WO1998007373A1 - Methodes et dispositifs pour administrer un traitement par ultrasons non invasif au cerveau a travers une boite cranienne intacte - Google Patents

Methodes et dispositifs pour administrer un traitement par ultrasons non invasif au cerveau a travers une boite cranienne intacte Download PDF

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Publication number
WO1998007373A1
WO1998007373A1 PCT/US1997/014760 US9714760W WO9807373A1 WO 1998007373 A1 WO1998007373 A1 WO 1998007373A1 US 9714760 W US9714760 W US 9714760W WO 9807373 A1 WO9807373 A1 WO 9807373A1
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Prior art keywords
transducers
ultrasound
skull
selected region
mhz
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PCT/US1997/014760
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English (en)
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WO1998007373A9 (fr
Inventor
Kullervo Hynynen
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Brigham & Women's Hospital
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Priority claimed from US08/711,289 external-priority patent/US5752515A/en
Application filed by Brigham & Women's Hospital filed Critical Brigham & Women's Hospital
Priority to AU42333/97A priority Critical patent/AU4233397A/en
Publication of WO1998007373A1 publication Critical patent/WO1998007373A1/fr
Publication of WO1998007373A9 publication Critical patent/WO1998007373A9/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B2017/22005—Effects, e.g. on tissue
    • A61B2017/22007—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing
    • A61B2017/22008—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing used or promoted
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B2017/22027—Features of transducers
    • A61B2017/22028—Features of transducers arrays, e.g. phased arrays
    • 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
    • A61B2090/374—NMR or MRI
    • 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
    • A61B2090/376—Surgical systems with images on a monitor during operation using X-rays, e.g. fluoroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A61B8/0808—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/48—Diagnostic techniques
    • A61B8/481—Diagnostic techniques involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0086—Beam steering
    • A61N2007/0095—Beam steering by modifying an excitation signal
    • 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
    • A61N2007/027—Localised ultrasound hyperthermia with multiple foci created simultaneously

Definitions

  • the invention pertains to medical systems and, more particularly, to methods and apparatus for non-invasive application of focused ultrasound to the brain
  • the invention can be used, for example, in the diagnosis and treatment of neural ailments.
  • ultrasound surgery has special appeal in the brain where it is often desirable to destroy or treat deep tissue volumes without disturbing the healthy tissues.
  • Focussed ultrasound beams have been used for noninvasive surgery in many other parts of the body. Ultrasound penetrates well through soft tissues and. due to the short wavelengths (1.5 mm at 1 MHz), it can be focused to spots with dimensions of a few millimeters. By heating tumorous or cancerous tissue in the abdomen, for example, it is possible to ablate the diseased portions without significant damage to surrounding healthy tissue.
  • an object of this invention is to provide improved medical methods and apparatus, for diagnosis and therapy of the brain.
  • a more particular object of the invention is to provide improved methods and apparatus for application of ultrasound to the brain.
  • a more particular object of the invention is to provide such methods and apparatus as do not require removal of portions of the skull, via craniectomy or other such procedures.
  • Still another object of the invention is to provide such methods and apparatus as can be used to precisely target regions within the brain.
  • Still yet another object of the invention is to provide such methods and apparatus as can be used to effect heating or other physiologic change at such precisely targeted regions, without effecting substantial change in the surrounding, or other, regions of the brain or skull.
  • Another object of the invention is to provide such methods and apparatus as can be utilized over a wide range of ultrasonic frequencies.
  • Still another object of the invention is to provide such methods and apparatus as can be implemented utilizing conventional materials.
  • Yet still another object of the invention is to provide such methods as can be implemented without excessive expense.
  • the invention provides in one aspect methods and apparatus for delivery of cavitating ultrasound to the brain, without requiring removal of portions of the skull.
  • the invention provides an apparatus for delivering ultrasound, through intact skull, to the brain comprising a plurality of transducers and an excitation source for driving each to induce cavitation at least at a selected region of the brain.
  • the excitation source is particularly arranged for driving at least selected transducers at differing phases with respect to one another, e.g., to compensate for phase shifts (or phase distortions) effected by the skull on the ultrasound output by each transducer.
  • the ultrasound waves reaching the selected region from the transducers arrive substantially in phase with one another, e.g., within 90° and, preferably, within 45° and, still more preferably, within 20° of one another.
  • the excitation source drives the transducers to deliver ultrasound to the selected region at a frequency ranging from 0.01 MHz to 10 MHz and, preferably, from 0.1 MHz to 2 MHz. Sonication duration for the ultrasound ranges, according to further aspects of the invention, from 100 nanoseconds to 30 minutes. According to still further aspects, the invention provides for delivery of ultrasound to the selected region with continuous wave operation or burst mode operation, where burst mode repetition varies from 0.01 Hz to 1 MHz.
  • Still further aspects of the invention provide methods for operating transducer arrays as described above.
  • Figure 1 depicts an embodiment of the invention and an experimental setup for testing it.
  • Figure 2 depicts an embodiment of the invention for application of ultrasound to the brain of an animal.
  • Figure 3 depicts a phased array for application of ultrasound to the brain in accord with one practice of the invention.
  • Figures 4A-4H illustrate the ultrasound pressure amplitude distribution in water across the focus of a transducer according to the invention at various frequencies, with and without skull sections in front of the transducer.
  • FIGS 5A and 5B illustrate the effect of applying ultrasound in accordance with the invention to brain tissue.
  • Figures 6A and 6B illustrate phase errors measured at the focus of ultrasound transducer arrays with a piece of skull in front of the transducers.
  • Figures 7A-7C illustrate the pressure amplitude profiles across the focus of an ultrasound transducer phased array in water, through the bone, and through the bone with phase correction.
  • Figure 8 illustrates the pressure amplitude distribution along the central axis of an ultrasound transducer array without and with the phase correction.
  • Figures 9A-9C illustrate the ultrasound pressure amplitude distribution measured across the focus of an ultrasound phased array in water, through skull without phase correction, and through skull with phase correction.
  • Figure 10 depicts an embodiment of the invention for delivery of cavitating ultrasound to a patient's brain through the skull using a multi-element transducer array.
  • Figure 11 depicts a method for delivery of cavitating ultrasound to a patient's brain through the skull using a transducer array.
  • tissue refers to fluids, tissues or other components on or within a patient's body.
  • Figure 10 depicts an apparatus according to the invention for delivery of ultrasound to the brain.
  • the apparatus 10 includes an array of transducers 12 disposed on or near the external surface of the head of a human patient.
  • the array 12 can constitute a single transducer, e.g., a spherically curved piezoelectric bowl of the type described below, though preferably, array 12 comprises a plurality of transducers arranged in a one-, two- or three-dimensional configuration.
  • array 12 comprises 60 individual piezoelectric ceramic transducers mounted in a bowl of circular cross-section.
  • the transducer elements which can be, for example, 1 cm 2 piezoelectric ceramic pieces, are mounted in silicone rubber or any other material suitable damping agent for minimizing the mechanical coupling therebetween.
  • Transducer arrays of this type are known in the art, as described, for example in Fan et al, "Control of the Necrosed Tissue Volume During Noninvasive Ultrasound Surgery Using a 16-Element Phased Array," Medical Physics, v. 22, pp.
  • each transducer of array 12 is independently driven by power and the control elements 18-22 to generate ultrasound for transmission through the patient's skull into the CNS tissues. More particularly, the transducers in array 12 are individually coupled, via coaxial cables 16, to separate channels of a driving system 18. Each channel of that system 18 includes an amplifier and a phase shifter, as shown. A common radio frequency (RF) signal is driven to each channel by radio frequency generator 22. Together, the radio frequency generator 22 and driving system 18 drive the individual transducers of array 12 at the same frequency, but at different phases, so as to transmit a focused ultrasound beam through the patient's skull to a selected region within the brain. Unlike prior art systems, there is no need to remove portions of the skull beneath the array 12, e.g., via craniectomy or other such surgical procedure.
  • RF radio frequency
  • the radio frequency generator 22 can be of any commercially available type.
  • a preferred such generator is available from Stanford Research Systems, Model DS345.
  • the generator is operated in a conventional way so as to generate an excitation signal, which is amplified and phase- shifted by the individual channels of driving system 18, in order to induce the corresponding transducers of array 12 to radiate ultrasound (e.g., in the range 0.01 MHz to 10 MHz).
  • each channel in the driving system 18 includes a radio frequency amplifier.
  • These can be any RF amplifiers of the type commercially available in the art.
  • each channel of driving system 18 is constructed and operated in the conventional manner known in the art. Particularly, each phase shifter shifts the phase of an incoming RF excitation signal, received from RF generator 22, by an amount a a 2 , a 3 , etc., as shown in the drawing.
  • These phase shift factors ⁇ ,, ⁇ 2 , ⁇ 3 , etc. can be pre-stored in the channels of driving system 18 or, preferably, generated by a controller 20.
  • That controller 20 can be a general purpose, or special purpose, digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.
  • phase shift factors, ⁇ ,, a ⁇ ⁇ 3 , etc. serve two purposes.
  • the first is to steer the composite ultrasound beam generated by transducer array 12 so that it is focused on a desired region within the patient's brain.
  • the component of each phase shift factor associated with steering is computed in the manner known in the art for steering phased arrays. See, for example, Buchanan et al, "Intracavitary Ultrasound Phased Array System," IEEE Transactions Biomedical Engineering, v. 41, pp. 1 178-1187, a copy of which is filed as an appendix hereto and the teachings of which are incorporated herein by reference.
  • Array steering, or focusing is particularly discussed in that article, for example, at pages 1 179-1181 and, more particularly, in the section entitled “Focusing Techniques,” the teachings of which are incorporated herein by reference.
  • each phase shift factor ⁇ ,, ⁇ 2 , ⁇ 3 , etc. compensates for phase distortion effected by the skull in the ultrasound ouput by each transducer.
  • the second component of the phase shift factors compensates for perturbations and distortions introduced by the skull, the skin/skull interface, the dura matter/skull interface, and by variations in the skull thickness.
  • the two components that make up the phase shift factor for each channel of the driving system 18 are summed in order to determine the composite phase shift factor for the respective channel.
  • phase corrections that constitute the aforementioned second component of each phase shift factor can be determined a number of ways.
  • that component is determined from measurements of the thickness of the patient's skull under each transducer in array 12.
  • Such skull thickness measurements can be made using conventional imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MR ).
  • the aforementioned second component of each phase shift factor is determined by placing the array 12 on the patient's head and exciting individual transducers with a short ultrasound pulse. The echo back from the inner surfaces of the skull are monitored by the transducer array 12. The effect of the skull on ultrasound generated by each transducer is determined from those echos in accord with conventionally known relations.
  • each phase shift factor is determined by implanting small hydrophones in the patient's brain. These are used to monitor the phase of the ultrasound generated by each transducer, e.g., in a manner similar to that described below in connection with Figure 1.
  • the transducer array 12 can be driven by a driving system of the type disclosed in Buchanan et al, supra e.g. at Figure 2 thereof, the teachings of which are incorporated herein by reference.
  • a driving system would, of course, require modification in accord with the teachings hereof in order to incorporate phase shift factors ⁇ 2 , ⁇ 3 , etc., having first and second components as described herein and above.
  • the system 10 is operated as described below in order to deliver ultrasound through the patient's skull to induce cavitation at a desired region of the brain.
  • the transducer array 24 is positioned on the patient's head. This is preferably accomplished in the conventional manner known in the art for insuring ultrasound transmission to the brain.
  • the array is typically positioned over, and as close to, the region in which cavitation is to be induced. However, where intervening or adjacent cranial or CNS tissues might be adversely affected, the array can be positioned elsewhere and focused accordingly.
  • step 26 the aforementioned second component of the phase shift factor for each transducer is determined. This is accomplished in the manner described above, e.g., by individual exciting each element of the array and measuring the echo back.
  • the alternative mechanisms described above can also be used to determine those components. Those skilled in the art will appreciate that in instances where the alternative mechanisms are used, they need not be performed after the array is positioned but, can be performed at some other prior time.
  • step 28 the remaining components of each transducers' phase shift factor are determined. Particularly, those components associated with steering the array for delivery of ultrasound to the desired region are determined. Such determination is made, as indicated above, in the conventional manner known in the art for steering phased arrays.
  • the array is excited, e.g., by control and driving elements 18-22, to focus ultrasound in the patient's head.
  • the invention provides correction for phased distortion induced by the skull, that ultrasound can be supplied directly through the skull without the need for removal of a piece thereof.
  • the ultrasound is applied in doses and timing sufficient to induce cavitation in the desired region, which may be, e.g., from 1 mm 3 - 1 cm 3 , or larger.
  • ultrasound waves in the frequency range of 0.01 MHz to 10 MHz and, preferably, from 0.10 MHz to 2 MHz can be applied with sonication duration ranging from 100 nanoseconds to 30 minutes, with continuous wave or burst mode operation.
  • the burst mode repetition varies from 0.01 Hz to 1 MHz.
  • the transducer array 12 includes only a single transducer, e.g., a
  • step 26 is not utilized.
  • the "array" is aimed based on its focal point. This is determined as a function of the size, radius of curvature and frequency output of the transducer in the manner known in the art. In a preferred embodiment, these factors are adjusted so that the transducer can be placed directly on the patient's skull, as above. However, where minor corrections are necessary, the transducer can be spaced apart from the skull, as necessary, in order to insure proper positioning of the focal point.
  • An ultrasound beam delivered to the brain can effect change in CNS tissues and fluids (herein, simply “tissue” or “brain tissue,” etc.) by two mechanisms: heating and cavitation.
  • the ultrasound beam can heat the tissue temperature due to energy absorption from the wave resulting in different degrees of thermal damage to the tissue depending on the temperature reached. For exposures of a few seconds, temperatures of above about 60° C are adequate to coagulate proteins and thus, necrose the tissue.
  • the induced temperature elevation during short ultrasound exposures depends mainly on the absorbed power ( ⁇ q>) although the shape and size of the focal spot can have a significant impact due to thermal conduction.
  • the rate of temperature rise (dT/dt) at the very beginning of an ultrasound pulse can be calculated from the pressure amplitude of the field (P), as follows:
  • ⁇ q> ⁇ PV pv
  • v is the speed of sound
  • the ultrasound beam In order to achieve the same temperature within the target volume as in the skull, the ultrasound beam has to be focused to overcome the difference in the acoustic properties.
  • the square of the pressure amplitude (P 2 ) is directly proportional to the ultrasound beam area allowing the required area gain (AG) to be calculated from Equations [1] and [2] by making the rates of temperature rise equal in the skull and the brain:
  • the area gain has to compensate for the energy loss due to the skull and attenuation in the brain between the skull and the focal point:
  • ⁇ is the insertion loss of skull
  • ⁇ is the amplitude attenuation coefficient
  • f is the frequency
  • x is the depth in the brain.
  • the total area gain is the product of these two area gains and is approximately 400 and 15000 at 0.5 MHz and 1.5 MHz, respectively when the focus is located at the depth of 6 cm in the brain.
  • cavitation requires negative pressure amplitudes that are large enough to form gas bubbles in the tissue.
  • the pressure wave causes the bubbles to expand and then collapse.
  • the collapse of the bubbles causes high temperatures and pressures that can cause direct mechanical damage to the tissue.
  • Cavitation can offer more therapeutic options than thermal exposures of brain.
  • the cavitation threshold in the soft tissues and in bone appears to be similar.
  • cavitation-inducing ultrasound beam overcomes the attenuation losses in the bone and brain, but need not overcome differences in absorption coefficients, as is the case with the heat-inducing exposures.
  • the beam area of cavitation-inducing ultrasound propagating through the skull has to be about 13 and 250 times larger than the focal area at frequencies of 0.5 and 1.5 MHz, respectively. These area gains are 30 and 60 times smaller than the gains required for induction of thermal effects.
  • the cavitation is not influenced by thermal conduction or perfusion effects. Therefore, it is clear that cavitation has significant advantages over the thermal effects. This is particularly true in instances where the ultrasound energy must be delivered to small focal regions that require high frequencies.
  • Cavitation requires high pressure amplitudes but only short exposure durations, therefore cavitational effects can be induced without significant temperature elevation.
  • sonications with durations of only 1 ms are adequate for bubble formation.
  • the required peak intensities at 0 936 MHz during these sonications are measured to be around 4000 Wcm' 2 and 2000 Wcm 2 at 1 ms and 1 s exposures, respectively.
  • the maximum peak temperature elevation in the brain can be estimated (from equations 1 and 2) to be about 60° C and 0.1° C during the 1 s and 1 ms exposures, respectively.
  • the corresponding temperature elevations in bone are 1800°C and 3.6° C.
  • the temperature elevation in the bone would be reduced proportionally with the area gain. These values are frequency dependent. For example, bone heating would be about 13° C for 1 ms pulse at 1.5 MHz. This short thermal exposure is below the threshold for tissue damage. Thermal exposures can be further reduced using multiple pulses that can be repeated at a low frequency (for example 0.1 Hz) thus, eliminating a temperature build up.
  • ultrasound was generated using a one-element transducer array having a spherically curved 10 cm diameter piezoelectric ceramic (PZT4) bowl mounted in a plastic holder using silicon rubber.
  • the ceramic had silver or gold electrodes both on the front and back surface.
  • the electrodes were attached to a coaxial cable that was connected to a LC matching network that matched the electrical impedance of the transducer and the cable to the RF amplifier output impedance of 50 ohm and zero phase.
  • the matching circuit was connected to an RF- amplifier (both ENI A240L and A500 were used in the tests).
  • the RF signal was generated by a signal generator (Stanford Research Systems, Model DS345).
  • the ultrasound pressure wave distributions were measured using needle hydrophones (spot diameter 0.5 and 1 mm) and an amplifier (Precision Acoustics Ltd).
  • the amplified signal was measured and stored by a oscilloscope (Tektronix, model 2431L ).
  • the hydrophone was moved by stepper motors in three dimensions under computer control.
  • the pressure amplitudes measured by the oscilloscope were stored by the computer for each location.
  • a piece of human skull (top part of the head: front to back 18 cm and maximum width 12 cm) was obtained and fixed in formaldehyde.
  • the acoustic properties of formaldehyde fixed skull and a fresh skull are almost identical.
  • the ultrasound transducer under test was positioned in a water tank the walls and bottom of which were covered by rubber mats to reduce ultrasound reflections.
  • the tank was filled with degassed deionized water.
  • the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.
  • the embodiment was tested at four different ultrasound frequencies: 0.246 MHz, 0.559 MHz, 1 MHz, and 1.68 MHz.
  • the maximum peak pressure amplitudes achievable through the skull at the focus of the transducer was measured at each frequency.
  • a shock wave hydrophone (Sonic Technologies Inc, ) was positioned at the acoustic focus. Bursts of 10-20 cycles were used to separate the acoustic signal from the electrical interference that was picked up by the hydrophone during sonication. Results of the testing are shown in Figures 4A-4H.
  • Figure 4A illustrates the ultrasound pressure amplitude distribution in water at the focal point of the single transducer driven at 0.246 MHz, without the skull section in place.
  • Figure 4B illustrates this same distribution when the skull was positioned in front of the transducer as illustrated in Figure 1.
  • Figures 4C and 4D illustrate the same distributions (i.e., with and without the skull section in place) for a frequency of 0.559 MHz.
  • Figures 4E and 4F illustrate the same distributions for a frequency of 1 MHz.
  • Figures 4G and 4H illustrate the same distributions for a frequency of 1.68 MHz.
  • thermocouple probe (0.05 mm constantan and copper wires were soldered together at the tip) was placed on the skull bone (on the side of the transducer that is expected to be the hottest location) under a thin layer of connective tissue that was still attached on the skull. Then 10 sonications at the maximum power level for the duration of 0.2 s were repeated with the rate of 1 Hz. The animal position was moved and the sonication repeated four times in the same location with a delay of about 5 min between the sonications to allow the bone temperature to return to the baseline. During the 10 s of pulsed sonication the bone temperature increased from the baseline of about 30° C to maximum of 43° C with rapid decay. After the sonications the rabbit was taken to a MRI scanner and Tl, T2 and contrast enhanced scan were performed. After the imaging the animal sacrificed.
  • Figure 5 A is a scan of the rabbit brain illustrating the effect of 10 sonications for the duration of 0.2 seconds, with a pressure amplitude of 8 MPa, repeated at a rate of 1. Hz.
  • the Figure is a T2-weighted fast spin echo image across the brain.
  • the arrow in the Figure shows tissue damage at the focal point of the transducer.
  • the skull window on the top of the head is facing down and, thus, the ultrasound beam propagated from bottom up.
  • Figure 4B is identical to Figure 4 A, except insofar as it shows the results where the above sonication was repeated four times.
  • FIG. 3 For embodiments of the invention, these embodiments utilize multi-element phase arrays of the types illustrated in Figures 3 and 10, in lieu of a single transducer.
  • phase of the ultrasound wave By controlling the phase of the ultrasound wave as a function of transducer location, these embodiments eliminate the phase distortion caused by the skull and thus, allow accurate aiming and use of higher frequencies, thus, permitting application of ultrasound to induce cavitation through the intact skull in regions of 1 mm to 1 cm 3 .
  • Two phased arrays comprising these further embodiments had similar structure and the same driving hardware; the resonant frequency being their only significant difference.
  • the two arrays operated at 0.6 MHz and 1.58 MHz.
  • the radius of curvature of both of the transducers was 10 cm and both of them were cut into approximately 1 cm 2 square elements, as shown in Figure 3.
  • the total number of elements in both arrays was 64 although only 60 were driven in the experiments due to hardware limitations.
  • the ceramic bowl was cut using a diamond wire saw so that the elements were completely separated by a 0.3-0.5 mm kerf.
  • the kerf was filled with silicone rubber that kept the array elements together and isolated them acoustically. The silicone rubber allowed the transducer elements to vibrate with minimum amount of clamping.
  • Each transducer element was connected to a coaxial cable and a matching circuit that was individually tuned.
  • the arrays were similar to the one described in Fan et al, supra, at Figure 1 and the accompanying text, the teachings of which are incorporated herein by reference.
  • the array was driven by an in-house manufactured 64 channel driving system that included an RF amplifier and phase shifter for each channel.
  • the phase and amplitude of the driving signal of each channel was under computer control, as described in Buchanan et al, supra, e.g., at Figure 2 and the accompanying text, the teachings of which are incorporated herein by reference.
  • phased arrays can also be constructed in accord with the arrangements described and shown in co-pending, commonly assigned patent application 08/747,033, filed November 8, 1996, the teachings of which are incorporated herein by reference.
  • FIG. 5 shows the image across the brain for the first of the sonications and demonstrate tissue damage indicated T2 changes. The tissue damage was also visible in Tl images with and without contrast enhancement.
  • phase distortion caused by the skull To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus. This was done with both of the arrays. The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.
  • FIG. 7 A illustrates the pressure amplitude profile across the focus of the 0.6 MHz phased array in water.
  • Figure 7B shows the pressure amplitude profile across the focus through bone.
  • Figure 7C shows the pressure amplitude profile through bone when a phase correction according to the invention is used.
  • Figure 8 likewise illustrates the pressure amplitude distribution along the central axis of the array with and without phased correction. The magnitude was reduced to 33 % and 40 % of its water value without and with the phase correction, respectively.
  • the embodiments of the invention discussed above and shown in the drawings provide improved methods and apparatus for neural diagnosis and therapy through application of short, high intensity ultrasound beams that induce cavitation at selected locations within the brain.
  • These and other embodiments can be beneficially used to deliver focused ultrasound beams to the CNS tissues and fluids, thereby, permitting their ablation or other physiological modification.
  • the embodiments can be used to ablate tumors, cancers and other undesirable tissues in the brain. They can also be used, for example, in connection with the technologies disclosed in copending, commonly-assigned U.S. Patent Application No. 08/711,289 (the teachings of which are incorporated herein by reference) for modification of the blood-brain barrier, e.g., to introduce therapeutic compounds into the brain. Because they do not require that portions of the skull be removed, the embodiments permit the foregoing to be performed noninvasively.
  • results show that adequate ultrasound transmission can be induced through human skull to induce cavitation in vivo. This can be done with single element applicators, e.g., preferably at frequencies less than 1 MHz and at higher frequencies with phased arrays that correct the phase distortion caused by the variable thickness of the skull.
  • the maximum pressure amplitude of 8 MPa induced through the skull at 0.559 MHz was able to induce cavitation damage in vivo rabbit brain. This value was reached through an area of 10 cm in diameter to a focal spot diameter of about 5 mm (50 % beam diameter). If the whole available skull surface around the brain is utilized, then a window of at least three times larger could be used. In addition, the geometric gain would allow the peak power through the skull to be increased. Acoustic power up to 30- 80 W/cm 2 of the transducer surface area for continuous wave sonication can be generated by ceramic transducers. Higher peak powers could be achieved with the pulsed sonication used for induction of cavitation. Thus, it is estimated that much higher pressure amplitudes than measured here can be induced in the brain through the skull.
  • phase measurements with the arrays support the observation made with the single element transducers showing that at 0.6 MHz 80 % of the phase errors caused by skull are less than 90° and thus, each wave is adding to the pressure wave at the focus. However, at 1.58 MHz over half of the waves had phase shifts that caused the waves to arrive out of phase at the focus. This observation can be explained by the difference in wavelength that is 2.50 mm at 0.6 MHz and 0.95 mm at 1.58 MHz.
  • the possibility of inducing selective thermal damage at the focus, without damaging the skin or brain surface, may be possible due to the small focal spots achieved with the phase correction.
  • the thermal exposures have to be short to reduce blood flow and perfusion effects that are strong in brain tissue.
  • the sharp temperature gradients at the focus transport more energy away from the focus than in the bone where the beam is wide and the gradients shallow.
  • full utilization of the skull surface may provide marginally adequate geometric gains to overcome the skull heating problem.
  • the focal brain tissue thermal therapy seems feasible although not as likely as utilization of cavitation effects.
  • the phase correction was calculated from hydrophone measurements.
  • the same corrections can be made by measuring the skull thickness from CT or MRI scans and then calculating the phase correction required for each array element.
  • the same may be accomplished by sending a short ultrasound pulse from each or selected elements of the of the phased array and then listening for the echo back from the inner surfaces of the skull or other structures in the brain.
  • the effect of the skull on the wave propagation at each location could then be calculated. This can also be done before therapy by mapping the skull effect using ultrasound.
  • the geometric gain of about 20 that is required to compensate for the losses caused by the skull can be easily achieved by focusing. This is larger than the gain of 10 required to compensate the average losses. This indicates that adequate power for induction of cavitation can be delivered using phased arrays through the skull even at frequencies that are too high with a single element applicator.
  • the invention provides methods and apparatus for noninvasive diagnosis and treatment of the brain using cavitational mechanism and pulsed ultrasound. It permits adequate power transmission through the human skull can be induced to cause tissue damage while keeping the exposures in the overlying tissues below the cavitation threshold.
  • the invention can be applied for purposes of tissue ablation, as well as in other procedures where focussed ultrasound is desired. These include opening the board-brain barrier, activation of therapeutic agents, occlusion of blood vessels, disruption of arteriosclerotic plaques and thrombi, etc. It will also be appreciated that the invention can be applied for treatment of humans, rabbits and other animals.
  • the embodiments discussed above and shown in the drawings are illustrative only. Other embodiments, incorporating substitutions, modifications and other changes therein, fall within the scope of the invention. These include embodiments with transducer arrays of different sizes, shapes and numbers of elements, as well as embodiments with different amplification and driving systems.
  • phased arrays CJ ⁇ focu iheir radiated presented as are the results of acoustical held measurements energy, they theoretically could heat tissues 10 therapeutic and in vino perfused phantom studies performed with the array. tempeiaturcs deeper lhan nonfocused arrays, The ultrasound Several techniques for heating realistically sized tumor volumes power dcpo-iuon pattern can be clecti omcalh tailored as • vere also investigated, including single focus scanning and two techniques for producing multiple stationarv foci.
  • INTRACAVITARY ultrasound arrays offer an attractive proposed or built I01 hype ⁇ hermic purposes These include means of inducing local hyperthermia in deep-seated tu Unier ⁇ ur and Cain ' s sccior-vouex and concentric ring applirnors located near body cav ities By locating Ihe radiators as cators
  • each of these arrays is composed of the acoustic w indow b> bone or gas, or simply the inability anyw here from 16 10 64 individual elements and operates at to attain adequate energy penetration, can be avoided Early frequencies between 500 kHz and 750 kHz. While these arrays results using multielement, nonfocused arravs of half-cylinder show significant potential, they ate meant to be used in external transducers operating at 1 6 MHz suggest lhal such arrays can applications and therefore aie unsuitable for intracavitary use be clinically useful in the treatment of prostate cancer ( I ] in their reported configurations
  • a ⁇ vt us Consn iic ri ⁇ n MOSFET ⁇ rn er £ r. c ihe amplifiers is capable oi deli v ⁇
  • nsducers operating in iheir resonant radial mode at 500 kH_ from each cnanncl cr _ :otai output power of about 850 W The array was made by slicing washer-shaped elements with The amplifiers er: digital lo ⁇ ic inpui signals into high a diamond wire saw (Laser Technologies.
  • the transducer simultaneously ov a ⁇ iusun ⁇ tne output voltage on a 1000 W slices ere elue ⁇ togeiner using a silicone adhesive i Dow DC supply cr tne ou'O'-i ol each cnannel can D ⁇ ind dualh Coming. Midland. MI ) with 0.17-mm thick silicon rubber conirolled bv varying '.he duly v ele of tne input signal.
  • T e c ⁇ c ⁇ e is tne percent of ' on " time of the input signal per clock stack of elements as then cut in half along the axis o the ocie i is a correspor.a'.ne decrease in tne amplitude of tne cy n ⁇ e: and the two half-cylinder sections glued together to ouiDut signal form tne full array
  • the array was bonded to a brass shell Since ihe ampiiner; require ⁇ igitai input signals, the phase lo form the complete applicator, as shown in Fig.
  • Wires shilling jn duiy-cvcie control is implemented using dizital were soldered to the inside wall of each array elemeni that .ouniers
  • . I 1 11. These circuits provide 22.5 pnase shift extended the length of the shell to tne handle where they were resolunon Horn 0-360" .
  • phased arrays One of the primary disadvantages of phased arrays is Ihe by power meters mat measure both the forward and reflected increased complexity of the driving equipment. Due to a l ack RF power 1 131 The power meters, wnich were also designed /07373
  • -TJI signals for a BIN en models the surface ot each of the cylindrical elements as an excitation p.naje ana amplitude i.-;.:c r ⁇ pe ⁇ me ⁇ tally b> a even ⁇ > spaced grid of simple hemispherical sources and uses needle hydrophone ⁇ ⁇ ' ⁇ tho- ⁇ tn .- ⁇ . zi. matcnin .
  • the acoustical pressure field was calculated in the z-plane
  • the technique solves the ayleigh-Sommerfeld integral for using an arrav wnh ⁇ ' elements, and a field of M control pom Pi')
  • P. I 7 P.. ,j(2'/ - 2 * ⁇ - *) speed ol sound in the medium, k is the wavenumber. 5' is ihe
  • the single focus case is the simplest Jorm ot to using that points ( M) This leads to an undcrdeienmtned system of can be done "* nh a phased array.
  • the single focus is produced equations w ith an infinite number of solutions.
  • the mu mum by senine ihe phases of the driving signals so thai constructive norm soiuiion I u i can be determined by using a least squares interference occurs at the desired focal position.
  • Delivered power was maximal at the RF power was measured using a Hewlett Packard 438A RF edges of the scan but was reduced to 64% ol maximum power power meter and ⁇ Werlat ⁇ ne C2625 (Brewstcr. NY ) dual at the center of the scan to flatten the temperature distribution direcnonal couoiei
  • the efficiency was calculated as the ratio in the perfused phantom expe ⁇ ments (the power distribution of the acoustical power to the RF electrical input power was experimentally determined).
  • the other technique multiple focusing, simultaneously produces more than one focus within the target volume.
  • the drivB Ultrasound Field Measurements ing signals necessary to produce multiple loci were calculated The ultrasound fields were mapped in a lank of degassed , using two techniques, solit focusing and the pseudo-inverse. deionized waier by mechanically scanning a thermocouple To create mulnple foci with the split focusing technique, the embedded in a small (2 mm diameter) plastic sphere The ther ⁇ array was divided into subarrays. eacn of whicn produce a mocouple was positioned bv a three-axis computer controlled single focus in ihe same manner as previously described.
  • the scanning table The applicator was mounted on a rotational pseudo- inverse method, developed by Ebbini and Cain ( 15).
  • device that allowed measurements to be made in a radial arc uses a series of control points that represent the magnitude around ihe array by rotating the array. Measurements were of the ultrasound field at given points.
  • a brief summary of made on a 1 x 1 mm gnd with the recorded data being the Ebbini and Cain s tec ⁇ nique follows. average of three consecutive measurements. I It- IEEE TRANSACTIONS OS BI0MED1C ⁇ L.E«G, ING. VOL -1.-A.0 ⁇ i:. DECEMBER. UWJ
  • Alcohol fixed canine kidneys were used as phantoms far studying the heating characteristics of the array.
  • the kidneys had previously been prepared as described by Holmes et al. [IS], and were rehydraied pnor 10 use.
  • the experiments were conducted at room temperature using degassed, dcionized water as the perfusate A metering pump (Fluid-Mete ⁇ n Inc RH1C C. Oyster Bay, NY) connected to the renal artery circulated water through the kidney while the renal vein was allowed to drain into the tank The kidney was held in place bv gently sandwiching it between two PVC membranes mounted to a Plexiglas frame.
  • the applicator was ⁇ rmlv clamped to the frame to maintain a fixed distance between tne surfaces of the Fip 1 Du? ram o ( ilic ... , kidney t»penmenul setup kidnev ana array
  • Fig 3 shows diagram of the experimental setup
  • the pull-back experiments were conducted b ⁇ pulling one or two single uncoated thermocouples (0.05-mm »M re J bv. . ⁇ computer controlled stepper motor along a track parallel to t 'ici. ic si Cow*'
  • the temperatures were p -- l A.
  • the arrays must be designed to minimize grating lobe formation. acoustical intensity is not at all uniform ana. in fact, vanes
  • the array with l.S-mm center-to-center spacing produced as much as 50% before tapering off at the eoges. All of the much better field distributions than (he array w ith 2.5-mm 2-D acoustical field plots shown nere were made at the 0' cemer-to-ctnter spacing. Therefore, in order to ha e center- rotation anele where tne intensity is only about 50% of the to-ce er spacing 1 S mm or smaller. 1.5-mm wide elements peak. Measurements made, but not shown here, show that this were used in the final array design and the dead space between fluctuation in pressure amplitude due to the rotation angle only elements * as reduced to 0.23 mm alters the peak intensity and does not effect tne overall snapc
  • Fie 7 Smcle dimensional radial field plot made »nh ⁇ n the focus -s . function of ⁇ h « .ntie o( rouu ⁇ of ihe arr.) Tl-.e center ⁇ l the jr ⁇ »c .r (55 mm and 42 mm from the surface of the array). The is defined as ihe lero point.
  • Fig. 9(a) shows the temperature rice ver ⁇ u* time along a v DISCUSSION AND SUMMARY fixed seven-sensor thermocouple probe located perpendicular to the array
  • the distances marked denote the distance of An intracav itary ultrasound phased arrav composed of half- the thermocouple from the edge of the kidney nearer to cylinder transducer elements has been constructed for inducing the array.
  • phased arrays show considerable temperature were caused by a variety of problems, including potential for improvement over currently used intracavitary morphological differences in kidneys and the location of the ultrasound hyoerthermia system. thermocouples within the kidneys, the inefficiency o the arra> . While phased arrays allow significantly more control over and the open loop manner in which the array was ooerated the acoustical field, the current design using half-cylinder
  • the electrical efficiency of the a ⁇ ay would usually drop radiators still lacks control in the angular direction t around the considerably during the first experiment, and during each subarc oi the array). Additionally, since the cylindrical radiators sequent experiment due to changes in the electrical lmoedance ⁇ o not have uniform angular intensities, the angular heating of the array elements T o primary factors were responsible pattern is somewhat degraded, though thermal conducuon will for the observed changes in the electrical impedance of the probably sm ⁇ otn the resulting temperature distribution. Similar array elements: The first was a thermally induced impedance fluctuations in the angular field distributions have been shown drift caused by the array self-heating du ⁇ ne sonication.
  • thermocouple location indicate the (b l from tne cun ac t oi ihe kidnev w ith ihe arrav positioned 2 ' rr.m trom the distance from the surface of the kianev u' ⁇
  • a possibly better arrav design ⁇ * ould utilize planer array the frequenc increased making array design more difficult elements mounted or, a rotating platrorm By tilling tne array A* a conc l usion tne intracavuarv.
  • Focused high-power ultrasound beams are well suited for noninvasive local destruction of deep target volumes In oroer to ovoid cavitation and to utilize only thermal tissue damage, .high frequencies ( 1 -5 MHzl are used in ultrasonic surgery However the focal spots generated by sharpl ) focused transducers become so small that only small tumors can be treated in a reasonable lime.
  • Phased array ultrasound transducers can be employed to electronically scan a focal spot or to produce multiple foci in the desired region to increase the treated volume.
  • the spne ⁇ cally curved 16 square-eiement phased array can produce useful results by varying the phase and amplitude setting Four focal points can oe easily generated with a distance of tw o or four wav elengths btiween the two closest peaks
  • the maximum necrosed tissue volume generated by the arrav can be up to sixteen times the volume induced by a similar spherical transducer Therefore the treatment time could be reduced compared w ith single transducer treatment.
  • Phased arra applicators were introduced to ultrasound given array Several simplified amplitude and phase setting? hyperthermia cancer therapy in the early 19S0's. During the based on the calculated amplitudes and phases wxre empast decade, many efforts have been made to inv estigate the ployed for ultrasound fielc calculations Tnes ⁇ d ⁇ ving signal advantages of phased arravs in hyperthermia. and several sets can be utilized when different focal spot sizes are rephased array applicators have been developed Phased array quired for the array proposed nere.
  • the transient bioheat applicators can be divided into the following categories: antransfer equation was employed to estimate the temperature nular or concent ⁇ c- ⁇ g arrays, 2 - 3 stacxed linear- phased elevation due to the ultrasound power deoosiuon. Then the arrays. 4 secior-vonex arrays,' tapered linear-phased arrays s necrosed tissue volume was predicted bv the isothermal dose cylindncal-section arrav s. 6 and square-element spherical - volume Computer programs were aiso used to do a parametsection arrays.
  • the bowl was cut into 16 elements, each with a length of 20 mm per si ⁇ e ⁇ 0 3-mm space between the elements was filled with s ⁇ icone rubber for electrical and mechanical 0. Inverse technique isolation. Each oi the elements u.
  • the inverse lecnnioue can be used to calculate ihe ampliarray was driven » un a custom made 16 channel amplifier tude anc ona e sellings irom selecleo control points wnerc (Labiherrmcs. Champaign. Illinois).
  • the driving signals a ere generated by an in-house manufacdS, .
  • the relative pressure amplitude squared distributions i p were measured in ⁇ egassed water using a needle hy ⁇ rophone (active spot sue 1 mmj scanned across the focal region.
  • the needle hydrophone as moved bv stepper motors, typically with 0 I -mm steps ... OS the beam.
  • the total acou'iic power (.' was measured using a radiation torce technique.
  • Tne eiemems ol matrix H are evaiuatec DV nume .cai inie -
  • wnerr H' is tne cseudomvt-rse ma x of H.
  • T is the temperature Sit Hfine; . . HhWoca ⁇ fS ' H,, , ' ' .£ ⁇ .
  • c ⁇ nir ⁇ l points are ) ⁇ - ied a ⁇ p, is the density of the tissue, c, is Ihe specific heal of the • :• ⁇ 129 mm plane Note die -n ⁇ t> fiir » and v are millimrtcrv ⁇ issue, k, is the thermal conductivity of the tissue. « is the blood perfusion rat. . c h is tl._ speci ic heal of the blot.i.
  • the thermal dose calculation was based on the i ⁇ chnique suggested Sapareto and Dewey ' Using this technique, the accumulated thermal dose was calculated at a reference temperature DV numerical integration under different temperature profiles
  • the thermal dose, i e.. equivalent time, at ihe reference temperature can be evaluated by ⁇ ⁇ r -"- ; -»' ⁇ r
  • the A iwo layered me ⁇ ium waier-tissue was assumed in the latter setup gives desiructive interference on the central axis simulations
  • the speed of sound and the density w ere 1500 thus, eliminating potential hot spots on tne axis 3
  • the attenulected control pomis used in the inverse calculations ar: ation coefficient of tne tissue w as assumed lo be 10 Np/m' grven in Table 1. MHz.
  • the thermal properties of the tissue are giver, in Tabic II.
  • T ⁇ ILE. IV The simplified phase and amplitude sellings for ihe I- sqvart- To understand the effect of radius of curvature on the element sphencillv curved phased array med in the necrosed tissue v ⁇ l ⁇ r ⁇ e necrosed tissue volume, the isothermal doses for ;ue IV of
  • the phased array can also enlarge the necrosed tisThe l o eiemen: pr.ased arrav can generate tcur foca sue volume in only one direction at a time, if desired. It is points w nn 3 near, to o-_ t distance as short as tw o important to be aole to control the focal spot size so thai i lengths T ne maximum Distance between the losest peans is large rumor could be treated in a reasonable time.
  • the array is similar to _ represents an unoerdete min ⁇ svstem. it producea a solution concentnc- ⁇ ne array witn two nngs. Theoretically, tne maxi at the control DOIM*. V> ns ⁇ multi ⁇ le loo art separated bv mure phase increment between adiacent elements if - distances large' tr.an A 6 mm.
  • the necrosed tissue volune phase difference Droouces displacements along the central can be enlarged oecause the focal spot increases oue to the axis of up to 23 mm f lO mm closer, 13 mm oeeper) In increased w avelength
  • the ratio of tne necrosed tissue shifting the focus sideways it is similar to a cyiind ⁇ cal- length to the u idtn w as xept almost the same As tne raoius secnon array with four elements.
  • necrosed tissue volume can also pnase difference between the smallest and largest pnases is be enlarred
  • necrosed tissue voiume is increased ma ⁇ nl> 3 w for shifting. the focus sideways Geometrically, mis phase in the aua.
  • Fio 6 Contour plots of po» er deposition for v inous amplitude ani pnase settings tai i; ihe uniform excitation case Tie cv.a) distance Irom ihe This sludy w as supported by NCI Grant No CA 4662 * transducer to ihe focus »as ⁇ a > 1.9 — m Ibi I-- mrr. " f I jb mm. and ⁇ o ⁇ 129 mm. shifted 1.5 mm
  • Theon Tech MTT-34 x;-; i ⁇ 19S6> is limited by the number of phased array elements.
  • a tapered number of field patterns that produce significantly different phased arrav ultrasound irancd ⁇ cr for hv perthermta treatment. IEEE shapes or sizes of the measured volume is limited.
  • Trans l ltrason Ferroelec Frcq Conir L FC 4 4J6--tf 3 09S7 ' only few amplitude and phase settings were presented in this 'E S Ebbini.

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Abstract

Méthodes et dispositif pour administrer des ultrasons au cerveau sans qu'il soit nécessaire d'enlever des parties de la boite crânienne, faisant appel à la transmission d'ultrasons par une pluralité de transducteurs orientés de manière à induire une cavitation dans une région choisie du cerveau au moins. Une source d'excitation permet d'actionner au moins les transducteurs choisis, à des phases qui diffèrent d'un transducteur à l'autre, par exemple pour compenser les déphasages (ou distorsions de phase) causés par le crâne sur l'émission d'ultrasons de chaque transducteur. Les ondes ultrason provenant des transducteurs atteignent ainsi la région choisie en étant sensiblement en phase les unes avec les autres, par exemple à moins de 90° et, de préférence, à 45° et mieux encore à 20° les une de l'autre.
PCT/US1997/014760 1996-08-21 1997-08-21 Methodes et dispositifs pour administrer un traitement par ultrasons non invasif au cerveau a travers une boite cranienne intacte WO1998007373A1 (fr)

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