Attorney Docket No.: 021834-00221 OPC

MINIMIZATION OF TISSUE STIMULATION ENERGY USING A MICROSTIMULATOR

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention. This invention relates generally to implantable devices used for delivery of stimulation treatment and particularly for stimulating tissue such as cardiac tissue using a microstimulator.

[0002] 2. Description of the Background Art. Electrical stimulation of body tissues is used for treatment of both chronic and acute medical conditions. Perhaps the best known medical application of electrical stimulation is that used to initiate a heart beat by stimulating cardiac tissue for the treatment of arrhythmias. Among several other examples, direct muscle stimulation is used to initiate contraction of functional muscles in paraplegics, peripheral muscle stimulation is known to accelerate healing of strains and tears; bone stimulation is likewise indicated to increase the rate of bone regrowth and repair in fractures; and nerve stimulation is used to alleviate chronic pain. Furthermore, there is encouraging research in the use of electrical stimulation to treat a variety of nerve and brain conditions, such as essential tremor, Parkinson's disease, migraine headaches, functional deficits due to stroke, and epileptic seizures.

[0003] Generally, stimulation of excitable tissues occurs when the current density at the tissue to be stimulated exceeds a stimulation threshold, resulting in depolarization of a critical mass of cells. The induced ionic current from this depolarization results in depolarization of neighboring cells resulting in a propagation wave through the tissue.

[0004] The most commonly implanted stimulation device is the cardiac pacemaker. A pacemaker is a battery-powered electronic device implanted under the skin, connected to the heart by an insulated metal lead wire with an electrode (a pacing lead) at a distal position on the lead either in contact with the tissue or very close to the tissue. Typically, this electrode is referred to as the pacing cathode or the active electrode. To complete the stimulation circuit, a second electrode referred to as the anode or the return electrode may be located proximal, but reasonably close to, the cathode on the lead and is used for what is referred to as bipolar pacing. Alternatively, the return electrode may be on another lead or located on the surface of the pacemaker enclosure and in these situations is used for what is referred to as unipolar

pacing. The active and return electrodes are also referred to as stimulation electrodes. Pacemakers were initially developed for and are most commonly used to treat bradycardia (slow heartbeat rate, usually less than 60 beats per minute) which may result from a number of conditions. More recently, advancements in pacemaker complexity, and associated sensing and pacing algorithms have allowed progress in using pacemakers for the treatment of other conditions, notably heart failure (HF) and fast heart rhythms (tachyarrhythmia-irregularity in the normal heart rhythm and tachycardia-rates generally ranging in adults from 100 to 160 beats per minutes).

[0005] Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation or pacing energy. In general, the stimulation or pacing energy of the cardiac pacemaker required to stimulate cardiac tissue is correlated to creating sufficient current density for sufficient time in a sufficient volume of excitable cells. In part, the creation of a sufficient current density is related to the size of the electrode. As noted earlier, for stimulation to occur, the current density at the stimulation site has to exceed a threshold. For a given stimulation energy, smaller electrodes provide a higher current density, compared to larger electrodes. Hence, a pacing electrode with a large surface area requires more energy to achieve the same current density compared to the smaller surface area pacing electrode that requires less energy for the same level of current density.

[0006] Pacing leads are typically secured to the cardiac tissue by one of several fixation mechanisms such as barbs, tines, helical screws, hooks, etc. Various methods of fixing the leads to cardiac tissue have been disclosed. For example, USPN 3,754,555 by Schmitt describes a repeatably implantable intracardial electrode on a lead with resilient prongs for attachment; USPN 5,522,876 by Rusink reveals a pacing lead with a screw-in type fixation members; and USPN 4,106,512 by Bisping discloses a transvenously implantable pacemaker lead with pins at the proximal end that is attached to the pulse generator and distal end attached to the body organ. Although these mechanisms are effective in anchoring the lead, they also traumatize the tissue. This trauma generated at the time of implant and subsequent inflammation lead to fibrosis and the formation of a fibrotic cap in the tissue, often surrounding the fixation mechanism. Additionally, the constant movement of the lead in the heart chamber, as the heart beats, applies mechanical forces to the anchor point of the lead further exacerbating the local fibrotic tissue formation. As conventional pacing systems are lead based, fibrotic tissue formation is a persistent issue.

[0007] The fibrous cap that forms in the vicinity of the distal end of the lead and therefore close to or around the cathode does not contain excitable cells. This results in increased distance - the thickness of the fibrous cap - from the surface of the electrode to the closest excitable tissue. The electrical stimulation current field falls off rapidly with distance from the electrode's surface requiring more current to be driven through the system to produce sufficient current density at the closest excitable tissue. The overall effect of the fibrous cap is, thus, to increase the energy required to stimulate. Therefore, to minimize energy required, it will be ideal to have an attachment arrangement that will result in no or minimal fibrous cap formation. [0008] Furthermore, there is significant variability from patient to patient in the thickness and time course of the fibrous cap growth. This results in a wide variance in chronic pacing energies required, a problem that prompted a constant improvement in the pacemaker lead designs.

[0009] Many strategies have been proposed and implemented for minimizing fibrous cap formation. Many of the earlier improvements were towards designs that would minimize the trauma associated with securing the lead to the body tissue. However, a quantum leap in lead technology occurred with the development of steroid eluting leads, which reduced inflammation and minimized the growth of fibrous cap formation resulting in more consistent and predictable chronic pacing energies. A few of the many patent references in the drug eluting cardiac leads include USPN 4,506,680 by Stokes that describes drug-dispensing body implantable lead; USPN 4,953,564 by Berthelsen disclosing a screw-in drug eluting lead; USPN 5,489,294 by McVenes discloses a steroid-eluting stitch-in chronic cardiac lead. While steroid-eluting electrodes are commonly used, it will be ideal if no drug, such as a steroid were to be used for minimizing inflammation and hence fibrous cap formation. [0010] One of the critical aspects of the pacemaker still remains to be minimizing the energy consumption and to enhance the device life, by reducing the surface area of the electrodes. Initially, pacing electrodes were designed to have a surface area on the order of 10mm ² . This spread the current density over a relatively large volume of tissue. This volume was obviously larger than the requisite mass of cells required to initiate a depolarization wave front. The excess energy that is required to achieve sufficient current density throughout this volume is essentially wasted. A significant optimization of pacing lead technology to reduce the required stimulation energy occurred with the development of leads with small surface

area electrodes. These have surface areas of approximately lmm . These are used commercially in state-of-the-art pacemaker systems. The power required to achieve a given current density is proportional the area of the electrode. Smaller area electrodes generate higher current densities and thus require less power to stimulate tissue compared to larger area electrodes.

[0011] However, once the size of the electrode becomes small compared to the thickness of the fibrous cap, there is no reduction in required stimulation energy because the region with the highest current density occurs within the non-excitable fibrous cap. Consequently, the current density at excitable tissue is also lower due to the thickness of the fibrous cap. Diminishing returns occur at the electrode-electrolyte boundary as impedance grows large due to the small surface area of the electrode. Therefore, increased stimulation energy must be applied to stimulate excitable cells outside of the fibrous cap. Thus, there is an optimal size electrode for a given thickness of fibrous cap with thinner fibrous caps calling for smaller electrodes to achieve optimal minimal pacing energies. [0012] In order to pass current through the tissue it must pass through an electrical system consisting of output circuitry, the pacing lead wires, the electrodes, and the electrode- electrolyte interface. Each of these has associated impedance that results in energy expenditure (loss) required to deliver current through the tissue. In general, new fractal coatings improve the pacing and sensing performance of pacing electrodes. Also, the impedance of the electrode-electrolyte can be minimized by using a fractal coating on the surface that effectively increases the surface area of the interface on a microscopic scale. This is one strategy that has been used effectively to reduce pacing/stimulation energy.

[0013] Although, in principle, reduced electrode surface area offers increased current densities and hence reduced energy requirements, there are certain practical limitations. In the conventional electrode design for tissue stimulation, reducing electrode area below 1 mm ² has not been desirable. For example, in pacemakers, the pacing energy with a 1 mm ² lead is reduced to a level comparable to the energy drain from other electrical components in the pacemaker system. As the electrode size gets smaller than this, the energy drain in the rest of the circuit becomes disproportionately higher; i.e., in conventional lead based pacing systems, there is diminishing return for energy optimization with decreasing electrode size. Hence, because of the higher energy drain in rest of the circuit (circuits, lead wires, electrode-

electrolyte interface, etc.), electrodes with surface area less than lmm ² are not commonly used.

[0014] Many designs have been disclosed to eliminate leads in stimulation systems or to develop systems that are locally implanted with integrated electrodes. For example, the following patents describe various stimulator designs: USPN 3,943,936 to Rasor describes a stimulator where a self-powered, self-contained pacer and stimulator implanted in the body and the system takes advantage of the body's movement to derive the energy needed for stimulation; USPN 3,486,506 to Auphan describes a spring driven cardiac stimulator where the motion of the heart is captured in a balance wheel, which in turns oscillates a permanent magnet motor that induces electric pulses that could be applied to stimulate the heart; USPN 5,193,540 to Schulman discloses an implantable microstimulator that could be expelled from a hypodermic needle and derives energy by RF induction; USPN 5,358,514 to Schulman describes an implantable micro-miniature stimulator and/or sensor with self-attaching electrodes; USPN 5,405,367 to Schulman describes a structure and method of manufacture of an implantable microstimulator that is described in USPN 5,358,514; USPN 5,41 1 ,535 to Fujii describes a cardiac pacemaker using wireless transmission; USPN 5,814,089 to Stokes discloses a leadless multisite implantable stimulus and diagnostic system that uses high frequency signals comprising a power component derived from a power source and using this power to stimulate tissue; USPN 6,141 ,588 to Cox describes an implantable stimulation system with multiple stimulators where the stimulators are described as satellites in wireless communication with a "planet" control unit and receive instructions and electric power wirelessly; USPN 6,654,638 to Sweeney discloses an implantable electrode that can be activated by ultrasound; USPN 7,003,350 to Denker describes intravenous cardiac pacing system with wireless power supply based on RF signals; and US Patent Application 10/632,265 to Penner discloses an implantable electrode that can be activated by ultrasound.

[0015] None of the above disclosures describe an efficient attachment mechanism or electrode configuration or combination of the two that would minimize energy consumption and improve energy efficiency for tissue stimulation. Further, none of the above addresses the mechanical effects of the attachment mechanisms on fibrous cap formation. [0016] Hence, it will be beneficial to have a tissue stimulation device and method that improves energy efficiency for tissue stimulation, particularly for use in devices such as pacemakers. More particularly, devices and methods that could minimize fibrous cap

formation and dissipate minimum energy in the circuit associated with pacing electrodes would be highly desirable.

BRIEF SUMMARY OF THE INVENTION

[0017] The present invention is generally directed to implantable stimulators that are used for tissue stimulation. More particularly, the present invention is directed to leadless, locally implanted systems with integrated electrodes and methods for minimizing energy used for tissue stimulation. These devices — microstimulators — are small, implantable tissue stimulation devices that deliver electrical current to the immediately surrounding biological tissues using electrodes that are integrated into the implanted device. These microstimulators are also devoid of the traditional lead wires that connect the energy source and the electrodes. Implants in accordance with the present invention may be used for various therapeutic functions, e.g., treating cardiac diseases such as arrhythmias, heart failure and the like, pain relief, neuro-stimulation, obesity treatment and the like.

[0018] In one aspect, this invention is an implantable system for minimizing energy required for tissue stimulation using a microstimulator by minimizing the amount of fibrous tissue formed due to implantation. More particularly, the thickness of the fibrous tissue or fibrous cap made of non-excitable tissue that is formed at the implant site is minimized by reducing trauma particularly in the area of a stimulation electrode. Such trauma reduction can be accomplished using different strategies, such as using a leadless microstimulator, distancing the attachment mechanism from a stimulation electrode and the like. The microstimulator is adapted to receive energy from a transmitter and convert that energy to stimulate tissue. The transmitted energy can be acoustic energy and the tissue that is stimulated could be cardiac tissue. The cardiac tissue stimulation could be carried out for treating cardiac diseases such as an arrhythmia and heart failure. [0019] In another aspect of this invention, an implantable microstimulator based tissue stimulation system is disclosed. The microstimulator is made up of an enclosure and an attachment mechanism, and a first and second electrode. The first electrode is designated the active electrode and could be located on or near the attachment device and the second electrode (designated the return electrode) is located on the enclosure. The microstimulator can be implanted using catheter based implantation procedures. The attachment mechanism could initially be contained inside the enclosure until the implantation location is reached and then deployed. The attachment mechanism could be in the form of tongs, corkscrew or

prongs that flare out upon deployment. They enable the enclosure to be fixed to the tissue and in due course embedded in the tissue by endothelial tissue growth around the enclosure. The attachment mechanism is also configured to minimize trauma to the tissue and thereby minimize the thickness of the fibrous cap that would be formed around the first electrode. [0020] In one embodiment of this invention, the surface area of the first electrode is chosen to optimize the current density for the thickness of the fibrous cap such that the energy spent on stimulating the tissue is minimized. Such minimization could be achieved by making the first electrode surface area small. In a preferred embodiment, the first electrode surface area is less than 1 mm ² . In another embodiment, the first electrode is configured to be distal to the attachment mechanism such that the first electrode lies in regions where the distance from the first electrode to the excitable tissue is optimal.

[0021] In another aspect, this invention is a microstimulator for stimulating excitable tissue, where the microstimulator contains two electrodes configured to deliver electrical energy to the tissue, and at least one electrode has a surface area less than 1 mm ² . This small electrode size minimizes the energy consumed by the device and prolongs the life of the implanted microstimulator or the stimulation system.

[0022] The invention described herein is also a method of minimizing energy consumption for tissue stimulation using a microstimulator by implanting a microstimulator and minimizing the amount of fibrous tissue formed around the microstimulator. The microstimulator components, such as the tissue attachment mechanism and electrodes, are designed to minimize the thickness of fibrous cap and increase the current density at the site of stimulation, thereby consuming less energy for tissue stimulation compared to a conventional microstimulator or to a conventional stimulation lead.

BRIEF DESCRIPTION OF THE DRAWINGS [0023] The invention has other advantages and features which will be more readily apparent from the following detailed description of the invention and the appended claims, when taken in conjunction with the accompanying drawings, in which:

[0024] Figure 1 shows a schematic of the microstimulator. [0025] Figure 2 shows a schematic of the enclosure. [0026] Figures 3A-3C show an attachment mechanism in various stages of deployment.

[0027] Figures 4A-4B show a helical attachment mechanism. [0028] Figure 5 shows a proboscis type electrode configuration.

DETAILED DESCRIPTION OF THE INVENTION

[0029] An implantable microstimulator is illustrated in Fig. 1. Microstimulator 100 has an enclosure or casing 110, which has a detachable connection 115 at the proximal end of the microstimulator 110 and an attachment mechanism 120 at the distal end of the microstimulator 110. The detachable connection 115 connects a delivery mechanism, such as a delivery catheter 112 at one end and the enclosure 110 at the other end. Detachable connection 115 could be a mechanical, electro-mechanical or other type of connection that is commonly known in the art. The attachment mechanism 120 enables the microstimulator 100 to be attached or embedded at the desired tissue location. Various attachment mechanisms that provide minimal tissue trauma can be used and are further described below.

[0030] Enclosure 110 is made of a biocompatible material that could be either a polymer such as polyamide, poly ether ether ketone (PEEK) or the like or a metal such as titanium. Because it is constantly bathed in bodily fluids, particularly blood, the casing is preferably hermetically sealed to protect the contents of the enclosure 110.

[0031] Figure 2 provides further details of the enclosure 110. In a preferred implementation, the enclosure houses ultrasound transducers 210, and circuitry 215. These transducers are made using standard materials and techniques used for making efficient acoustic transducers. Typically, transducers are piezoelectric ceramics that are about lmm thick. An ultrasound transmitter (not shown), generates an acoustic beam that intersects transducers 210. These transducers 210 convert the acoustic energy to an A-C electrical signal. Circuitry 215 is configured to rectify the electrical signals on the transducers to lower frequency electrical output, stimulation energy, that is applied at the stimulation site using the active electrode (not shown) and return electrode 220. Various aspects of the circuitry 215 are described in detail in co-pending application 11/535,857 and 11/315,524. The return electrode 220 is located on the enclosure 210. If the enclosure 210 is made of metal, the entire enclosure or a portion of the enclosure could serve as the return electrode 220. Alternatively, the casing or enclosure 110 could be made of a non-conductive polymer a portion of the enclosure 110 could be covered with a conductive metal that could serve as the return electrode 220.

[0032] The enclosure 110 could take various convenient shapes. It could be in the form of a cylindrical element with the transducers and circuitry packed inside the cylinder as shown in Fig. 2. Typically the enclosure 110 could be about 40 to 200 mm ³ , with the preferred volume around 55 mm ³ . In a cylindrical embodiment, enclosure 110 is about 10mm long with a diameter of about 2.3mm.

[0033] One objective of this invention is to minimize the thickness of the fibrotic cap that is generally formed around the attachment mechanism 120. Generally, as described herein, tissue attachment mechanisms 120 have in one aspect a sharp, pointed and relatively small element at the distal end of the microstimulator 100 that easily penetrates into the tissue. At the tip of this element is a small surface area electrode. In another aspect of the tissue attachment mechanism there are fixation elements that affix the microstimulator into tissue at the implant site. With time, generally non-excitable, fibrous tissue grows around the attachment mechanism but preferably less fibrous growth occurs at the small distal end in the area of the small surface area electrode. The fibrous tissue around the attachment mechanism in part prevents the microstimulator 100 from drifting away from the location where it was implanted. Another requirement for the attachment mechanism 120 is that the attachment mechanism 120 remains constrained until the desired implant location is reached using a delivery system. As the preferred method of microstimulator implantation is using minimally invasive interventional means, preferably percutaneous, the sharp elements of the attachment mechanism need to remain constrained from the time of insertion into a body lumen till the tissue implant location is reached.

[0034] Figures 3A-3C show one type of attachment mechanism in various stages of deployment and satisfies the above requirements. Fig. 3 A shows the state of the attachment mechanism where the elements of the attachment mechanism are yet to be deployed and are concealed and constrained inside the enclosure 110. The state shown in Fig. 3A (with the tissue fixation element in its undeployed state) is how the microstimulator is likely to be advanced through the lumen of a vessel towards the location where the microstimulator will be implanted. Upon reaching the implant location the sharp, pointed element 300 emerges from the enclosure 110 and enters the tissue with the fixation element still in a constrained form. Multiple fixation element prongs 310 are still retained as they are constrained by retaining ring 315. Upon reaching the desired penetration depth, using a trigger mechanism with its distal end to the retaining ring 315 and the proximal end attached to the catheter or the handle portion of the catheter's proximal end, the retaining ring 315 is deactivated. This

releases the constrained prongs 310 and they flare out (310a) and embed into the tissue. The first (active) electrode 320, which is a small surface area electrode, at the distal tip of the sharp pointed penetration element 300 is now in intimate contact with the tissue that is to be stimulated. Return electrode 220 is on the enclosure 110. Together, electrodes 320 and 220 stimulate the tissue when current flows between the two electrodes. The microstimulator is retained in its desired location by the combination of the fixation element 310 being in this embodiment the flared out prongs and subsequent endothelialization of the microstimulator 100 . Furthermore, fibrotic tissue is minimized at the first electrode 320 as this is the point of least trauma incurred by implanting the attachment mechanism and overall trauma is minimized by the endothelialization of the microstimulator 100 at the implant location.

[0035] Hence, unlike traditional pacing leads, which pull against the tissue and induce further fibrosis, there is less fibrotic tissue formed around microstimulators of the present invention. Furthermore, the attachment mechanism remains constrained, particularly the sharp elements of the attachment mechanism, until the microstimulator 100 has reached its implant location. Upon reaching the implant location, the attachment mechanism is deployed, with minimal tissue trauma. Fibrotic tissue is still likely to be formed around the attachment mechanism, but because of the reduced trauma the thickness of the fibrotic tissue around the attachment mechanism, particularly around the active electrode 320, is reduced. As noted earlier, this reduced fibrotic cap thickness enables the use of less stimulation energy compared to traditional attachment and electrode configurations to achieve the desired tissue stimulation.

[0036] Figures 4A-4B show a helical type tissue attachment mechanism that minimizes tissue trauma, provide a fixed depth of location of the electrode within the tissue, and meets the above requirements. Attachment mechanism 400 contains a forward screw 410 and a reverse screw 420 attached to the body of the enclosure 110. Forward screw 410 has a fixed length. In a preferred embodiment, this length is about 3mm. Active electrode 405 is located on the distal tip of a sharp, pointed element 430 of the attachment mechanism 400. The sharp, pointed element 430 may be extended beyond the helical screw elements as shown in Figure 4B or may be advanced before the attachment of the helical elements to penetrate the tissue, as described in the previous embodiment. Turning or twisting the microstimulator 100 advances the forward screw 410 until the length of the forward screw has penetrated the tissue. If the operator continues to turn the microstimulator 100, the reverse screw 420 engages the tissue and prevents the microstimulator from disengaging from the tissue.

Alternatively, if the sharp pointed element 430 is not extended beyond the helical elements as described in one of the above alternatives, continued twisting of the microstimulator would advance the element 430 and the active electrode 405 out of the forward screw into the tissue, again getting the active electrode 405 away from the fibrotic tissue zone immediately around the helical attachment elements, or at least to a region where the fibrotic tissue thickness is minimized by the sharp, pointed element.

[0037] Figure 5 shows another embodiment of this invention where the active electrode is in contact with tissue that has minimal fibrotic tissue surrounding the active electrode. Similar to the attachment mechanisms shown in Figures 3 and 4, the attachment mechanism could be prongs that flare out or screws that could be advanced into the tissue. The active electrode 505 is now mounted on the distal tip of a proboscis like element 510. Proboscis 510 is made of a material that is stiff enough to be guided out of the lumen 520 in the center of the attachment mechanism but is sufficiently flexible to minimize the forces on tissue that could cause trauma and lead to fibrous tissue formation. The proboscis is made of a conductive material that is insulated, except for the conductive active electrode tip 505 at the distal end. This arrangement allows the active electrode to be distanced from the bulk of the non-excitable fibrotic tissue that tends to form close to the attachment mechanisms that induce tissue trauma.

[0038] Although particular embodiments of the present invention have been shown and described, it should be understood that the above discussion is not intended to limit the present invention to these embodiments. It will be obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present invention. Thus, the present invention is intended to cover alternatives, modifications, and equivalents that may fall within the spirit and scope of the present invention as defined by the claims.