Classifications

• • 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
  • A61B17/225—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 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
  • A61B17/2251—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 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
• • A—HUMAN NECESSITIES
  • A45—HAND OR TRAVELLING ARTICLES
  • A45D—HAIRDRESSING OR SHAVING EQUIPMENT; EQUIPMENT FOR COSMETICS OR COSMETIC TREATMENTS, e.g. FOR MANICURING OR PEDICURING
  • A45D26/00—Hair-singeing apparatus; Apparatus for removing superfluous hair, e.g. tweezers
• • 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
  • 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
  • A61B2017/00743—Type of operation; Specification of treatment sites
  • A61B2017/00747—Dermatology
  • A61B2017/00752—Hair removal or transplantation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
  • A61B8/42—Details of probe positioning or probe attachment to the patient
  • A61B8/4272—Details of probe positioning or probe attachment to the patient involving the acoustic interface between the transducer and the tissue
  • A61B8/4281—Details of probe positioning or probe attachment to the patient involving the acoustic interface between the transducer and the tissue characterised by sound-transmitting media or devices for coupling the transducer to the tissue

Definitions

• the present invention concerns an ultrasound system for the administration of a focused ultrasound beam and methods for using this system both for therapeutical and/or cosmetic purposes as well as for processing of non-biological material.
• Ultrasound is a mechanical wave with a frequency above the audible range that propagates by motion of particles within the medium.
• the motion causes compressions and refractions of the particles so that a pressure wave travels along with mechanical disturbance.
• a system which utilizes ultrasound for diagnostic purposes usually comprises a wave-generating transducer capable of generating an ultrasonic wave, and an ultrasonic receiving transducer capable of receiving the ultrasonic wave. Since the density of the tissue through which the ultrasound wave propagates, has an effect on the speed and attenuation of the wave, if the ultrasound wave passes through tissues having different densities, for example due to a presence of a tumor therein, the wave is distorted, which distortion can be monitored by the receiving transducer.
• the wave-generating transducer should be coupled to the body of the patient to be diagnosed through a specific fluid medium, such as an ultrasonic gel.
• a specific fluid medium such as an ultrasonic gel.
• US 4,434,799 discloses an ultrasonic apparatus for medical examination wherein the patient organ to be diagnosed, for example a breast, is positioned between an ultrasonic wave-generating transducer and an ultrasonic receiving transducer. In contact with the skin, and at some distance from both the wave-generating transducer and the second receiving transducer, are first and second ultrasonic windows, respectively.
• the system contains two guiding devices containing a fluid medium, one for guiding ultrasonic waves from the transducer to the first window and from there to the body of the patient, and one for guiding the ultrasonic waves from the body of the patient to the second ultrasonic window and from there to the receiving transducer.
• This diagnostic apparatus which emits a non-focused ultrasound wave, enables guiding of the ultrasound wave through a liquid medium, and eliminates the need to use a coupling gel on the body of the patient, or the need to immerse the body of the patient to be examined in a water tank.
• Ultrasound has also been proposed for therapeutical purposes, used in the area of physiotherapy, cardiology, ophthalmology, cancer therapy, and dentistry.
• Non-focused waves are used, for example, in physiotherapy and focused ultrasonic beams are used for selectively destroying a living tissue in a desired location, for example, for destroying a malignant tissue.
• destruction by a focused ultrasound beam is combined with diagnostic ultrasound imaging which locates precisely the region of the tissue to be destroyed.
• diagnostic ultrasound imaging which locates precisely the region of the tissue to be destroyed.
• Another therapeutical application of the ultrasound is its use to disintegrate kidney stones where the ultrasound high energy pulses produced by a lithotripter are absorbed in the condensed stone. The stone is slowly broken into small fragments by the energy forces, and is simultaneously monitored by X-ray vision or ultrasound vision.
• the ultrasound application continues until the broken stone fragments are small enough to be washed through the urinary tract.
• the body of the patient, or at least the area containing the organs to be treated is immersed during the ultrasound administration phase in a water tank.
• Ultrasound beams can be focused by using self-focusing radiators or special transducers, lenses or reflectors, or by electrical focusing.
• the thermal elevation of the tissue caused by energy absorption is inversely proportional to the beamed area.
• the greatest temperature elevation is induced at the focus of the beam, termed "the focal point" where it can be several hundred times more than the overlying tissue. This allows tissue at the focal point to be selectively destroyed while temperature elevation of the surrounding tissue is negligible.
• Sharp focusing also allows fast energy delivery so that tempera- ture levels that cause proteins to coagulate and cells to die can be reached in only a few seconds or seconds parts.
• the short exposure to sharply focus beams produces sharp temperature gradients and the transition distance between the coagulated cells and damaged cells may be only a few cells wide.
• Focused ultrasound was also demonstrated in vivo to be able to occlude blood vessels and coagulate capillaries and larger arteries.
• Non-invasive treatment using focused ultrasound is being hindered by the fact that in order for the ultrasound wave to propagate, the treated organs of the patient's body has to be immersed in a water tank, which is extremely cumbersome, especially where the patient is handicapped or elderly. Such immersion is almost impossible in cases where the treated area is the face. Even where immersion of the patient's body in a water bank is feasible, it hinders the manipulation of the focused ultrasound beam.
• the present invention concerns an ultrasonic system for the administration of a focused ultrasound beam to a patient for example, for therapeutical, i.e. non-diagnostic purposes.
• the concept of the present invention is that rather than immersing the patient in a liquid tank, or rather than immersing the whole ultrasound system in a liquid filled container, to couple to the ultrasound generating element a container holding a liquid medium.
• This container serves as a guide of the focused ultrasound beam from the ultrasound generating element to the body of the patient so that only the acoustic beam, and not the whole ultrasound system, is engulfed in the liquid medium.
• the present invention provides an ultrasound system for the administration of a focused ultrasound beam to a desired location comprising:
• At least one ultrasound generating element capable of producing a focused ultrasound beam
• the system of the invention may be used for therapeutical or cosmetic purposes and in such a case the desired location is a region in the body of the treated patient.
• the system may be used for processing non-biological material, as will be explained hereinbelow.
• the ultrasound system of the invention is intended for therapeutical and/or cosmetic purposes, rather than for diagnostic purposes, it is intended to administer a focused ultrasonic beam to a desired location of the patient and at a desired depth in that location.
• a certain target tissue of the patient such as a neoplastic tissue; for fusion of blood vessels; for destroying various epithelial regions showing undesired patterns such as pre-cancerous regions, beauty spots, broken capillaries, birth marks, viral warts, etc.; for localizing and activating agents capable of being sensitized by ultrasound, for example, agents which are capable of releasing free radicals and thus affectively destroying the surrounding tissue (Kessel et al, Photochem. Photobiol. B., 28:219-221, 1995) and for similar applications.
• focused ultrasound beam refers to an ultrasound beam which area is becoming progressively smaller and its intensity progressively higher as the beam is further away from the ultrasound generator, at the acoustic focal zone the area of the beam is smallest and the intensity the highest.
• the beam's area is equivalent to the near zone in a regular beam, where the beam runs in parallel before being dispersed.
• ultrasound generating element capable of producing a focused ultrasound beam may refer to a signal generator, power amplifier, matching unit, a transducer which is capable of producing a focused beam or to a complex of these elements which produce a regular, i.e. unfocused beam coupled to focusing means such as self-focusing radiators, reflectors or lenses and the like.
• the focused beam is created by the transducer itself, for example, by constructing the transducer so that its irradiation zone has a certain curvature or by other means.
• the ultrasound generating element may alternatively comprise a regular transducer, i.e. having a straight irradiation zone, coupled to focusing means such as a self-focusing radiator, reflector or electrical focusing unit or lens capable of focusing the ultrasonic wave and thus creating the focused ultrasound beam.
• the focusing means are acoustic lenses.
• the lenses are typically high-density plastic lenses, of different curved diameters, which curve depends on the desired properties of beam to be produced.
• the lenses are made of plexiglass.
• the system may comprise a plurality of lenses, of various curved dimensions, capable of detachably engaging with the transducer, in order to produce a wide variety of focused beams having varying properties.
• the ultrasound generating element is coupled to a container holding a liquid medium capable of transmitting ultrasound waves, which liquid medium serves as a guide of the focused ultrasound beam from the ultrasound generating element to the body of the patient.
• the container may be, a priori filled with the liquid medium or may be initially empty and filled with the appropriate liquid medium only immediately before the administration of the focused beam.
• the liquid may be a degassed solution, such as water, in order to reduce loss of the energy of the beam due to formation of cavitation bubbles.
• a degassed liquid is preferable where the focal point of the beam is at some depth inside the body as will be explained hereinbelow.
• regular solutions or even gassed solutions may be used, so that external cavitation effects of the liquid medium may contribute to the destruction process together with the sonothermolytic and other effects of the ultrasonic energy.
• the container should have an essentially conical shape, in order to adapt to the general shape of the focused beam which is also conical.
• the dimensions of the liquid holding container should be such as to accommodate the full width of the focused acoustic beam, i.e. that the container at each point is wider than the ultrasound beam at that point so as to avoid "bouncing" of the beam on the walls of the container.
• the width of the cone in its base and the angle of its slopes should match, almost precisely, the dimensions of the acoustic beam in order to reduce to a minimum the turbulence of the liquid caused by the energy transducer.
• the internal part of the beam-holding container has dimensions greater than the diameter of the beam at each point along the axis, it can be of different shapes. It is also possible that at least part of the inner space of the container is made of a whole solid material, and not aquatic solutions, albeit at the cost of higher energy losses.
• F number refers to the relation between r (curvature) of lens and d (diameter) of the transducer. Since the construction of the cone is preferably according to the shape of beam, it is preferable that irradiation is performed using rather small F numbers (1-5). The advantage of using small F numbers is that the heat loss is smaller since the beam passes through a smaller distance; the slope of beam is higher, so that the effects are more localized; and the distance of influence is shorter and undesired effects on surrounding tissues are reduced.
• the length of the container should be such that the focal point of the acoustic beam is outside the distal (uncoupled) part of the container, i.e. the length of the container is shorter than the length of the ultrasound beam from its point of origin to the focal point. If the focused ultrasound is to be used to treat a region on the external surface of the body, the length of the container is infinitely smaller than that of the ultrasound beam so that the beam is focused immediately outside the distal part container or alternatively at least a part of the focal zone or other part of the ultrasonic beam is outside of the container.
• the conic container has typically a tempered distal end.
• the container is considerably shorter than the beam's length, and thus the distal part of the container is considerably larger than the distal part of a container used to treat external parts of the body, and typically has a blunt end.
• the free uncoupled end may be completely closed, or may have an opening. Normally this opening site will be directly attached to the treated zone. However, attachment might be also carried out via accessories, such as sleeve to hold part of the focal zone or acoustic fiber to carry the acoustic wave further.
• An opening has the additional advantage, when treating external surfaces of the body, of allowing direct contact between the surface of the body and the liquid medium which may contain therapeutical substances such as sono-sensitized agents as explained above. If it is desired to administer the ultrasound to deeper regions of the body, the diameter of the cone at its distal side is respectively increased as to accommodate the beam's width in its medial part, and the opening should thereof be closed so as to avoid leakage. This closure can be done permanently, e.g. by using thin elastic film which absorbs only minor part of the ultrasonic energy.
• a temporary closure may be used until contact of the cone to the particular body zone, and then the closure can be removed since the pressure of the container against the skin serves to seal the opening.
• the temporary closure may be also from a material punctured by a seal-destructive ultrasound pulse.
• the closure may be made of material having low melting point, so that it is destroyed due to the heat produced by the ultrasonic beam; made of a thin layer of degradable polymer destroyed by the beam; made of thin film sensitive to cavitation in the liquid caused by ultrasound; or made of a porousive layer where the size of the pores can be largely increased by ultrasound.
• the container is preferably made from material which is a poor heat conductive material. For external usage, transparent material which enables better observation of the treated zone may be used or the distal end of the container may be attached to an optic fiber.
• the distance between the cone and ultrasound generating element is adjustable, in order to change the location of the container in respect to the focal point.
• the system may comprise a plurality of containers, of various sizes, each one capable of detachably engaging with the ultrasound generating element, in order to accommodate for the various dimensions of the beams.
• the cone can be composed of a flexible material which can be modulated (elongated or shortened) according to the varying beam sizes.
• the system comprises three varying elements in combination: - a series of acoustic lenses of different curve dimensions, capable of detachably engaging with the other components of the ultrasound generating element, typically with the transducer in order to provide a plurality of focused beams of varying sizes and focal depths; means for varying the distance between the ultrasound generating element and the coupled guiding container holding the liquid medium; a plurality of liquid-holding containers capable of detachably engaging either with the ultrasound generating element, in order to accommodate for the varying beam sizes and focal depths.
• the depth of the focal point may be changed either by changing the ultrasound generating element (for example by changing the lens, or using curved transducers with different curvatures); or the distances between the container and the ultrasound generating element.
• the size of the liquid holding container may be changed in order to accommodate the different depths of the focal point.
• focal zone of the ultrasound beam is of extreme importance, since it determines the exact depth of the ultrasound administration in the patient's body and determines which curve dimensions of the lens or of the transducer, distance between the ultrasound generating element and the liquid-holding container and which container's size should be chosen for a specific application.
• the focal point may be determined theoretically by utilizing the following formula (Gordon S.K. 1990 Acoustic Waves: devices, imaging and analog signal processing. Prentice Hall Inc. Englewood Cliffs, New Jersey pp 652).
• the focal point may also be determined experimentally. It is well known that the intensity of the ultrasonic beam is highest at the affected area of the exact focal point. The highest intensity is determined by the smallest mark to appear in the shortest time on exposed surfaces. For example, for specific system parameters, determined by the specific curve dimensions of the lens, and the characteristic of the lens material and of the liquid medium, a movable thin disc of plastic may be used, capable of changing its distance from the lens. The distance where the ultrasound causes the desired smallest mark in the plastic at the shortest period of time, is the focal point, and according to the experimentally determined focal point, the exact size of the liquid-holding container, and its distance from the lens may be chosen. Other physical methods for determining the focal zone are well known in the art and may be used in addition or instead of the method outlined above.
• the slope of the inner part of the container e.g. a cone should be such that at any distance along the beam, it is fully engulfed by the cone.
• the inner diameter of the cone is about 1 mm greater than the outer diameter of the ultrasound beam engulfed thereon at the same point, Damianou C. and Hynynen K, J. Acoust. Soc. Am. 95, 1641-1649 (1993)].
• the system of the invention can also be composed of several containers used concomitantly, for example, for the treatment of deep tumors by multi- frequency irradiation.
• Certain frequencies and intensities of unfocused beams will be used to activate specific sensitizers located in the treated tissue, while other frequencies (not affecting the sensitizers) will be used to create focused beams delivered by the cone device for causing direct degenerative effect at a desired location.
• Such dual activation can be done with the same container or with more than one container, all oriented to same location or to different locations according to the requirements.
• the system of the invention can be composed of advanced and flexible materials, enabling change of the lens curvature and therefore the focal length, without replacing the lens themselves. Similar materials can be used to form a container that the size of its opening can be changed, (such as in a diaphragm). Such a construction enables the same container to form narrow or wide openings at its distal part, enabling transfer of narrow or wide beams therethrough, this can save the use of many replaceable containers of different openings and sizes.
• the above two elements can be concomitantly operated, using a particular threading applying force on both flexible lens and the container to change their dimensions, enabling to change focal length and its location during irradiation.
• the present invention also concerns a method for administering to a patient, for therapeutical or cosmetic purposes, a focused ultrasonic beam.
• the system of the invention is placed over the desired location of administration, with the uncoupled, distal end of the liquid-holding container in contact with the patient's skin, and then the ultrasound generating element is activated to provide an ultrasonic wave of desired parameters (i.e. of desired frequency, duration and intensity).
• desired parameters i.e. of desired frequency, duration and intensity
• the focused ultrasound beam creates focused heat and since the system of the invention is small of size capable of being operated outside of a water tank, it is possible to use the system for processing, for example by melting, scarring, etching or destroying (penetrating), also no-biological material in a similar manner as carried out by a laser beam.
• the advantage of the cone-delivered ultrasound, above the laser beam, is that with the former but not with the latter, it is possible to melt non-biological materials at different depths of the material, leaving the material surface completely intact.
• the duration, intensity and speed of movement of the focused beam can determine whether the melting will cause etching, perforation or cutting or fusion of the irradiated non-biological material, and the depth of this phenomena deeper to, or at the material surface.
• FIG. 1 shows a planar view of an ultrasound system in accordance with one embodiment of the invention suitable for administration of ultrasound to external surfaces of the body or treated material;
• Fig. 2 shows a planar view of an ultrasound system in accordance with another embodiment of the invention suitable for administration of ultrasound to inner parts of the body or to deeper regions of treated material;
• Fig. 3 shows a planar view of an ultrasound system comprising means for adjusting the distance between the liquid-holding container and the acoustic lens;
• Fig. 4 shows a planar view of an experimental setup for determining the focal length of the focused ultrasound beam.
• the ultrasound system 10 of the invention is shown schematically in Fig. 1.
• This system is suitable for administration to any ultrasound beam to an external surface of the body or to outer regions of a non-biological material.
• the system comprises a signal generator coupled to an amplifier and matching unit (not shown) and an ultrasonic transducer 11, coupled directly or via an acoustic fiber, to an acoustic lens 12 made of plexiglass, having a curvature r.
• the length of the beam to the focal point is designated as F.
• the coupling is a detachable attachment, for example by constructing the uncurved side of the lens to be engraved so it has a step that exactly fits the transducer (not shown).
• the lens and transducer are attached to each and by application of force they can be detached, which construction enables detaching a lens having a specific curve dimension from the transducer and replacing it by another lens of a different curve dimension in order to change the length of the focal point F.
• the container 13 is attached to the rims of the transducer by a screw mechanism (not shown).
• Container 13 for example a container having a conical shape
• Container 13 has a tapered end 14 and holds within water, acoustic gel or any other substance that preferably has an impedance similar to that of the treated region, (either biological or non biological materials) for example an impedance similar to a biological membrane.
• Focal point F is exactly outside the container's tapered end 14. Since the focal point is elongated in the direction of the irradiation, it is possible to add a short sleeve (not shown) attached to the distal part of tapered end 14, so as to harbour part of the focal zone outside of the treated zone.
• the arrangement of system 10 is such that the focused ultrasound beam is administered to the surface of the body of a patient 15, since the focal point of the beam falls exactly outside the distal end of the container, i.e. at the surface of the body.
• Such a system is suitable for selectively destroying a region on the surface of the patient for example a cancerous or pre-cancerous skin region, for treating broken capillaries present on the skin surface, warts or birth marks; for hair removing or wrinkle removing purposes, and is also suitable for affectively destroying desired regions of other superficial tissues in particular, but not limited to external epithelium of the mouth and other parts of the digestive tract, hemorrhoids, the eyes, the formal reproductive tract (including the vagina) and the like.
• This system is also suitable for the processing the external tissues of a body or another non-human animal and surfaces of non-biological material.
• the system 20 in accordance with another embodiment of the invention is shown in Fig. 2.
• This system is suitable for treating deeper regions of the body.
• the system comprises a transducer 21, lens 22 and container 23 preferably detachably attached to each other as described above in connection with Fig. 1.
• Container 23, which is conical in shape, has a blunt end 24 and an opening 26. End 24 is placed against the surface of a patient's body 25 in a tight manner and this placement seals the opening 26 of the container and eliminates leaks of liquid therefrom.
• Focal point F falls beyond blunt end 24 at distance d inside the body of patient 25.
• the system in accordance with the second embodiment of the invention is suitable for administering a focused ultrasound beam into the body of a patient, i.e. at a certain depth below the skin.
• Such a system is used where it is desirable to destroy a certain tissue, for example a tumor or to close blood vessels within the body. Care should be taken that the path of the focused ultrasound beam does not encounter air (such as in the lungs) or bone. Alternatively, this system may be used to process deeper regions inside non-biological material.
• Fig. 3 shows an ultrasonic system 30 of the invention which comprises a transducer 31, lens 32 and liquid-holding container 33 having a blunt end 34 with opening 36.
• System 30 further comprises means for adjusting the distance between container 33 and lens 32.
• the adjusting means are a cylinder 38 mounted on the transducer and enclosing within also lens 32.
• Conical container 33 can slide within cylinder 38 by protrusion 39, present at the outer circumference of the container which is slidably engaged with the inner walls of the cylinder 38. Since the container 33 is in tight contact with the inner walls of a cylinder 38, considerable force has to be employed in order to slide the container within the cylinder thus avoiding accidental displacement during operation.
• System 30 also comprises a pocket container 35 filled with air or other material characterized by high absorbance.
• a pocket container 35 filled with air or other material characterized by high absorbance.
• Fig. 4 shows an experimental setup 40 for determining the focal length of a specific ultrasonic system i.e. the distance to the exact focal point by a lens of a specific material and of a specific curvature r.
• the system comprises a transducer 41, lens 42 and cylinder 44 attached to the transducers via screws 43.
• the cylinder is filled with the same liquid as the one about to be used in the container during the actual therapeutic application.
• Slidingly engaged within the inner walls of cylinder 44 is a movable plastic disc 45.
• the intensity of the beam is the highest and affected area the smallest.
• the distance between the movable plastic disc and the lens which the beam transmitted by the .transducer causes the smallest diameter but most pronounced scar on the plastic disc is the distance which defines the focal point.
• Example 1 An ultrasound system used for irradiation
• the transducer 11 used was either 1 or 3 Mhz transducers operated at 1.7 or 2 w/cm contmuous mode and the effect of both frequencies was similar.
• the calculated acoustic focus length (F) of the beam produced was 40 mm. Actually the proximal part of the focal zone was located at that distance of 40 mm.
• the length of the curved lens 12 and cone 13 together was 38 mm.
• Condition A the cone was either attached to the lens so that the focal point was about 2 mm outside of the distal side termed hereinafter as "Condition A” or the cone was spaced about 2 mm from the lens so that the focal point was at the cone's distal end termed hereinafter as "Condition B”.
• Example 2 Irradiation in a fish fin model
• Example 3 Irradiation in a chorio-allantoic-membrane (CAM)
• Fertilized eggs from fish were irradiated with the system as specified in Example 1 under Condition A or Condition B.

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• 1997
  • 1997-01-27 IL IL12007997A patent/IL120079A/xx not_active IP Right Cessation
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  • 1997-12-12 AU AU52346/98A patent/AU5234698A/en not_active Abandoned
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