US20140257262A1 - Interstitial ultrasonic disposable applicator and method for tissue thermal conformal volume ablation and monitoring the same - Google Patents

Interstitial ultrasonic disposable applicator and method for tissue thermal conformal volume ablation and monitoring the same Download PDF

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Publication number
US20140257262A1
US20140257262A1 US13/794,347 US201313794347A US2014257262A1 US 20140257262 A1 US20140257262 A1 US 20140257262A1 US 201313794347 A US201313794347 A US 201313794347A US 2014257262 A1 US2014257262 A1 US 2014257262A1
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Prior art keywords
thermal ablation
applicator
treatment
transducer
interstitial
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Alexandre Carpentier
An Nguyen-Dinh
Jean-Yves Chapelon
Rémi Dufait
Christophe Notard
Françoise Chavrier
Cyril Lafon
Michael Canney
William Apoutou N'DJIN
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Universite Pierre et Marie Curie Paris 6
Institut National de la Sante et de la Recherche Medicale INSERM
Carthera SAS
Vermon SA
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Individual
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Assigned to CARTHERA S.A.S. reassignment CARTHERA S.A.S. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CANNEY, MICHAEL
Assigned to UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6) reassignment UNIVERSITE PIERRE ET MARIE CURIE (PARIS 6) ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CARPENTIER, ALEXANDRE
Assigned to Vermon S.A. reassignment Vermon S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NGUYEN-DINH, AN, DUFAIT, REMI, NOTARD, CHRISTOPHE
Assigned to INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) reassignment INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) CHANGE OF ADDRESS Assignors: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Priority to PCT/IB2014/059604 priority patent/WO2014141052A1/en
Priority to EP14713915.8A priority patent/EP2968982B1/de
Priority to CN201480024123.7A priority patent/CN105555362B/zh
Publication of US20140257262A1 publication Critical patent/US20140257262A1/en
Priority to US15/789,426 priority patent/US10987524B2/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia
    • A61N7/022—Localised ultrasound hyperthermia intracavitary
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0043—Ultrasound therapy intra-cavitary
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0047—Ultrasound therapy interstitial
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0078—Ultrasound therapy with multiple treatment transducers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia
    • A61N2007/025—Localised ultrasound hyperthermia interstitial

Definitions

  • the present invention relates generally to an ultrasound medical method and device for interstitial disposable use having multiple ultrasound capacitive micromachined ultrasonic transducers (CMUT) to thermally ablate a conformal volume lesion and to monitor the ablated volume with the same apparatus.
  • CMUT ultrasound capacitive micromachined ultrasonic transducers
  • Minimally invasive procedures such as endoscopy, endovascular surgery or percutaneous procedures can be accompanied with thermal or cryogenic therapies using probes/applicators that are inserted directly inside or are placed adjacent to the target tissue volume.
  • Radio Frequency (RF) ablation and Laser Interstitial Thermal Therapy (LITT) have been successfully employed to treat different types of metastasis/tumors under MRI guidance. Preliminary results demonstrate significant improvement of life expectancy, though the current devices cannot be used to create lesions that perfectly match the target volume. Since RF antennas or LITT devices use omnidirectional sources for heating the surrounding tissue, no focusing or steering of the energy radiating pattern can be done without mechanically moving the probe or treatment devices. Other drawbacks in RF and LITT hyperthermia treatments are overheating, which occurs for tissue in contact with or in close vicinity of the treatment device, lack of control in lesion homogeneity due to blood flow, and difficulty in real-time monitoring of the therapy.
  • HIFU High Intensity Focused Ultrasound
  • HICU High Intensity Contact Ultrasound
  • piezoelectric-based devices are widely used to locally heat malignant tissue.
  • current piezoelectric-based HIFU/HICU applicators show undesirable effects and shortcomings such as local tissue overheating at the transducer tissue interface and lack of control for the treatment volume (risk of ablation of healthy tissue or under treatment).
  • the treatment of pathologic tissue requires a small diameter needle shaped applicator (maximum 3-4 mm) to access the site of treatment with minimal damage to the surrounding tissue and interstitial procedures provide the advantage of more accurate control of the ablated volume as well as the assurance of avoiding damage for healthy tissue since the HIFU/HICU source is located at the center of the tissues to be ablated.
  • Current surgical products for interstitial HIFU/HICU procedures exhibit limited ablation capability features (focusing, conformal volume) and all require an active cooling system to avoid overheating of tissue in contact with the ultrasound source and therefore cannot be placed in direct contact with biologic tissue.
  • current products may not exhibit optimal MR compatibility since artifacts may occur due to the presence of air bubbles, metal parts etc.
  • European Patent Application Publication No. 0 643 982 A1 (Burdette et al.) and International Patent Application Publication No. WO2007/124458 A2 (Diederich et al.) relate to a device and a method for treatment of prostatic or uterine tissue.
  • the ultrasound transducers are mounted inside a delivery system housing that prevents the emitting devices from directly contacting the tissue during operation.
  • Multi-segment transducers can be used and a combination of multiple transducer arrangements can provide focusing of the acoustic energy.
  • the apparatus as described still requires cooling fluid to be circulated inside said delivery system to regulate the temperature of the probe.
  • no conformal volume treatment methodology is described therein.
  • a percutaneous MRI compatible probe comprising a longitudinal body to be inserted into the body and having a plurality of ultrasonic transducers designed for focused and non-focused therapeutic ultrasound with an aspiration channel passing through the probe body longitudinally.
  • the transducers can be arranged both longitudinally and circumferentially.
  • a fluid-based cooling system is provided to control the temperature of the device. While transducers can be easily arranged longitudinally to form a linear phased array in circumference, it is not clear how the probe can achieve any focusing since the number of sectors is limited and no indication is provided for making it. No detail is disclosed for conformal volume treatment and the probe still requires a cooling system.
  • U.S. Pat. No. 5,697,897 (Buchholtz et al.) describes a therapeutic endoscope having a single linear array ultrasonic transducer mounted in the longitudinal axis for treatment and diagnosis.
  • the diagnostic transducer can be separate from the one for therapy.
  • the document disclosure is limited to one plane focusing and requires the apparatus to be rotated to achieve a volume treatment.
  • U.S. Patent Application Publication No. US WO 02/32506 A1 and U.S. Patent Application Publication No. US 2006/0206105 A1 disclose a thermal therapy device using a multi-element ultrasound heating applicator.
  • the ultrasonic applicator is located under an acoustic window.
  • the ultrasonic transducer can be electronically activated to cover the geometry of the treated area in a 2D plane, and a volumetric lesion (3D) can be obtained by rotating or moving the apparatus.
  • the applicator has the capability for varying the power and switching the frequency of each ultrasound element enabling the temperature to be adjusted both radially and along the length of the applicator.
  • the frequency control is limited to switching between discrete frequencies within multiple narrowband harmonics of the fundamental.
  • U.S. Pat. No. 6,379,320 (Lafon et al.) describes an ultrasonic applicator for intra tissue heating wherein a planar emitting surface is provided within the applicator head and is separated from the tissue to be treated by a sealed membrane. The space between the ultrasonic device and the membrane is filled with liquid which also serves as temperature regulation for the applicator.
  • the applicator has no focusing or steering capability, so the treatment volume will only be obtained by rotating the applicator on site.
  • European Patent Application Publication No. 1,090,658 discloses methods or structures which include improvements over the above application requirements. However a number of problems still remain unsolved regarding, specifically, a conformal volume treatment method, a dedicated ultrasonic thermal ablation device, and a method of making the same.
  • a broad bandwidth e.g. 2-30 MHz
  • an interstitial ultrasound thermal ablation applicator for conformal treatment of inhomogeneous tumor lesions includes: a body having a longitudinal needle shape and a longitudinal axis, the body defining a hollow central channel along the longitudinal axis, the hollow central channel serving as a passage for biopsy needles or tools for aspiration of biologic materials or providing in-situ drug delivery; and a plurality of capacitive micromachined ultrasonic transducer (CMUT) array transducers mounted on said body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to a longitudinal axis of the body, each of the plurality of CMUT array transducers having elevation dimensions predetermined to steer emitted ultrasonic waves to obtain a conformal volume treatment of the tumor lesions.
  • CMUT capacitive micromachined ultrasonic transducer
  • each of the plurality of CMUT array transducers includes an emitting surface covered with an electrically insulating protective layer such that the interstitial ultrasound thermal ablation applicator can be placed in direct contact with the tissue.
  • the elevation dimensions of each of the plurality of CMUT array transducers are no larger than three (3) wavelengths.
  • Each of the plurality of CMUT array transducers may include a silicon substrate, such that the device is MRI compatible due to the silicon substrates.
  • the plurality of CMUT array transducers may have a thickness of less than 100 microns, and are flexible so as to conform an external surface of the body.
  • interstitial ultrasound thermal ablation applicator may further include a biocompatible protection film covering the body and the plurality of CMUT array transducers.
  • an interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions, includes: a body having a longitudinal needle shape and a longitudinal axis; a plurality of capacitive micromachined ultrasonic transducer (CMUT) linear array transducers mounted on said body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to the longitudinal axis of the body, each of the plurality of CMUT linear array transducers having elevation dimensions predetermined to steer emitted ultrasonic waves to control smoothness of a resulting ablation volume; and at least one of an integrated sensor and an integrated sensing device to monitor at least one of a physical parameter and a physiological parameter of an organ.
  • CMUT capacitive micromachined ultrasonic transducer
  • At least one of an integrated sensor and an integrated sensing device is one or more of the following: a temperature sensor; a pressure sensor; a gas sensor; a biosensor; and a laser emitter.
  • an interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions, includes: a body having a longitudinal catheter shape and a longitudinal axis; a plurality of capacitive micromachined ultrasonic transducer (CMUT) linear array transducers mounted on said body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to the longitudinal axis of the body, each of the plurality of CMUT linear array transducers having elevation dimensions predetermined to steer emitted ultrasonic waves to control smoothness of a resulting ablation volume; an integrated sensor for monitoring at least one of a physical parameter and a physiological parameter of an organ; and an integrated Lab-on-Chip (LoC) device located within a surface of one of the plurality of CMUT linear array transducers for in-situ analyzing of tissue.
  • CMUT capacitive micromachined ultrasonic transducer
  • the LoC device is a microfluidic device for one of cytometry assays and biological assays.
  • Another aspect of the invention is an electronic driving method for driving an interstitial ultrasound thermal ablation applicator having multiple independent transducer elements arranged in rows and columns disposed on a periphery of the interstitial ultrasound thermal ablation applicator.
  • the method includes: controlling focal parameters of each row and column of transducer elements; and controlling a contribution of each row and column of transducer elements in a manner to provide a conformal ablated volume.
  • the method further includes: shunting electrically adjacent transducer elements two by two in each respective row; and controlling the transducer elements in columns independently to achieve conformal volume sonication/treatment.
  • the method further includes: shunting together top electrodes of the transducer elements in each respective row, such that all rows are electrically isolated; shunting together bottom electrodes of the transducers in each respective column, such that all columns are electrically isolated; and activating a desired transducer element by connecting the top electrodes of a selected row and the bottom electrodes of a selected column to a power supply simultaneously to polarize the desired transducer element located in both the selected row and the selected column.
  • the rows are disposed symmetrically with a symmetry line at a middle of the interstitial ultrasound thermal ablation applicator, wherein the rows are arranged in a position order from P 1 to P N and Q N to Q 1 , respectively, around the symmetry line.
  • the method then includes: shunting together top electrodes of the transducer elements forming a row P X and a row Q X of same order, such that rows of different orders are electrically isolated; arranging rows P and rows Q in reverse chronology so as to obtain the last order row P N adjacent to the last order row Q N and therefor first order row P 1 and first order Q 1 are located at opposite ends of the interstitial ultrasound thermal ablation applicator; shunting together bottom electrodes of transducer elements forming in each respective column, such that all columns are electrically isolated; and activating a desired transducer element by connecting the top electrodes of a selected row and the bottom electrodes of a selected column to a power supply simultaneously to polarize the desired transducer element located in both the selected row and the selected column.
  • a method of providing thermal ablation of a tissue region by an interstitial procedure using an interstitial ultrasound thermal ablation applicator comprising a plurality of ultrasonic transducers includes: inserting and positioning the interstitial ultrasound thermal ablation applicator at a center of one of incriminated tissue and a tumor; applying electrical actuation individually to the plurality of ultrasonic transducers, each of the plurality of ultrasonic transducers having respective custom focal characteristics; controlling ultrasonic energy supplied and treatment duration for each of the plurality of ultrasonic transducers to control tissue temperature elevation and distribution; and removing ablated material from a treatment site for assessment.
  • a method of providing thermal ablation of a tissue region by an interstitial procedure using an interstitial ultrasound thermal ablation applicator comprising a plurality of ultrasonic transducers includes: inserting and positioning the interstitial ultrasound thermal ablation applicator at a center of one of incriminated tissue and a tumor; applying electrical actuation individually to the plurality of ultrasonic transducers, each of the plurality of ultrasonic transducers having respective custom focal characteristics; controlling ultrasonic power supplied; controlling the frequency and phase of said supply ultrasonic energy and controlling treatment duration for each of the plurality of ultrasonic transducers to control tissue temperature elevation and distribution; and removing ablated material from a treatment site for assessment.
  • the procedure is performed under magnetic resonance imaging (MRI) scanning to monitor local temperatures.
  • MRI magnetic resonance imaging
  • the treatment procedure is performed using at least one of those strategies: Power Modulation (PM), Frequency Modulation (FM) or Phase Modulation (PhM) of the ultrasound wave generated by each independent element to adjust, based on MR-thermometry feedback control, the amount and location of the heat deposited in the 3D volume surrounding the applicator.
  • PM Power Modulation
  • FM Frequency Modulation
  • PrM Phase Modulation
  • the interstitial ultrasound thermal ablation applicator has a needle shape with a diameter smaller than 4 mm so as to not damage healthy tissue during insertion.
  • FIGS. 1A , 1 B, and 1 C are a sequence of figures illustrating an exemplary procedure for tumor interstitial treatment according to the invention.
  • FIG. 2 is a graphical view of a section of a treatment volume of a conformal lesion.
  • FIGS. 3 , 4 , and 5 show several embodiments of an exemplary interstitial ultrasound thermal ablation applicator according to the invention.
  • FIGS. 6A through 6D are graphical renderings of examples of 3D conformal volumes obtained using an exemplary thermal ablation applicator according to the invention.
  • FIG. 7 is a side sectional view of an internal structure of an exemplary capacitive micromachined ultrasonic transducer (CMUT), according to the invention.
  • CMUT capacitive micromachined ultrasonic transducer
  • FIG. 8 is a perspective view of another embodiment of an exemplary thermal ablation applicator.
  • FIG. 8A is an enlarged view of a proximal end of the exemplary thermal ablation applicator as identified by the broken lines labeled 8 A in FIG. 8 .
  • FIG. 9A is a sectional view showing one assembly of the exemplary thermal ablation applicator taken at the plane identified as 9 - 9 in FIG. 8 .
  • FIG. 9B is a sectional view showing another assembly of the exemplary thermal ablation applicator taken at the plane identified as 9 - 9 in FIG. 8 .
  • FIG. 10 is a perspective view of another embodiment of an exemplary thermal ablation applicator.
  • FIG. 11 is a perspective view of another embodiment of an exemplary thermal ablation applicator.
  • FIGS. 12 , 13 A, and 13 B are functional block diagrams of an electrical system of an interstitial ultrasonic disposable applicator, according to the invention.
  • the term “about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ⁇ 20%, in some embodiments ⁇ 10%, in some embodiments ⁇ 5%, in some embodiments ⁇ 1%, in some embodiments ⁇ 0.5%, and in some embodiments ⁇ 0.1% from the specified amount, as such variations are appropriate to perform the disclosed subject matter.
  • ranges can be expressed as from “about” one particular value, and/or to “about” another particular value. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
  • array transducer or “transducer array” are used herein to describe a transducer device obtained by geometric arrangement of a plurality of individual transducers (i.e., transducer elements) having dimensions compatible with desired ultrasonic beam focusing and steering features.
  • linear array is generally used to describe a one-dimensional array and can be applied to arrays with flat or curved shapes.
  • element transducer or “transducer element” or “transducer” are used herein to describe an individual ultrasonic transducer component of an array transducer.
  • an element transducer of an array transducer has planar dimensions suitable for electronic steering and focusing of ultrasonic beams.
  • the present invention relates to a method and an apparatus for thermal conformal ablation. It should be noted that the invention is not limited to the description or arrangement illustrated in the accompanying drawings and description. It is also understood that any embodiments can be combined with the other embodiments or can be implemented into other apparatus with no change in the principle. Another major aspect of the present invention relates to the compatibility of the ablation device to be used under MRI imaging/monitoring with acceptable artifacts; this will be performed by the utilization of non-metallic materials and absence of air volume within the device body.
  • FIGS. 1A , 1 B, and 1 C illustrate steps of an interstitial thermal ablation procedure by high intensity focused ultrasound (HIFU) or high intensity contact ultrasound (HICU) that can be used to treat cancerous or non-cancerous tumors and more particularly can be advantageously applied to brain tumor treatment.
  • HIFU high intensity focused ultrasound
  • HICU high intensity contact ultrasound
  • the therapeutic depth depends on the exposure conditions in general but more particularly on the operating frequency.
  • Broadband CMUT transducers are advantageous as they allow performing conformal ablation by adjusting the depth of treatment with the operating frequency.
  • cMUT transducers allow using Frequency Modulation (FM) strategies over a broad continuous spectrum (e.g. 2-30 MHz) for precise optimization of the ultrasonic frequencies as a function of the targeted tissue depths.
  • FM Frequency Modulation
  • Multiple independent broadband cMUT elements integrated on the same applicator allow combining multiple ultrasound beams at various frequencies over a broad continuous spectrum (e.g. 2-30 MHz) for performing conformal thermal ablation.
  • Adjuvant drug delivery can also be achieved with CMUT transducers emitting low frequency waves.
  • FIG. 1A shows a thermal ablation applicator 4 inserted into brain tissue 2 by hole 6 created through a skull 1 .
  • the applicator 4 penetrates the brain tissue 2 to reach a malignant tumor 3 to be treated.
  • the applicator 4 defines a hollow channel 5 and an opening 7 located at the distal end of the applicator 4 .
  • the hollow channel 5 has a diameter that is large enough to accommodate a diameter of a biopsy mandrel 8 ( FIG. 1B ).
  • the applicator 4 can be inserted into the brain tissue 2 with the biopsy mandrel 8 ( FIG. 1B ) in position in a manner to provide more stiffness to the applicator 4 .
  • FIG. 1B shows a biopsy mandrel 8 inserted into the malignant tumor 3 for tissue extraction or analysis.
  • FIG. 1C shows the applicator 4 inserted through the malignant tumor 3 .
  • the applicator is inserted without moving the biopsy mandrel such that a tumor sample is then trapped into the biopsy mandrel 8 .
  • the biopsy mandrel 8 is then removed from the applicator for tissue extraction or analysis without further moving the applicator.
  • the biopsy mandrel 8 will not disturb (i.e., create artifacts) the monitoring of the malignant tumor 3 under Magnetic Resonance Imaging (MRI) for upcoming treatment.
  • MRI Magnetic Resonance Imaging
  • the medical procedure as depicted in FIGS. 1A , 1 B and 1 C is well adapted for brain tumor treatment since the diameter of the applicator 4 remains reasonable (3 mm-4 mm) and the applicator 4 is MRI compatible. Furthermore, the hollow channel 5 enables physicians to extract ablated tissue from the tumor. Once the treatment procedure is complete and monitored with MRI or ultrasonic imaging, an aspiration of a liquefied portion of treated tissue can be drawn through the hollow channel 5 from the opening 7 of the applicator 4 . At the end of the procedure, the applicator 4 is removed from the brain tissue 2 and a stitch is performed on the skin for closing.
  • the applicator 4 is equipped with a plurality of ultrasonic array transducers arranged and symmetrically disposed around and along a longitudinal axis of the applicator 4 to provide a 360 degree ultrasonic sonication.
  • a plurality of ultrasonic array transducers arranged and symmetrically disposed around and along a longitudinal axis of the applicator 4 to provide a 360 degree ultrasonic sonication.
  • Such an applicator 4 suitable for treatment of a malignant tumor 3 will be further described in more detail below.
  • the applicator 4 and method use multi-focused ultrasound to obtain a conformal volume treatment of tumor tissue regions.
  • FIG. 2 is a graph of a numerical modeling performed using an exemplary applicator having eight faces in a polygonal arrangement. As shown in FIG. 2 , a smooth volume can be achieved by using independent control of the arrays and taking into account the acoustic absorption and thermal conductivity of the tissue, and lesion boundary conditions.
  • each transducer Tx1, Tx2, Tx3, . . . Tx(N ⁇ 2), Tx(N ⁇ 1), T ⁇ N is connected to independent driving electronics (i.e., controllers) C1, C2, C3, . . . C(N ⁇ 2), C(N ⁇ 1), CN that may consist of electrical impedance matching networks and DC bias controller, and which may be controlled by a system mainframe 1200 in communication with an output power management system 1202 that controls the amplitude (A N ), frequency (f N ) and phase ( ⁇ N) for each individual element for electronic focusing or steering. As shown schematically, the configuration is repeated for M arrays.
  • independent driving electronics i.e., controllers
  • C1, C2, C3, . . . C(N ⁇ 2), C(N ⁇ 1), CN that may consist of electrical impedance matching networks and DC bias controller, and which may be controlled by a system mainframe 1200 in communication with an output power management system 1202 that controls the amplitude (A N ), frequency
  • the electronic driving system may include a separate DC bias controller 1201 for activation of specific subgroups of elements or arrays of the device that allows for a row-column control system.
  • the DC bias voltage level delivered to a specific subgroup of elements may be used to modulate the acoustic output of a specific subgroup of elements that have a common bottom electrode.
  • the elements are wired electrically according to the configuration shown in FIG. 13 b , where the AC driving voltage is applied at the top electrode to a single element or group of elements and the DC bias voltage is applied at the bottom electrode.
  • the bottom electrode may be common to a single element, several elements, one entire linear array of the transducer, or to all of the elements of the transducer.
  • CMUT device for high intensity ultrasound is its intrinsic absence of self-heating during long (several seconds to several minutes) and continuous driving operations. Indeed, electrostatic vibration forces created by capacitive membranes are based on voltage variations with no need for current intensity. Since a cavity gap is vacuum sealed, low parasitic capacitance is expected so a self-heating effect is therefore negligible as well.
  • FIG. 7 is a sectional view of an exemplary CMUT cell 21 , which is described in more detail below.
  • FIGS. 3 , 4 and 5 show exemplary configurations for array transducers (e.g., FIG. 12 , Tx1, Tx2, Tx3, . . . Tx(N ⁇ 2), Tx(N ⁇ 1), T ⁇ N, for M arrays) mounted on an exemplary thermal ablation applicator 4 (see FIG. 1A-FIG . 1 C) to perform conformal volume ablation.
  • array transducers e.g., FIG. 12 , Tx1, Tx2, Tx3, . . . Tx(N ⁇ 2), Tx(N ⁇ 1), T ⁇ N, for M arrays
  • the purpose of this array configuration is to achieve optimal tissue ablation efficiency under accurate volume control while limiting the number of independent driving channels at reasonable numbers (e.g., 64) for mastering of cost and design complexity.
  • FIG. 3 shows an array configuration of the thermal ablation applicator 4 comprising an assembly of ten transducer arrays 17 (i.e., columns of transducer elements 18 , also referred to as array transducers) arranged in a polygonal manner.
  • Each of the transducer arrays 17 preferably includes a plurality of transducer elements 18 , which can be either identical to each other or under customized specifications with no change in principle.
  • all of the transducer arrays 17 are identical geometrically and, for simplicity, the transducer elements 18 operate at a resonance frequency that maximizes a ratio between output energy and penetration.
  • an optimal frequency range is from about 3 to 10 MHz and an optimal acoustic surface intensity is between about 10-30 watts/cm 2 for a tumor having a diameter of around 30 mm.
  • Such frequency range and output acoustic intensity are here given as an example and should not be considered as design limitations for the present invention, as other combinations of frequency/intensity may be applied to the description of the invention with no change in the principle thereof.
  • the transducer elements 18 are electrically connected or shunted by pair (two adjacent transducer elements 18 are to be connected together) in a transverse sectional plan of the applicator 4 , as highlighted in the figure.
  • the shunting of adjacent transducer elements 18 reduces the number of active channels while keeping smooth polygon angles for the applicator 4 .
  • the applicator 4 comprises a plurality of rows 19 of transducer elements 18 , each of the rows 19 of transducers formed by several transducer elements 18 shunted two by two in order to reduce the number of connections.
  • transducer 3 is preferably composed of ten transducer arrays 17 (i.e., columns of transducer elements) and twelve rows 19 of transducer elements (not all shown).
  • the number of transducer arrays 17 equates to the number of transducer elements 18 in each row 19 .
  • the adjacent transducer elements 18 in each row 19 are shunted two by two, the number of electrical connections is reduced to sixty instead of one hundred twenty.
  • FIG. 6A through FIG. 6D are graphs of modeling results of conformal volumes obtained with a configuration of transducer arrays 17 mounted on an exemplary thermal ablation applicator 4 , such as described above.
  • FIG. 6A shows an example of a 3D complex volume 41 (i.e., heating volume shape or ablated lesion volume) that is obtained using such an applicator 4 .
  • the acoustic power is independently programmed for each transducer element 18 ( FIGS. 3-5 ) to achieved the desired 3D complex volume 41 (i.e., heating volume shape or ablated lesion volume).
  • FIG. 6B is a sectional view of the exemplary ablated lesion volume 41 with thermal doses spreading around such an applicator 4 .
  • This graph clearly indicates the capability of such an applicator 4 to provide localized and well-controlled thermal dose distribution to lesion tissue in a 3D complex volume (i.e., heating volume shape).
  • FIG. 6C is a longitudinal view of the exemplary ablated lesion volume 41 of FIG. 6B , showing thermal doses distribution around such an applicator 4 .
  • the asymmetrical distribution shown in this figure and in FIG. 6B illustrate conformal volume treatment.
  • FIG. 6D shows an example of a different 3D complex volume 42 that is obtained using such an applicator 4 with twelve (12) transducer arrays operated at 6 MHz.
  • the illustration of FIG. 6D only shows the 1 ⁇ 2 volume with its symmetrical sectional face (the whole volume is to be considered when treated with all transducers in operation).
  • An output acoustic power sufficient to generate a surface intensity of 20 W/cm 2 is applied at the surface of array transducer under the following sequence: 105 seconds ON.
  • the exemplary thermal ablation applicator 4 of the invention may also advantageously utilize continuous Frequency Modulation (FM) to control tissue penetration and thermal dose distribution since the CMUT operations are sensitive within a large frequency range.
  • FM strategies can be applied on each electrically independent cMUT transducer to control ultrasonic frequencies over a broad continuous spectrum and achieve simultaneously various treatment depths in 3D.
  • the transducers elements 18 and by extension the transducer arrays 17 can be excited at different frequencies so as to better fit tissue ablation requirements and conditions, or to emphasize the conformal effect by the possibility of applying a particular emitting frequency on each transducer element 18 or transducer array 17 .
  • an exemplary CMUT cell 21 includes a membrane 23 that is excited by oscillations of electrostatic forces exerted via a bottom electrode 24 and an opposing top electrode 25 .
  • the electrostatic forces are created by an electrical field exerted between the opposite electrodes 24 and 25 and a capacitance value is controlled by a gap of a sealed cavity 26 (i.e., a capacitance gap) these electrostatic forces are governed by the following equation
  • V0 represents the DC voltage
  • V1 represents the AC voltage applied to the CMUT for oscillation
  • the structure of the exemplary CMUT cell 21 desired is formed on a silicon substrate 22 (and an oxide layer 22 a ), but other materials such as glass or polymers may be utilized as a base structure as well.
  • Other complementary layers can be added to the exemplary CMUT cell 21 to provide better protection or to improve acoustic performance of the structure.
  • the operational principle of the CMUT cell 21 is substantially as described herein.
  • an exemplary thermal ablation applicator 4 includes transducer arrays 17 (columns of transducer elements 18 ) and rows 19 of transducer elements 18 , as in the embodiment of FIG. 3 .
  • the top electrodes see FIG. 7 , top electrode 25
  • the bottom electrodes (see FIG. 7 , bottom electrode 24 ) of the transducer elements 18 of a preselected transducer array 17 a (i.e., column of transducer elements 18 ) are also connected together.
  • Each of the transducer elements 18 i.e., a CMUT cell 21 ( FIG.
  • the control of a selected transducer element 18 a on the exemplary thermal ablation applicator 4 is obtained by selecting the particular transducer array 17 a (i.e., column) and the particular row 19 a of transducer elements 18 of the selected transducer element 18 a , and applying a voltage excitation function with suitable frequency (typically 6 MHz but can also be adjusted in the range of 3-10 MHz) and acoustic surface intensities (from 5 to 20 w/cm 2 ) across the corresponding bottom electrodes and top electrodes to produce the desired ultrasonic vibration effect.
  • suitable frequency typically 6 MHz but can also be adjusted in the range of 3-10 MHz
  • acoustic surface intensities from 5 to 20 w/cm 2
  • the exemplary applicator 4 of FIG. 4 further has the top electrodes of each respective row 19 of transducer elements 18 connected together, and the bottom electrodes of each respective transducer array (i.e. column) of transducer elements 18 connected together.
  • this array configuration reduces the number of connections required for polarization of individual transducer elements 18 to control the active surface of the applicator 4 .
  • This voltage will pre-stress the CMUT to react to any voltage variation by moving the membrane to modify the capacitance gap accordingly. This, consequently, also creates ultrasonic waves.
  • this structure and method enables control of any of the individual transducer elements 18 of the exemplary thermal ablation applicator 4 by applying suitable voltage to the corresponding top electrode 25 and bottom electrode 24 (see: FIG. 7 ).
  • the number of control connections will then depend on the number of independent columns (n) (transducer arrays 17 ) and rows (m) (rows 19 of transducer elements 18 ) to be controlled.
  • all of the transducer elements 18 of the array configuration can be individually address using n+m control connections instead of n ⁇ m control connections to connect each transducer element separately.
  • FIG. 5 shows another exemplary thermal ablation applicator 4 which is composed of rows 19 b on one end and rows 19 c on the other end of the applicator 4 .
  • Rows 19 b and rows 19 c are symmetrically disposed with a symmetry line 20 defined at a middle of the exemplary thermal ablation applicator 4 .
  • Transducer arrays 17 i.e., columns
  • each transducer array 17 comprises aligned transducer elements 18 from all rows 19 b and rows 19 c .
  • adjacent transducer arrays 17 are electrically shunted two by two in order to reduce the number of output connections for the applicator.
  • Rows 19 b and 19 c are arranged respectively in the position order from P 1 to P N for rows 19 b and from Q 1 to Q N for rows 19 c . Furthermore, the row of position P 1 is shunted to the row of position Q 1 to form a unique electrical connection and so on in manner to divide by two the number of output connections for rows 19 b and 19 c .
  • the bottom electrodes of the CMUT cells of the respective transducer arrays 17 are connected together, and the top electrodes of the CMUT cells of the respective rows 19 b and rows 19 c are connected together, so that the control of the active surfaces of the exemplary thermal ablation applicator 4 is identical to control described with respect to the exemplary applicator of FIG. 4 .
  • the exemplary thermal ablation applicator 4 of FIG. 5 having transducer rows 19 b and transducer rows 19 c that can be excited in shunted mode two by two expands the ablation volume (especially in long axis dimension) that can be treated with a single applicator 4 .
  • FIG. 8 shows yet another embodiment of an ultrasonic thermal ablation applicator 4 , including array transducers 10 comprised of CMUT (not shown) elementary transducers that are arranged along a long axis of the array transducers 10 .
  • the number of array transducers 10 of the thermal ablation applicator 4 is dependent on the application and type of tumor to be treated, and this number may extend from eight to twelve, typically, for achieving a reasonable compromise. Twelve array transducers 10 mounted on the periphery of the thermal ablation applicator 4 is preferable, but not so limited.
  • array transducers 10 are identical in shape and dimensions but may differ in CMUT arrangement on their active face.
  • Array transducers 10 are electrically connected to flexible electrical collectors 9 that provide electric contacts of the CMUT elements to an external interface (not shown).
  • a coaxial cable (not shown) is connected to interface with the system mainframe (not shown).
  • the flexible electrical collectors 9 are preferably comprised of flexible PCB circuits using Kapton® or any polyimide-based material with a thickness thinner than 25 ⁇ m.
  • the array transducers 10 may be assembled directly on an applicator body 14 as shown in FIG. 9A , or may be pre-assembled with a backing support 16 as shown in FIG. 9B prior to mounting on the applicator body 14 .
  • the backing support 16 can be made up of acoustic absorbent materials such as particle filled resin, plastic, ceramic, or any other nonmetallic (i.e., transparent to x-rays and other medical imaging radiation) acoustic absorbent material.
  • a guiding piece 12 in a substantially conical shape is provided as protection for the array transducer mounting.
  • the guiding piece 12 has an opening 7 located at a center position in alignment with a hollow channel 5 (see: FIG. 1A-FIG . 1 C) of the thermal ablation applicator 4 .
  • a ring 11 is provided to secure an interface between the array transducers 10 and the flexible electrical collectors 9 .
  • FIG. 8A shows a magnified view of the proximal end of applicator 4 where assembly details are provided for the array transducers 10 , the ring 11 , and the flexible electrical collectors 9 .
  • the ring 11 is preferably mounted to the probe body or structure and secures a flex extension part in the vicinity of the array transducers 10 .
  • the flexible electrical collectors 9 can be made of thin polyimide PCBs (e.g., 12 ⁇ m thick polyimide film), with copper/gold plated tracks on one or both sides.
  • FIG. 9A is a sectional view of one assembly of the exemplary thermal ablation applicator 4 taken through plane 9 - 9 as shown in FIG. 8 .
  • the figure shows the assembly of array transducer components and construction details of the applicator 4 wherein a body 14 is provided with the hollow channel 5 .
  • the body 14 may have a plurality of faces regularly disposed on its periphery to form a polygon.
  • a number of faces for the body 14 may preferably range from eight units at a minimum and have an optimum number of twelve, however no limitation is made on the number of faces, as the number will only be limited by available miniaturization and integration process/technology.
  • a cylindrical shape for the body 14 is ideally desirable, but this inherently constrains the transducer to be made flexible and conformable at such a small diameter (3-4 mm).
  • the array transducers 10 are disposed on external faces of the body 14 with optional acoustic absorbing material 15 that also comprises electrical contacts.
  • the electrical contacts can be, for example, flexible printed circuit boards (flexible PCB), as the thickness of flexible PCBs is thin as compared to the other components.
  • the flexible PCBs are sandwiched between the array transducers 10 and the external faces of the body 14 .
  • the optional absorbent material can be particle filled resins or rigid nonmetallic materials with high backscattering properties.
  • the array transducers 10 may be directly secured to the body 14 with electrical contacts disposed there between.
  • the array transducers 10 may be provided with a matching layer (not shown) laminated on a front surface to improve the acoustic performance and electrical safety for patients.
  • the exemplary thermal ablation applicator 4 is covered with a protective layer 13 to complete the assembly.
  • the protective layer 13 can be made up of electrically insulated silicon rubber or resin and preferably molded onto the thermal ablation applicator 4 to obtain a cylindrical external shape.
  • a polygonal external section is also possible with the use of a flat thin electrically insulated protective layer that will be conformal to the front surfaces of the array transducers 10 .
  • FIG. 10 shows, in yet another embodiment of the invention, an exemplary thermal ablation applicator 4 having a similar shape and dimensions to the exemplary thermal ablation applicator 4 of FIG. 8 .
  • the exemplary thermal ablation applicator 4 is having different active portions that comprise equal number of transducer arrays 10 , from the proximal to distal end of the applicator there are preferably and respectively portions 27 , 29 and 28 that are mounted in adjacent manner.
  • Portion 29 is dedicated to thermal ablation operations as previously described and the portions 27 and 28 can be equipped with other type of sensors or detectors provided that they can be micro manufactured on substrates compatible with the dimensions herein required.
  • CMUTs are mainly fabricated on a Si substrate, as are other sensors such as: pressure sensors, targeted bio-sensors (enzymes, antibodies and nucleic acids), chemical sensors, temperature sensors, and micro arrays of electrodes.
  • sensors such as: pressure sensors, targeted bio-sensors (enzymes, antibodies and nucleic acids), chemical sensors, temperature sensors, and micro arrays of electrodes.
  • portions 27 and 28 can be provided with any of the previously mentioned sensors to complete the instrument upon clinical requirements or needs.
  • portion 29 is still present for thermal ablation and the portion 27 or portion 28 is equipped with chemical sensors to measuring physiological parameters of the tissue in contact.
  • FIG. 11 shows, in yet one further embodiment, an exemplary thermal ablation applicator 4 including thermal ablation operations portion 29 , as well as portion 27 and portion 28 .
  • Portion 27 and portion 28 comprise integrated nano laser oscillator emitters to allow in vivo sub-cellular tissue identification by near-infrared multi photon-induced auto fluorescence microscopy.
  • the nano laser oscillator emitters are located on the periphery of portion 27 and/or portion 28 to dispatch light energy to the surrounding structure

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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PCT/IB2014/059604 WO2014141052A1 (en) 2013-03-11 2014-03-10 Interstitial ultrasonic disposable applicator for tissue thermal conformal volume ablation and monitoring the same
EP14713915.8A EP2968982B1 (de) 2013-03-11 2014-03-10 Interstitieller einweg-ultraschallapplikator für eine wärmekonforme gewebevolumenablation und deren überwachung
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US20180036558A1 (en) 2018-02-08
EP2968982B1 (de) 2022-09-28
WO2014141052A1 (en) 2014-09-18
CN105555362B (zh) 2020-01-10
US10987524B2 (en) 2021-04-27
EP2968982A1 (de) 2016-01-20

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Free format text: CHANGE OF ADDRESS;ASSIGNOR:INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM);REEL/FRAME:031438/0227

Effective date: 20131018

STCB Information on status: application discontinuation

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