Patent Application
20090149782
The field of the invention is non-contact stimulation of excitable tissue. Particular applications include neural stimulation for the treatment of pain, migraine, angina symptoms, urinary incontinence, and activation of muscular contraction.
In order for pain to be perceived, a neural signal generally travels along an afferent nerve from the site of the pain, through the spinal cord and up to the brain. If the signal is inhibited, interrupted or “confused” along the way, the pain is relieved to some extent or replaced by paresthesia or tingling.
Neurons are specialized excitable cells that can transmit electrical signals via ionic transport across their membranes. The energy needed to initiate the excitement of the nervous tissue can be any of several different forms. Biologically, this ionic transport (depolarization) is generally initiated by chemical energy. This initiates depolarization at a synapse between neighboring neurons. Neurotransmitters released by one neuron can initiate the depolarization in the next neuron. In sensory afferent neurons the initiation energy can be one of many different forms of energy. It can be photons (as in the retina of the eye), mechanical air pressure (as in the ear), mechanical force (as in the skin), etc.
Within the first couple of mm of skin, there are several types of neurons specialized to be particularly susceptible to excitation by a particular mechanical stimulus. Below are some examples of the neurons, their typical skin depths and the particular sensitivity.
The threshold energy needed to initiate depolarization is most efficient for the particular form associated in the preceding list. Each neuron can be stimulated by different energy expressions, but is most suited to a particular one.
In the case of neural stimulator devices the initiating energy is electrical. A voltage is applied between electrodes that are placed in the vicinity of nervous tissue that is intended to be stimulated. Current flows between the electrodes and through the nerve cells. When the electrical energy is above a certain threshold, the nerve cells in that region will be depolarized.
Depolarization is also achievable using ultrasound energy even if the threshold energy level for ultrasound is higher than for electrical stimulation. Similarly, axonal stimulation (along the length of the neuron rather than at the end suited for stimulation) is possible though not as efficient. In other words, a greater intensity will be needed to stimulate neurons in the middle.
Many people who suffer from intractable chronic pain achieve a measure of relief from the use of implantable spinal cord stimulation systems. Generally, leads containing multiple electrodes are implanted on top of the dorsal surface of the spinal cord and connected to a pulse generator/processor located several inches away. Electrode stimulation configuration is chosen to optimize the effectiveness of the stimulating pulsations. More information about neuron-stimulation equipment and how it works can be found at the following:
For relief of muscle pain, unfocused ultrasonic therapy has been used to promote healing and relief of pain.
Ultrasound has been used to promote bone healing. More information may be found at http://ortho.smith-nephew.com/us/node.asp?NodeId=2865. Excerpted:
“Treatment of fractures with the EXOGEN™ 4000+* Bone Healing System (low-intensity pulsed ultrasound) may speed healing, lower the need for further surgery, and get patients back to their normal activities faster . . . . The EXOGEN™ Bone Healing System utilizes low-intensity ultrasound to accelerate the healing of indicated fresh fractures up to 38% faster than normal healing. The Exogen™ Bone Healing System is also highly effective for use on non-healing fractures. The ultrasound device is a portable, lightweight unit that delivers the prescribed treatment in a convenient 20 minute daily regimen . . . treat themselves at home, thus freeing hospital resources from this task. The treatment is safe and has no contra-indications. It has been clinically proven in many thousands of patients worldwide.”
Exogen U.S. Pat. No. 6,432,070 Exogen, Inc. (Piscataway, N.J.), and all other extrinsic materials discussed herein, are incorporated by reference in their entirety. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply. Also, unless a contrary intent is apparent from the context, all ranges recited herein are inclusive of their endpoints, and open-ended ranges should be interpreted to include only commercially practical values.
Another way to address unrelenting, unmanageable pain (as in cancer patients) is to irreversibly destroy nerves associated with the pain. High Intensity Focused Ultrasound has been used to destroy nerve cells in the interest of relieving pain. See for example
Other techniques have also been used to destroy nerve cells for this purpose. See for example Critical Evaluation of Chemical Neurolysis from Cancer Control: Journal of the Moffitt Cancer Center http://www.medscape.com/viewarticle/408975—3.
It has been shown that ultrasonic energy can stimulate nerves and cause tactile sensations. See for example http://www.biomedical-engineering-online.com/content/2/1/6 Can ultrasound be used to stimulate nerve tissue? Stephen J Norton, BioMedical Engineering OnLine 2003, 2:6doi:10.1186/1475-925X-2-6 and http://www.alab.t.u-tokyo.acjp/˜shino/research/pdf/icat01.pdf ICAT Dec. 5-7, 2001 Tokyo, JAPAN Focused Ultrasound for Tactile Feeling Display, Takayuki IWAMOTO, Taro MAEDA, and Hiroyuki SHINODA, The University of Tokyo.
Furthermore, it is well known that ultrasound can be transmitted into the human body, as illustrated for example in figures at the website http://www.sprawls.org/ppmi2/USPRO/.
Accordingly, ultrasound can be transmitted to non-superficial tissues to stimulate nerves.
Transcutaneous Electrical Nerve Stimulations (TENS) is a safe non-invasive drug-free method of pain management. Such units relieve pain by sending small electrical impulses through electrode pads placed on the skin to underlying nerve fibers http://www.vitalityweb.com/backstore/tenswork.htm
There are several proposed explanations for how TENS may work:
Transcranial magnetic stimulation (TMS) has been used to stimulate neurons, particularly in the brain. It uses very strong magnetic fields to create electrical fields that can stimulate neurons. The field strength decays rapidly with distance, so TMS is only used to create cortical stimulation—not deep brain stimulation. http://www.neuronetics.com/default.asp
When using electrodes to deliver stimuli to excitable tissue, electrical voltage gradient generally diminishes with distance from electrodes. It is very difficult to stimulate a target nerve without also stimulating many unintended nerves and muscles too. The nerves that are closest to the electrodes generally experience the highest voltage gradient, highest current flow, and are thus the most likely to be stimulated by the electrical pulse. The location of supra-threshold pulses can be adjusted by varying the location, quantity of and voltage of or current from the electrodes—but the supra-threshold region is always located between or very close to the electrodes.
Non-invasive electrical and unfocused ultrasonic neural stimulators do not do a good job of stimulating only the target nerves. The selection of nerves stimulated by the implantable system can be influenced by the placement of the electrodes and by selection of which electrode combination is actually utilized. Though this does a much better job of limiting the stimulating to the desired tissue, it has the considerable drawback of requiring invasive surgery.
Another drawback of implantable electrodes and leads is the eventual loss of effectiveness. This is often attributable to migration of electrodes with respect to the target nervous tissue. It is sometimes attributable to the necrosis of nervous tissue due to prolonged mechanical stress imposed by the electrodes and/or leads. Effectiveness can sometimes be re-established by changing the characteristics of the electrical pulses or by using different electrode combinations. In the extreme, the electrodes can be invasively re-positioned.
Loss of effectiveness can also be caused by an increase of excitability threshold of the target tissue. This degradation of tissue can be a response to the physical presence of the electrodes and leads and to the associated stresses.
Focused ultrasound has been used to destroy tissue and thus block pain. This has the drawback of not being reversible. Neural stimulation can be reversed, but neurolysis is essentially permanent. Targeting mistakes in are thus much more severe in focused ultrasound neurolysis than in neuro stimulation.
Thus, there is still a need for methods and devices that stimulate target nervous tissue without simultaneously inadvertently stimulating appreciable quantities of intervening and neighboring nerve and muscle tissue; and to do so without the need for invasive surgery. There is also a need to manipulate the position of the subcutaneous supra-threshold stimulus non-invasively, and to avoid degradation, necrosis or lysis of excitable target tissue.
It is an objective of various embodiments the current invention to deliver stimuli to target excitable tissue without direct contact, and without undue stimulation of other intervening or neighboring excitable tissue. It is a further objective of such embodiments to have the capability to adjust the location and timing and magnitude of the stimuli. It is a still further objective of such embodiments to have the capability of automatically adjusting the characteristics of the stimuli, including pulse strength, timing and location.
Weblinks
Journal Articles
US Patent Applications 20060184069
The inventive subject matter provides apparatus, systems and methods in which a non-contact device stimulates excitable tissue beneath the skin without causing unduly uncomfortable stimulation of intervening tissue. The purpose of the stimulation can be for the relief of the perception of pain, for stimulating tissue to contribute to urinary continence, for behavior modification, or for stimulating other tissue.
a shows a representation of a front view of transducer head containing a number of individual transducers, each transducer depicted with a beam (depicted as translucent) emanating from it. The transducers are mounted along two crossing different radius curves. The beams emanating from the transducers parallel to the front plane can be seen to cross at a focal point beneath the transducer head.
b shows a representation of a side view of the transducer head of
c shows a representation of an isometric view of the transducer head of
a shows a representation of a front view of transducer head containing nine individual transducers. The transducers are mounted so that the centerline of each one crosses directly through target focal points represented as small spheres. In the configuration depicted in this figure, three of the nine each transducer are depicted with a translucent beam emanating—each beam representing ultrasonic energy emanating from each transducer. These three beams can be seen to cross at the bottom target focal point.
b shows a representation of the bottom view of the transducer head depicted in
c shows a representation of an isometric view of the transducer head depicted in
a shows a representation of the front view of the transducer head of
b shows a representation of the front view of the transducer head of
c shows a representation of the front view of the transducer head of
d shows a representation of the front view of the transducer head of
a shows a representation of an isometric view of the transducer head of
b shows a representation of an isometric view of the transducer head of
c shows a representation of an isometric view of the transducer head of
a shows an isometric view of a gimbal mounted focused transducer; one lever that controls rotations about an axis, a second lever that controls rotation about a second perpendicular axis; and a third that allows for helical rotation to adjust travel along the third axis that is orthogonal to that established by the plan of the prior two axes.
b is an isometric view of the gimbal mounted focused transducer of
a is a representation of a prior art technology, ultrasound phased array beam intensity.
b is a representation of a prior art technology from Olympus NDT, ultrasound phased array, used to form a focal point of ultrasound energy; depicted showing the wavefronts at four times after the wavefronts have left the transducers; the bottom ones showing how they meet at a central focal point.
c is a representation of a prior art technology from Olympus NDT, ultrasound phased array, used to form a focal point of ultrasound energy; depicted showing the wavefronts at four times after the wavefronts have left the transducers; the bottom ones showing how they meet at an eccentric focal point.
d graphically shows the delay values used in a 32 element ultrasound phased array that are used to create different focal depths.
e illustrates different focal depths that are created below a 32 element ultrasound phased array by using the delay values of
a illustrates the intensity (as determined by Shafiri et. al. of the University of Tehran) that can be achieved at a single focus using a planar array of ultrasound elements.
b illustrates on possible orientation of ultrasonic transducers in a planar phased array.
Patent Application 61/012,851 is included by reference.
Without desiring to be held to any particular theory or mechanism of action, it is currently contemplated that stimulation (or capture) of the correct tissue is very important to eliciting the desired response. It is also contemplated that another important factor is doing so without stimulating too much neighboring or intervening tissue. Preferred embodiments of the present invention achieve this by creating a supra-threshold high intensity region remote from the energy emitter, and the energy intensity in the intervening region is sub-threshold. The supra-threshold region is located several millimeters away from the energy emitter interface with the body. In especially preferred embodiments this is accomplished with focused ultrasound energy or with overlapping or interfering ultrasound beams. The location of this supra-threshold spot must be adjustable—upon initial placement and on occasion when there is need to reposition due to loss of capture, or when there is need for optimization or when there is a desire to stimulate other tissue. This adjustment can be done electrically, mechanically, electromechanically or equivalent.
Electrical adjustment of the high intensity spot position can be done by choosing which group of ultrasound crystals to energize from among several to create a high intensity region achieved by overlapping beams as illustrated in
In these figures, nine discrete crystals are used—selecting the proper combination of three of these allows the user to select from among five points that surround a central location. These neighboring regions can be overlapping. One point is directly above, and one point is directly below the central target. The other 3 points are in a plane between the upper and lower point, and they surround the center. Since the five points are neighboring, perhaps even overlapping, the high intensity region can be moved up or down, side to side or forward or back without moving the transducer head mechanically at all.
Alternatively, the electrical spot location adjustment could use a different number of overlapping beams. Using just two beams makes it practically simpler to define many more high intensity spots—though there would not be as distinct and abrupt intensity differentiation from surrounding tissue. Using more overlapping beams improves the resolution of the high intensity region—i.e. the overlapping region has a much higher intensity than the environs and therefore there is even less likely to be inadvertent ancillary stimulation.
Other embodiments for creating an adjustable high intensity spot mechanically move an ultrasonic focal spot. An example of this is the gimbal mounted focused ultrasonic crystal depicted in
The gimbal can be designed to allow Cartesian (x, y, z), polar (θ, φ, r) or other equivalent positional translation. The adjustment controls can be mounted (i) directly on the gimbal mount, or alternatively (ii) mechanically coupled though located remotely, as a joystick at the end of a cable for easier patient control, or alternatively (iii) located remotely, by radio control of three separately addressable motors, or (iv) an equivalent control system.
Another alternative to allow for adjustment of the high intensity supra-threshold spot is a variable focus mechanism instead of a fixed focus one. Some of the ways to achieve the variable focus are: the spacing of multiple focusing elements can be adjusted, the density of the lens can be adjusted, the shape of the lens can be adjusted, the location of elements of the transducer can be adjusted, or equivalent.
Another alternative to create an ultrasound focus is to use phased array technology as depicted in
Using additional array elements positioned in a different plane, e.g. an orthogonal plane, a shaped phase delay can shift the focus in an orthogonal direction. Adjusting the delays to each of the crystals within such an array will allow essentially infinitely variable focal adjustment beneath the array.
Use of a phased array of multiple elements arranged on a surface (rather than just in a line) as in
In yet another alternative embodiment of an array of energy emitters to create a focal region that can be adjusted, the array elements would be electrodes rather than ultrasonic emitters. In a similar manner, the timing of the application of voltage to each electrode would be adjusted to allow for creation of a region of high intensity at a location remote from the electrode array. Ideally, the timing of the application of voltage to each electrode would be adjusted to allow for adjustment of the location of the high intensity, supra-threshold region in space; ±X, ±Y, ±Z.
During the course of operation, it is likely that the stimulation of the target spot becomes compromised. The desired tissue stimulation may no longer be achieved because of threshold change or positional change. Either way—the pulsing that was once effective would be effective no longer. Adjustments could be made to spot location or pulse characteristics to recapture the target tissue. The adjustments could be made by the patient or by a practitioner or by the neuro-modulation system. It could be most convenient, prompt and accurate if the adjustments to spot location and pulse characteristics were done automatically by the system—transparent to the patient.
In order to make the adjustment automatically, it is necessary to be able to detect capture of the target tissue—i.e. a sensor that is an indicator of efficacy. The indicator could be an action potential sensor, an EMG or equivalent. One example of such a capture sensor is an electromyogram (EMG). As an example, a patient experiencing pain is likely to feel tense. This tension would often be expressed as contraction of muscles; and this muscle contraction can be detected by EMG, preferably non-invasively. Relief of the pain by successful capture could be expressed as relaxation of the contraction of indicator muscles. The effectiveness of the neuro-stimulation would result in relaxation of the muscles, and this would be reflected in the EMG sensor.
Electrical characteristics of the pulse can be modified while monitoring the indicator EMG. A decline in the indicator EMG frequency is an indication of successful capture.
Similarly, the system can alter the position of the high intensity pulse while monitoring the indicator EMG; decline in EMG frequency indicates successful capture of the right tissue.
The muscle group to serve as source of the EMG indicator could be individualized for each patient. The muscle group could be located near to the location of the perception of the pain source. For example, in a patient that experiences pain radiated in the foot, the EMG electrodes could be place on the foot. Alternatively, a more general selection—such as the trapezius muscle may be a good indicator for most patients. Relaxation of this muscle would be an indication that the perception of pain has subsided—and that the stimulation parameters are adequate.
The feedback could be binary or analog. In other words, in a binary system, feedback could be used to indicate whether the neurostimulation system has achieved capture or has failed to capture. In an analog system, the feedback would be used qualitatively to indicate how effective the stimulation treats the symptoms.
After manual determination of a baseline threshold, location and adequate sensor for feedback, the automatic adjustment process can be initiated. Capture detection can be automatically checked and adjusted periodically—for example once every 5 minutes. To check for capture and for optimization, each of the following parameters could be incremented to check for improvement of degradation of performance as indicated by the sensor response:
Ultrasound Power
Ultrasound Intensity
Ultrasound Frequency
Ultrasound Waveform
Pulse Envelope Shape
Pulse Duration
Pulse Repetition Rate
X position
Y position
Z position
This adjustment of aim and intensity of the stimulating waveform could be performed frequently to allow for refinement in stimulation in response to patient position, activity level, sympathetic tone or acute intensification of perceived pain.
The settings of energy, timing and position may be adjusted within a very large range. In a preferred embodiment, the energy source is ultrasonic; the peak power is 10 watts; the power intensity in the high intensity region is 10 the fundamental resonant frequency is 1 MHz; the repetition rate is 50 Hz; the pulse duration is 2 milliseconds; the focal point is 15 mm sub-dermal.
The waveform may be a simple sine wave or a complex waveform. The envelope of the repetition pulsing may be square or more complex. The amplitude could ramp up or down for example during the course of a pulse.
The pulsing frequency is chosen so that there is enough transmission so that there is enough penetration into the flesh to the desired target level. It is also chosen so that enough energy is absorbed so that there is tissue excitation.
The system may be used continuously to stimulate; alternatively, the system is quiescent for periods. The timing of stimulation and quiescence may be programmable. Ideally, the stimulation is maximized during periods when especially needed, for example when trying to get to sleep. It would be minimized when not needed as much, for example when the patient is already asleep. It may be programmed automatically to be quiescent for periods, such as for 40 minutes of each hour.
Though the stimulation has been described as fairly regular, it need not be. The pulse duration may be variable for example. Particular pulse durations and pulse duration intervals may be suited to particular applications.
The non-contact neural stimulation device invention can be used for any of several different applications. It can be used in the treatment of pain in a manner similar to spinal cord stimulation (SCS). Just as with SCS, supra-threshold stimuli can be delivered to neural tissue to create a tingling sensation that blocks or inhibits the perception of pain. The current invention has several significant advantages and some limitations with respect to SCS. One major advantage is that it does not mandate invasive surgery. For this application, the ultrasonic transducer would be located on the skin of the back near the spinal cord. The bony structures of the spine partially obscure ultrasonic energy access to the nerves within the cord—but there is still access.
SCS generally stimulates the nerves along the dorsal horn of the spinal cord. Stimulation of deeper nerves is not practical with SCS unless the SCS lead and electrodes are placed within the cord itself (entailing extra risks and complications). An important advantage of the present invention is that it is not limited to stimulating only the most dorsal surface of the spine. The present invention may be used to stimulate within the spinal cord without stimulating the dorsal surface. This makes possible many other neural stimulation targets that are not typically accessible by SCS.
Targeting neural stimulation targets within the spinal cord can be even more precisely achieved with the ultrasonic transducer placed even closer to the target nerves. In one embodiment, the ultrasonic transducer is implanted within the body close to the spinal cord. A high intensity supra-threshold region is created in front of the transducer spaced apart from it. This invasive application of the present invention allows for more precise targeting of excitable tissue than SCS does. A focused ultrasonic transducer of the present invention can create a supra-threshold region more precisely than the SCS electrical stimulation. The supra-threshold spot can be smaller and the intensity relative to the surrounding tissue can be more dramatic compared to SCS.
The present invention may also be used to target excitable tissues in other areas for other applications. It many be used to excite nerve roots near to where they exit the spinal cord. It may be used to excite peripheral nerves for applications analogous to peripheral nerve stimulation. These include treatment of craniofacial neuropathic pain or restoration of motor functions in patients who have experienced stroke or spinal cord injury. Stimulation of the occipital nerve for example is a way to treat migraine headaches. Other applications include treatment of angina symptoms, urinary incontinence, etc.
Because the present invention can stimulate excitable tissue remotely, it may be used to stimulate cardiac tissue. It can be used to pace the sinoatrial node, the atrioventricular node, myocardial tissue or equivalent. It could be useful as a way to quickly, easily and non-invasively provide emergency cardiac pacing.
Other applications include stimulation of other anatomical structures. An example is stimulation of excitable structures associated with the stomach and other organs of digestion to elicit a sensation of satiety for the purpose of bariatric treatment.
Other applications include stimulation of other nerves for systemic influence. Cardiac, Vagus or other nerves can be stimulated. Applications could be treatment of anxiety, depression, hypertension, etc.
Thus, specific embodiments and applications of non-invasive neural stimulation have been disclosed. It should be apparent, however, to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The inventive subject matter, therefore, is not to be restricted except in the spirit of the appended claims. Moreover, in interpreting both the specification and the claims, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms “comprises” and “comprising” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced. Where the specification claims refers to at least one of something selected from the group consisting of A, B, C . . . and N, the text should be interpreted as requiring only one element from the group, not A plus N, or B plus N, etc.
This application claims the benefit of priority to U.S. Provisional Application having Ser. No. 61/012,851 filed on Dec. 11, 2007
| Number | Date | Country | |
|---|---|---|---|
| 61012851 | Dec 2007 | US |
