This invention relates generally to methods and apparatus for utilizing energy, e.g., optical radiation, to treat various dermatological and cosmetic conditions. More particularly, the invention provides a handheld dermatological device that facilitates viewing and measuring parameters of a treatment area before, during, and after application of a treatment modality.
Energy such as electromagnetic, mechanical, thermal, acoustic, and particle beam radiation has been utilized for many years in medical and non-medical facilities to treat various medical and cosmetic conditions. Such treatments include, but are not limited to, hair growth management, including limiting or eliminating hair growth in undesired areas and stimulating hair growth in desired areas, treatments for PFB (razor bumps), skin rejuvenation, anti-aging treatments including improving skin texture, elasticity, wrinkles and skin lifting and tightening, pore size reduction, reduction of non-uniform skin pigmentation, improving vascular and lymphatic systems, treatment of vascular lesions such as spider veins, leg vein, varicose veins, port wine stain, rosacea, telangiectasia, removal of pigmented lesions, repigmentation, improved skin moistening, treatment of acne including non-inflammatory, inflammatory and cysts, treatment of psoriasis, reduction of body odor, reduction of oiliness, reduction of sweat, reduction/removal of scars, prophylactic and prevention of skin diseases, including skin cancer, improvement of subcutaneous regions, including fat reduction and cellulite reduction, as well as numerous treatments for other conditions.
The treatments can be performed, for example, by employing optical energy (including ultraviolet, visible, and infrared), microwave energy, radiofrequency, low frequency or DC current energy, acoustic energy, mechanical energy and kinetic energy of particles (for example, sapphire particles), skin cooling or heating. The flow of energy can be delivered to the treatment region via a handpiece, which can include a housing, energy distribution system (comprising, for example, a radiation source, optics and a scanner), and an optional skin cooling element. In rare cases, the handpiece can also include a diagnostic sensor (i.e., skin temperature radiometer). The diagnostic sensor in such systems is used to protect the skin from unwanted damage (i.e., due to overheating or over cooling).
While various handheld devices have been disclosed for applying dermatological treatments, currently, present systems lack efficient mechanisms for positioning the treatment head of the handpiece over a selected target treatment area and/or viewing the target area while a treatment modality is being applied. Further, such conventional handheld devices lack systems for preferential imaging of subsurface skin tissue.
Accordingly, there exists a need for handheld dermatological devices that provide mechanisms for positioning the device's treatment head over a target area and/or viewing the target area even as the treatment is being applied.
There is also a need for such handheld dermatological devices that can provide better targeting and evaluation of a treatment target and surrounding tissue before, during, and after treatment to improve efficacy and safety of the treatment and provide an opportunity for self treatment with a cosmetic device suitable for home use.
Methods and devices for treating dermatological or cosmetic conditions that include imaging a target skin region, e.g., skin tissue, are disclosed that allow preferential illumination of the skin region, obtaining its image and displaying it to a user for better alignment of flow of a treatment energy relative to a target region and performing diagnostic of the target before, during and after treatment. A user of such devices can be, for example, a physician, an aesthetician, or a person who can utilize the device for self treatment of a cosmetic condition. In some embodiments, the device provide diagnostic functionality. In some embodiments, the devices include handheld devices that can, in addition to imaging capability, provide treatment energy to a subject's skin. The term “treatment energy” as used herein can refer to therapeutic energy to treat diseased condition or energy suitable for treating cosmetic conditions.
In one aspect, a handheld dermatological device is disclosed that allows application of treatment energy to a target skin region as well as visualizing the skin treatment region prior to, during, or after application of the treatment energy. Such a device can include, for example, an image capture device and a display device that is mounted to a housing of the handheld device and is coupled (electrically, optically or otherwise (wireless)) to the image capture device to present acquired images to a user, e.g., a medical professional or a consumer. The image capture device can be connected to the display through a microprocessor, which can be integrated with the display or the image capture device itself. The handheld device can further include a head that can be precisely aligned by a user relative to a patient's skin by utilizing one or more images presented in the display, and through which treatment energy can be applied to a target skin region.
A dermatological device, as used herein, can refer to a therapeutic device or a cosmetic device, including a home cosmetic device.
In one aspect, a handheld dermatological device is disclosed that includes a housing capable of being manually manipulated to position a head portion thereof in proximity to a person's skin, and is adapted for delivery of treatment energy to a target skin region. The handheld device can further include an illumination source coupled to the housing for generating radiation to illuminate the target skin region, and a detector disposed in the housing and adapted to primarily detect tissue scattered radiation emanating from the target skin region. As used herein, the term “primarily detect tissue scattered radiation emanating from the target skin region” is intended to mean detecting radiation from the illumination source that is primarily scattered by tissue below and around the target skin region depth and thus reaches the detector from beneath the skin surface thereby emanating or coming from the target skin region. This may also be referred to as “translucent radiation” where the radiation is coming from below the target skin region to make the target skin region more visible. The term “primarily” in this context is used to distinguish between such tissue scattered radiation and light that reaches the detector by reflection of illuminating or ambient light from the surface of the skin and skin above the target skin region. Thus, “primarily” typically means greater than 50%, preferably greater than 60%, more preferably greater than 70%, more preferably greater than 80%, more preferably greater than 90%, more preferably greater than 95%, of the detected radiation corresponds to scattered radiation emanating from below and around the target skin region depth as opposed to light reflected by the skin surface and scattered from the skin above depth of target skin region.
The detector can be positioned relative to the illumination source so as to primarily detect the scattered radiation. The detector can optionally include an image capture device for generating an image of the target skin region. Further, a display can be mounted to the housing for displaying the image.
The illumination source can be adapted to deliver radiation to a first skin surface segment so as to illuminate the target region such that at least a portion of the scattered radiation reaches the detector via a second skin surface segment. A shield mounted to the head portion can shield the second skin surface segment from direct (via skin surface) application of radiation from the illumination source. In some embodiments, the device can further include additional illumination sources. In some cases, the illumination sources can be selected to generate radiation with different wavelengths. A control unit can be further included for selectively activating at least one, or more of the illumination sources. For example, the control unit can activate the illumination sources according to a preset temporal pattern.
In some embodiments, the housing can include an aperture through which the scattered radiation can reach the detector. The illumination source is preferably offset relative to the aperture such that illuminating radiation reaches the target region along different paths than those along which scattered light from the target region is collected by the detector. In some embodiment, the illumination source can be positioned at an angle relative to an optical axis of the device.
In other aspects, a treatment source can be disposed in the housing for generating the treatment energy. By way of example, the treatment source can generate electromagnetic radiation having one or more wavelengths in a range of about 290 nm to about 3000 nm, or preferably in a range of about 500 to about 3000 nm, or preferably in a range of about 600 nm to about 1900 nm, or more preferably in a range of about 800 nm to about 1100. The treatment source can generate pulsed radiation having a fluence in a range of about 1 to about 200 J/cm2 with pulse widths in a range of about 1 ns to about 10 seconds. For example, the treatment source can be a neodymium (Nd) laser, such as a Nd:YAG laser.
In another aspect, the housing can be adapted for receiving the treatment energy from an external treatment source, such as a radiation source. For example, the device can further include an optical fiber for directing radiation from an external treatment source to the target skin region. Optical fiber can be utilized for delivery of illumination light from illuminating sources to the skin.
In further aspects, the device can further include a first polarizer coupled to the illumination source and a second polarizer coupled to the detector, wherein the polarizers have substantially orthogonal or parallel polarization axes.
In another aspect, the device can further include a radiation guiding that is adapted to contact a skin surface region. The illumination source can be optically coupled to the guiding element for coupling radiation into the guiding element so as to generate illumination waves refractively coupled to at least a portion of the target region. A polarizer can be coupled to the detector to substantially prevent radiation reflected from the skin surface region from reaching the detector while allowing detection of radiation scattered from the target region in response to the refractively coupled waves. The device can further include another polarizer coupled to the illumination source having a polarization axis substantially orthogonal to that of the polarizer coupled to the detector.
In another aspect, a method of treating a target skin region is disclosed comprising illuminating the target skin region, detecting primarily tissue scattered radiation emanating from the target region in response to the illumination, and directing treatment energy to at least a portion of the target skin region. A first portion (segment) of skin surface can be illuminated with illuminating radiation propagating along a first direction such that at least a portion of the radiation penetrates the skin tissue below a second segment of skin surface. The second segment of the skin surface can be shielded from direct application of the radiation. The scattered radiation can be detected along a second direction offset relative to the first direction. The radiation emanating from the second segment of skin surface can be detected to obtain an image of the target skin region. The image can be used to align a treatment energy beam with a portion of skin tissue in the target skin region so as to apply treatment energy to that portion. By way of example, the illumination radiation can be selected to have one or more wavelengths in a range of about 290 nm to about 3000 nm. One or more images of the target skin region can be monitored before, during or after application of the treatment energy.
In another aspect, a handheld dermatological device is disclosed comprising a housing capable of being manually manipulated to position a head portion thereof in proximity to a person's skin surface, an illuminating source mounted to the housing for illuminating a target skin region, a neodymium (Nd) laser, e.g., a Nd:YAG laser, disposed in the housing for generating radiation, an optical system coupled to the laser for directing radiation from the laser to the target skin region, an image capture device mounted in the housing for generating an image of the illuminated target skin region, and a display coupled to the housing and in communication with the image capture device to display the image. The device can further include a shield mounted to the head portion for shielding a portion of a skin surface through which the image capture device obtains an image of the target skin region from direct illumination by the illumination source. A zoom lens system coupled to the laser can adjust a dimension, e.g., a diameter, of a radiation beam generated by the laser. The device can further include a microprocessor in communication with the image capture device for processing one or more images obtained by the image capture device. The image capture device can be a CCD camera, a video camera or any other suitable analog or digital imaging system. The device can also include imaging optics optically coupled to the image capture device for directing at least a portion of radiation emanating from the target skin region to the image capture device. In some embodiments, the device further includes additional illumination sources. In some cases, the illumination sources can generate radiation with different wavelengths. A control unit can be further included for selectively activating the illumination sources according to a desired temporal pattern so as to illuminate the target region with radiation having different wavelengths and/or from different angles.
In another aspect, a method of treating skin is disclosed comprising applying treatment radiation, for example, radiation generated by a neodymium (Nd) laser (e.g., Nd:YAG) to selected vasculature located in a target skin region, generating an image of the target skin region, and displaying the image. In another aspect, a method of treating skin is disclosed that comprises applying fluorescence or pumping radiation from sources providing treatment energy, for example, fluorescence from a neodymium (Nd) laser, to illuminate a target skin region, generating an image of the target region, and displaying the image. As used herein, the term “treating skin” is intended to encompass both medical and cosmetic treatments, such as hair removal, hair growth management, removal of vascular lesions (e.g., telangiectasia, psoriasis, rosacea, spider vein, leg vein), pigmented lesions, treatment of nail disorders, fat reduction, acne treatment, skin rejuvenation, wrinkle reduction and tattoo removal and the like. The image can be displayed before, during or after application of the treatment radiation. The image can be used to align a treatment radiation beam with the selected vasculature.
In another aspect, a handheld dermatological device is disclosed comprising a housing, a source disposed in the housing for generating both treatment radiation and illuminating radiation, an optical system for directing the treatment and illuminating radiation to a target skin region, an image capture device mounted in the housing for acquiring an image of the target region, and a display mounted to the housing for displaying the image. By way of example, the source can include a Nd:YAG laser. The Nd:YAG laser can generate lasing treatment radiation and the laser rod can generate fluorescence illumination radiation. The image capture device can be adapted to detect scattered radiation emanating from the target skin region in response to illumination by the illuminating radiation.
In another aspect, a handheld dermatological device is disclosed comprising a housing through which treatment energy can be applied to a skin target region, an illumination source coupled to the housing for illuminating the target region, an image capture device mounted in the housing for acquiring one or more images of the target region, goggles suitable for wearing by an operator of the device. The goggles can incorporate one or more display devices in communication with the image capture device for displaying the images to the operator. The device can include a treatment source disposed in the housing. Alternatively, the housing can be adapted to receive the treatment energy from an external source, e.g., via an optical fiber or other energy delivery systems.
In another aspect, a handheld dermatological device is disclosed comprising a housing through which treatment energy can be applied to a target skin region, an illumination source coupled to the housing for generating radiation for delivery to a first skin surface segment to illuminate the skin target region such that at least a portion of radiation emanating from the target region in response to the illumination reaches a second skin surface segment, and an image capture device capable of detecting the portion of radiation emanating from the target region to form an image thereof. The device further can further comprise a treatment source disposed in the housing for generating the treatment energy. The treatment source can be a laser or a broadband source, such as LED or lamps. In some embodiments, the device further comprises a shield for shielding the second skin surface segment from direct application of the illumination radiation. For example, the shield can be disposed in proximity of the illumination source to substantially prevent direct illumination of the second skin surface segment.
In another aspect, the invention discloses a method for treating a target region of skin tissue comprising illuminating a first skin surface with radiation such that at least a portion of the radiation penetrates the skin tissue below a second skin surface, shielding the second skin surface from direct application of the radiation, detecting radiation emanating from the second skin surface to obtain an image of the target skin region, and directing treatment energy to the target skin region through the second skin surface.
In yet another aspect, the invention discloses a handheld dermatological device comprising a housing for applying treatment energy to a portion of a person's skin surface to treat a target skin region, an illumination source coupled to the housing for illuminating the target skin region from below the portion of the skin surface, and a shield disposed in the housing so as to substantially prevent the illumination source from directly illuminating the portion of the skin surface from above the portion of the skin surface. The device can further include a detector mounted in the housing to detect at least a portion of the illumination radiation scattered by the target skin region. For example, the detector can be positioned in the housing so as to detect at least a portion of the illumination radiation emanating from the portion of the skin surface.
In another aspect, a dermatological device is disclosed comprising a housing through which treatment energy can be applied to a target skin region, a radiation guiding element coupled to the housing and adapted to contact a skin surface region, at least one illumination source optically coupled to the guiding element for coupling radiation into the guiding element so as to generate illumination electromagnetic radiation (wave) refractively coupled to at least a portion of skin in contact with the guiding element, and an image capture device capable of detecting radiation scattered from the target region in response to the refractively coupled illumination radiation. The image capture device can form an image of the target region. The radiating guiding element can be formed of any suitable transparent material as discussed in more detail below. For example, the guiding element can be formed of sapphire or quartz and can have an index of refraction in a range of about 1.3 to about 1.9. In another aspect, images exhibiting interruptions of total internal reflection of illumination light at the contact surface of the guiding element and skin surface can be used for visualization of targets on the skin surface. The device can further comprise a polarizer coupled to the image capture device so as to prevent radiation having a selected polarization from reaching the image capture device. A filter coupled to the image capture device can be included in the device so as to prevent radiation having one or more selected wavelengths from reaching the image capture device.
In another aspect, a method of treating person's skin is disclosed comprising placing an optical guidance element on a portion of the skin surface, coupling illuminating radiation into the guidance element so as to generate refractively coupled waves penetrating a subsurface region below the portion of the skin surface, detecting at least a portion of radiation scattered by the subsurface region in response to the refractively coupled waves to form an image of the subsurface region, and directing treatment energy to at least a portion of the subsurface region.
In a related aspect, radiation can be coupled to the guidance element so as to generate evanescent waves at the interface of the guidance element with the skin. Such waves can be utilized for imaging and diagnosis of dermatological structures and conditions, as discussed in more detail below.
In another aspect, a handheld dermatological device is disclosed comprising a housing through which treatment energy can be applied to a person's skin, two illumination sources capable of generating radiation having at least two different wavelengths, the sources being mounted to a head portion of the housing for illuminating a target skin region, a control unit for selectively activating the sources, and an image capture device disposed in the housing for detecting at least a portion of radiation scattered by the target skin region in response to illumination by at least one of the sources. The control can be adapted for activating the sources in different temporal intervals and/or for triggering the image capture device to form an image of the target region upon activation of at least one of the sources. The device can include a shield positioned in proximity of at least one of the illumination sources for shielding a selected skin surface segment from direct illumination by that source. The image capture device can be adapted to collect radiation via the shielded skin surface segment radiation scattered by the target skin region. The device can further include a treatment source disposed in the housing for applying treatment energy to the target skin region through the shielded skin surface segment.
In another aspect, the invention provides a device for imaging a subsurface target region of skin tissue that includes an illumination source for illuminating a skin surface with illuminating radiation such that at least a portion of the radiation penetrates the skin tissue below the surface and is at least partially scattered by the skin tissue. The device can further include a detector that is capable of detecting radiation scattered by the subsurface target region, and a shield for shielding the detector from illuminating radiation that is directly reflected by the skin surface. The detector can comprise an image capture device that can generate an image of the subsurface target region. Any suitable image capture device can be employed. For example, the image capture device can be a CCD/CMOS camera or a video camera.
The device can include a handheld housing through which treatment energy can be directed to the skin. The treatment energy can be provided by a source mounted to the housing, or alternatively, it can be provided by an external source and guided through a path within the housing to the skin. In some embodiments, the treatment source is a radiation source, such as a laser or a broad band source (e.g., a lamp, LED).
In a related aspect, in the above imaging or the handheld device, the shield can comprise a polarizer coupled to the detector to prevent radiation having a selected polarization direction from reaching the detector. In some embodiments, another polarizer having a polarization axis orthogonal or parallel to the shield polarizer, can be coupled to the illumination source. Alternatively, the shield can be formed from a material that is substantially opaque to the radiation generated by the illumination source, and can be placed in proximity of the illumination source to prevent direct illumination of a portion of the skin surface of the target region.
In further aspects, the invention provides a method for imaging a subsurface target region of skin tissue that includes illuminating a skin surface with illumination radiation such that a significant portion of the radiation penetrates the skin tissue below the surface and is at least partially scattered by that tissue while minimizing scattering signal from skin tissue located deeper than the target tissue. A detector is positioned so as to detect at least a portion of radiation scattered by the subsurface target region. The detector is shielded from illumination radiation that is directly reflected by the skin surface (and scattered from tissue above the target region depth) while enhancing detection of radiation that is primarily scattered by tissue below and around target skin region depth, and an image of the subsurface target region is obtained based on the detected scattered radiation. The illumination radiation can have one or more wavelengths in a range of about 350 nm to about 2000 nm. The illumination sources can be, for example, light emitting diodes (LED), diode lasers, lamps, or other suitable sources of electromagnetic energy. In some cases, treatment energy, e.g., radiation having one or more wavelengths in a range of about 290 nm to about 20,000,000 nm, can be applied to the subsurface target region in conjunction with monitoring one or more images of this region prior to, during, and/or after application of the treatment energy.
In a related aspect, the invention provides a handheld dermatological device that includes a housing capable of being manually manipulated to direct treatment energy to a skin target region, an image capture device coupled to the housing to generate an image of at least a portion of the target region, and a display device mounted to the housing and electrically coupled to the image capture device to display images captured by the image capture device. The term “mounted,” as used herein, is intended to encompass mechanical coupling to the housing such that the housing and the display can be simultaneously, or separately, manually manipulated by the user to direct treatment radiation to a target area and/or view the target. The housing can further comprise a head capable of transmitting the treatment energy. The user can precisely position the head over a desired portion of the treatment region by using the display as a guide. The user can therefore diagnose and/or view the treatment region before, during and after treatment more effectively. Thus, more effective and safer treatment will be possible than are currently available as the user can directly monitor the results of the treatment in real-time.
In some embodiments, the handheld device can include an optical system, such as an objective, optical filter, spectral filter, spatial filter, polarizer, phase elements, masks and illumination system for facilitating acquisition of images and/or enhancing their presentation. For example, such an optical system can be disposed between the image capture device and the patient's skin to prevent radiation having selected wavelengths and/or polarizations from reaching the image capture device.
Further, an image of the treatment region can be processed by an image processor and/or a microprocessor, for example, to enhance its resolution (or contrast), color and brightness. For example, the microprocessor can be positioned between an image capture device and a display. In some embodiments, the microprocessor can be coupled to the image capture device such that the user can be alerted when a treatment has reached a desired preset limit. The microprocessor can provide image processing for magnification, improved contrast of the image, and/or synchronization of the image capture with skin illumination, as discussed in more detail below. For example, the image capture device can send multiple images of the treatment region during treatment to the microprocessor. The microprocessor can compare changes in selected parameters of the treatment region to threshold values previously stored, for example, in a database. Various parameters, such as color or a change of fluorescence emission, can be used to monitor the applied treatment. Skin conditions, such as, pigmented lesions, spider veins, port wine stains, psoriasis, can change color during and after treatment. The treatment radiation can also coagulate and/or destroy vessels resulting in a color change in images of such vessels. Additionally, treatment of acne can be monitored through a measurement of fluorescence. Among microbial population of pilosebaceous unit, most prominent is Propionibacterium Acnes (P. Acnes). These bacteria are causative in forming inflammatory acne. P. Acnes can exhibit fluorescence. Upon treatment, the fluorescence will decrease.
Images of the treatment region can be stored in a memory card, which can be attached to the microprocessor, or sent to a computer via a wireless or hard-wired connection. These images can be used to compile a patient or treatment history file.
In some embodiments, the display device can be fixedly mounted onto the housing. In other embodiments, the display device can be hingedly attached to the housing. For example, the display device can be attached to a railing or flexible wire such that the display device can be extended by the user for ease of viewing and can be folded for ease of storage. Such an adjustable display device can be utilized, for example, by a patient for self-treatment In other aspects, the displays can be built into goggles to be worn by a user or a patient. The display device can be permanently attached to the housing of the handheld device, or it can be mounted to the housing in a removable and replaceable manner. In some embodiments, a large display can be used for providing better image resolution, and facilitating simultaneous observation of an image by an operator and a patient.
The image capture device can detect a change in at least one of optical signals, infrared, electro capacitance, or acoustic signals. An electro capacitor image capture device can be preferable for skin surface and epidermis imaging. The image capture device can be either an analog or digital device. In some embodiments, the image capture device is a camera. In a preferred embodiment, the image capture device is a CCD/CMOS camera or a video camera.
A handheld dermatological device according to the teachings of the invention can be utilized to deliver different types of treatment energy to a patient. Some exemplary optical radiation wavelengths and examples of conditions that can be treated by these wavelengths are provided in Table 1 below.
In embodiments in which the treatment energy is applied as pulses, the pulsewidths can be in a range of about 1 nanosecond to about 10 seconds and the pulses can have a fluence in a range of about 1 to about 200 J/cm2.
In other aspects, the invention provides a dermatological imaging device that includes a radiation guiding element that is adapted to contact a skin surface region to provide refractive coupling of light into the skin (refractive illumination). The device can further include at least one illumination source that is optically coupled to the guiding element for coupling radiation into the guiding element so as to generate electromagnetic waves penetrating into a controlled depth of subsurface skin region. The device also includes an image capture device that is capable of detecting radiation scattered from the subsurface skin region in response to the refractive wave illumination. The image capture device can form an image of the subsurface skin region by employing the detected radiation. Further, in some embodiments, a filter and/or a polarizer can be coupled to the image capture device to prevent radiation having a selected polarization, or one or more selected wavelengths, from reaching the image capture device. The refractive coupling of radiation into the skin can be utilized for precise control of treatment and/or imaging of skin surface conditions and/or features, such as, stratum corneum structure, pores, sebaceous follicle openings, hair follicle openings, skin texture, wrinkles, psoriasis. By controlling the refractive index of the guiding element and the incident angle of radiation coupled into the guiding element at the contact surface of the guiding element and the skin, the imaging contrast of a visualized target can be enhanced, as discussed in more detail below.
In further aspects, the invention provides a handheld dermatological device that includes a housing through which treatment energy can be applied to a patient's skin, and further includes one or more sensors mounted to a head portion of the housing, which are capable of generating a dielectric image of a target skin region. Such a dielectric image can provide a distribution of dielectric sensitivity of the skin surface of a target skin region, which can be measured, e.g., by an electro capacitor image capture device. The device can further include a display for displaying the dielectric image. In some embodiments, one or more transducer elements can be coupled to the housing for applying an electric current or acoustic energy to the patient's skin.
In another aspect, the invention provides a handheld dermatological device having a housing through which treatment energy can be applied to a patient's skin, and two or more illumination sources that generate radiation having wavelengths in different wavelength bands. The sources are mounted to a head portion of the housing for illuminating a target skin region. The handheld device can further include a control for selectively activating the sources and a image capture device disposed in the housing for detecting at least a portion of radiation scattered by the target skin region in response to illumination by one or both of the sources.
Further understanding of the invention can be obtained by reference to the following detailed description in conjunction with the associated drawings, described briefly below.
The present invention relates generally to dermatological devices, and more particularly to handheld dermatological devices for applying a variety of treatment modalities to a patient's skin while allowing a user to view the treatment area and target before, during, and after application of the treatment. In some embodiments, the handheld device can include one or more radiation sources for illuminating a target region of the patient's skin so as to facilitate imaging that region by an image capture device, and can further include a display in which an image of the target region can be presented.
Although the display 102 is fixedly attached to the housing in this embodiment, in another embodiment shown schematically in
With reference to
In some embodiments, a variety of optical filters and polarizing elements can be incorporated in a handpiece device of the invention to manipulate, and/or enhance, an image of the treatment area generated by the image capture device. By way of example,
With reference to
In some embodiments, a handpiece according to the teachings of the invention allows preferentially obtaining an image of a portion of a target treatment region that lies a distance below the skin surface. By way of example, in the embodiment shown schematically in
In some embodiments, a handpiece device according to the teachings of the invention is designed to preferentially provide an image of a target region 307 at a depth below the skin surface. For example,
In some embodiments, the optical shield 308 can also function as a mechanism for coupling a current, RF or acoustic energy into the patient's body. For example, the shield 308 can be formed as a plurality of electrodes or transducers that not only prevent photons emitted by the light sources 301 from reaching the observation area or optical system 304 but also allow coupling of a current or acoustic energy into the patient's body.
In some embodiment, radiation generated by the treatment source 413 can be utilized not only for treating a target region but also for illuminating that region for imaging. For example, the lasing radiation generated by the Nd:YAG laser can be employed for treatment and fluorescence radiation emitted by the laser rod can be utilized for illumination.
The illustrative handheld device 112 further includes an image capture device 414, e.g., a CCD camera, for generating an image of a target region of the subject's skin. More particularly, as discussed in more detail below, radiation reflected from a skin target region can be directed by a beam splitter 415 to a lens 416 that in turn focuses the radiation onto the image capture device 414.
A sapphire window 417 mounted at the tip of the head portion allows extracting heat from a portion of the skin surface that can be in thermal contact therewith before, during or after application of treatment radiation.
A shield 418 is mounted in the head 412 between the sapphire window and the illumination sources 411 so as to inhibit, and preferably prevent, radiation generated by the sources 411 from reaching a surface of a skin segment that will be in contact with a surface 417a of the window formed of sapphire or other transparent thermo conductive material, when the device is utilized for imaging and/or treating a target skin portion, as discussed in more detail below. In other words, the shield prevents radiation from the illumination sources 411 from intersecting a portion of an optical path 419 (through which treatment radiation from treatment source 413 can be transmitted to a target region and through which radiation emanating from the target region, e.g., in response to illumination by illuminating sources 411, can reach the image capture device 414) that extends through the sapphire window 417. The shield 418 is preferably formed of a material that is opaque to the radiation wavelengths generated by the illumination sources 411. Some examples of materials from which the shield 418 can be formed include, without limitation, glass, metal or plastic. In some embodiments, the internal shield surface can be coated with a material that is highly reflective to the treatment radiation to minimize heating by the treatment light, and hence minimize potential skin damage due to such heating. In addition, the reflective coating can improve the treatment efficiency by providing a photon recycling effect.
With reference to
A portion of the “banana photons” illuminating the target region 422 are reflected or scattered by the skin tissue in the target region 422 into a solid angle extending to the skin surface segment 419. In other words, a portion of the “banana photons” are scattered by tissue in the target region, mostly from below the target, so as to exit the skin via the skin surface segment 419, which is shielded from direct illumination by illumination sources 411. The beam splitter 415 directs this radiation towards the image capture device 414, via the lens 416, while allowing the treatment radiation generated by the treatment source 413 to pass through and reach the skin segment 422 via the sapphire window 417. The treatment radiation can penetrate the skin to treat a dermatological condition present in the target region. The fluorescence light from the laser rod or simmer mode light from a lamp can be used for illumination. In addition, the treatment light itself can be employed for illumination to provide, for example, a better resolution of the target coagulation process during a treatment pulse.
As noted above, the shield 418 prevents the radiation generated by the illumination sources 411 from illuminating the skin surface segment 419 so as to avoid reflection of this radiation from the skin surface onto the image capture device 414, thereby maximizing the signal-to-noise ratio of the image of the target region formed by the image capture device through detection of a portion of the “banana photons” scattered by the target region.
The image of the target region 422 can be utilized by an operator, e.g., a medical professional, to select a portion of the target region, or the entire target region for treatment. For example,
A plurality of images can be obtained during application of treatment radiation to assess the progression of the applied treatment in real-time. Further, such images can indicate when the application of the treatment radiation should be terminated. Alternatively, subsequent to treating a target region, one or more images of that region can be obtained to determine if the applied treatment was successful. For example, a color change exhibited by a vessel under treatment can indicate whether that vessel has been coagulated in response to treatment radiation. The images can be presented to a user in a display (not shown) mounted to the housing in a manner described in connection with the above embodiments. Further, one or more images of vessels can be used to control a pressure by which the handheld device is pressed against the skin. By controlling the pressure, blood can be removed from or pumped into certain portions of the vessels to provide control of the treated vessel, thereby enhancing the treatment efficiency and preventing over-treatment. For example, for highly dense spider veins, the blood volume within the veins can be minimized before application of a treatment pulse by applying a positive pressure to prevent side effects. The treatment can be repeated several times in the same area with different pressures. Using a negative pressure, it is possible to increase the blood volume within vessels before treatment. Hence, the described image techniques can be utilized to control treatment results. Moreover, heating of the blood can result in transformation of oxy-hemoglobin into other forms that exhibit different absorption spectra (e.g., met hemoglobin). Thus, utilizing broad spectrum sources or multiwavelength sources, the temperature transformation of blood can be detected. For example, green LEDs (490-560 nm) can be used for visualization of vessels, such as leg veins or facial spider veins, before treatment while red and IR LEDs (600-670 nm, 900-1200 nm) can be used for visualization of heated blood. LED illumination in a range of about 670 nm to about 750 nm can be used to distinguish blood vessels and veins with different oxy-hemoglobin concentrations. Further, coagulation of vessels can be detected through the loss of image of the vessels due to stoppage of blood supply through the vessels or high scattering of coagulated tissue.
Referring again to
In addition, in this exemplary embodiment, a snap-in lens 427 can be employed to augment the zoom assembly and/or to modify the cross-sectional shape of the treatment beam. For example, the lens 427 can be a cylindrical lens to impart an elliptical cross-sectional shape to the treatment beam. Other lens types can also be employed.
In some embodiments, the image capture device 414 can be a video camera for generating a movie that can show, for example, a temporal progression of an applied treatment. Providing visualization techniques in combination with treatment energy in one single device affords a user the opportunity to control a number of treatment pulses in a pulse stacking mode. For example, the device can deliver energy to a target region every 1 second (stacking mode) until coagulation of the target is completed. At this point, the user can interrupt firing of the pulses.
In some embodiments, the illumination sources mounted in the head portion of the handheld device can provide radiation in different spectral ranges (e.g., different colors) for illuminating a target region. For example,
In some embodiments, the image capture device can be activated in synchrony with activation of one or more radiation sources utilized for illuminating a skin target region. By way of example, the image capture device can be activated to acquire an image of the target region each time the illumination sources in one of the quadrants (
With reference to
Alternatively, with reference to
In some embodiments, the image of the target region can be analyzed by employing image recognition techniques to extract selected features, e.g., vascular legions. These extracted features can be displayed on a display mounted to the handheld device, such as a display similar to that shown above in
With reference to
The graphical elements suitable for displaying the position of a treatment beam relative to an image of a target region are not limited to that described above. For example, referring again to
With reference to
In some embodiments, the handheld device can track the position of a target region, e.g., a treatment site, which can be identified by a marker in an image, from one image to the next. For example, with reference to
In one exemplary tracking algorithm, the motion of an image pixel can be modeled as a combination of translation in the image plane (herein referred to as x-y plane) and rotation about an axis perpendicular to this plane. The following notations are employed in describing the algorithm: x, y denote a pixel coordinates, Vx, Vy velocity components of a pixel along the x and y coordinates; Ux, Uy indicate components of translation velocity (the same for all pixels in each image but may vary from one image to another); Rx, Ry denote the coordinates of the center of rotation at which the rotation axis cross the x-y plane (all pixels in each image rotate around the same center but the center may vary from one image to another); and ω denotes the angular velocity of rotation. An optical flow model of the pixels can then be described by the following relations:
Vx=Ux−ω·(y−Ry),
Vy=Uy+ω·(x−Rx). (1)
The above equations can be cast in a linear format by introducing variables X1, X2 and X3 defined as follows:
X1=Ux+ω·Ry, X2=ω·Rx, X3=ω. (2)
More specifically equations (1) take the following form when the variables X1, X2 and X3 are employed:
Vx=X1−y·X3,
Vy=X2+x·X3. (3)
The following optical flow constraint equation can be utilized to determine the change in the position of a pixel between images:
The above equation (5) should be valid for every point of an image. When a region of the image represented by several pixels is selected, a system of equations can be obtained, which can be defined as follows:
Ixk·X1+Iyk·X2+(xk·Iyk−yk·Ixk)·X3=−Itk, (6)
wherein the index k=1, 2, . . . n can represent the point number.
The coefficients of X1, X2 and X3 in the above set of equations can be represented by the following matrix:
By way of example, if the number of points (n) is selected to be three (n=3), then A is a square matrix, and the values of X1, X2 and X3 can be obtained by utilizing the following relation:
In many embodiments of the invention, the number of points is chosen to be much larger than 3 so that the matrix A is not square and the system of equations (6) is redundant. Utilizing the least square criteria, the following solution can be obtained:
The algorithm for tracking a marker initially positioned at xm,ym in a first image can then include the steps of choosing a number of points (preferably larger than 3) in a central portion of the first image and evaluating derivatives Ixk, Iyk at these points to generate the matrix A. In many embodiments, the determinant of the matrix ATA is calculated to ensure that it is not too small. If the determinant is too small, additional points can be selected and the matrix A regenerated. Using the first image and a second image, the time derivative Itk are evaluated at the selected points (e.g., by assuming dt=1). The above relation (9) is then employed to evaluate X1, X2 and X3. The values of Vx and Vy are evaluated at the marker position (x=xm, Y=ym). The marker position in the second image can then be determined as follows:
With reference to
If arcsin(n3/n1)<α2<arcsin(n2/n1), the illumination wave propagates mostly into stratum coreum. If arcsin(n4/n1)<α2<arcsin(n2/n1), the illumination wave propagates mostly into epidermis and stratum corneum. If arcsin(n5/n1)<α2<arcsin(n2/n1), the illumination wave propagate mostly into upper dermis, epidermis and stratum corneum. These conditions are applicable for wavelengths with low absorption and scattering in the skin bulk (500-1400 nm, 1500-1800 nm). If α3>arcsin(n2/n1), the illuminating light totally internally reflects from contact surface of coupling element 1309. In this case, an image on imaging capture device 1303 looks like uniform field and can not be used for subsurface target visualization. However, this condition can be very effective for obtaining high contrast image of skin surface. For example, with reference to
In other embodiments, the total internal reflection from a contact surface of the element 1309 with the skin can be interrupted by a material on the skin having a high absorption coefficient at the illumination wavelengths. For example, for detection of water distribution on the skin surface, radiation with wavelengths around 1450, 1900 or 2940 nm can be used. Further, wavelengths corresponding to the peaks of lipid absorption can be employed for visualization of oil or sebum distribution on the skin. By way of example, this embodiment can be used for control of topical drug or lotion distribution on the skin.
Further, a lotion (not shown) can be applied to the skin surface 1306 below the optical element 1309. The lotion's refractive index can be selected to adjust the penetration depth of photons illuminating the subsurface region, thereby controlling the depth of observation. The use of refractively coupled illumination waves for imaging shallow subsurface regions of a patient's skin can provide certain advantages. For example, the evanescent waves, which exponentially decay within the skin, can effectively illuminate a selected subsurface region of interest and not deeper regions. This selective illumination advantageously enhances signal-to-noise ratio of an image generated by capturing photons reflected from the skin in response to illumination.
The above exemplary system in which refractively coupled illumination waves are employed to image subsurface skin regions can be incorporated in a handheld device according to one embodiment of the invention. In some cases, the optical guidance element 1309, in addition to facilitating generation of illumination subsurface waves, or evanescent waves, can also extract heat from the skin portion with which it is in thermal contact.
With reference to
With reference to
The exemplary handpiece 1620 further includes a contact cooling window 1607 that thermally couples to a selected portion of the patient's skin so as to cool the patient's epidermis in the area of the skin exposed to treatment energy as the energy is deposited into a target treatment region. The cooling window 1607 is substantially transparent to both the treatment energy as well as the optical radiation generated by the light source 1602.
A variety of designs can be employed for constructing a handheld dermatological device according to the teachings of the invention, such as the device schematically depicted above in
With reference to
Those having ordinary skill in the art will appreciate that various changes can be made to the above embodiments without departing from the scope of the invention.
The present application claims priority to a provisional application entitled “Dermatological Treatment With Visualization” filed on Dec. 31, 2003 and having a Ser. No. 60/534,060.
Number | Name | Date | Kind |
---|---|---|---|
1706161 | Hollnagel | Mar 1929 | A |
2472385 | Rollman | Jun 1949 | A |
3327712 | Kaufman et al. | Jun 1967 | A |
3486070 | Engel | Dec 1969 | A |
3527932 | Thomas | Sep 1970 | A |
3538919 | Meyer | Nov 1970 | A |
3622743 | Muncheryan | Nov 1971 | A |
3693623 | Harte et al. | Sep 1972 | A |
3818914 | Bender | Jun 1974 | A |
3834391 | Block | Sep 1974 | A |
3846811 | Nakamura et al. | Nov 1974 | A |
3857015 | Clark et al. | Dec 1974 | A |
3900034 | Katz | Aug 1975 | A |
4233493 | Nath | Nov 1980 | A |
4273109 | Enderby | Jun 1981 | A |
4275335 | Ishida | Jun 1981 | A |
4316467 | Muckerheide | Feb 1982 | A |
4388924 | Weissman et al. | Jun 1983 | A |
4456872 | Froeschle | Jun 1984 | A |
4461294 | Baron | Jul 1984 | A |
4524289 | Hammond et al. | Jun 1985 | A |
4539987 | Nath et al. | Sep 1985 | A |
4591762 | Nakamura | May 1986 | A |
4608978 | Rohr | Sep 1986 | A |
4617926 | Sutton | Oct 1986 | A |
4677347 | Nakamura | Jun 1987 | A |
4695697 | Kosa | Sep 1987 | A |
4718416 | Nanaumi | Jan 1988 | A |
4733660 | Itzkan | Mar 1988 | A |
4745909 | Pelton et al. | May 1988 | A |
4747660 | Nishioka et al. | May 1988 | A |
4749913 | Stuermer et al. | Jun 1988 | A |
4819669 | Politzer | Apr 1989 | A |
4832024 | Boussignac et al. | May 1989 | A |
4860172 | Schlager et al. | Aug 1989 | A |
4860744 | Johnson et al. | Aug 1989 | A |
4884560 | Kuracina | Dec 1989 | A |
4917084 | Sinofsky | Apr 1990 | A |
4926227 | Jensen | May 1990 | A |
4928038 | Nerone | May 1990 | A |
4945239 | Wist et al. | Jul 1990 | A |
5000752 | Hoskin et al. | Mar 1991 | A |
5057104 | Chess | Oct 1991 | A |
5059192 | Zaias | Oct 1991 | A |
5065515 | Iderosa | Nov 1991 | A |
5071417 | Sinofsky | Dec 1991 | A |
5108388 | Trokel | Apr 1992 | A |
5127395 | Bontemps | Jul 1992 | A |
5137530 | Sand | Aug 1992 | A |
5140984 | Dew et al. | Aug 1992 | A |
5178617 | Kuizenga et al. | Jan 1993 | A |
5182557 | Lang | Jan 1993 | A |
5182857 | Simon | Feb 1993 | A |
5196004 | Sinofsky | Mar 1993 | A |
5207671 | Franken et al. | May 1993 | A |
5225926 | Cuomo et al. | Jul 1993 | A |
5226907 | Tankovich | Jul 1993 | A |
5267399 | Johnston | Dec 1993 | A |
5282797 | Chess | Feb 1994 | A |
5300097 | Lerner et al. | Apr 1994 | A |
5304170 | Green | Apr 1994 | A |
5306274 | Long | Apr 1994 | A |
5320618 | Gustafsson | Jun 1994 | A |
5334191 | Poppas et al. | Aug 1994 | A |
5334193 | Nardella | Aug 1994 | A |
5344418 | Ghaffari | Sep 1994 | A |
5344434 | Talmore | Sep 1994 | A |
5348551 | Spears et al. | Sep 1994 | A |
5350376 | Brown | Sep 1994 | A |
5380317 | Everett et al. | Jan 1995 | A |
5403306 | Edwards et al. | Apr 1995 | A |
5405368 | Eckhouse | Apr 1995 | A |
5415654 | Daikuzono | May 1995 | A |
5425728 | Tankovich | Jun 1995 | A |
5458140 | Eppstein et al. | Oct 1995 | A |
5474549 | Ortiz et al. | Dec 1995 | A |
5486172 | Chess | Jan 1996 | A |
5505726 | Meserol | Apr 1996 | A |
5505727 | Keller | Apr 1996 | A |
5519534 | Smith | May 1996 | A |
5522813 | Trelles | Jun 1996 | A |
5531739 | Trelles | Jul 1996 | A |
5531740 | Black | Jul 1996 | A |
5558667 | Yarborough et al. | Sep 1996 | A |
5578866 | DePoorter et al. | Nov 1996 | A |
5595568 | Anderson et al. | Jan 1997 | A |
5616140 | Prescott | Apr 1997 | A |
5620478 | Eckhouse | Apr 1997 | A |
5626631 | Eckhouse | May 1997 | A |
5630811 | Miller | May 1997 | A |
5649972 | Hochstein | Jul 1997 | A |
5653706 | Zavislan et al. | Aug 1997 | A |
5655547 | Karni | Aug 1997 | A |
5658323 | Miller | Aug 1997 | A |
5660836 | Knowlton | Aug 1997 | A |
5662643 | Kung et al. | Sep 1997 | A |
5662644 | Swor | Sep 1997 | A |
5683380 | Eckhouse et al. | Nov 1997 | A |
5698866 | Doiron et al. | Dec 1997 | A |
5707403 | Grove et al. | Jan 1998 | A |
5720772 | Eckhouse | Feb 1998 | A |
5722397 | Eppstein | Mar 1998 | A |
5735844 | Anderson et al. | Apr 1998 | A |
5735884 | Thompson et al. | Apr 1998 | A |
5742392 | Anderson et al. | Apr 1998 | A |
5743901 | Grove et al. | Apr 1998 | A |
5755751 | Eckhouse | May 1998 | A |
5759200 | Azar | Jun 1998 | A |
5769076 | Mackawa et al. | Jun 1998 | A |
5782249 | Weber et al. | Jul 1998 | A |
5810801 | Anderson et al. | Sep 1998 | A |
5814008 | Chen et al. | Sep 1998 | A |
5814040 | Nelson et al. | Sep 1998 | A |
5814041 | Anderson et al. | Sep 1998 | A |
5817089 | Tankovich et al. | Oct 1998 | A |
5820625 | Izawa et al. | Oct 1998 | A |
5820626 | Baumgardner | Oct 1998 | A |
5824023 | Anderson | Oct 1998 | A |
5828803 | Eckhouse | Oct 1998 | A |
5830208 | Muller | Nov 1998 | A |
5836877 | Zavislan | Nov 1998 | A |
5836999 | Eckhouse et al. | Nov 1998 | A |
5840048 | Cheng | Nov 1998 | A |
5849029 | Eckhouse et al. | Dec 1998 | A |
5851181 | Talmor | Dec 1998 | A |
5853407 | Miller | Dec 1998 | A |
5860967 | Zavislan et al. | Jan 1999 | A |
5868731 | Budnik et al. | Feb 1999 | A |
5883471 | Rodman et al. | Mar 1999 | A |
5885211 | Eppstein et al. | Mar 1999 | A |
5885273 | Eckhouse et al. | Mar 1999 | A |
5885274 | Fullmer et al. | Mar 1999 | A |
5891063 | Vigil | Apr 1999 | A |
5893828 | Uram | Apr 1999 | A |
5913883 | Alexander et al. | Jun 1999 | A |
5920374 | Vaphiades et al. | Jul 1999 | A |
5944748 | Mager et al. | Aug 1999 | A |
5948011 | Knowlton | Sep 1999 | A |
5949222 | Buono | Sep 1999 | A |
5954710 | Paolini et al. | Sep 1999 | A |
5964749 | Eckhouse et al. | Oct 1999 | A |
5968033 | Fuller | Oct 1999 | A |
5968034 | Fullmer et al. | Oct 1999 | A |
5977723 | Yoon | Nov 1999 | A |
6015404 | Altshuler et al. | Jan 2000 | A |
6022316 | Eppstein et al. | Feb 2000 | A |
6026828 | Altshuler | Feb 2000 | A |
6027495 | Miller | Feb 2000 | A |
6030399 | Ignotz et al. | Feb 2000 | A |
6032071 | Binder | Feb 2000 | A |
RE36634 | Ghaffari | Mar 2000 | E |
6050990 | Tankovich et al. | Apr 2000 | A |
D424197 | Sydlowski et al. | May 2000 | S |
6056738 | Marchitto et al. | May 2000 | A |
6059820 | Baronov | May 2000 | A |
6074382 | Asah et al. | Jun 2000 | A |
6080146 | Altshuler et al. | Jun 2000 | A |
6086580 | Mordon et al. | Jul 2000 | A |
6096029 | O'Donnell, Jr. | Aug 2000 | A |
6096209 | O'Brien et al. | Aug 2000 | A |
6104959 | Spertell | Aug 2000 | A |
6117129 | Mukai | Sep 2000 | A |
6120497 | Anderson | Sep 2000 | A |
6142650 | Brown et al. | Nov 2000 | A |
6142939 | Eppstein et al. | Nov 2000 | A |
6149644 | Xie | Nov 2000 | A |
6162211 | Tankovich et al. | Dec 2000 | A |
6162212 | Kreindel et al. | Dec 2000 | A |
6173202 | Eppstein et al. | Jan 2001 | B1 |
6174325 | Eckhouse | Jan 2001 | B1 |
6183434 | Eppstein | Feb 2001 | B1 |
6183500 | Kohler | Feb 2001 | B1 |
6183773 | Anderson | Feb 2001 | B1 |
6197020 | O'Donnell | Mar 2001 | B1 |
6210425 | Chen | Apr 2001 | B1 |
6214034 | Azar | Apr 2001 | B1 |
6229831 | Nightingale et al. | May 2001 | B1 |
6235016 | Stewart | May 2001 | B1 |
6236891 | Ingel et al. | May 2001 | B1 |
6263233 | Zavislan et al. | Jul 2001 | B1 |
6264649 | Whitcroft et al. | Jul 2001 | B1 |
6267779 | Gerdes | Jul 2001 | B1 |
6267780 | Streeter | Jul 2001 | B1 |
6273884 | Altshuler et al. | Aug 2001 | B1 |
6273885 | Koop et al. | Aug 2001 | B1 |
6280438 | Eckhouse et al. | Aug 2001 | B1 |
6290713 | Russell | Sep 2001 | B1 |
6306130 | Anderson et al. | Oct 2001 | B1 |
6306160 | Nidetzky | Oct 2001 | B1 |
6319274 | Shadduck | Nov 2001 | B1 |
6340495 | Sumian et al. | Jan 2002 | B1 |
6350276 | Knowlton | Feb 2002 | B1 |
6354370 | Miller et al. | Mar 2002 | B1 |
6358272 | Wilden | Mar 2002 | B1 |
6383177 | Balle-Petersen et al. | May 2002 | B1 |
6387089 | Kreindel et al. | May 2002 | B1 |
6402739 | Neev | Jun 2002 | B1 |
6406474 | Neuberger et al. | Jun 2002 | B1 |
6424852 | Zavislan | Jul 2002 | B1 |
6436094 | Reuter | Aug 2002 | B1 |
6471712 | Burres | Oct 2002 | B2 |
6475211 | Chess et al. | Nov 2002 | B2 |
6508785 | Eppstein | Jan 2003 | B1 |
6508813 | Altshuler | Jan 2003 | B1 |
6511475 | Altshuler et al. | Jan 2003 | B1 |
6514242 | Vasily et al. | Feb 2003 | B1 |
6514243 | Eckhouse et al. | Feb 2003 | B1 |
6517532 | Altshuler et al. | Feb 2003 | B1 |
6530915 | Eppstein et al. | Mar 2003 | B1 |
6537270 | Elbrecht et al. | Mar 2003 | B1 |
6558372 | Altshuler | May 2003 | B1 |
6602245 | Thiberg | Aug 2003 | B1 |
6605080 | Altshuler et al. | Aug 2003 | B1 |
6629971 | McDaniel | Oct 2003 | B2 |
6632219 | Baranov et al. | Oct 2003 | B1 |
6641578 | Mukai | Nov 2003 | B2 |
6648904 | Altshuler et al. | Nov 2003 | B2 |
6653618 | Zenzie | Nov 2003 | B2 |
6660000 | Neuberger et al. | Dec 2003 | B2 |
6663620 | Altshuler et al. | Dec 2003 | B2 |
6663659 | McDaniel | Dec 2003 | B2 |
6676654 | Balle-Petersen et al. | Jan 2004 | B1 |
6679837 | Daikuzono | Jan 2004 | B2 |
6685699 | Eppstein et al. | Feb 2004 | B1 |
6689124 | Thiberg | Feb 2004 | B1 |
6706035 | Cense et al. | Mar 2004 | B2 |
6709269 | Altshuler | Mar 2004 | B1 |
6723090 | Altshuler et al. | Apr 2004 | B2 |
6743222 | Durkin et al. | Jun 2004 | B2 |
6790205 | Yamazaki et al. | Sep 2004 | B1 |
6801595 | Grodzins et al. | Oct 2004 | B2 |
6808532 | Andersen et al. | Oct 2004 | B2 |
RE38670 | Asah et al. | Dec 2004 | E |
6878144 | Altshuler et al. | Apr 2005 | B2 |
6888319 | Inochkin et al. | May 2005 | B2 |
7001413 | Butler | Feb 2006 | B2 |
20010041886 | Durkin et al. | Nov 2001 | A1 |
20020005475 | Zenzie | Jan 2002 | A1 |
20020026225 | Segal | Feb 2002 | A1 |
20020091377 | Anderson | Jul 2002 | A1 |
20020123745 | Svaasand et al. | Sep 2002 | A1 |
20020128635 | Altshuler et al. | Sep 2002 | A1 |
20020161357 | Anderson | Oct 2002 | A1 |
20020173780 | Altshuler et al. | Nov 2002 | A1 |
20030023235 | Cense et al. | Jan 2003 | A1 |
20030023283 | McDaniel | Jan 2003 | A1 |
20030032900 | Ella | Feb 2003 | A1 |
20030032950 | Altshuler et al. | Feb 2003 | A1 |
20030036680 | Black | Feb 2003 | A1 |
20030055414 | Altshuler et al. | Mar 2003 | A1 |
20030057875 | Inochkin et al. | Mar 2003 | A1 |
20030065314 | Altshuler et al. | Apr 2003 | A1 |
20030100936 | Altshuler et al. | May 2003 | A1 |
20030109787 | Black | Jun 2003 | A1 |
20030109860 | Black | Jun 2003 | A1 |
20030129154 | McDaniel | Jul 2003 | A1 |
20030169433 | Koele et al. | Sep 2003 | A1 |
20030195494 | Altshuler et al. | Oct 2003 | A1 |
20030199859 | Altshuler et al. | Oct 2003 | A1 |
20030232303 | Black | Dec 2003 | A1 |
20040006332 | Black | Jan 2004 | A1 |
20040010298 | Altshuler et al. | Jan 2004 | A1 |
20040015156 | Vasily | Jan 2004 | A1 |
20040024388 | Altshuler | Feb 2004 | A1 |
20040030326 | Altshuler et al. | Feb 2004 | A1 |
20040034319 | Anderson et al. | Feb 2004 | A1 |
20040034341 | Altshuler et al. | Feb 2004 | A1 |
20040073079 | Altshuler et al. | Apr 2004 | A1 |
20040082940 | Black et al. | Apr 2004 | A1 |
20040085026 | Inochkin et al. | May 2004 | A1 |
20040093042 | Altshuler et al. | May 2004 | A1 |
20040133251 | Altshuler et al. | Jul 2004 | A1 |
20040147984 | Altshuler et al. | Jul 2004 | A1 |
20040162549 | Altshuler | Aug 2004 | A1 |
20040162596 | Altshuler et al. | Aug 2004 | A1 |
20040191729 | Altshuler et al. | Sep 2004 | A1 |
20040193235 | Altshuler et al. | Sep 2004 | A1 |
20040193236 | Altshuler et al. | Sep 2004 | A1 |
20040199227 | Altshuler et al. | Oct 2004 | A1 |
20040204745 | Altshuler et al. | Oct 2004 | A1 |
20040210276 | Altshuler et al. | Oct 2004 | A1 |
20040214132 | Altshuler | Oct 2004 | A1 |
20040225339 | Yaroslavsky et al. | Nov 2004 | A1 |
20040230258 | Altshuler et al. | Nov 2004 | A1 |
20050038418 | Altshuler et al. | Feb 2005 | A1 |
20050049582 | DeBenedictis et al. | Mar 2005 | A1 |
20050049658 | Connors et al. | Mar 2005 | A1 |
20050107849 | Altshuler et al. | May 2005 | A1 |
Number | Date | Country |
---|---|---|
1851583 | Mar 1984 | AU |
0142671 | May 1985 | EP |
0565331 | Oct 1993 | EP |
0598984 | Jun 1994 | EP |
0724894 | Aug 1996 | EP |
0726083 | Aug 1996 | EP |
0736308 | Oct 1996 | EP |
0755698 | Jan 1997 | EP |
0763371 | Mar 1997 | EP |
0765673 | Apr 1997 | EP |
0765674 | Apr 1997 | EP |
0783904 | Jul 1997 | EP |
0885629 | Dec 1998 | EP |
1219258 | Jul 2002 | EP |
1226787 | Jul 2002 | EP |
1 457 234 | Sep 2004 | EP |
2044908 | Oct 1980 | GB |
2123287 | Feb 1984 | GB |
2360946 | Oct 2001 | GB |
2001145520 | May 2001 | JP |
208233795105406 | Jun 1997 | RU |
208912694012665 | Oct 1997 | RU |
208912794040344 | Oct 1997 | RU |
209605195012749 | Nov 1997 | RU |
21228484954402 | Oct 1998 | RU |
WO 8602783 | May 1986 | WO |
WO 9000420 | Jan 1990 | WO |
WO 9216338 | Jan 1992 | WO |
WO 9219165 | Nov 1992 | WO |
WO 9305920 | Apr 1993 | WO |
WO 9515725 | Jun 1995 | WO |
WO 9532441 | Nov 1995 | WO |
WO 9623447 | Aug 1996 | WO |
WO 9625979 | Aug 1996 | WO |
WO 9713458 | Apr 1997 | WO |
WO 9804317 | Feb 1998 | WO |
WO 9824507 | Jun 1998 | WO |
WO 9851235 | Nov 1998 | WO |
WO 9852481 | Nov 1998 | WO |
WO 9927997 | Jun 1999 | WO |
WO 9929243 | Jun 1999 | WO |
WO 9938569 | Aug 1999 | WO |
WO 9946005 | Sep 1999 | WO |
WO 9949937 | Oct 1999 | WO |
WO 0003257 | Jan 2000 | WO |
WO 0043070 | Jul 2000 | WO |
WO 0071045 | Nov 2000 | WO |
WO 0074781 | Dec 2000 | WO |
WO 0078242 | Dec 2000 | WO |
WO 0103257 | Jan 2001 | WO |
WO 0126573 | Apr 2001 | WO |
WO 0134048 | May 2001 | WO |
WO 0142671 | Jun 2001 | WO |
WO 0154606 | Aug 2001 | WO |
WO 02053050 | Jul 2002 | WO |
WO 02094116 | Nov 2002 | WO |
WO 2004073537 | Sep 2004 | WO |
WO 2004084752 | Oct 2004 | WO |
WO 2004086947 | Oct 2004 | WO |
WO 2005007003 | Jan 2005 | WO |
Number | Date | Country | |
---|---|---|---|
20050154381 A1 | Jul 2005 | US |
Number | Date | Country | |
---|---|---|---|
60534060 | Dec 2003 | US |