WO2018011431A1 - Marqueur de détection implantable de manière temporaire - Google Patents

Marqueur de détection implantable de manière temporaire Download PDF

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Publication number
WO2018011431A1
WO2018011431A1 PCT/EP2017/067961 EP2017067961W WO2018011431A1 WO 2018011431 A1 WO2018011431 A1 WO 2018011431A1 EP 2017067961 W EP2017067961 W EP 2017067961W WO 2018011431 A1 WO2018011431 A1 WO 2018011431A1
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WIPO (PCT)
Prior art keywords
tissue
light
module
treatment
mode
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PCT/EP2017/067961
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English (en)
Inventor
Bernardus Hendrikus Wilhelmus Hendriks
Michel Paul Barbara Van Bruggen
Harold Agnes Wilhelmus Schmeitz
Torre Michelle BYDLON
Drazenko Babic
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Koninklijke Philips N.V.
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Publication of WO2018011431A1 publication Critical patent/WO2018011431A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0031—Implanted circuitry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00022—Sensing or detecting at the treatment site
    • A61B2017/00057—Light
    • A61B2017/00061—Light spectrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00022—Sensing or detecting at the treatment site
    • A61B2017/00084—Temperature
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/30—Devices for illuminating a surgical field, the devices having an interrelation with other surgical devices or with a surgical procedure
    • A61B2090/309—Devices for illuminating a surgical field, the devices having an interrelation with other surgical devices or with a surgical procedure using white LEDs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/373—Surgical systems with images on a monitor during operation using light, e.g. by using optical scanners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/373—Surgical systems with images on a monitor during operation using light, e.g. by using optical scanners
    • A61B2090/3735—Optical coherence tomography [OCT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/392—Radioactive markers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3925—Markers, e.g. radio-opaque or breast lesions markers ultrasonic
    • A61B2090/3929—Active markers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3937—Visible markers
    • A61B2090/3945—Active visible markers, e.g. light emitting diodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14539—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring pH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A61N2005/0612—Apparatus for use inside the body using probes penetrating tissue; interstitial probes

Definitions

  • the invention relates to an implantable device, to a system for assessing tissue response, to a method for assessing tissue response, to a computer program element and to a computer readable medium.
  • Neoadjuvant and adjuvant therapy are an important treatment options in oncology.
  • therapies for instance, chemotherapy
  • Selecting the most effective one may sometimes be a challenging task.
  • evaluation of the effectiveness of different therapies (for instance, chemotherapy) in a short time frame, especially during the early phase of treatment administration, is not an easy task.
  • MRI imaging and PET-CT have shown to be able to detect therapy response
  • a drawback is that it takes a significant time frame and can only be performed at a limited number of time points. Additionally new therapy agents are not always showing morphological changes of the tumor making tumor response detection more difficult by imaging (i.e. the size is not changing).
  • Another way is to analyze the resected tumor after neoadjuvant therapy. Although this allows detailed molecular analysis, the drawback is that only one therapy can be tested.
  • intra- operative imaging Another issue in oncology is that there may be a need to provide intra- operative imaging. This is because the anatomy that has been imaged pre-operatively may change significantly during surgery. For example, deformations may be caused by tissue cutting or by the movement of an organ, e.g. the liver, in the human body. Thus, there may be a significant non-linear deformation of the tissue and a simple registration of intra-operative imaging with preoperative imaging may be difficult.
  • tissue markers in order to find back the relevant tissue identified in preoperative imaging during a subsequent procedure.
  • Such markers are introduced into the tissue during the pre-operative phase.
  • X-ray absorbing markers may be used that are visible in an X-ray image acquired intra-operatively.
  • the usage of X-rays during surgery should be limited, not only to limit a dose of harmful radiation received by a patient, but also for example due to the fact that the surgery environment has to be sterile. This is more difficult when applying X-ray imaging, as intraoperative X-ray imaging requires the surgeon to wear lead shielding cloths, which may be inconvenient.
  • an implantable device comprising a light module as a first signaling module, a switch configured to switch the light module between i) a beacon mode to emit light as a localization signal to allow localization of the device whilst implanted in tissue, and ii) a monitoring support mode to generate interrogator light; and a monitoring module operable in a monitoring mode to monitor for a change in tissue in which the device is implantable, the monitoring module comprising a sensor unit configured to measure a physical property of the interrogator light in relation to tissue surrounding the device.
  • the monitoring module comprises a memory module configured to store measurement data, preferably a time series of measurement data, representing the measured physical property.
  • the sensor unit is configured to measure a physical property of the interrogator light as it is reflected back from surrounding tissue.
  • the light module when in interrogation mode, is configured to switch between different light emission wavelength bands.
  • the light module is further switchable into a data transmission mode to transmit to a receiver measurement data representing the measured physical property, the data being transmitted by means of modulated light.
  • the device may comprise a wireless transmission component configured to transmit measurement data representing the measured physical property.
  • the light module is further switchable into a treatment mode wherein said change in tissue is effected by means of light treatment.
  • the device may comprise a dedicated treatment module configured to at least partially effect said change in tissue, for example by means of radio frequency, chemical or ultrasound treatment of the tissue.
  • the sensor unit may further comprise i) an ultrasound sensor, ii) a pH sensor, iii) an oxygenation sensor, and/or iv) a temperature sensor.
  • the different light when in monitoring support mode, is emitted by the light module i) as a series of light pulses at respective, different frequencies or ii) as a non-pulsed light beam.
  • the measurement signal is suitable for spectroscopic analysis.
  • the at least a part of the signaling module and/or at least a part of the monitoring module is/are at least partly embedded in an optically transparent substrate. This allows for better transmission of the light signal to the outside of the device.
  • an ultrasound emitting module may be provided as a second signaling module.
  • radioactive radiation is used and emitted by a radioactive element for the second signaling module, with the signal being radioactive radiation.
  • a system for assessing tissue response comprising a device as per any one of the previous, and a signal analyzer module configured to analyze the measurement signal to quantify the change in the tissue.
  • the signal analyzer module is configured for spectroscopic analysis.
  • a system comprising two or more of said devices, at least one operated in treatment support mode and at least one other device operated in monitoring mode. This allows covering larger regions or anatomies.
  • the proposed device forms an active marker device that can be tracked, e.g. by cameras or other devices or simply by visual inspection whilst at the same time the marker can be used to monitor therapy/treatment response, preferably through spectral analysis of light in relation to tissue to which the therapy/treatment is administered.
  • This allows for an efficient workflow, in particular when the device is mainly envisaged for an only temporary implantation.
  • Prompt localization and hence removal can be achieved with the proposed device.
  • X-ray based makers can be avoided and the device allows essentially continuous measurement of treatment effectiveness in a very short time frame, of days or even hours. In addition it can be easily localized and hence quickly removed at the conclusion of the treatment monitoring.
  • the marker device can also at least partially provide the treatment.
  • the proposed device allows measuring the changes in the tissue over time, based on multiple wavelength bands spectroscopy and at the same time the device is capable of producing a light beacon (e.g., during surgery) that allows local tissue localization/tracking.
  • the switch allows activation of the device for different modes: (1) monitoring mode for therapy response monitoring and (2) a beacon mode (e.g., light based) to allow localization of the device.
  • the light module is used switchably in different modes: in a beacon mode or a sensing/monitoring support mode where the signal emitted is used as an interrogator signal to learn about change that occur in the tissue during treatment.
  • the proposed device can be used prior to surgery for therapy response measurements and during any surgical procedure that requires precise tissue resection.
  • a method of assessing tissue response comprising:
  • Figure 1 shows a block diagram of components of an implantable device
  • Figure 2 shows a flow chart of a method of assessing tissue response based on an implantable device.
  • FIG. 1 With reference to Figure 1 , there is shown a schematic block diagram of an implantable device ID as envisaged herein in one embodiment.
  • the device ID is implantable in human tissue, for instance at a lesioned site such as a cancer site or similar.
  • the overall shape is in one embodiment elongated or of cylindrical shape or of ellipsoidal shape with pointed tip portions as shown in Figure 1 in side-elevation. But this is not to exclude other shapes such as spherical, cuboidal, disk or lens-shaped or others, also envisaged herein in alternative embodiments.
  • the device is implantable at the desired site in the human tissue TS and is envisaged to remain inside INS the patient body at the intended site during its use.
  • the device may include suitably formed anchor portions to ensure the device does not move during use relative to the tissue TS into which it is implanted.
  • the implantable device is suitably dimensioned and can be very small such as a few mms in length and approximately 1 mm in diameter or width. Other, larger devices are also envisaged depending on the task at hand.
  • the device is suitably small dimensioned so that it fits into a cannula or a syringe or injector (manual or automatic) for delivery into the human body at the lesioned site.
  • the device may be implanted in key-hole surgery inventions by suitable delivery tools or during an open surgical invention.
  • An example of such interventions is cancer resection. After removal of cancer tissue, the marker is inserted in proximity to the resection site.
  • the device may also be used in other surgical interventions or indications, not just cancer related.
  • the implantable device ID comprises a body portion B or a capsule formed from a bio-compatible material.
  • a number of components are partially or fully embedded in the capsule. The components will be described in more detail below. Broadly, the
  • implantable device ID serves a dual function: one function is that it can be localized from the outside OTS by emitting a localization signal whilst the device ID is implanted inside INS the human body/tissue.
  • the other, additional function of the implantable device ID is to perform tissue monitoring in order to monitor efficacy of one or more different treatment types or regimes applied to the patient whilst the device resides in the tissue TS.
  • the implantable device ID is envisaged to reside in the tissue whilst one or more, preferably a plurality of different regimes are administered.
  • the treatment types or regimens include acting in any one or a combination of different manners on the body or surrounding tissue in order to destroy or mitigate the lesion.
  • the treatment type may include acting directly on the tissue or the action is indirect by acting on the metabolism of the patient.
  • the implanted device ID performs a monitoring functionality of the surrounding tissue in which it is embedded and in doing so acquires different sets of measurements collected at or from the tissue. The different measurements are taken during the respective treatment deliveries so that each set measures a property of or on relation to the tissue whilst the respective one of the treatment types or regimens is being delivered.
  • tissue property measurements are preferably a tell-tale about the success of the respective treatment types or regimens delivered.
  • the sets of measurements can then be analyzed in order to establish efficacy of the treatment regimens. More particularly it can be established which one of the many of the plurality of treatment regimens delivered is the most effective one.
  • the different treatment regimens may be delivered as respective test trials whilst collecting the measurements to establish the most effective treatment type or regimen.
  • the implantable device In addition to the implantable device being configured to monitor treatment trials, and is also localizable from the outside through a localizing signal which is emitted by the device. This allows easier in-situ tracking of the device, for instance to efficiently recover the device from the human tissue. Because of its localizability through the localization signal, the implantable device may also be referred to as an active marker. The device allows a surgeon for instance to localize or re-find the lesioned site, in case further re-sectioning or other interventions are necessary.
  • components of the implantable device ID include a monitoring module MM and a light module LX as a signaling module, also referred to as a localization module LX.
  • a monitoring module MM and a light module LX as a signaling module, also referred to as a localization module LX.
  • switch SW to operate the localization module.
  • the localization module LX may be switched to operate in different modes.
  • the switch SW is switchable wirelessly, such as via RF activation or other.
  • a power source PS to power operation of the device, in particular to supply energy to the various components, in particular the monitoring module and the localization module.
  • a single, central, power source supplying all or some of the components or, alternatively or in addition, there are additional different, dedicated power sources supplying each ones of only the respective components with energy.
  • the localization module LX of the active marker ID may be activated or switched to a different mode when the active marker device is already implanted in the patient body TS, e.g., by sending an RF activation signal or other.
  • the monitoring module MM may be remotely switched on or off to start or cease the monitoring at a user's request. This is useful when changing from one treatment regimen to another. The monitoring module is switched off at the end of one treatment trial. Arrangements (e.g. drug delivery, etc.) are then made to put the next treatment regimen into place, and the monitoring module MM is then switched on again, and so on.
  • the components are fully or partly embedded in the body B formed from a bio-compatible material such an epoxy resin (e.g., EPO-TEK® 301 or 301-2) or other.
  • a bio-compatible material such as an epoxy resin (e.g., EPO-TEK® 301 or 301-2) or other.
  • the material complies at least with USP class VI Biocompatibility Standards.
  • the material is as a whole (or at least includes portions that are) optically transparent.
  • index of refraction is about 1.5.
  • optical transmission is about 90% at 3000 Angstrom or about 98-99% at 3100 Angstrom to 2.5 microns or is greater than 97% at 3200-9000 Angstrom or is greater than 80% at 9100 Angstrom to 2.6 microns.
  • the localization module is capable of being operated in a beacon mode (for instance by operating the switch SW) to issue a localization signal that allows localization of the device whilst device ID is resident in the tissue. That is, the localization signal should be capable of penetrating through the surrounding tissue to the outside OTS where it can then be registered by a localization sensor, camera or by visual inspection.
  • the localization module is a light module capable of emitting light preferably in the optical range.
  • the intensity of the light is high enough so that it can penetrate through one or more layers of tissue to the outside of a patient, and can then be registered by medical personnel either with a tool (camera) or simply by visual examination.
  • the light in the beacon mode, the light has an easily discernible, ostensible color against the surrounding skin, such as orange, red or green or other.
  • the intensity of the emitted beacon light should be strong enough so that it can penetrate through two, three or more cm of human tissue for it to be discernible from the outside.
  • the monitoring module MM in more detail, this includes a sensor unit SU and, optionally, a permanent data memory MEM.
  • the sensor unit SU is configured to measure a physical property of the interrogator light in relation to the surrounding tissue in which the device is embedded. This property, for example a spectrum of the interrogator light as it is reflected back from surrounding tissue, is then converted via suitable circuitry (ADC, filtering, amplification etc., or other conditioning) into a DC signal.
  • ADC analog to digital converter
  • the measurements are performed over time repeatedly at as suitable sampling rate (days, hours, or minutes or seconds) whilst the respective treatment type or regimen is delivered.
  • a time series of measurement signals is acquired and optionally these may be stored in suitable format in the memory.
  • the measurement signal is so chosen that it is thought to capture an ongoing change in the surrounding tissue caused by the administration of the treatment.
  • the measurement signals may be digitalized by suitable ADC circuitry and possible other signal conditioning circuitry into digital values tagged with a time stamp that indicates the point in time at which they have been acquired.
  • the time tag may indicate the absolute time (date and time) or it may simply indicate an ordinal number.
  • the separate measurement values can then be stored in association with their respective time tags in the permanent on-board memory CMEM.
  • these stored measurement values and their corresponding time stamps form a respective time series. For example, these represent a change or development in spectral characteristics of the tissue surrounding an implanted device over time.
  • the sensor unit SU includes firstly one or more light sensors and further, optionally, a pH sensor, a blood/tissue oxygenization sensor, a temperature sensor and/or others.
  • the monitoring unit is configured to support spectroscopic analysis of the tissue.
  • the sensor unit SU is (or at least includes) a light sensor responsive to optical light with wavelength in the range between 200 nm and 1700 nm, preferably between 400 nm and 1000 nm.
  • the light sensor SU (preferably of the CMOS type) may be arranged as one or more photodiodes which are sensitive to in particular the later wavelength range mentioned in the previous sentence. For example, different photodiodes may be used each being sensitive to a particular sub-band in the operating wavelength range.
  • the optical light is received as the feedback signal from the tissue.
  • the light is issued into the tissue.
  • the tissue then reflects the light back and it is this reflected light which is then registered by the light sensor unit as SU.
  • the reflected light may include back-scattered light, diffusely reflected light or fluorescent light as the case may be.
  • Interrogating light may be issued from an interrogator source outside the device, but preferably the integrator light source is included as a component of the implantable device ID.
  • the device may include in one embodiment a dedicated interrogator light source (not shown) but most preferably the interrogator light function is likewise performed by the earlier mentioned light source LX that sends out the beacon light for the purpose of localization.
  • light module LX is switchable by switch SW between two modes to serve a dual function: a) in the beacon mode it emits light localizing the device whilst resident in tissue, for example light at a frequency and intensity suitable for penetrating through one or more tissue layers ue and b) the same light source LX can be switched into an interrogator or monitoring support mode to generate the interrogator light that is preferably suitable for spectral analysis of the tissue which is then reflected back from the tissue to the sensor SU.
  • a response of e.g. tumor tissue to treatment can be determined through changes in frequency response of the light being reflected by the tumor tissue compared to the initial frequency spectrum of the interrogating light signal.
  • the light source LX when in interrogation mode, or the dedicated interrogator light source is switchable by switch SW (or by a different switch) between different light emission wavelength bands. Changes in the tissue over time caused by the treatment can be measured based on multiple wavelength bands spectroscopy in one embodiment.
  • the light source LX or the dedicated interrogator light source is operable to emit several different wavelength bands of light in a repetitive way.
  • the interrogator light source is operated by the switch SW to emit in sequence the respective different wavelengths.
  • this "cycling" through the different wavebands is repeated a number of times.
  • the sensor SU is read-out by the module MM's read-out electronics with the same repetition rate. This synchronized operation allows detection of parts of the diffuse reflectance spectroscopy spectrum. With proper selection of the wavelength bands, information on the therapy response can be obtained. See for instance J. Spliethoff et al in their “Monitoring of tumor response to cisplatin using optical spectroscopy" Translational Oncology 7 (2014) pp230-239).
  • the light source LX (or the dedicated interrogator light source, if any) includes one or more LEDs. These are envisaged to small (up to 1.5 mm in any dimension, preferably even less than 1 mm) and are configured to emit white light. Preferably the LEDs are low power. Suitably LEDs include Nichia's NESL 157AT-H3 LED or the like. The LED(s)s as envisaged herein preferably have a luminous flux of typical 11.5 lm (lumens) and a luminous intensity of typically 4.0 cd (Candelas). The various LEDs emit preferably at different wavelength emission bands. Another example of a suitable LED type envisaged herein is the HSMW white ChipLEDs.
  • LEDs have sizes 1.5x0.8x0.6mm.
  • PICOLED® model of ROHM is the PICOLED® model of ROHM. These LEDs have sizes 1.0x0.52x0.2mm.
  • the LEDs are connected to a dedicated (small) battery and the switch circuit SW. Alternatively, the LEDs are powered by the common power source PS.
  • a single LED is used in conjunction with several photodetectors, each being coupled with different wavelength filters in order to perform multi-band spectroscopy by switching between the wavebands as preferred herein. It should be noted that other types of spectroscopic methods and hardware setups are specifically envisaged herein in alternative embodiments.
  • the light used for the spectral analysis may be administered not as pulses but as a non-pulsed light beam whilst changing the wavelength.
  • diffuse reflectance spectroscopy there is envisaged fluorescence spectroscopy, Raman spectroscopy, OCT (Optical coherence tomography), and others.
  • OCT Optical coherence tomography
  • the implantable device ID may then be recovered from the body. Because of the localization functionality this is particularly easy as the surgeon may easily re-find where the device was implanted.
  • the memory is coupled with the read-out device that is suitable to transmit the data from the memory to an analyzer unit SM.
  • the analyzer unit SM may be a general purpose computer running suitable analyzing software.
  • the measurement data from the memory can then be loaded on to the computer by USB connection or wirelessly by Bluetooth or otherwise.
  • the measurements can then be analyzed to determine the best treatment regime.
  • the implantable device is not only localizable from the outside but it supports treatment trials in-situ monitoring of tissue response to find the best suitable treatment for the human or animal patient.
  • the measured wavelength bands are translated by the analyzer SM into relevant parameters linked to the changes in the tissue brought about by the treatment regime.
  • the measured wavelength bands are translated into parameters linked to water and fat content as well as scattering.
  • Another way is to make use of the wavelength segments and translate them into combined parameters as described by B. Hendriks et al. in “Nerve detection with optical spectroscopy for regional anesthesia procedures", Journal of Translational Medicine, 2015 Dec 15;13:380.
  • Corresponding translation schemes into relevant parameters are implemented by the analyzer SAM for the other monitoring embodiments where different tissue properties are measured (US, temperature, pH-values, etc.).
  • the measurement memory MEM is optional.
  • the measured values are transmitted through a wireless transmission component TX (preferably an RF or Wi-Fi transmitter) to the outside world OTS where they are received by a receiver RX.
  • a wireless transmission component TX preferably an RF or Wi-Fi transmitter
  • the measurement values are directly transmitted to the receiver outside the body as they are acquired. This may not exclude of course temporary storage in a buffer or otherwise to ensure that no data gets lost in the transmission.
  • the signal which is used to transmit the measurement data must be suitably chosen to allow passage through the surrounding tissue.
  • a dedicated transmission component TX is not necessary in other embodiments where the respective interrogation component is used in a data transmission mode to effect the data transmission to the outside world OTS.
  • the monitoring module MM operates on optical light
  • it is the respective light module LX that may operate to transmit suitably modulated light to effect the data transmission.
  • the switch SW or a different, dedicated switch, is used to switch the light module LX into a further mode, i.e. a transmission mode, to transmit the data to the outside world to a suitable receiver RX.
  • the transmitted modulated light can be captured by a smartphone, tablet or other mobile or even desktop device.
  • a suitable receiver "app" may be provided on the handled device (e.g. smartphone) to interpret the data sent by the marker ID.
  • the measured data captured during the monitoring may be transmitted as the data is acquired.
  • the light module LX oscillates between the two modes, data acquisition or monitoring support mode, and transmission mode.
  • light module LX remains in a data acquisition mode for a number of cycles and only then is there a switchover to transmission mode so as to transmit a plurality of measurement data acquisitions at once in a bundle or a packet.
  • the localization module LX is used for all three of these functions and is suitably switched by the switch between these modes. More specifically, the light source LX in one embodiment is used a) for localization purposes, b) is used for sending out an interrogating light to support spectroscopic analysis (in other words, this light is registered by the sensor unit SU) and c) the emitted light may also be suitably modulated in data transmission mode to transmit the acquired data to the outside world.
  • the proposed implantable device can be used while the treatment is administered by outside agents (not included in the implantable device), it is a preferred embodiment that the device includes a treatment module TM to effect the different treatment types or regimens.
  • the implantable device ID can support a wide range of different treatment types or regimens. More particularly, if a multi-sensor is used, the implantable device can support different types of treatment or regimens at the same time.
  • the treatment types or regimens supportable by the proposed implantable device ID include any one or a combination of the following: light or laser therapy, chemical therapy (which includes immuno -therapy), radio frequency based therapy or ultrasound treatment therapy, or any other.
  • the treatment module of the implantable device is configured for light treatment.
  • the light of the smart marker ID is used to perform photodynamic therapy (PDT).
  • the treatment module is configured for radiative treatment.
  • the treatment module TM includes a radiative element allowing local radiation therapy.
  • the power source may be a nuclear battery, converting part of the radiation into electric current.
  • the treatment module is configured for thermo -therapy. In this
  • the treatment module TM in arranged as a heating element suitable for thermotherapy.
  • the treatment module includes a container unit and a discharger.
  • the (bio-)chemical substance e.g., a drug or a protein or other biological material such as in immuno -therapy
  • the dosage regime is held in memory of the treatment module and controlling signals are issued to the discharger to effect at pre-defined times a pre-defined quantity of the chemical into the tissue to effect the treatment.
  • a similar control- setup via suitable actuators is also envisaged for the other treatment module embodiments mentioned above. Operation of the treatment module may also be controlled remotely by a user.
  • the treatment module may include the dedicated light source to effect the treatment but most preferably the treatment functionality is again integrated into the same light module that is used for any one or all of the previous three functionalities.
  • the light source performs four functionalities: those are - the three earlier mentioned ones in addition to the treatment functionality.
  • a dedicated light with a specific intensity or frequency is emitted and this is controlled by the switch.
  • the switch merely serves as a trigger device to trigger when the measurements are to be taken.
  • the nature of the light frequency, intensity etc. is not changed for some or any of the four functionalities.
  • the capsule B material is preferably not only bio-compatible but also light transparent as a whole.
  • the whole of the body may not necessarily be light transparent but it may suffice for it to include one or more window portions (formed from light transparent material) at which the sensors and/or light source are situated to allow transmission there through to the surrounding tissue.
  • the whole of the body is formed from optical light transparent material although this is envisaged in a preferred embodiment.
  • the components of the active marker ID in particular the monitoring module MM and/or the switch SW may be arranged in hardware such as a suitably programmed
  • the analyzer SM may also be integrated as a microchip in the marker ID but may run instead external to the device ID as a software module or routine on a general purpose computing unit PU or a mobile or handheld device such as a laptop, smartphone, tablet, etc.
  • At least two of the above described active markers ID are implanted.
  • the two smart markers ID can be operated so that the light emitted from the first marker can be detected by the second marker. This allows measurement over larger tissue length because the measurement is performed in transmission (from one smart marker to the other) rather than in diffuse reflection (emission and collection by the same marker).
  • respective sets of measurements are collected by the in-situ device ID resident in the tissue of a patient.
  • the sets of measurements represent a physical property of interrogator light.
  • the interrogator light is provided by the light module of the device, with the light module switched to the monitoring support mode.
  • the measurements of the physical property of the interrogator light are in relation to the surrounding tissue, whilst the tissue is acted upon in respective manners. These different manners represent different treatment types or regimes that differ in nature and/or intensity.
  • the light module is switched to a beacon mode wherein light as a beacon signal is emitted by the device.
  • the beacon signal allows the device to be localized whilst resident in tissue.
  • the beacon signal can be emitted upon user request, e.g., via remote control of the switch.
  • the beacon signal may be issued before, after or while the data measurements are collected; in the latter case, the light module is switched between beacon mode and monitoring support mode in an alternating manner.. Because the device is envisaged to remain in tissue only temporary, the beacon signal allows quickly find the device and hence support efficient workflow.
  • step S230 the sets of measurements are then retrieved from the device. This can be done after removal of the device from the tissue (the beacon signal facilitates finding the device quickly so it can be promptly removed) and connecting or coupling the same communicatively with an analyzer module such as a data analyzer software tool or other that runs on a general purpose computer, or that runs as a program ("(mobile) app") on a hand held device such as a tablet or smart phone or other device.
  • the measurement data are preferably retrieved from a memory module that is part of the device.
  • the measurements are transmitted from the implanted device to a receiver located outside the body of the patient, either by modulating a light being outputted by a light module of the device so as to encode the measurement data, or by a wireless transmitter such as a Wi-Fi transmitter.
  • step S240 the sets of measurements so retrieved from the device are then analyzed to establish the respective changes in the tissue that occurred during the respective treatment courses. In this way, the most effective treatment course can be established for the human or animal patient.
  • a processing unit such as microprocessor
  • an outside computing unit based on computer code held in memory.
  • the proposed active sensing marker is inserted into the body, for instance in the tumor.
  • the next step is to administer a treatment regimen, such as a specific
  • the monitoring module MM then operates to measure the
  • the surgeon activates the smart sensing marker by switching the light module to beacon mode, so that the marker functions as a light beacon for performing local tumor tissue tracking.
  • the marker storage device is read out to analyze the effect of the various chemotherapies. Finally, a selection is made of the most effective chemotherapy for follow up therapy after surgery.
  • a computer program product comprises instructions to cause an appropriate system to execute the method steps of the method according to one of the preceding embodiments.
  • the computer program element might therefore be stored on a computer unit, which might also be part of an embodiment of the system.
  • This computing unit may be adapted to perform or induce a performing of the steps of the method described above.
  • the computing unit can be adapted to operate automatically and/or to execute the orders of a user.
  • a computer program may be loaded into a working memory of a data processor.
  • the data processor may thus be equipped to carry out the method of the invention.
  • This exemplary embodiment of the invention covers both, a computer program that right from the beginning uses the invention and a computer program that by means of an up-date turns an existing program into a program that uses the invention.
  • the computer program product might be able to provide all necessary steps to fulfill the procedure of an exemplary embodiment of the method as described above.
  • a computer readable medium such as a CD-ROM
  • the computer readable medium has a computer program product stored on it as described by the preceding section.
  • a computer program may be stored and/or distributed on a suitable medium
  • non-transitory medium such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the internet or other wired or wireless telecommunication systems.
  • the computer program may also be presented over a network like the
  • World Wide Web can be downloaded into the working memory of a data processor from such a network.
  • a medium for making a computer program element available for downloading is provided, which computer program element is arranged to perform a method according to one of the previously described embodiments of the invention.

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  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Surgery (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biophysics (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Computer Networks & Wireless Communication (AREA)
  • Physics & Mathematics (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

L'invention concerne un dispositif implantable (ID), comprenant un premier module de signalisation de la localisation (LX) pouvant fonctionner en mode balise pour émettre un signal de localisation afin de permettre la localisation du dispositif une fois implanté. L'invention concerne également un module de surveillance (MM) pouvant fonctionner en mode surveillance pour surveiller les modifications du tissu dans lequel le dispositif est implanté.
PCT/EP2017/067961 2016-07-15 2017-07-17 Marqueur de détection implantable de manière temporaire WO2018011431A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16179591.9 2016-07-15
EP16179591 2016-07-15

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WO2018011431A1 true WO2018011431A1 (fr) 2018-01-18

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EP3725257A1 (fr) * 2019-04-16 2020-10-21 Koninklijke Philips N.V. Marqueur de tissu électroluminescent actionné par la lumière

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US20030139661A1 (en) * 2001-01-22 2003-07-24 Yoav Kimchy Ingestible device
WO2004091361A2 (fr) * 2002-12-24 2004-10-28 Entrack, Inc. Capsule optique et procede spectroscopique pour le traitement ou le diagnostic du tractus intestinal
US20090097725A1 (en) * 2007-10-15 2009-04-16 Hagai Krupnik Device, system and method for estimating the size of an object in a body lumen
WO2012066553A1 (fr) * 2010-11-16 2012-05-24 Given Imaging Ltd. Dispositif d'imagerie in vivo et procédé permettant d'effectuer une analyse spectrale

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WO2004091361A2 (fr) * 2002-12-24 2004-10-28 Entrack, Inc. Capsule optique et procede spectroscopique pour le traitement ou le diagnostic du tractus intestinal
US20090097725A1 (en) * 2007-10-15 2009-04-16 Hagai Krupnik Device, system and method for estimating the size of an object in a body lumen
WO2012066553A1 (fr) * 2010-11-16 2012-05-24 Given Imaging Ltd. Dispositif d'imagerie in vivo et procédé permettant d'effectuer une analyse spectrale

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3725257A1 (fr) * 2019-04-16 2020-10-21 Koninklijke Philips N.V. Marqueur de tissu électroluminescent actionné par la lumière
WO2020212466A1 (fr) 2019-04-16 2020-10-22 Koninklijke Philips N.V. Marqueur de tissu électroluminescent alimenté par lumière

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