WO2007080572A1

WO2007080572A1 - Medical probe

Info

Publication number: WO2007080572A1
Application number: PCT/IL2007/000017
Authority: WO
Inventors: Gideon Tolkowsky; Nirit Eshkar-Tolkowsky; Tal Rabinovich
Original assignee: Bme Capital Holdings Ltd.
Priority date: 2006-01-10
Filing date: 2007-01-08
Publication date: 2007-07-19

Abstract

A medical probe is presented. The probe includes a tube-like grip member carrying a target neural tissue (TNT) affecting unit. The TNT affecting unit is permanently threaded through the tube-like grip member extending along the grip member thereinside, and has a tip portion, which carries at least one electrode or at least one substance delivery elastic shunt or at least one brachytherapy element. The tip portion is plastically bent into a predetermined shape. The grip member has a cross-sectional dimension such as to allow movement of the TNT affecting unit relative to the grip member while substantially preventing bending of the TNT affecting unit or a part thereof located inside the tube-like grip member, such that the TNT affecting unit permanently resides within the grip member with a small space between the TNT affecting unit and the grip tube lumen. The mass of the TNT affecting unit itself thereby contributes to the strength of the probe structure and to its resistance to buckling during pull-back. The probe is thus adapted for operating the TNT affecting unit to be at least partially projecting outside the grip tube resulting in the bending of the projecting part of the tip portion, thus allowing fine-tuning of the tip location inside the target tissue by providing axial and angular adjustability of the tip location. This enables periodic correction of the tip location inside the target tissue, during the placement procedure or later in the course of the patient's life, without a repeat surgical procedure. In the preferred embodiments of the invention the tip portion of the TNT affecting unit has a circular-arc shaped portion. Two or more probes may be bundled in a single probe device.

Description

MEDICAL PROBE

FIELD OF THE INVENTION

This invention is in the field of medical probes and relates to a probe for electrical neural stimulation and lesioning of deep tissue, or for local delivery of therapeutic and diagnostic substances to deep tissue. The probe is particularly useful for such medical procedures as neural stimulation including deep brain stimulation, biopsy, brachitherapy, electroporation, ablation, placement of radioactive pellets, local drug delivery, hyperthermia, hypothermia, and insertion of stem cells.

BACKGROUND OF THE INVENTION

There are a variety of minimally invasive surgical procedures that require precise placement of a probe within a tissue, either temporary placement for the duration of the procedure, or permanently. These include biopsy procedures, electroporation, RF or microwave ablation, neural stimulation, local drug delivery, placement of radioactive pellets for radiation therapy, hyperthermia, hypothermia and other procedures. Neural stimulation involves electrical stimulation of nerve cells in order to treat various pathologies in the nervous system. These include, for instance, spinal cord electrical stimulators, which are used to relieve chronic pain. Sample devices include Medtronic's Pain Pacemaker, Cyberonics' VNS Therapy device and the Precision System made by Advanced Bionics that has been acquired by Boston Scientific. In back-pain control application, a compact electronic device is surgically implanted in the wall of the lower abdomen and connected by wire to a strip of electrodes placed next to the back of the spinal cord. The electronics supply low- voltage electrical pulses at the electrodes, which alter the pain signals in the spinal cord and provide partial or complete pain relief. The stimulators are programmable, so that the signal can be adjusted for optimal pain relief after implantation. Another example is the Medtronic InterStim System for urinary control. It is used to treat urinary retention and the symptoms of an overactive bladder, including urinary urge incontinence and significant symptoms of urgency-frequency.

Yet another example of therapeutic electrical neural stimulation is Deep Brain Stimulation ('DBS'). DBS is a surgical procedure used to treat a variety of disabling neurological symptoms, most commonly the debilitating symptoms of essential tremor, and Parkinson's disease (PD), such as tremor, rigidity, stiffness, slowed movement, and walking problems. DBS involves the use of a battery-operated medical device called a neurostimulator (similar to a heart pacemaker and approximately the size of a stopwatch) to deliver electrical stimulation to targeted areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and PD symptoms. Before the procedure, a neurosurgeon uses magnetic resonance imaging (MRI) or computed tomography (CT) scanning to identify and locate the exact target within the brain where electrical nerve signals generate the PD symptoms. Some surgeons may use microelectrode recording, which involves insertion of one or more small wires into the brain and monitoring the activity of nerve cells in the target area, three-dimensionally, so as to identify the precise brain target that will be stimulated. Generally, these targets are in the thalamus, subthalamic nucleus, and globus pallidus. Generally, a DBS system (e.g. Medtronic' s Activa system) consists of three components: the lead (also called an 'electrode'), the extension, and the neurostimulator. The lead is a thin, insulated wire that is inserted through a small opening in the skull and implanted in the brain. The tip of the electrode is positioned within the targeted brain area. The extension is an insulated wire that is passed under the skin of the head, neck, and shoulder, connecting the lead to the neurostimulator. The neurostimulator (the "battery pack") is the third component and is usually implanted under the skin near the collarbone. In some cases it may be implanted lower in the chest or under the skin over the abdomen (Fig. 1). Once the system is in place, electrical impulses are sent from the neurostimulator up along the extension wire and the lead and into the brain. These impulses interfere with and block the electrical signals that cause PD symptoms.

The electrical stimulation procedure of the kind specified is also used for treating movement disorder, epilepsy, Tourette syndrome, and other disorders. Sometimes, more than one electrode is implanted, e.g. two electrodes in the two hemispheres of the brain. Currently, the DBS electrode is placed in the patient's brain in the following manner. A hole is bored in the patient's skull. A thin but relatively rigid tube ('insertion tube', or 'cannula') is inserted through the hole and pushed toward the target tissue, until its distal end is about 1-2 cm from the target. Then, a thin electrode (often referred to as a 'lead') is threaded through the tube and its distal tip brought to the target. For illustration of typical dimensions - the Activa system's electrode has an outer diameter of 1.27 mm. After the electrode is inserted, the tube is pulled out, leaving the electrode in place. The electrode may actually consist of several electrodes on a single element (normally up to four of them, e.g. in Medtronic's Activa system). The electrode is electrically insulated by non-conductive material, except for one or more short segments, located several millimeters apart along the electrode's distal segment, which are exposed from the isolating material and therefore come in electrical contact with the surrounding tissue. The multitude of exposed electrode segments enables electrical stimulation of more than one locus in the target tissue. The electrostimulator is programmed to fire electrical stimuli from the different exposed segments of the electrode in such manner so as to maximize the clinical outcome. One purpose of this multiple electrode configuration is to compensate for inaccuracy in the initial placement of the electrode, for changes in its location after implantation due to surgical closure of the patient and due to patient movement in day-to-day life, and for changes in the location of the pathology with time.

Various techniques and probe designs have been developed, and are disclosed for example in the following patents: US 6,343,226; US 6,714,822; US 5,121,754; US 6,606,521; US 6,609,020.

In addition or alternatively to performing neural stimulation, electrodes are often inserted into tissue in order to deliver therapeutic substances into cells, or in order to ablate pathological, e.g., cancerous cells. For example, one such procedure — often referred to electroporation - involves applying electrical shocks that open up pores in the cells' membranes. Therapeutic molecules then enter the cells through the pores. Subsequently, the cells use natural mechanisms to mend the pores. Alternatively, whenever it is desirable to kill the cells, stronger electrical shocks are delivered to open up large, irreparable pores in the cells' membranes, leading to cell death.

In addition or alternatively to electrodes, shunts and injection needles are often inserted into living tissue in order to locally deliver therapeutic and/or diagnostic substances, be it for one-time delivery, or for sustained delivery where the shunt is implanted for prolonged duration. Most drugs are administered either orally or by injection. When a clinical disorder, such as cancer, is localized in nature, relatively large quantities of a drug must be administered in order to achieve therapeutically effective concentrations at the target site. These large dosages can produce undesirable side effects. Furthermore, some therapeutic and/or diagnostic substances have a short half- life, requiring rapid distribution and uptake by tissue. In brain diseases, the Blood Brain Barrier (BBB) substantially amplifies the difficulties in creating sufficiently high drug concentrations in the target tissue. Therefore, there is an advantage in local delivery of therapeutic and diagnostic substances in neural and other tissue.

In addition or alternatively to electrodes, shunts and needles, other probes are often inserted into living tissue in order to locally deliver non-electrical energy, such as heat (or 'negative heat' — i.e., cold), microwave, and ultrasound, to treat various pathologies, e.g. to kill cancerous cells. In some cases, particularly in treating certain brain pathologies, direct access to the target tissue, e.g., to a tumor, by way of inserting a straight electrode, shunt or needle, is problematic, as some critical tissue is located somewhere along the straight- line insertion path. Insertion through the critical tissue would damage it. In these cases, there is an advantage in circumventing, the critical tissue during insertion, i.e., inserting the electrode, shunt or needle along a curved path.

Also, there are cases where there is a clinical need to infuse or inject a therapeutic or diagnostic material into a volume of tissue that is too large to be covered by a single injection. Yet, there is clinical disadvantage in inserting the infusion shunt, or injection needle, several times, into neighboring locations in the target volume of tissue, as the insertion itself involves clinical risks (e.g., in brain tissue). In such cases, there is an advantage in inserting a single shunt, or syringe, a single time, where only the tip of the shunt or syringe alters its location to deliver the substance to different places within the target volume of tissue.

Among the procedures for local delivery of therapeutic substances, there is also a procedure that involves placement of rice-size radioactive pellets in several loci inside a malignant tumor, such as in prostate or brain tumor. In such procedures it is important to place the pellets precisely at the right loci, in order to assure application of the radiation to the entire malignant tumor, with minimal damage to healthy tissue around it. The pellets are normally inserted through a needle, tied to a thread. In some cases, they can be implanted in-situ for long durations.

SUMMARY OF THE INVENTION

There is a need in the art to facilitate such procedures as electrical neural stimulation or other electrical treatment, infusion and injection of substances, etc., utilizing medical probes (implantable or not), by providing a novel probe design enabling precise placement of the probe tip with respect to a region of interest and allowing periodic and efficient correction of the electrode/shunt tip location during and after the probe insertion procedure, without a need for a repeat surgical or insertion procedure. There is also a need in the art for utilizing medical implantable and non- implantable probes that can reach their target location in-vivo via a curved insertion path.

The main idea of the present invention is associated with the following: Existing systems of the kind specified make use of a removable guiding tube (cannula) to guide an electrode, or a shunt, or a syringe, to the region of interest. Once the electrode or shunt is properly placed, the tube is removed. It is often the case that, in order to achieve the desired level of placement accuracy, advance calculation of the path of insertion of a probe is needed as well as the probe insertion under imaging. In the case of brain procedures, tool insertion is often aided by placement of a stereotactic frame on the patient's skull and attaching tool(s) to it, thus registering the spatial coordinates of the tool with those of the target tissue. Notably, due to the elasticity of some surgical tools (e.g. neural stimulation electrodes, or biopsy needles), and the resistance of the tissue to the tool during insertion, the actual path of the tool often differs from the intended, calculated path. Similarly, the location of the tip of the probe often tends to change when the patient is 'closed' at the end of the procedure. In the case of programmable electrical probes, there is generally a limit to the degree to which a sub- optimal tip location can be compensated for by programming the electrical signals delivered to a few exposed sections of the lead.

Furthermore, if the clinical application involves permanent, or long-term residence of the probe in-vivo (e.g. in certain neural stimulation therapies, including DBS), then the location of the electrode often changes in the course of the patient's day- to-day life and thus must be corrected periodically. The same applies to cases where the location of the treated pathology changes with time.

In most cases, once the probe is inserted, any lateral or angular correction of its location relatively to the target tissue involves pulling out the probe and re-inserting it, along a new path. Moving the probe sideways, or altering its angle of entry, after it is already inserted, is physically difficult, and potentially clinically harmful, as sideway movement applies pressure on the neighboring tissue and cuts through it. Similarly, reinsertion of the probe, for the purpose of correcting its tip location, is not only time consuming but also increases (e.g. doubles) the risk of damaging tissue along the insertion path. The risks involved in repeat insertion are particularly high in the case of brain surgery, where any cutting through the tissue increases the risk of hemorrhage, which can be extremely harmful.

For all these reasons, there are distinct clinical and economic benefits to being able to alter the location of the tip of the electrode during and after the DBS insertion procedure, without a repeat surgical procedure. The same applies to electrodes used for other therapeutic and diagnostic purposes (e.g., tissue ablation or biopsy), and to shunts and syringes for substance delivery, including placement of radioactive pellets to treat cancer.

The present invention solves the above problems by providing a novel medical probe to be used intra-operatively and/or post-operatively for electrical neural stimulation and lesioning of deep tissue (e.g. inner regions of the brain), or for local delivery of therapeutic and/or diagnostic substances to deep tissue or for brachytherapy or for tissue ablation by way of delivering energy that kills cells. The probe may be used for delivery of at least one of therapeutic and diagnostic substances to a given volume of tissue by way of multiple sequential infusions, or injections, into several different loci within the same volume, by way of a single probe device making a single passage leading to the target tissue. The probe configuration is aimed at facilitating precise placement of an electrode or substance delivery shunt or syringe or tissue ablation tool with respect to target tissues, to enable corrections of the tip location, as well as circumvention of critical tissue during probe insertion, and delivery of substances to different locations within a given volume of the target tissue, by more than a single infusion or injection, but by way of a single probe making a single passage along the path leading to the target tissue. It should be understood that the term "substance delivery shunt" used herein signifies a thin tube, e.g., syringe, or a catheter (normally up to 5mm in diameter), that is used to locally deliver therapeutic or diagnostic substances, including radioactive pellets, percutaneously (such as a shunt used to deliver therapeutic substances to a chosen deep-brain location, under hydraulic pressure - a technique known as Convection Enhanced Delivery, or 'CED'), or is used as a brachytherapy element, or as a biopsy needle. Such a shunt can be made of a metallic (e.g. steel), or plastic, or other material that is bio-compatible. Such materials are known to practitioners in the field.

The term "target tissue " refers herein to a volume of living tissue, including but not limited to neural tissue, in any body organ, where a pathology resides, or is suspected of residing.

The term "neural tissue" refers here to an individual nerve cell, or to a bundle of nerve cells (such as the spinal cord), or to any other conglomeration of nerve cells (such as the brain or a particular zone in it). The term "neural stimulation" refers here to electrical stimulation of neural tissue, for the purpose of curing, or containing the symptoms of neurological and related pathologies, such as Parkinson's Disease, Alzheimer's Disease, Huntington's Disease, seizures, depression, migraine, chronic back pain, other chronic pain, obesity, urological incontinence, hearing impairment and other conditions. The terms "lesioning" and "neural lesioning" refer here to the application of energy (e.g. radio-frequency, electrical pulses, or microwave, or heat, or cold, or ultrasound) in order to cause a lesion in a particular locus in the tissue or in the neural tissue, respectively, for clinical applications that involve killing of pathological cells.

The expression "local delivery of therapeutic substances" used herein refers to the infusion, through a temporarily or permanently implanted shunt (a thin tube), of therapeutic substances into a particular location in-vivo. These substances may include drugs, DNA, sRNA, RNAi, stem cells, contrast agents, radioactive pellets, and more, for treating neurological or other disorders.

The expression "local delivery of diagnostic substances" used herein refers to the infusion, through a temporarily or permanently implanted shunt (a thin tube), of substances used to enhance the performance of imaging modalities such as ultrasound, CT, nuclear imaging, MRI and PET. The probe of the present invention includes a tube-like grip member (flexible or rigid), and a target neural tissue (TNT) affecting unit permanently threaded through the grip tube while being movable with respect to the tube to allow its projection out of the tube and its rotation relatively to the tube. The TNT affecting unit carries one or more electrodes or substance delivery shunts, and is plastically bent at fabrication into a desired shape. It should be understood that the term "grip tube" used herein refers to any flexible or rigid tube-like device that has a proximal end and a distal end. Such a grip tube may be of a certain fixed cross-sectional size (e.g. diameter) or may have a variable lumen diameter along the tube. The term "target neural tissue (TNT) affecting unit" refers here to an elastic electrode or a conductive wire, or other thin, elongated and elastic conductive element, or an elastic shunt (e.g. a syringe), which is permanently threaded through the grip tube but can move along its lumen in both directions. The TNT affecting unit is used to apply electrical stimulation or lesioning to the target tissue, neural tissue or other, or to deliver therapeutic or diagnostic substances to the target tissue, neural tissue or other. Such a TNT affecting unit is also termed here as electrode when referring to an electrical stimulation, as well as lesioning electrode or substance delivery shunt, by virtue of the latter' s similarity to an electrode in its geometry (other than having a lumen) and methods of insertion. The cross-sectional dimensions and the elastic properties of the grip tube and of the TNT affecting unit may be such that when the TNT affecting unit is completely inside the grip tube, the TNT affecting unit is substantially unbent. This is achieved by either using a less elastic material for the grip tube than for the TNT affecting unit, or constructing the grip tube's wall so that it is thick enough to prevent the TNT affecting unit from bending the tube while housed within it. Moving the TNT affecting unit relative to the grip tube causes the TNT affecting unit to at least partially project outside the grip tube resulting in the bending of the projecting part of the distal end, thus allowing fine-tuning of the distal end location inside the target tissue by providing axial and angular adjustability of the distal end location. The probe configuration enables correction of the distal end location inside the target tissue during the placement procedure or later in the course of the patient's life without a repeat surgical procedure, and enables circumvention of critical tissue during probe insertion. This is achieved by manipulating the probe's distal tip (i.e., that of the TNT affecting unit) from the outside so as to adjust its location in the target tissue, in all spatial directions.

The grip tube may be guided by an available guiding tube (e.g., cannula) and can permanently reside within the patient's body, or, if used intra-operatively, be pulled out at the end of the surgical procedure. The grip tube is aimed at containing and supporting the electrode's bent tip in its clinically desired Orientation, when the tip is partially or fully deployed. The grip tube and the electrode (TNT affecting unit) are inseparable, integrated parts of the same probe. The use of such a permanent grip tube enables periodic correction of the location of its tip, as clinically needed. The TNT affecting unit can be partially or fully deployed out of the tube. This configuration of the TNT affecting unit, as combined with its bent tip (e.g., circular-arc bent) that can be partially or fully deployed, can figuratively be referred to as a 'cat nail probe'. It offers a high degree of flexibility in placing the electrode; a high degree of placement accuracy; minimal tissue damage due to minimal lateral movement; adjustability of the electrode's position, in-situ, during and after the procedure; circumvention of critical tissue, so as not to damage it, during insertion; and multiple deliveries of electrical or other energy, or of therapeutic or diagnostic substances, to different but adjacent locations in a given tissue volume, along a single penetration path.

The tube's lumen grips the curved (bent) TNT affecting unit (i.e., elastic electrode(s), or shunt), that is permanently threaded through it, thus forcing the TNT affecting unit to assume the longitudinal shape of the tube's lumen for so long as the electrode or shunt is in its un-deployed position. Once the TNT affecting unit is pushed from its proximal end, its distal segment is deployed out of the tube's distal end and re- assumes its prebent shape. The grip tube can be made of any suitable bio-compatible and electrically insulating materials of the types that are currently used for implanted medical devices and are known to practitioners in this field, e.g. metal (e.g. stainless steel covered by plastic material or entirely made of plastic material).

It should be noted that the tube needs not necessarily be strong, as it may serve solely for gripping the bent tip, rather than guiding and inserting against tissue resistance. The latter functions may be performed by other available devices (tubes or cannulas), through which the probe of the present invention (grip tube carrying the TNT affecting unit) is to be inserted. The grip tube merely needs to be strong enough to satisfy two conditions: 1) not to bend under the radial force applied by the TNT affecting unit's bent tip while housed inside the tube's lumen, and 2) not to buckle under the longitudinal pressure inflicted on it when an operator pulls the deployed TNT affecting unit back into the grip tube. This is achieved by either constructing the grip tube of less elastic material than that of the TNT affecting unit (e.g. coated stainless steel for the tube and tungsten for the TNT affecting unit), or by constructing the grip tube and the TNT affecting unit from the same material, or from another material with similar elasticity, but where the tube is thick enough to force the TNT affecting unit to a straight shape while housed within the tube. For example, if the grip tube's lumen has a 1-2 mm diameter, then the thickness of its wall should be no less than 0.1 -0.2 mm.

Notably, since the TNT affecting unit permanently resides within the grip tube, with a small radial gap between the TNT affecting unit and the grip tube's lumen, then the mass of the TNT affecting unit itself contributes to the strength of the probe and to its resistance to buckling during pull-back. The grip tube can also be made of plastic material, if the tip of the TNT affecting unit that is threaded through it is coated with silicon, or another softer-than-metal material (as in the available stimulation electrodes), hence it will not cut through the wall of the tube. If the TNT affecting unit is used as a shunt, then it can be made of plastic material. This embodiment is less demanding on the strength of the grip tube.

The TNT affecting unit is generally elastic but is plastically bent at fabrication along its distal segment so as to assume a desired curvature at its distal segment. The distal segment (also sometimes termed "tip") can generally be bent in any shape, including particularly useful shapes defining a curved segment, e.g. an arc-like segment. Preferably, the distal segment of the TNT has a circular arc shape. This may not be a full-circle arc, but may for example be a quarter circle, half circle, or any other portion of a full circle. The advantages of using this geometry are described more specifically further below.

The bending of the TNT affecting unit may be achieved by simply applying a mechanical force to appropriately shape the tip portion thereof; or by applying thermal treatment or any other known method suitable for the specific material that is used, during the manufacturing process. Such manufacturing processes incorporate into the bent element a property known as 'shape memory', i.e., the material 'remembers' its pre-bent shape and re-assumes it after it is released from the straight shape that is forced on it while the electrode is housed within the grip tube.

The TNT affecting unit may be manufactured by way of heat treatment and, in some cases, if it is made of metal and depending on the metallic material used, cold draw process can be used as well, where the metallic material undergoes several cycles of heating and cooling. Heat treatment, and cold draw, assign to a metallic TNT affecting unit such properties as 'shape memory'; strength; and elasticity. The TNT affecting unit can be made of several types of bio-compatible metals, all of which are routinely used in medical devices that are in touch with biological tissue. One example of such material is Stainless Steel Chrome Nickel type 316 (AISI). Other examples are tungsten or nitinol. Yet another example, particularly applicable to the use of the TNT affecting unit as an electrode, is a platinum/iridium alloy. If the TNT affecting unit is metallic and serves as an electrode, it can be coated with an electrically isolating material (such as silicon), except for one or more short segments close to its distal end where the metal is exposed, so as to come in electrical contact with the surrounding tissue (as is the case in the available electrodes). The TNT affecting unit can also be made of a bio-compatible plastic material. The tip of the TNT affecting unit, or part of it, can be made of or covered with a material that makes it opaque to the intra-operative or post-operative medical imaging modality in use, if any (e.g., CT, or MRI, or PET). In describing the curved shape of the distal segment of the TNT affecting unit, the term "circular arc" refers to a curve of a substantially constant radius. It should be understood that this is the only arc geometry that enables zero lateral movement of any of the points along the arc during extension or pull-back of the curved arc segment. Using such a circular arc distal segment of the TNT affecting unit provides for preventing lateral cut through tissue during extension and pull-back. Furthermore, the circular arc geometry guarantees that, during deployment, the surrounding tissue does not apply any lateral (or, differently put, radial) forces on the deployed arc segment. Consequently, the deployed segment is not deformed during deployment and maintains its circular arc shape. This enables an operator of the probe to place the circular arc's distal tip precisely at the intended location.

The TNT affecting unit may have a bent shape of a segment of circular arc with a further (distal) substantially straight segment integral with the arc segment. This configuration allows for initial aiming of the TNT affecting unit directly at the presumed target location, with no lateral offset. Then, if the tip's lateral position needs to be corrected due to an error in assessing target location, or change in location of the pathology, then the unit can be further pushed out of the grip tube and start bending due to the arc-shaped segment to which it is attached. The straight distal part of the arc segment tip portion may be of a variable length, from a very small ("zero") to a predetermined one. Generally, a non-circular arc segment may be used as well.

In various embodiments of the invention, the tip can be in the shape of any part of a circular arc that is shorter than a half circle (180 degrees), e.g. a quarter of a circle (90 degrees). The TNT affecting unit is permanently threaded through the grip tube. While in its un-deployed position, the bent tip is gripped by the tube and forced into the substantially straight, or other longitudinal shape of the tube's lumen. When the tip is deployed out of the tube's distal end, it re-assumes its pre-bent shape. However, it is important to note that the tip may be left partially deployed. By altering the degree to which the tip peeks out of the tube, and by rotating the electrode relatively to the tube, the operator can alter the locus of the tip within the target tissue, in all directions. Furthermore, by pushing or pulling the entire probe further in or out of the patient's body (while the electrode is in an un-deployed position), the bent tip can be made to reach different loci along the path of insertion. By combining the partial 'peeking' effect, the rotation of the electrode, and the push and pull of the entire probe, the electrode's tip can be made to reach any locus in the target tissue within a cylindrical volume around the probe's longitudinal axis that has a radius of several millimeters, or several centimeters, depending on the scale of the probe. This feature is useful, for example, for seeking the optimal locus for neural stimulation within a given volume of tissue; or for the delivery of therapeutic or diagnostic substances to the given volume of tissue by way of multiple infusions, or injections, into several different loci, by way of a single probe making a single passage along the path leading to the target tissue.

It is important to note that if the tip has the shape of a circular arc (i.e., with a constant radius) then, due to this geometry, the bent tip does not laterally cut through tissue as it is deployed out of the tube or pulled back into it (to the undeployed position). The movement of the tip's most distal end-point is only axial, (along the axial direction of the curved TNT affecting unit), not lateral (perpendicular to the curved axis). For most clinical applications, the tip's length would be from several millimeters to 1 centimeter. The diameter of the TNT affecting unit can vary, normally from 1- 2 mm if used for electrical stimulation, or larger, normally up to 1 cm, if used as a shunt.

The diameter of the TNT affecting unit is only slightly smaller than the inner diameter of the grip tube (e.g. about 10% smaller), so as to enable minimization of the tube's outer diameter while still allowing free axial movement of the TNT affecting unit through the tube's lumen. It is not necessary to have a larger difference between the diameter of the lumen and of the TNT affecting unit, as the latter is threaded into the tube at fabrication and resides there permanently.

The grip tube may have a larger inner diameter thus enabling the TNT affecting unit to be partially bent while in the grip tube according to its initial bent shape and successively reach the complete bend shape as it is being projected out of the grip tube.

The grip tube may have a varying cross-section lumen along a longitudinal axis of its distal end portion, namely increasing cross-section towards the tip portion. This can be achieved by making the grip tube with a gradually increasing lumen diameter towards the distal end of tube; or a step-like increase of the cross-sectional lumen size such that it is larger at the distal end than at the proximal end. These configurations enable the tip portion of the TNT affecting unit to begin to assume its bent shape (i.e. start bending) before it emerges out of the grip tube's distal end. Also, this enables partial deployment (as opposed to full deployment) of the tip of TNT affecting unit and, with it, partial sideway movement of the tip so as to reach a tissue locus that is slightly off the probe's longitudinal axis. In other words, these configurations facilitate placement of the tip portion of the TNT affecting unit off the longitudinal axis of the grip lumen, within that portion of the target tissue that is immediately neighboring to the grip tube's distal end. Comparing the probe of the present invention to the probes known in the art, it should be noted that with most of the known probes an operator needs to thread an electrode through an insertion tube during the time of the procedure, hence requiring a larger difference in diameters for easier threading.

A plurality (generally, at least two) probes configured as described above can be bundled together, being separately operated. This allows for simultaneously placing multiple TNT affecting units in the target tissue, in different locations (different from one another in their axial and angular positions). This feature may be useful in applications requiring simultaneous delivery of electrical or other energy, or a therapeutic and/or diagnostic substance, including radioactive pellets, to an entire volume of tissue. Thus, according to one broad aspect of the invention, there is provided a medical probe comprising a structure, which is formed by a tube-like grip member carrying a target neural tissue (TNT) affecting unit; the TNT affecting unit being permanently threaded through the tube-like grip member extending along the grip member thereinside, and having a tip portion, which carries at least one elastic electrode or at least one substance delivery elastic shunt, and which is plastically bent into a predetermined shape; the grip member having a cross-sectional dimension such as to allow movement of the TNT affecting unit relative to the grip member while substantially preventing bending of the TNT affecting unit or a part thereof located inside the tube-like grip member, such that the TNT affecting unit permanently resides within the grip member with a small space between the TNT affecting unit and the grip tube lumen, the mass of the TNT affecting unit itself thereby contributing to the strength of the probe structure and to its resistance to buckling during pull-back; the probe structure being thereby adapted for operating the TNT affecting unit to be at least partially projecting outside the grip tube resulting in the bending of the projecting part of the tip portion, thus allowing fine-tuning of the tip location inside the target tissue by providing axial and angular adjustability of the tip location, thus enabling periodic correction of the tip location inside the target tissue, during the placement procedure or later in the course of the patient's life, without a repeat surgical procedure. In some embodiments of the invention, the predetermined shape of the tip portion of the TNT affecting unit defines an arc-like segment. In the preferred embodiments, this is the segment of a circular arc.

In some embodiments of the invention, the predetermined shape of the tip portion of the TNT affecting unit, defines a substantially straight segment extending from a distal end of the arc-like segment. This substantially straight segment may have a certain fixed length; or may have a variable length, allowing it to be extendable from the distal end of the arc-like segment to a desired length (for example by configuring this straight segment as a telescopic member of the variable length).

The cross-sectional dimension of the TNT affecting unit may be only slightly smaller than the inner cross-sectional dimensions of the tube-like grip member, thereby enabling minimization of an outer cross-sectional dimension of the grip member while still allowing free axial movement of the TNT affecting unit thereinside. For example, the cross-sectional dimension of the TNT affecting unit can be about 10% smaller than the inner cross-sectional dimension of the tube-like grip member.

The length of the tip portion of the TNT affecting unit may be in a range from a few millimeters to a few centimeters, for example it may be up to 2-3 centimeters. The cross-sectional dimension of the TNT affecting unit may be about 0.5-5 mm.

At least a part of the tip portion of the TNT affecting unit may be made of a material opaque to certain external radiation, thereby enabling use of medical imaging modality for intra-operative or post-operative procedures.

The grip member itself may carry at least one electrode on its outer surface. In some embodiments of the invention, the lumen of the grip member has a certain substantially constant inner cross-sectional dimension all along the grip member.

In some other embodiments of the invention, the lumen of the grip member has a varying cross-section along a longitudinal axis thereof, such that the cross-section of the lumen is larger at the distal end than at the proximal end. The inner cross-sectional dimensions of the grip tube and cross-sectional dimensions of the TNT affecting unit may be selected so as to enable the TNT affecting unit to be partially bent while in the grip tube according to its initial bent shape and successively reach the complete bent shape as it is being projected out of the grip tube. Thus, this configuration allows variation of the bent condition of the TNT affecting unit while moving it through the grip member, thus allowing adjustment of the placement of the tip portion of the TNT affecting unit with respect to the target tissue. Such a varying cross-section design can be achieved by gradually increasing the cross-sectional size of the lumen towards its distal end; or by a step like change of the cross-sectional size such that said size at the distal end is larger than at the proximal end. In some embodiments of the invention, the grip member and the TNT affecting unit may be made of the same material. The grip tube may be substantially thick to force the pre-bent TNT affecting unit into a straight shape thereof while it is housed within the grip member.

In some other embodiments of the invention, the grip member is made of a material that is less elastic than material of the TNT affecting unit. In this case, the grip member is adapted to force the pre-bent TNT affecting unit into a straight shape while it is housed within the grip member. The TNT affecting unit may be configured as a substance delivery shunt and is made of plastic material, thereby applying weaker bending force on the grip member while housed within it. hi some embodiments of the invention, the probe is configured for placement of radioactive pellets in tumor. The pellets may be tied to threads and inserted through the lumen of the TNT affecting unit.

The distal tip of the TNT affecting unit may be made of radioactive material, such as iridium used to apply radiation therapy to a tumor. In some other embodiments, the distal tip of the TNT affecting unit is a hyperthermal or hypothermal probe configured for delivering heat to tissue or to cool down tissue in order to kill pathological cells. In some other embodiments, the distal tip of the TNT affecting unit is an RF-ablation, or electroporation, or sonoporation probe, to kill pathological cells. The TNT affecting unit may also be configured as a syringe, or as a biopsy needle.

According to another aspect of the invention, there is provided a medical probe device for use in at least one of electrical neural stimulation and lesioning of deep tissue, and local delivery of therapeutic or diagnostic substances to deep tissue. This medical probe device comprises at least two of the above-described probes bundled together, thereby enabling treatment of different locations in the tissue via a single path leading to the target tissue. The probes are mounted within a common bundling tube which is configured such that each of the probes is free to move axially within the bundling tube, independently of the other probes. This enables simultaneous placement of the multiple TNT affecting units within the target tissue, in multiple locations, respectively, which are different from one another in their axial and angular positions relatively to the bundling tube; and enables simultaneous coverage of a certain volume of the target tissue. One of the bundled probes may comprises a positive electrode on its TNT affecting unit, and the other probe may comprises a negative electrode on its TNT affecting unit, thus creating a bi-polar electromagnetic field in the target tissue. At least some of the TNT affecting units may be configured for delivery of at least one of therapeutic and diagnostic substances to a given volume of tissue by way of multiple sequential infusions, or injections, into several different locations within said volume, or placement of several radioactive pellets, by way of a single probe making a single passage along the path leading to the target tissue. According to yet another aspect of the invention, there is provided a kit for use in electrical neural stimulation and lesioning of deep tissue or local delivery of therapeutic or diagnostic substances to deep tissue or brachytherapy, the kit comprising a set of medical probe devices, each probe device including one or more probes, each probe comprising a tube-like grip member carrying a target neural tissue (TNT) affecting unit, the TNT affecting unit being permanently threaded through the respective grip member extending along the grip member thereinside, and having a tip portion, which carries at least one elastic electrode or at least one substance delivery elastic shunt, and which is plastically bent at fabrication into a predetermined shape, the probe devices of the set differing from each other in at least one of the following: (a) TNT affecting units of different probe devices being plastically bent at fabrication into a different shape; and (b) the tube-like grip members of different probe devices having different profiles of its lumen cross-section.

One of the clinical applications addressed by the present invention is neural stimulation in general, and the special case of Deep Brain Stimulation in particular. Another example of a clinical application addressed by the present invention is the local delivery of therapeutic or diagnostic substances into deep tissue, including the placement of radioactive pellets.

There are a number of functions that would benefit from a probe designed as described above for accurate and unharmful insertion and reinsertion. These include biopsies (e.g., in the brain), brachitherapy (placement of radio-active pellets (or "seeds") within tissue so as to destroy malignant cells or to serve as markers), electroporation, ablation (killing malignant cells by the local delivery of intense energy, be it electrical, thermal, or other), local drug delivery (e.g., to malignant cells in the brain, and other organs) including Convection Enhanced Delivery, insertion of stem cells (to replace damaged tissue), placement of radioactive pellets in tumors, and more. Such a probe would be particularly useful for neural stimulation and its special case of Deep Brain Stimulation (DBS). During some procedures, such as in the case of PD, in epileptic seizures, and in pain control outside the brain (e.g. in the spine), the patient may be awake during the surgical implantation of the electrodes carried by the probe, while the surgeon moves the TNT affecting unit's (in this case electrode's) tip around, until the measured electrical activity in the pathological zone of the brain reaches a minimum or until the patient reports of minimal pain or until other debilitating symptoms of the treated disease become minimized (like tremor in the case of PD).

BMEF DESCRIPTION OF THE DRAWINGS In order to understand the invention and to see how it may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

Fig. 1 is a schematic illustration of a system suitable .for using the present invention, the system in the present example being an implanted deep brain stimulation system configured for stimulating both sides of the brain;

Fig. 2A is a schematic illustration of an example of the probe of the present invention utilizing a TNT affecting unit with a tip portion pre-bent at fabrication to a curved shape, including the special case of a circular arc shape with a constant radius;

Figs. 2B to 2D schematically illustrate operational steps in operation of the probe device of the present invention, e.g. the probe of Fig. 2A;

Fig. 2E schematically exemplifies some features of the present invention; Fig. 3 schematically illustrates another example of the probe device of the present invention, utilizing an arc-segment shape of the tip portion of the TNT affecting unit; Figs. 4A-4D show another example of the probe of the present invention;

Fig. 5 schematically illustrates yet another example of the TNT affecting unit suitable to be used in the probe device of present invention, the TNT affecting unit having a tip portion defining a circular arc segment and a substantially straight segment extending from the distal end of the circular arc segment; Fig. 6 exemplifies a configuration of the probe device of the present invention utilizing multiple electrodes, some carried by the TNT affecting unit and some being placed on an outer surface of the grip tube;

Fig. 7 shows yet another example of the probe device of the present invention utilizing a grip member of a varying cross section; Fig. 8 illustrates some features of the probe of the present invention; and

Fig. 9 illustrates an example of a medical probe device of the present invention utilizing a plurality (generally at least two) probes bundled together. DETAILED DESCRIPTION OF THE INVENTION

Fig. 1 schematically illustrates a conventional implanted deep brain stimulation system. The present invention may advantageously be used in such system to facilitate precise location of brain stimulating elements (electrodes) with respect to a brain region of interest.

Referring to Fig. 2A, there is schematically exemplified a side view of a probe device 200 of the present invention. Generally, the probe device of the present invention is a single- or multi-probe device. In the present example, the single-probe configuration of the device is shown. Probe device 200 includes two elements: a tube- like grip member 220, and a target neural tissue (TNT) affecting unit 240, which is permanently threaded through grip tube 220. The grip member may be flexible or rigid or may include a combination of flexible and rigid portions. The TNT affecting unit extends along the grip tube thereinside, and has a tip portion 245 plastically bent at fabrication to a predetermined shape. In this particular example, tip portion 245 is plastically bent into a segment of a circular arc.

The cross sectional dimensions of the TNT affecting unit and of the grip tube are such that TNT affecting unit 240 is movable with respect to tube 220 to allow its projection out of the tube and its rotation relative to the tube. The movement of TNT affecting unit 240 enables it to at least partially project outside grip tube 220. Manipulating the movement of unit 240 to project out of tube 220 results in the bending of the projecting part 246. In the example of Fig. 2 A, the pre-bent tip portion 245 of TNT affecting unit 245 is completely deployed.

Probe 200, i.e., the grip tube with the TNT affecting unit permanently threaded therethrough, may be permanently left in situ. The configuration of the probe of the present invention (e.g., probe 200 of Fig. 2A) allows for axial and angular adjustability of the location of the tip portion 245 (e.g. its projecting part 246) and enables correction of its location inside the target tissue, be it during the placement procedure or later in the course of the patient's life, without a repeat surgical procedure. After returning to normal life, the patient is periodically called to the clinic for the pathology and the TNT affecting unit's tip location check, which may be followed by tip location correction procedure if necessary. No repeat surgical procedure is required. This feature of the present invention may be referred to as 'dynamic accuracy'. It is the ability to accurately reach a desired locus, and maintain this accuracy even if and when the locus moves with time, with no repeat surgical procedure.

Hence, such axial and angular adjustability of the distal end location allows for fine-tuning of the probe location inside the target tissue, as well as enables circumvention of critical tissue during the probe insertion, hi such a case, the probe is to be inserted with an offset to the target tissue, and then the TNT affecting unit tip can reach the target tissue from the side, due to the tip's curvature. For instance, local delivery of therapeutic agents to the brain, such as chemotherapeutic and other drugs, DNA material, or imaging contrast agents, may require placement of a delivery catheter (a shunt) along the longitudinal axis of a nucleus or neural structure. It may not be possible or safe to insert the catheter along this desired axis with a straight trajectory from the skull surface, hi these circumstances, the shunt may be inserted through a safe trajectory to one side of the desired target site, and then the TNT effecting unit's bent tip can be employed to reach the target, within the scope of the present invention. Generally, for as long as the TNT affecting unit is completely housed within the tube's lumen, thus being in its undeployed state, its bent tip segment is forced to take a shape similar to that of the longitudinal dimension of the tube's lumen. At the beginning of the probe placement procedure, the probe is in the undeployed configuration and is placed inside the patient's body, e.g. in the brain, for example through an insertion tube or cannula (generally known in the art). Generally, the probe device of the present invention may not need any additional tube (e.g. the cannula that is currently in use) but inserted into the body independently with the grip tube serving the guiding purpose similar to the cannula. When the distal end of grip tube (with the undeployed TNT affecting unit) reaches the right location relative to the target tissue, an operator manipulates (pushes) the TNT affecting unit relatively to the grip tube. Consequently, the bent tip of the TNT affecting unit can be partially or fully deployed out of the grip tube. By adjusting the degree of the tip deployment out of the grip tube, as well as rotating the TNT affecting unit relatively to the tube while the probe is in the undeployed state, and pushing or pulling the entire probe into or out of the tissue, fine- tuning of the location of the TNT affecting unit is achieved. It should be noted that the grip tube is preferably rigid enough so as not to buckle under the tissue pressure if during the procedure its distal end needs to move further into the tissue, and not to buckle during 'pull back' of the TNT affecting unit into the grip tube at the conclusion of the procedure.

It is important to note that, since the main function of the grip tube is to grip the TNT affecting unit, while an insertion tube if any is used for inserting and guiding the probe, the grip tube's wall can be thinner than that needed in case the grip tube also serves as an insertion tube cannula. In case the additional insertion tube is used, it is the insertion tube, and not the grip tube, that needs to be sufficiently rigid to advance against the tissue resistance. Also, the fact that the TNT affecting unit is permanently located inside the grip tube contributes to the grip tube's rigidity and strength, hence allowing for a thinner grip tube wall.

As indicated above, in the example of Fig. 2A, tip portion 245 of TNT affecting unit 240 has pre-bent shape of any curve, including the arc of a circle. This shape allows for the tip's movement in and out of grip tube 220 without laterally cutting through the tissue, thus minimizing damage to the tissue. Furthermore, the circular arc shape prevents the application of any lateral force on the arc segment by the surrounding tissue during deployment, thus facilitating precise placement of the arc's distal tip at the intended location. The circular arc shape is the only geometrical shape that offers such features. As the TNT affecting unit's tip emerges out of the tube it advances into the tissue, assuming its final shape. The tip's momentarily movement can be represented as a sum of two translational vectors: one is a lateral movement (i.e. movement of the tip sideways relatively to its longitudinal axis), and the other is a reciprocating (puncture- like) movement (i.e. movement of the tip along its longitudinal axis). The former type of movement (lateral) can damage the surrounding tissue, which is especially important in the case of brain tissue. This movement causes the tissue to be pushed aside and/or cuts through it. Furthermore, lateral movement involves greater mechanical resistance to the TNT affecting unit tip by the surrounding tissue, an effect which may cause unpredictable bending of the tip. This latter effect, in turn, may impair the accuracy of placement of the TNT affecting unit tip inside the target tissue. For these reasons, it would be advantageous to use the TNT affecting unit with a tip portion having such a pre-bent shape that would involve mim^'mal lateral movement during deployment and maximal puncture-like (axial) movement. This desired shape is a segment of a circular arc, e.g., a quarter of a circular arc, a half of a circular arc, or any other circular arc segment. Thus, the above-described probe design of the present invention is advantageous over the probes known in the art, because it enables safer and less traumatic initial placement of the probe, as well as safer and less traumatic correction of the location of the TNT affecting unit tip in the target tissue after implantation, according to varying clinical needs.

It should be noted that, common for example of the probe design of the present invention, the probe can be placed into the tissue with minimal side effects of an invasive surgical procedure. The probe (grip tube with TNT affecting unit) can be guided and inserted to its place through any of the currently used tubes, or cannulas as they are often referred to, which are inserted into the patient's body, and are used to guide other tools to the target tissue, only to be removed at the end of the placement procedure.

There is an advantage in using a probe that can be quickly inserted, to a location that is in proximity to the target spot, and then refining the location of the probe's tip while in-situ specifically when this can be done outside of the operating room. In those cases where the probe remains inside the patient's body for a long duration, there is also an advantage to occasional correction of the location of the probe's tip, so as to assure its long-term clinical efficacy.

Figs. 2B to 2D illustrates operational steps in manipulating the probe device (e.g., that of Fig. 2A) to adjust the location of the distal end of the TNT affecting unit with respect to the target tissue. Fig. 2B shows an inoperative or undeployed state of a TNT affecting unit 240, not projecting outside a grip tube 220 at the tube's distal end. As shown, the opposite end of unit 240 projects outside the tube and can be used for manipulation purposes. As also shown in the figure, unit 240 has a bent tip portion 245, which in its undeployed state presents a straight portion of the entire unit 240. In this specific but not limiting example, the grip tube has substantially constant cross- sectional dimensions all along the tube. The cross-sectional dimension (diameter) of the lumen of the TNT affecting unit 240 is only slightly smaller (e.g. 10% smaller) than the diameter of tube 220. Fig. 2C shows a result of the unit 240 movement along the tube's axis: a part 246 of a bent tip portion 245 projects outside the tube. Fig. 2D shows a further projected state (completely deployed state) of the bent tip portion 245. In this example, the tip portion is plastically bent at fabrication to an arc-like shape. Fig. 2E illustrates some features of the probe device of the present invention. As shown, the probe enables refinement of the TNT affecting unit tip location (during a minimally invasive procedure), as well as correction of the tip's location (after the procedure is completed). This is achieved by angular (in all spatial directions) and axial (along the longitudinal dimension of the probe) manipulation of the tip's position from the outside. An appropriate combination of these movements of unit 240 allows for reaching by its distal end any point within a certain radius (defined by the length of the tip portion, e.g., of several millimeters or even several centimeters), from the grip tube distal end, without altering the lateral or angular position of the grip tube i.e., at a given position of the grip tube). A volume 250 is that covered by all possible locations of the distal end of the tip portion 246 obtainable with the probe design. It should be understood that possible locations are those defined by a relative movement between the TNT affecting unit and grip tube along the tube axis at a distance between lines 220L and 220H and a 360° rotation of the TNT affecting unit relative to the tube. It should also be understood that the volume coverable by the TNT effecting unit manipulation is defined by the shape of its tip portion, as well as the cross-sectional profile of the tube's lumen as will be described further below.

In reference to Fig. 3, there is shown a probe 300 according to yet another example of the invention. Probe 300 includes a tube-like grip member 320 (which in the present example is of a certain non-varying diameter), and a TNT affecting unit 340 having a bent tip portion 345. Here, tip portion 345 is bent to an oval-like arc shape. In this example, tip 345 is used for circumvention of a critical tissue region 370 in order to reach a region 380 of the target tissue (region of interest). It is feasible to use such an oval-like arc tip 345 in this case, because of the larger lateral size of region 370 to be circumvented relatively to a distance between regions 370 and 380.

It should be noted that generally TNT affecting unit may be of various shapes, in particular it may be of arc-like shapes of different curvatures and lengths and different elastic properties.

Reference is made to Figs. 4A-4D illustrating another example for a probe 400 of the present invention, in which a grip tube 420 has a slightly larger inner diameter with respect to the diameter of a TNT affecting unit 440 (as compared to the previous example). This allows a tip portion 445 of the TNT affecting unit to partially assume the shape of its initially bent position rather than being straight, and successively shift into its completely bent shape while emerging out of the grip tube. This enables partial deployment (as opposed to full deployment) of the TNT affecting unit's tip and, with it, partial sideway movement of the tip so as to reach a tissue locus that is slightly off the probe's longitudinal axis. This enables further variability in aiming of the TNT affecting unit tip emerging from the grip tube, in other words various additional angles of emergence of the TNT affecting unit tip out of the grip tube can be achieved, due to the tip being not completely straight (due to tip bending) while still inside the tube.

Reference is made to Fig. 5, showing an example of a TNT affecting unit 540 suitable to be used in a probe device of the present invention. Here, unit 540 has a tip portion having a pre-bent arc-like segment (e.g. circular arc) 545 A and a substantially straight segment 545B extendable from the distal end of bent segment 545A. This configuration enables direct aiming (as opposed to offset aiming) at the target region while inserting the probe into the patient's body. Once the distal end of the probe (i.e. that of the grip tube) reaches a distance of several millimeters from the target (normally up to 1 cm), deployment of straight segment 545B out of the grip tube's distal end can begin. This allows for reaching the target loci on the grip tube's longitudinal axis, distally to the tube. However, if straight segment 545B misses the target in the lateral direction, then the whole probe can be pulled backwards, and thereafter TNT affecting unit 540 can be pushed forward, so as to allow its bent segment 545A to emerge out of the tube and thereby direct the straight segment to the target loci off the grip tube's longitudinal axis. It should be noted, although not specifically shown here, that straight segment 545B may be of a certain fixed length, or may be of a varying length (from "zero" to a certain maximal length), for example by making this part 545B of the tip portion a telescopic member. Fig. 6 illustrates some other features suitable to be used in the probe device of the present invention, e.g., probe designs exemplified herein. A probe 600 is shown having a grip tube 620 and a TNT affecting unit 640 (shown in the figure in its partially deployed state). TNT affecting unit 640 carries an electrode at its projectable portion (e.g., distal end). Also, in the present example, grip tube 620 has one or more electrodes - three such electrodes 625A-625C in the present example, arranged in a spaced-apart relationship on its outer surface along the grip tube. In the present example, electrodes 625A-625C are of a ring-like shape. This enables for affecting an additional volume of the target tissue, in addition to that achieved by TNT affecting unit 640. Furthermore, if TNT affecting unit 640 is an electrode to be operated in a bipolar mode, then one electrical pole can reside at the tip of the electrode carried by unit 640 while the other can reside on the outer surface of the grip tube. Generally speaking, in this case the grip tube itself also incorporates functions of a TNT affecting unit. Also in the latter case, pushing or pulling of TNT affecting unit 640 through grip tube 620 changes a distance between electrodes carried by the grip tube and that on unit 640, thus offering a multitude of electrical stimulation patterns.

It should be noted that for DBS and for some other applications, neural stimulation electrodes available in the market are implanted by way of percutaneously inserting into the patient's body an insertion tube ('cannula') that is to be removed at the conclusion of the procedure. Through this tube, the electrode is inserted. When the electrode reaches the target location, the cannula is removed. The same principle often applies to substance delivery shunts. Within the scope of the present invention, the grip tube is primarily used for gripping the electrode or the TNT affecting unit. The two components of the probe, the grip tube and the TNT affecting unit (where the grip tube may by itself carry one or more electrodes), are integral and after being implanted, remain in the patient's body unseparated. The fact that the grip tube remains in the patient's body enables periodic correction of the TNT affecting unit location, by way of a simple non-surgical procedure. Reference is made to Fig. 7 showing schematically yet another example of the invention. Probe 700 includes a grip tube 720 and a TNT affecting unit 740. In this example, the grip tube 720 is configured with its inner lumen 721 geometry of a varying cross-section. Such a varying cross section may be achieved by one of the following configurations: gradually increasing cross-sectional lumen size (not shown here), a step like increase of the cross-sectional size (diameter) - as shown in the figure, or a different shape of the distal end portion (opening) as compared to that of the proximal end (not shown). These configurations enable the tip portion of the TNT affecting unit to begin to assume its bent shape before it emerges out of the grip tube's distal end. Also, this enables partial deployment (as opposed to full deployment) of the tip of TNT affecting unit and, with it, partial sideway movement of the tip so as to reach a tissue locus that is slightly off the probe's longitudinal axis. Such a lumen geometry of the grip tube enables variability in aiming of TNT affecting unit emerging from the grip tube, in other words various angles of emergence of TNT affecting unit tip out of the grip tube can be achieved, due to the tip being not completely straight (due to tip bending) while still inside the tube. The lumen 721 design of grip tube 720 allows adjustment of placement of the TNT affecting unit tip 745 with respect to the target tissue due to varying the bent condition of the TNT affecting unit while moving through the tube. In reference to Fig. 8 there is shown an example of an arrangement 800 for controlling probe's angular orientation. In this case, the angular orientation of a grip tube 820 is defined, inside the patient's body, by using an orientation disc 850 with angular marks, generally at 852, on it. The disc resides outside the patient's body and rests on his skin (e.g. on the skin of the skull, in the case of a DBS application). A proximal segment 848 of TNT affecting unit 840 remains outside the patient's body; in the present example it is bent sideways, in a predetermined direction relatively to the bend of the TNT affecting unit (distal) tip 846. Both ends, proximal and distal, are bent in the same direction, for ease of operator orientation. On the disc's surface that faces away from the skin, there are radial markings — from 0 to 360 degrees. Hence, the operator is able to mark to himself the direction in which the distal tip would bend once it is deployed out of the grip tube's distal end.

Once a TNT affecting unit tip 846 reaches a desired location, it is fixated in this position in respect to grip tube 820. The fixation can be done using any available locking mechanism, e.g., that used in the Medtronic's Activa system. Then, the patient's skull is closed and the location of the TNT affecting unit tip is re-examined and corrected to the extent needed. This latter part of the procedure can be done outside the operating room, e.g. in an MRI suite, which is less costly to use. Thus fast insertion of the probe can be achieved.

Reference is now made to Fig. 9 showing yet another embodiment of the present invention, where a probe device 900 has a multi-probe configuration, formed by at least two probes - two such probes 900A and 900B being shown in the present example, each probe consisting of its own TNT affecting unit 940A, 940B and grip tube 920A, 920B. Probes 900A and 900B are bundled together within a third tubular element, herein referred to as a 'bundling tube' 960. Each of the probes 900A and 900B is free to move axially within the bundling tube 960, independently of the other probe(s). This configuration enables simultaneous placement of multiple TNT affecting units 940A, 940B in the target tissue, in different locations, which are different from one another both in their axial and angular positions. This enables simultaneous coverage of a certain volume of target tissue, which is useful, for instance, in such applications where it is desirable to simultaneously deliver electrical or other energy, or a therapeutic and/or diagnostic substance, including radioactive pellets, to the entire volume. Such a multi-probe device may be used for delivery of at least one of therapeutic and diagnostic substances to a given volume of tissue by way of multiple infusions, or injections, into several different loci within said volume, by way of a single probe device making a single passage leading to the target tissue.

Also, the configuration may be such that at least one of the so bundled probes includes a string threaded through the TNT affecting unit, where a radioactive pellet is tied to the string's distal end, for brachytherapy. The pellet is initially positioned outside the distal tip of the TNT affecting unit, in contact with the tip. Once the pellet is placed by the probe in its clinically desirable location, the probe is pulled out, leaving the pellet in place, tied to the string. Later, when the pellet needs to be removed, it is pulled out of the patient's body by pulling the string. Also, the configuration may be such that at least one of the so bundled probes includes a positive electrode on its TNT affecting unit and at least one other of the probes includes a negative electrode on its TNT affecting unit. This creates a bi-polar electromagnetic field in the target tissue.

It should be noted that the present invention may be used independently or with available systems for various neural-stimulating and substance delivery applications, such as Medtronic' s Activa system for DBS. In the latter case, the Activa tube that is used to guide the electrode during implantation would contain and guide the presently invented probe. The Activa electrode would have to be replaced with the probe of the present invention, which can be made to have the same outside diameter (of 1.27 mm) as the Activa electrode. Other elements of the Activa system, such as the neurostimulator, the extension cord that connects it to the electrode, the mechanism that is used to lock the proximal end of the electrode in place after implantation, and the guiding cannula, would remain the same or would require minimal modifications to utilize the probe of the present invention. The probe of the present invention enables relocation of the TNT affecting unit tip without pulling out and reinserting the cannula.

The probe of the present invention may be supplied to the operator in the following form: the TNT affecting unit is already threaded through the grip tube, with the TNT affecting unit's tip deployed out of the grip tube's distal end, so as to preserve the tip's curved shape during its shelf life.

The probe of the present invention may be used as follows. In the first step, before insertion, the TNT affecting unit is pulled into the grip tube, so as to cause its bent tip to enter into the tube's lumen through the tube's distal end. In the second step, the probe in its undeployed configuration is inserted into a guiding and insertion tube (i.e. 'cannula'), for example into a cannula of any of the available systems. Further, the probe is pushed through the cannula until the probe's distal end emerges out of the cannula's distal end. If it is desired to bypass a critical tissue located in the shortest of possible insertion paths, cannula may be inserted in the tissue with an offset to the target. Knowing the prefabricated geometry (e.g. a circular arc corresponding to a quarter of a circle) of the TNT affecting unit bent tip, optimal position for the grip tube's distal end can be evaluated. If the grip tube distal end is in the optimal position, the target locus within the target tissue will be within geometrical reach of the TNT affecting unit tip. For example, if the TNT affecting unit tip is shaped as a quartile circular arc, with 1 cm radius, then the grip tube's distal end optimal position can be defined (arbitrarily chosen) as a point located 0.5 cm sideways and-\/3 /2 « 0.87 cm proximal to the target locus. Even if during the insertion this optimal position is not achieved, such choice leaves enough room for lateral corrections. In particular, the target neural tissue would still be in the geometrical reach of the TNT affecting unit tip even if a real position of the grip tube distal end would be 0.5cm sideways further; as well as the critical tissue would not be damaged, even if this real position of the grip tube distal end would be almost 0.5cm sideways closer to it.

In the next step, the TNT affecting unit tip is pushed (deployed) out of the grip tube. The tip emerges out of the tube's distal end, reassuming its pre-fabricated bent form. If the tip is of a circular arc shape, it pierces into the tissue without making any movement lateral to the tissue (without cutting the tissue), and without being subjected to any lateral force by the surrounding tissue. Thus damage to the tissue can be minimized, and precision of tip placement can be maximized. The volume of tissue that can be reached can be extended in the axial dimension by pulling the TNT affecting unit back into the grip tube and moving the entire probe proximally or distally, as needed, while the TNT affecting unit is entirely housed within the grip tube, and then pushing the unit out one again.

Claims

CLAIMS:

1. A medical probe comprising a structure, which is formed by a tube-like grip member carrying a target neural tissue (TNT) affecting unit; the TNT affecting unit being permanently threaded through the tube-like grip member extending along the grip member thereinside, and having a tip portion, which carries at least one elastic electrode or at least one substance delivery elastic shunt, and which is plastically bent into a predetermined shape; the grip member having a cross-sectional dimension such as to allow movement of the TNT affecting unit relative to the grip member while substantially preventing bending of the TNT affecting unit or a part thereof located inside the tube-like grip member, such that the TNT affecting unit permanently resides within the grip member with a small space between the TNT affecting unit and the grip tube lumen, the mass of the TNT affecting unit itself thereby contributing to the strength of the probe structure and to its resistance to buckling during pull-back; the probe structure being thereby adapted for operating the TNT affecting unit to be at least partially projecting outside the grip tube resulting in the bending of the projecting part of the tip portion, thus allowing fine-tuning of the tip location inside the target tissue by providing axial and angular adjustability of the tip location, thus enabling periodic correction of the tip location inside the target tissue, during the placement procedure or later in the course of the patient's life, without a repeat surgical procedure.

2. The probe according to Claim 1, wherein said predetermined shape defines an arc-like segment.

3. The probe according to Claim 2, wherein said arc-like segment is the segment of a circular arc.

4. The probe according to Claim 2 or 3, wherein said predetermined shape defines a substantially straight segment extending from a distal end of the arc-like segment.

5. The probe according to Claim 4, wherein said substantially straight segment has a certain fixed length.

6. The probe according to Claim 4, wherein said substantially straight segment has a variable length, allowing it to be extendable from the distal end of the arc-like segment to a desired length.

7. The probe according to Claim 6, wherein said substantially straight segment is configured as a telescopic member of the variable length.

8. The probe according to any one of preceding Claims, wherein inner cross-sectional dimensions of the grip tube and cross-sectional dimensions of the TNT affecting unit are selected so as to enable the TNT affecting unit to be partially bent while in the grip tube according to its initial bent shape and successively reach the complete bent shape as it is being projected out of the grip tube.

9. The probe according to any one of preceding Claims, wherein a cross- sectional dimension of the TNT affecting unit is slightly smaller than the inner cross- sectional dimensions of the tube-like grip member, thereby enabling minimization of an outer cross-sectional dimension of the grip member while still allowing free axial movement of the TNT affecting unit thereinside.

10. The probe according to Claim 9, wherein the cross-sectional dimension of the TNT affecting unit is about 10% smaller than the inner cross-sectional dimension of the tube-like grip member.

11. The probe according to Claim 9 or 10, wherein the lumen of the grip member has a certain substantially constant inner cross-sectional dimension all along the grip member.

12. The probe according to any one of Claims 1 to 11, wherein the lumen of the grip member has a varying cross-section along a longitudinal axis of its distal end portion.

13. The probe according to any one of Claims 1 to 11, wherein the lumen of the grip member has a cross-section increasing along a longitudinal axis of the lumen towards its distal end portion, thereby causing variation of the bent condition of the TNT affecting unit while moving it through the grip member, thus allowing adjustment of the placement of the tip portion of the TNT affecting unit with respect to the target tissue.

14. The probe according to Claim 12 or 13, wherein the lumen of the grip member has one of the following configurations: has gradually increasing cross- sectional size towards its distal end; and has a step like change of the cross-sectional size such that said size at the distal end is larger than at the proximal end.

15. The probe according to any one of preceding Claims, wherein a length of said tip portion of the TNT affecting unit is in a range from a few millimeters to a few centimeters.

16. The probe according to Claim 15, wherein the length of said tip portion of the TNT affecting unit is up to 2-3 centimeters.

17. The probe according to any one of preceding Claims, wherein a cross- sectional dimension of the TNT affecting unit is about 0.5- 5 mm.

18. The probe according to any one preceding Claims, wherein at least a part of the tip portion of the TNT affecting unit is made of a material opaque to certain external radiation, thereby enabling use of medical imaging modality for intra-operative or post-operative procedures.

19. The probe according to any one of preceding Claims, wherein the grip member carries at its outer surface at least one electrode.

20. The probe according to any one of preceding Claims, wherein the grip member and the TNT affecting unit are made of the same material, the grip tube being substantially thick to force the pre-bent TNT affecting unit into a straight shape thereof while it is housed within the grip member.

21. The probe according to any one of Claims 1 to 19, wherein the grip member is made of a material that is less elastic than material of the TNT affecting unit, the grip member therefore being adapted to force the pre-bent TNT affecting unit into a straight shape while it is housed within the grip member.

22. The probe according to any one of preceding Claims, wherein the TNT affecting unit is configured as a substance delivery shunt and is made of plastic material, thereby applying weaker bending force on the grip member while housed within it.

23. A probe according to any one of preceding Claims, configured for placement of radioactive pellets in a tumor, the pellets being tied to threads and inserted through the lumen of the TNT affecting unit.

24. A probe according to any one of preceding Claims, wherein the distal tip of the TNT affecting unit is made of radioactive material, such as iridium, used to apply radiation therapy to a tumor.

25. A probe according to any one of Claims 1 to 23, wherein the distal tip of the TNT affecting unit is a hyperthermal probe configured for delivering heat to tissue in order to kill pathological cells.

26. A probe according to any one of Claims 1 to 23, wherein the distal tip of the TNT affecting unit is a hypothermal probe configured to cool down tissue in order to kill pathological cells.

27. A probe according to any one of preceding Claims, where the TNT affecting unit is configured as a syringe.

28. A medical probe device for use in at least one of electrical neural stimulation and lesioning of deep tissue, and local delivery of therapeutic or diagnostic substances to deep tissue, the device comprising one or more of the probes of any one of preceding Claims, thereby enabling treatment of different locations in the tissue via a single path leading to the target tissue.

29. The probe device according to Claim 28, comprising the single probe formed by the grip member carrying the TNT affecting unit.

30. A probe device according to Claim 29, wherein the TNT affecting unit is configured for delivery of at least one of therapeutic and diagnostic substances to a given volume of tissue by way of multiple sequential infusions, or injections, into several different locations within said volume, by way of a single probe making a single passage along the path leading to the target tissue.

31. The probe device according to Claim 28, comprising a bundle of at least two of the probes each formed by the grip member carrying the TNT affecting unit, said at least two probes being mounted within a common bundling tube which is configured such that each of the probes is free to move axially within the bundling tube, independently of the other probes.

32. The probe device according to Claim 28, comprising a bundle of at least two of the probes each formed by the grip member carrying the TNT affecting unit, said at least two probes being mounted within a common bundling tube which is configured such that each of the probes is free to move axially within the bundling tube, independently of the other probes, thereby enabling simultaneous placement of the multiple TNT affecting units within the target tissue, in multiple locations, respectively, which are different from one another in their axial and angular positions relative to the bundling tube.

33. The probe device according to Claim 28, comprising a bundle of at least two of the probes each formed by the grip member carrying the TNT affecting unit, said at least two probes being mounted within a common bundling tube which is configured such that each of the probes is free to move axially within the bundling tube, independently of the other probes, thereby enabling simultaneous placement of the multiple TNT affecting units within the target tissue, in multiple locations, respectively, which are different from one another in their axial and angular positions relative to the bundling tube, thus allowing enables simultaneous coverage of a certain volume of the target tissue.

34. The probe according to Claim 31, wherein at least one of the bundled probes comprises a positive electrode on its TNT affecting unit, and at least one other probe comprises a negative electrode on its TNT affecting unit, thus creating a bi-polar electromagnetic field in the target tissue.

35. A kit for use in electrical neural stimulation and lesioning of deep tissue or local delivery of therapeutic or diagnostic substances to deep tissue or brachytherapy, the kit comprising a set of medical probe devices, each probe device including one or more probes, each probe comprising a tube-like grip member carrying a target neural tissue (TNT) affecting unit, the TNT affecting unit being permanently threaded through the respective grip member extending along the grip member thereinside, and having a tip portion, which carries at least one elastic electrode or at least one substance delivery elastic shunt, and which is plastically bent at fabrication into a predetermined shape, the probe devices of the set differing from each other in at least one of the following: (a) TNT affecting units of different probe devices being plastically bent at fabrication into a different shape; and (b) the tube-like grip members of different probe devices having different profiles of its lumen cross-section.