Methods, systems, and associated implantable devices for dynamic monitoring of physiological and biological properties of tumors

• US 7,010,340 B2
• Filed: 02/18/2002
• Issued: 03/07/2006
• Est. Priority Date: 09/30/1998
• Status: Expired due to Term

• Current Assignee: SNC Holdings Corp.
• Original Assignee: Sicel Technologies, Inc., North Carolina State University (University of North Carolina System)
• Inventors: Mueller, Jeffrey, Nagle, H. Troy, Scarantino, Charles W., Kermani, Bahram Ghaffarzadeh, Hall, Lester C.
• Primary Examiner(s): Winakur, Eric F.
• Application Number:
  US10/078,310
• Publication Number:
  US 20020137991A1
• Time in Patent Office: 1,478 Days
• Field of Search: 600/361, 600/355, 600/364, 600/549, 600/436, 600/302, 128/903
• US Class Current: 600/436
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/085 combined with means for recording calibration data
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61N 5/1048 Monitoring, verifying, controlling systems and methods
• CPC Class Codes: A61N 5/1071 for verifying the dose delivered by the treatment plan
• CPC Class Codes: G16H 20/40 relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• CPC Class Codes: G16H 40/67 for remote operation
• CPC Class Codes: Y10S 128/903 Radio telemetry
• CPC Class Codes: Y10S 128/904 Telephone telemetry
• CPC Class Codes: Y10S 128/92 Computer assisted medical diagnostics

Abstract

Methods of monitoring and evaluating the status of a tumor undergoing treatment includes monitoring in vivo at least one physiological parameter associated with a tumor in a subject undergoing treatment, transmitting data from an in situ located sensor to a receiver external of the subject, analyzing the transmitted data, repeating the monitoring and transmitting steps at sequential points in time and evaluating a treatment strategy. The method provides dynamic tracking of the monitored parameters over time. The method can also include identifying in a substantially real time manner when conditions are favorable for treatment and when conditions are unfavorable for treatment and can verify or quantify how much of a known drug dose or radiation dose was actually received at the tumor. The method can include remote transmission from a non-clinical site to allow oversight of the tumor'"'"'s condition even during non-active treatment periods (in between active treatments). The disclosure also includes monitoring systems with in situ in vivo biocompatible sensors and telemetry based operations and related computer program products.

Claims

1. An implantable biocompatible sensor, comprising:

a sensor body having at least one sensor element configured for in vivo placement proximate a tumor site and to provide data responsive to at least one sensed internal parameter, and a transmitter coil and associated electronic components configured for wireless transmittal of the sensor data to a spatially remote receiver, said sensor body comprising a biocompatible material, wherein the sensor is inductively powered, wherein said sensor body is sized and configured to be chronically implanted in a subject, and wherein the at least one sensor element comprises a MOSFET-based radiation sensor element that is configured to detect ionizing radiation delivered to the subject.

2. An implantable biocompatible sensor unit according to claim 1, wherein the sensor is configured to be implanted in the subject for greater than four weeks, and wherein the MOSFET-based radiation sensor element is configured to detect radiation present proximate the tumor site for each of a plurality of temporally spaced apart therapeutic oncology radiation treatment sessions.

3. An implantable biocompatible sensor unit according to claim 1, wherein the at least one sensed internal parameter is a plurality of different internal parameters including radiation dose and temperature proximate the tumor site.

4. An implantable biocompatible sensor device comprising:

a first sensor body configured for chronic in viva implantation proximate a tumor site in a subject and to output data corresponding to at least one predetermined parameter and a transmitter coil and associated electronic components configured for wireless transmittal of the sensor output data to a spatially remote receiver, wherein the first sensor body comprises a radiation sensor element with a MOSFET-based radiation detection circuit, the radiation detection circuit being configured to provide MOSFET-based radiation data corresponding to detected radiation delivered to the subject in an oncology therapeutic treatment; and

a second sensor body having at least one sensor element configured for in vivo implantation at a location that is spaced apart from the first sensor body, the second sensor body configured to output data corresponding to at least one sensed internal predetermined parameter, the second sensor body comprising a transmitter coil and associated electronic components configured for wireless transmittal of the sensor output data to the spatially remote receiver.

5. An implantable biocompatibe sensor device according to claim 4, wherein said first sensor body is configured with an anchor portion to positionally attach to a desired portion thereby allowing attachment to a surface of or at a depth into the tumor.

6. An implantable biocompatible sensor device according to claim 4, wherein the first and second sensor bodies include internal electronic circuitry that is operative over an oncology therapeutic dose range of external beam radiation, and wherein the second sensor body comprises a MOSFET-based radiation detection circuit that detects local radiation.

7. An implantable biocompatible sensor device according to claim 6, wherein each of said first and second sensor bodies are chronically implantable and configured to sense temperature and wirelessly transmit temperature data to the remote reader for adjusting detected MOSPET-derived radiation data transmitted from the first and second sensors to provide calculated radiation dose values.

8. An implantable biocompatible sensor device according to claim 6, wherein the first and second bodies are configured to output MOSFET-based radiation exposure data associated with the amount of radiation that is received in vivo internally at their respective locations, the radiation corresponding to an oncology therapeutic radiation treatment session.

9. An implantable biocompatible sensor device according to claim 4, wherein said first and second sensor bodies are generally cylindrically shaped and sized and configured with a volume of about 1 cm³ or less and to be injectable into a desired implanted position in a subject.

10. An implantable biocompatible sensor device according to claim 4, wherein the first and second bodies are configured for chronic implantation in a subject, the chronic implantation being greater than about 4 weeks in length and to be able to provide radiation measurements while implanted in the subject.

11. An implantable biocompatible sensor device according to claim 4, wherein the first and second sensor bodies are configured to periodically output data associated with predetermined sensed internal parameters of the subject to generate dynamic data associated therewith.

12. An implantable biocompatible sensor device according to claim 11, wherein the sensor bodies are configured to output data periodically over a treatment period of at least about 4 weeks.

13. An implantable biocompatible sensor device according to claim 4, wherein the second sensor body is adapted to be positioned proximate normal tissue in a different region of the subject away from the first sensor body, and wherein the first and second sensor bodies are configured to periodically output data over time to provide substantially real-time data of the internal condition of a tumor or tissue proximate thereto and/or to evaluate the localized amount of radiation proximate the first and second sensor bodies.

14. An implantable biocompatible sensor device according to claim 4, wherein the first and second sensor bodies are configured to provide substantially real-time response data proximate in time to an active oncology treatment delivery to the subject.

15. An implantable biocompatible sensor device according to claim 4, wherein the second sensor body is configured to provide data on the potential toxicity of a treatment on normal tissue proximate the tumor site.

16. An implantable biocompatible sensor device according to claim 4, wherein the first and second sensor bodies are configured to periodically output data over an active cancer treatment period that comprises at least one of radiation and/or chemotherapy to provide data regarding the responsiveness of the tumor to the treatment.

17. An implantable oncology sensor, comprising:

a chronically implantable biocompatible sensor body configured to be implanted in vivo, the sensor body comprising a radiation detection circuit that is configured to provide MOSFET-based radiation exposure data, and electronics for wirelessly communicating with an external reader, wherein the radiation detection circuit is configured during an ionizing radiation exposure and inductively powered to wirelessly transmit radiation exposure data at a desired evaluation time.

18. An implantable sensor according to claim 17, wherein the sensor is configured to remain implanted and operate over a service life that includes a plurality of therapeutic oncology doses of radiation, wherein the sensor body is configured to be implanted proximate a target cancer treatment site, and wherein the sensor body comprises a temperature sensor that is configured to detect temperature of the target cancer treatment site.

19. An implantable sensor according to claim 18, wherein the temperature sensor is configured to detect an internally local temperature proximate in time to a therapeutic hyperthermia procedure.

20. An implantable sensor according to claim 19, wherein the MOSPET-based radiation detection circuit is configured to be unpowered during exposure to ionizing radiation delivered by external beam radiation therapy, and to be inductively powered after a radiation exposure to wirelessly transmit data corresponding to a dose of radiation that was delivered internally at the target site while remaining implanted.

21. An implantable senior according to claim 18, wherein the sensor electronics are configured to wirelessly transmit data corresponding to the amount of radiation delivered in vivo to the tumor site and the status of at least one internal condition to monitor the influence of at least one of a thermal, chemical, or radiation therapy on the tumor based on data transferred before, during, and after the therapy.

22. An implantable sensor according to claim 18, wherein the sensor is adapted to remain implanted in the subject to provide data regarding the minor site over a chronic treatment period of greater than about six weeks including during an active therapeutic cytotoxic chemical treatment period and a radiation treatment period to provide patient-specific response data to a clinician to allow oncologic therapeutic treatment decisions based on the data provided by the implanted sensor.

23. An implantable sensor according to claim 22, wherein the sensor is adapted to he implanted proximate one of a carcinoma or scarcoma.

24. An implantable sensor according to claim 23, wherein the sensor is adapted to be implanted proximate a solid mass tumor.

25. An implantable sensor according to claim 17, wherein the sensor has an enclosed body with a size of about 1 cm³ or less.

26. An implantable sensor according to claim 17, wherein the implanted sensor unit has an operational in vivo service life of at least about 4 weeks.

27. An implantable sensor according to claim 17, in combination with at least one additional implantable sensor comprising a MOSFET-based radiation detection circuit for detecting radiation during therapeutic medical procedures, wherein the implantable sensors are implanted at spaced apart positions in the subject, and wherein the sensors are individually electronically identifiable to allow a remote reader to serially communicate with the different sensors.

28. An implantable sensor according so claim 17, wherein the sensor body is a self-contained capsule unit that is sized and configured to be injectably positioned in the body using a canula wish a bore.

29. An implantable sensor according to claim 17, further comprising an integrated chip residing inside the sensor body that includes at least some of the sensor circuitry and/or radiation detection circuit components, and a coil for inductive powering that cylindrically extends about at least a portion of the perimeter of the integrated chip.

30. An oncology medical kit comprising:

a plurality of discrete sterilized chronically implantable sensors for oncology patients, the implantable sensors having a biocompatible sensor body and are configured to wirelessly communicate with a common external reader, wherein the implantable sensors are inductively powered, wherein a plurality of the sensors are configured to remain concurrently implanted and operative in a patient over an oncology treatment period, and wherein the sensors comprise a MOSFET-based radiation detection circuit in the sensor body configured to detect radiation associated with oncology treatments received in vivo.

31. A kit according to claim 30, wherein the sensors further comprise a temperature sensor in the sensor body in communication with the wireless communication circuit and configured to sense temperatures at a target tumor treatment site to provide temperature data.

32. A kit according to claim 31, further comprising an integrated chip residing inside the sensor body that includes at least some of the sensor circuitry and/or radiation detection circuit components, and a coil for inductive powering that cylindrically extends about at least a portion of the perimeter of the integrated chip.

33. A kit according to claim 31, further comprising an integrated chip residing inside the sensor body that includes at least some of the sensor circuitry and/or radiation detection circuit components and a ferrite substrate for inductive powering.

34. A kit according to claim 31, wherein the temperature sensor is configured to determine elevated local temperatures to provide temperature data that can be monitored by a clinician to evaluate whether the target tumor treatment region is appropriately heated during a hyperthermia treatment.

35. A kit according to claim 30, further comprising an injection delivery device configured and sized with a canula bore that injectably holds at least one of the sensor bodies therein for injectable placement in the patient at a subsurface target tumor treatment site.

36. A kit according to claim 30, wherein the sensors are configured to sense at least one additional local predetermined biocondition to provide a clinician data for assessing patient receptiveness for and/or efficacy of an oncology treatment.

37. A kit according to claim 30, wherein the sensors are configured to remain implanted and operative in the patient for at least about 4 weeks, and wherein the sensors are unitized and sized and configured to have a volume of about 1 cm³ or less.

38. A kit according to claim 30, wherein the sensor electronics are configured to wirelessly transmit data corresponding to the status of at least one additional internal condition to monitor the influence of at least one of a thermal, chemical, or radiation therapy on the tumor based on data transferred before, during, and after an active therapy session and/or treatment.