicaciónDE19506363 A1
Tipo de publicaciónSolicitud
Número de solicitudDE1995106363
Fecha de publicación29 Ago 1996
Fecha de presentación24 Feb 1995
Fecha de prioridad24 Feb 1995
Número de publicación1995106363, 95106363, DE 19506363 A1, DE 19506363A1, DE-A1-19506363, DE19506363 A1, DE19506363A1, DE1995106363, DE95106363
InventoresDietrich Prof Dr Frost, Klaus Dieter Prof Dr Kramer, Bernhard Dr Kleffner, Klaus Thomas Dr Bende, Benedikt Prof Dr Jean
SolicitanteFrost Lore Geb Haupt, Klaus Dieter Prof Dr Kramer, Kleffner Bernhard Dr Rer Nat, Bende Thomas Dr Habil, Benedikt Prof Dr Jean
Exportar citaBiBTeX, EndNote, RefMan
Enlaces externos: DPMA, Espacenet
Non-invasive thermometry in organs under hyperthermia and coagulation conditions
DE 19506363 A1
Resumen
The ultrasonic reflectometry is used for monitoring or controlling thermally induced, biological effects. Also using ultrasonic reflectometry with laser radiation, temp. gradients, coagulated or denatured vols. are determined also are used for therapy control or for control of the laser. The medical method of the diagnostic ultrasonic A-scan is used, yet these specific electronic detector units are replaced or supplemented by an integrator technology, e.g. according to the box car principle. The specific detector units are supplemented by a synchronising unit for identifying the patient movements.
Reclamaciones(10)  traducido del alemán
1. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen, dadurch gekennzeichnet, daß die an der Grenzfläche des überwärmten Gewebes auftretenden Ultraschall-Reflexionssignale zur Tiefenmessung, Identifikation des Zielvolumens und Temperaturbestimmung herangezogen werden. 1. A method for non-invasive thermometry in organs in medical hyperthermia and coagulation conditions, characterized in that the occurring at the interface of the over-heated tissue ultrasonic reflection signals for depth measurement, identification of the target volume and temperature determination may be used.
2. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Anspruch 1), dadurch gekennzeichnet, daß die Ultraschall- Reflektometrie zur Überwachung oder Steuerung thermisch induzierter, biologischer Effekte benutzt wird. 2. A method for non-invasive thermometry in organs under medical hyperthermia and coagulation according to claim 1), characterized in that the ultrasonic reflectometry is used to monitor or control of thermally induced, biological effects.
3. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Anspruch 1-2), dadurch gekennzeichnet, daß mittels Ultraschall- Reflektometrie bei Lasereinstrahlung Temperaturgradienten, koaguliertes- oder denaturiertes Volumen ermittelt und zur Therapiekontrolle oder Steuerung des Lasers verwendet werden. 3. A method for non-invasive thermometry in organs under medical hyperthermia and coagulation as claimed in claim 1-2), characterized in that using ultrasonic reflectometry with laser irradiation temperature gradient koaguliertes- or denatured determined volume and is used for therapy control or control of the laser ,
4. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-3), dadurch gekennzeichnet, daß die medizinische Methode des diagnostischen Ultraschall-A-Scans verwendet wird, jedoch die diesen Geräten spezifische Nachweiselektronik durch eine Integratortechnik (z. B. nach dem Box Car-Prinzip) ersetzt oder ergänzt wird. 4. A method for non-invasive thermometry in organs under medical hyperthermia and coagulation according to claims 1-3), characterized in that the method of the medical diagnostic ultrasound A-scan is used, however these devices the specific detection electronics by an integrator art ( z. B. after the Box Car principle) is replaced or supplemented.
5. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-4), dadurch gekennzeichnet, daß die den diagnosti schen Ultraschallgeräten spezifische Nachweiselektronik durch eine Synchronisiereinheit zur Ausmittelung von Patientenbewegungen ergänzt wird. 5. A method for non-invasive thermometry in institutions under medical hyperthermia and coagulation of claims 1-4), characterized in that the diagnosed rule ultrasound equipment specific detection electronics is complemented by a synchronization unit for averaging of patient motion.
6. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-5), dadurch gekennzeichnet, daß ein nach dem Verfahren des Ultraschall-Compoundscan oder Ultraschall-B-Scan arbeitendes Diagnosegerät so modifiziert wird, daß eine zweidimensionale Darstellung der signifikanten, temperatur zugeordneten Flächenumrandungen erreicht wird. 6. A method for non-invasive thermometry in organs under medical hyperthermia and coagulation according to claims 1-5), characterized in that one operating according to the method of the ultrasonic Compound scan or B-scan ultrasonic diagnostic apparatus is modified so that a two-dimensional representing the significant temperature-associated surface boundaries is achieved.
7. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-6), dadurch gekennzeichnet, daß ein nach dem Verfahren des diagnostischen Ultraschall-B-Scans arbeitendes Gerät so modifiziert wird, daß eine farbcodierte oder räumliche Darstellung der signifikanten temperaturzugeordneten oder zur Therapiekontrolle geeigneten Meßgrößen erreicht wird. 7. A method for non-invasive thermometry in institutions under medical hyperthermia and coagulation according to claims 1-6), characterized in that an operating according to the method of diagnostic ultrasound B-scan device is modified so that a color-coded or spatial representation the significant temperature associated or suitable for therapy monitoring process variables is achieved.
8. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-7), dadurch gekennzeichnet, daß die Ultraschall- Reflektometrie zur Therapiekontrolle oder zur Therapiesteuerung von Laserkoagulationen in der Augenheilkunde benutzt wird (z. B. Thermokeratoplastik, Koagulation der Netzhaut, Trabeculoplastik, Cyclophotokoagulation oder Cyclokryokoagulation) sowie in Kombination mit anderen koagulativen Prozessen verwendet wird. 8. A method for non-invasive thermometry in institutions under medical hyperthermia and coagulation according to claims 1-7), characterized in that the ultrasonic reflectometry is used to control therapy or therapy control of laser coagulation in ophthalmology (z. B. thermokeratoplasty, coagulation of the retina, Trabeculoplastik, Cyclophotocoagulation or Cyclokryokoagulation) and is used in combination with other coagulative processes.
9. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-8), dadurch gekennzeichnet, daß die Ultraschall- Reflektometrie zur Kontrolle der autolytischen Denaturierung (z. B. Viabilitätstest) herangezogen wird. 9. A method for non-invasive thermometry in institutions under medical hyperthermia and coagulation according to claims 1-8), characterized in that the ultrasonic reflectometry is used to control the autolytic denaturation (z. B. viability test).
10. Verfahren zur nicht-invasiven Thermometrie in Organen unter medizinischen Hyperthermie- und Koagulationsbedingungen nach Ansprüchen 1-9), dadurch gekennzeichnet, daß aus der Ultraschall-Reflektometrie im Hinblick auf Temperatur und Ausdehnungsgrößen ermittelt werden, welche eine Lasereinstrahlung rückgekoppelt beeinflussen und den Vorgang teilautomatisieren. 10. A method for non-invasive thermometry in organs under medical hyperthermia and coagulation as claimed in claims 1-9), characterized in that are determined from the ultrasound reflectometry with regard to temperature and expansion variables which affect fed back a laser radiation and the process teilautomatisieren ,
Descripción  traducido del alemán

Die gezielte Überwärmung begrenzter Gewebevolumina wird als nichtchirurgische Zusatztherapie zur Unterstützung der Chemo- und Radiotherapie eingesetzt. The targeted hyperthermia limited volumes of tissue is used as a non-surgical adjunct therapy to support chemotherapy and radiotherapy. Darüberhinaus finden laserinduzierte Koagulationsprozesse in der Onkologie (bspw. endoskopische Chirurgie in der Gastroenterologie und minimalinvasiven Chirurgie) sowie der Ophthalmologie (bspw. Glaukombehandlung) ihre Anwendung. In addition, find laser-induced coagulation processes in oncology (eg. Endoscopic surgery in gastroenterology and minimally invasive surgery) and ophthalmology (eg. Glaucoma treatment) their application. Die klinische Durchsetzbarkeit dieser Therapieformen ist mit der Verfügbarkeit eines Verfahrens zu deren Kontrolle eng verknüpft. The clinical effectiveness of such therapies is closely linked with the availability of a method for their control.

Unter Hyperthermie versteht man die Überwärmung eines im Körper inneren gelegenen Volumens durch Einstrahlung von hochfrequenten Feldern von außen. Under hyperthermia refers to the overheating of the body inner volume located by exposure to radio frequency fields from the outside. Als Signifikanzgröße dient die Temperatur erhöhung im Zielvolumen gegenüber der physiologischen Körper temperatur des Gesamtorganismus. The significance size, the temperature is increase in the target volume with respect to the physiological body temperature of the whole organism. Nach dem gegenwärtig geübten Stand der medizinischen Anwendung werden nadelartige Sonden mit einem temperaturempfindlichen Halbleiterelement an ihrer Spitze in den Patienten eingestochen und bis zum Zielvolumen vorgeschoben According to the currently practiced prior medical use needle-like probes are inserted with a temperature-sensitive semiconductor element at its tip into the patient and advanced to the target volume
Es sind Versuche unternommen worden, die erreichte Überwärmung nicht-invasiv nachzuweisen (bspw. Messung der NMR-Relaxations zeiten der Protonen des Zielvolumens, aktive und passive Mikro wellentomografie; einen Überblick bietet [I]). Attempts have been made to demonstrate the achieved overheating non-invasive (eg measurement of NMR relaxation times of the protons of the target volume, active and passive micro-wave tomography;. Provides an overview [I]). Aufgrund der teilweise sich widersprechenden Anforderungen (im wesentlichen: ausreichende Nachweistiefe und -empfindlichkeit, Darstellung der Kontrollparameter in Echtzeit, Kompensation von Störeinflüssen, verursacht durch Patientenbewegungen sowie die Kompatibilität mit dem Hyperthermiesystem) ist bis heute noch kein handhabbares und universell einsetzbares Kontrollsystem bekannt geworden. Because of the sometimes conflicting requirements (essentially: sufficient evidence depth and sensitivity, presentation of control parameters in real-time compensation of interferences caused by patient motion, and compatibility with the hyperthermia system) is to date still not aware of any handled and universal control system. Es sind auch Versuche publiziert worden, die Änderung der Schallgeschwin digkeit bei Einstrahlung von Ultraschall als Signifikanzgröße zur Temperaturbestimmung heranzuziehen [II]. Attempts have also been published to refer to the change in the Schallgeschwin speed during irradiation of ultrasound as a significance size for determining the temperature [II]. Da sich aber die Schall geschwindigkeit in Abhängigkeit von der Temperatur des biologi schen Materials nur sehr gering und monoton ändert, hat sich daraus kein technisches Meßverfahren ableiten lassen. However, since a change in the sound speed as a function of the temperature of the biological material is very low and monotonous, has can be derived from any technical measurement methods.

Erfindungsgemäße Lösung Inventive Solution

Die Erfindung geht von dem Grundgedanken aus, daß an der Grenz fläche zwischen biologisch - physiologischem Gewebe und erwärmtem Volumen eine Ultraschallreflexion auftritt. The invention is based on the basic idea that at the boundary surface between biological - physiological tissue volume and heated ultrasonic reflection occurs. Der Amplituden reflexionsfaktor ist als Signal meßtechnisch erfaßbar. The amplitude reflection coefficient measurement technology is detectable as a signal. Größe und Änderung des Signals im Nachweispfad hängen eindeutig von der Temperaturdifferenz und deren zeitliche Änderung während der Überwärmung ab. Size and modification of the signal in the detection path is clearly dependent on the temperature difference and its temporal changes during hyperthermia. Im Bereich der beginnenden irreversiblen Änderung des biologischen Zielvolumens gestattet das erfindungsgemäße Verfahren ein Temperaturauflösungsvermögen von ΔT 0.25 grd. In the range of the initial irreversible change in the biological target volume, the inventive method allows a temperature resolution of .DELTA.T 0:25 deg. Das Verfahren nach der Erfindung benutzt als Nachweis die Methode des A-Scans diagnostischer Ultraschallgeräte, jedoch wird zur Sicherstellung der geforderten strengen Linearität der Reflexions- Signalamplitude die Ultraschall-Hochfrequenz direkt abgegriffen, von der eingestrahlten Hyperthermie-Hochfrequenz gesäubert und durch eine Elektronik nach dem Prinzip des Box Car-Integrators verarbeitet und dargestellt. The method of the invention used as proof of the method of the A-scan diagnostic ultrasound devices, but the required strict linearity of the reflection signal amplitude is to ensure the ultrasonic high frequency directly picked, cleaned of the irradiated hyperthermia high frequency and by electronics on the principle of the box car integrator processed and displayed.

Um eine quantitative Auswertung auch unter dem Einfluß von Patientenbewegungen zu ermöglichen, darf der Triggerzeitpunkt für die die Darstellung regierenden Größen wie Verzögerungszeit und Fensterbreite nicht am Sendesignal festgemacht, sondern muß am interessierenden Echo selbst verankert werden. To enable quantitative evaluation under the influence of patient motion, the trigger time for the presentation reigning variables such as delay and window width must not secured to the transmit signal, but must be anchored to the interest echo itself. Eine Synchronisier einheit verschafft sich aus Flankenwert und -steigung des n-ten Echos den Triggerzeitpunkt des darauffolgenden Echos. A synchronizing unit gives off edge and gradient value of the nth echo the trigger time of the subsequent echoes. Die Eindeu tigkeit des Triggerzeitpunktes wird durch eine Komparatorschaltung sichergestellt. The Eindeu activity of the trigger timing is ensured by a comparator circuit.

Alle Komponenten der Synchronisiereinheit sind analog aufgebaut, wodurch diese zentrale Steuereinheit wie das gesamte Nachweis systems in Echtzeit arbeitet. All components of the synchronization unit are constructed analogously, whereby said central control unit such as the entire detection system operates in real time.

Weitere Anwendungen Other applications

Unter medizinischen Hyperthermiebedingungen sind auch diejenigen therapeutischen Verfahren zusammenzufassen, denen Koagulations prozesse zugrunde liegen. Under medical hyperthermia conditions even those therapeutic methods are summarized, which coagulation processes are based. Die Kongruenz der Anforderungen an ein Kontroll- oder Steuerungssystem bei diesen Behandlungsformen resultiert daraus, daß auch hier Therapierisiko und -wirkung nach den erzeugten Temperaturgradienten sowie der räumlichen Ausdehnung der erzeugten Herde zu bewerten ist. The congruence of the requirements of a control or control system for these forms of treatment results from the fact that here Therapy risk and effect according to the generated temperature gradients as well as the spatial extent of the herd is generated to evaluate. Zur on line-Messung und geeigneten Darstellung dieser beiden Kriterien am Patienten sind alle Komponenten des erfindungsgemäßen Verfahrens notwendig, wobei die Ultraschall-Arbeitsfrequenz der jeweiligen Aufgabenstellung anzupassen ist. For the on-line measurement and appropriate representations of these two criteria the patient all the components of the inventive method are necessary, the ultrasonic operating frequency must be adapted to the respective task.

In der endoskopischen und minimal-invasiven Chirurgie werden Laser- und Plasmasysteme zur Koagulation maligner Gewebevolumina eingesetzt. In endoscopic and minimally invasive surgery, laser and plasma systems are used for coagulation of malignant tissue volumes. Mit der Festlegung des koagulierten Volumens ist die Frage der örtlichen Abtötung des Tumors sowie die Frage möglicher Tumorabsiedelungen eng verknüpft. With the establishment of the coagulated volume, the question of local destruction of the tumor as well as the question of possible Tumorabsiedelungen is closely linked. Da weder tatsächlich erreichte Temperaturen noch tatsächlich erreichte Eindringtiefen sicher nachweisbar sind, sind beide Verfahren zur curativen Behandlung (bspw. in der gastroenterologischen Chirurgie und der Gynäkologie) bislang nicht anwendbar. Since neither actually reached temperatures still average achieved penetration depths are sure detectable, both methods for curative treatment (eg. In gastroenterological surgery and gynecology) not yet applicable.

Durch Einsatz des erfindungsgemäßen Thermometrieverfahrens hat der Laserchirurg die Möglichkeit, Temperaturgradienten und koagulierte Volumenbereiche on line zu überwachen. By using the present invention, the laser Thermometrieverfahrens surgeon has the opportunity to temperature gradients and coagulated volume areas on line to be monitored. Daraus resultieren ganz erhebliche Fortschritte für die Therapie kleiner Tumoren im Hinblick auf ambulante Operationsmöglichkeiten ohne ausräumende Exzision und eine Verbreiterung des Anwendungsspektrums. This achieves significant advances in the treatment of small tumors in terms of outpatient surgical options without ausräumende excision and an expansion of the range.

In der Ophthalmologie wird die Laserkoagulation ua bei der Glaukombehandlung (transskerale Cyclophotokoagulation TSCPC) und zu Fehlsichtigkeitskorrekturen (Thermokeratoplastik) eingesetzt. In ophthalmology laser coagulation among others in glaucoma treatment (transskerale Cyclophotocoagulation TSCPC) and visual correction (thermokeratoplasty) is used. Alleiniger Steuerparameter während der TSCPC sind bislang bei vorgewählter Laserleistung die vorab geschätzte Bestrahlungsdauer. Sole control parameters during TSCPC are currently in selective laser power, the estimated pre-irradiation time. Darüberhinaus kann nicht beurteilt werden ob der Ziliarkörper oder angrenzende Strukturen getroffen werden. Moreover, it can not be judged whether the ciliary body or adjacent structures are taken. Die Effektivität dieses Eingriffs wird durch die Therapiekontrolle mit dem on line- Thermometrieverfahren deutlich verbessert. The effectiveness of this intervention is significantly improved by the treatment with the control on line- Thermometrieverfahren.

Aufstellung der verwendeten Bezugszeichen und Begriffe List of Reference symbols and terms used

Bild 1 : Ausführungsbeispiel Therapiekontrolle Figure 1: embodiment therapy monitoring
1 Zielvolumen 1 target volume
2 Laser, laserübertragender Wellenleiter oder (hochfrequenzübertragende Dipolanordnung) 2 laser, laser-transmitting waveguide or (radio frequency transmitting dipole)
3 Ein oder mehrere Schallwandler 3 One or more transducers
4 Akustischer Nachweispfad 4 Acoustic detection path

Literatur Literature

I) M. GAUTHERIE (Hrsg.) I) Gautherie M. (ed.)
Methods of Hyperthermia Control Springer Berlin Heidelberg (1990) Methods of Hyperthermia Control Springer Berlin Heidelberg (1990)
II) RL NASONI, T. BOWEN II) RL NASONI, T. BOWEN
Ultrasonic Speed as a Parameter for Non-Invasive Thermometry In: MIZUSHINA (Hrsg.): Non-Invasive Temperature Measurement Gordon & Breach Publishers 1 (1989), 101-107. Ultrasonic speed as a parameter for Non-invasive thermometry In: MIZUSHINA (ed.): Non-Invasive Temperature Measurement Gordon & Breach Publishers 1 (1989), 101-107.

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Clasificaciones
Clasificación internacionalA61N7/02, A61F9/008, A61B18/22, A61F9/011, A61B17/00
Clasificación cooperativaA61F9/008, A61F2009/00868, A61B18/22, A61F2009/00863, A61N7/02, A61B2017/00084, A61F2009/00853, A61F9/00821, A61F2009/00891, A61F2009/00844
Clasificación europeaA61B18/22, A61N7/02, A61F9/008, A61F9/008C
Eventos legales
FechaCódigoEventoDescripción
2 Oct 19968122Nonbinding interest in granting licenses declared
22 Nov 20018127New person/name/address of the applicant
Owner name: BENDE, THOMAS, DR.HABIL., 72116 MOESSINGEN, DE JEA
14 Mar 20028110Request for examination paragraph 44
12 Ene 20068131Rejection