Method of determining target treatment locations
11263745 · 2022-03-01
Assignee
Inventors
Cpc classification
A61B34/20
HUMAN NECESSITIES
A61B5/1076
HUMAN NECESSITIES
A61B5/02007
HUMAN NECESSITIES
International classification
A61B5/02
HUMAN NECESSITIES
A61B34/20
HUMAN NECESSITIES
A61B5/00
HUMAN NECESSITIES
Abstract
A method and system for automatic location of a target treatment structure, such as a pulmonary vein ostium, from an anatomical image. The method includes calculating a most likely path of blood flow through a pulmonary vein based on a cross-sectional area minimization technique and calculating pulmonary vein geometry as a function of length. For example, a pulmonary vein ostium may be located by analyzing a change in pulmonary vein dimensional size or other anatomical factors, such as absolute size. The method may also include determining tissue thickness at the pulmonary vein ostium or other treatment size for treatment dose optimization. The method may be an algorithm performed by a processing unit of a navigation system or other component of a medical system.
Claims
1. A system for determining tissue thickness, the system comprising: a processing unit configured to: determine a thickness of an area of an anatomical structure, the anatomical structure being a target treatment site, the target treatment site being an ostium of a pulmonary vein, the anatomical structure having an inner surface and an outer surface, by calculating a distance between the outer surface and the inner surface of the anatomical structure; determine a treatment energy dose of cryoablation energy for delivery at the anatomical structure, the determined treatment energy dose of cryoablation energy being based at least, in part, on the determined thickness; determine a plurality of planes, each of the plurality of planes having a center and extending across a cross-sectional area of an anatomical structure, the plurality of planes being over a length of the anatomical structure; calculate a surface area of each of the plurality of planes; calculate a difference between surface areas of each pair of adjacent planes of the plurality of planes; and a control unit in communication with the processing unit, the control unit being configured to adjust at least one of a temperature of the treatment energy dose of cryoablation energy and a treatment time duration of the treatment energy dose of cryoablation energy based on the determined thickness.
2. The system of claim 1, further comprising: a navigation system, the navigation system being configured to store an anatomical image of an area of tissue.
3. The system of claim 2, further comprising: a medical device including at least one treatment element and at least one mapping electrode, the at least one mapping electrode being in communication with the navigation system.
4. The system of claim 3, wherein the navigation system further includes: a display; and at least one navigation electrode.
5. The system of claim 4, wherein the processing unit is further configured to: determine a target position for the medical device; and displaying to a user the target position of the medical device on the display of the navigation system.
6. The system of claim 1, wherein the processing unit is further configured to: identify a target treatment site based at least in part on the calculated difference between surface areas of each pair of adjacent planes of the plurality of planes.
7. A system for treating tissue, the system comprising: a processing unit configured to: receive a value representing tissue thickness; determine a treatment energy dose of cryoablation energy based upon the value representing tissue thickness; determine a plurality of planes, each of the plurality of planes having a center and extending across a cross-sectional area of an anatomical structure, the plurality of planes being over a length of the anatomical structure; calculate a surface area of each of the plurality of planes; calculate a difference between surface areas of each pair of adjacent planes of the plurality of planes; and identify a target treatment site based at least in part on the calculated difference between surface areas of each pair of adjacent planes of the plurality of planes.
8. The system of claim 7, wherein the processing unit includes a processing circuitry including a memory and a processor, the memory in communication with the processor.
9. The system of claim 8, further comprising: a navigation system, the navigation system being configured to store an anatomical image of an area of tissue.
10. The system of claim 9, wherein the processing unit is part of the navigation system.
11. The system of claim 9, wherein the processor is further configured to: determine a target position for a medical device, the medical device having at least one treatment element and at least one mapping electrode, the at least one mapping electrode being in communication with the navigation system.
12. A method for ablating tissue comprising: determining tissue thickness; ablating tissue with cryoablation energy based upon the determined tissue thickness; determining a plurality of planes, each of the plurality of planes having a center and extending across a cross-sectional area of an anatomical structure, the plurality of planes being over a length of the anatomical structure; calculating a surface area of each of the plurality of planes; calculating a difference between surface areas of each pair of adjacent planes of the plurality of planes; and identify a target treatment site based at least in part on the calculated difference between surface areas of each pair of adjacent planes of the plurality of planes.
13. The method of claim 12, wherein the determination of tissue thickness further includes determining a center, an inner surface, and an outer surface of an anatomical structure.
14. The method of claim 13, further comprising: determining a target position for a medical device based upon the determined tissue thickness.
15. The method of claim 14, further comprising: adjusting at least one of a temperature of a treatment element and a treatment time based upon the determined tissue thickness.
16. The method of claim 15, wherein the method further comprises: calculating a distance between the outer surface and the inner surface.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) A more complete understanding of the present invention, and the attendant advantages and features thereof, will be more readily understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein:
(2)
(3)
(4)
(5)
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(7)
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(9)
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(12)
DETAILED DESCRIPTION
(13) The method and system disclosed herein allows automatic location of a target treatment structure, such as a pulmonary vein ostium, from an anatomical image. The method includes calculating a most likely path of blood flow through a pulmonary vein based on a cross-sectional area minimization technique and calculating pulmonary vein geometry as a function of length. For example, a pulmonary vein ostium may be located by analyzing a change in pulmonary vein dimensional size or other anatomical factors, such as absolute size. The method may also include determining tissue thickness at the pulmonary vein ostium or other treatment size for treatment dose optimization. The method may be an algorithm performed by a processing unit of a navigation system or other component of a medical system.
(14) Before describing in detail exemplary embodiments that are in accordance with the disclosure, it is noted that components have been represented where appropriate by conventional symbols in drawings, showing only those specific details that are pertinent to understanding the embodiments of the disclosure so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein.
(15) As used herein, relational terms, such as “first,” “second,” “top” and “bottom,” and the like, may be used solely to distinguish one entity or element from another entity or element without necessarily requiring or implying any physical or logical relationship or order between such entities or elements. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the concepts described herein. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes” and/or “including” when used herein, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
(16) Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be further understood that terms used herein should be interpreted as having a meaning that is consistent with their meaning in the context of this specification and the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
(17) In embodiments described herein, the joining term, “in communication with” and the like, may be used to indicate electrical or data communication, which may be accomplished by physical contact, induction, electromagnetic radiation, radio signaling, infrared signaling or optical signaling, for example. One having ordinary skill in the art will appreciate that multiple components may interoperate and modifications and variations are possible of achieving the electrical and data communication.
(18) Referring now to the drawing figures in which like reference designations refer to like elements, an embodiment of a medical system constructed in accordance with the principles of the present invention is shown in
(19) The medical device 16 may be a treatment and/or mapping device. The medical device 16 may include an elongate body 22 passable through a patient's vasculature and/or proximate to a tissue region for diagnosis or treatment. For example, the device 16 may be a catheter that is deliverable to the tissue region via a sheath or intravascular introducer (not shown). The elongate body 22 may define a proximal portion 26, a distal portion 28, and a longitudinal axis 30, and may further include one or more lumens disposed within the elongate body 22 thereby providing mechanical, electrical, and/or fluid communication between the elongate body proximal portion 26 and the elongate distal portion 28.
(20) The medical device 16 may further include one or more treatment elements 34 at, coupled to, or on the elongate body distal portion 28 for energetic, therapeutic, and/or investigatory interaction between the medical device 16 and a treatment site or region. The treatment region element(s) 34 may deliver, for example, cryogenic therapy, radiofrequency energy, ultrasound energy, laser energy, or other energetic transfer with a tissue area in proximity to the treatment element(s), including cardiac tissue. For example, the treatment element(s) 34 may include thermally transmissive regions in thermal communication with a coolant or heat source, thermally transmissive regions in electrically communication with a power source, surface therapeutic elements such as surface radiofrequency electrodes, or the like. Additionally, the device 16 may include more than one type of treatment element 34. In the exemplary system shown in
(21) Alternatively, the device 16 may include one or more treatment elements that are not expandable. For example, the device 16 may be a focal catheter that includes one or more electrodes on the distal portion, or may be a device that includes at least one carrier arm bearing one or more treatment electrodes 34 (as shown in the exemplary system of
(22) The device 16 may also include one or more mapping electrodes 40 that are used by the navigation system 12 to visualize the device 16 on a control unit display and/or a navigation system display. For example, the device 16 shown in
(23) Each mapping electrode 40 and treatment element 34 in communication with a power source may be electrically conductive segments for conveying an electrical signal, current, or voltage to a designated tissue region and/or for measuring, recording, receiving, receiving, assessing, or otherwise using one or more electrical properties or characteristics of surrounding tissue or other electrodes. The electrodes may be configured in a myriad of different geometric configurations or controllably deployable shapes, and may also vary in number to suit a particular application, targeted tissue structure or physiological feature.
(24) Although not shown, the system 10 may include one or more sensors to monitor the operating parameters throughout the system, including for example, pressure, temperature, flow rates, volume, power delivery, impedance, or the like in the control unit 14 and/or the medical device 16, in addition to monitoring, recording or otherwise conveying measurements or conditions within the medical device 16 or the ambient environment at the distal portion of the medical device 16. The sensor(s) may be in communication with the control unit 14 for initiating or triggering one or more alerts or therapeutic delivery modifications during operation of the medical device 16. One or more valves, controllers, or the like may be in communication with the sensor(s) to provide for the controlled dispersion or circulation of fluid through the lumens/fluid paths of the medical device 16. Such valves, controllers, or the like may be located in a portion of the medical device 16 and/or in the control unit 14.
(25) The medical device 12 may include a handle 50 coupled to the elongate body proximal portion 26. The handle 50 may include circuitry for identification and/or use in controlling of the medical device 16 or another component of the system. Additionally, the handle 50 may also include connectors that are mateable to the control unit 14 to establish communication between the medical device 16 and one or more components or portions of the control unit 14. The handle 50 may also include one or more actuation or control features that allow a user to control, deflect, steer, or otherwise manipulate a distal portion of the medical device 16 from the proximal portion of the medical device 16. For example, the handle 50 may include one or more components such as a lever or knob for manipulating the elongate body 22 and/or additional components of the medical device 16.
(26) As used herein, the term “control unit 14” for simplicity may include any system components that are not part of the medical device 16 itself, other than components of the navigation system 12 and the imaging system 18, regardless of whether the component is physically located within or external to the control unit 14. Further, the navigation system 12 may be a standalone system in communication with the control unit 14 or may be contained within or integrated with the control unit 14, even though it is shown as being physically separated from the control unit in
(27) The control unit 14 may include one or more controllers, processors, and/or software modules 64 containing processing circuitry configured to execute instructions or algorithms to provide for the automated operation and performance of the features, sequences, calculations, or procedures described herein and/or required for a given medical procedure. Further, the control unit 14 may include one or more user input devices, controllers, and displays 66 for collecting and conveying information from and to the user.
(28) The navigation system 12 may be any commercially available navigation system suitable for use with the control unit 14, device 16, and type of procedure. As a non-limiting example, the navigation system 12 may include a plurality of navigation electrodes 70, a reference electrode (not shown), and a processing unit 72 that collects and processes signals from the device mapping electrodes 40, and a display 76 that displays to the user the location of the device 12 within the patient's body 78 and/or relative to the target anatomical feature (for example, a pulmonary vein ostium), recommended treatment areas, tissue thickness, or the like. The processing unit 72 may include processing circuitry including a memory and a processor, the memory in communication with the processor and having instructions that, when executed by the processor, configure the processor to perform the calculations and determinations discussed herein. Additionally or alternatively, this information may be displayed on the display 66 of the control unit 14. The navigation system 12 may also include an energy source (not shown) for delivering energy to the plurality of navigation electrodes 70. Alternatively, the navigation system 12 may be in communication with the control unit energy source 60. For example, the processing unit 72 may be configured, programmed, or programmable to perform the calculations and make the determinations discussed in greater detail below to identify an anatomical feature and/or a target location for a medical device. Further, the processing unit 72 may execute software and display a software interface 80 with which the user may interact to make a selection, rotate and flag an image, open folders, control the navigation system 12, or the like. As a non-limiting example, the user may interact with the software interface 80 using a touch screen, a keyboard, a mouse, or other input device.
(29) It will be understood that although the navigation system processing unit 72 is disclosed herein as performing the calculations discussed herein, it will be understood that the calculations may additionally or alternatively be performed by one or more processors 64 within the control unit 14.
(30) As shown in
(31) The processing unit 72 may perform this calculation many times during a procedure, frequently updating the registered location and displaying such to the user so the user can visualize the location of the device relative to the target anatomical feature in real time.
(32) The imaging system 18 may be a computed tomography (CT) system, a magnetic resonance imaging (MRI) system, or other system suitable for creating images of locations within a patient's body. For example, the imaging system may create images in Digital Imaging and Communications in Medicine (DICOM) format. The imaging system 18 may be in communication with and digitally transmit images to the navigation system 12 and/or the control unit 14 for further processing. Alternatively, images recorded by the imaging system 18 may be recorded and transferred to the navigation system 12 and/or the control unit 14 by a user.
(33)
(34) Referring now to
(35) The user may select initial target positions on the segmented image 82 using the software interface 80 (Step 3 in
(36) The processing unit 72 may then calculate a centerpoint 102 within the LA 84 represented by the coordinates (x.sub.C, y.sub.C, z.sub.C) (Step 4 in
(x.sub.C,y.sub.C,z.sub.C)=[¼(x.sub.RS+x.sub.RI+x.sub.LS+x.sub.LI),¼(y.sub.RS+y.sub.RI+y.sub.LS+y.sub.LI),¼(z.sub.RS+z.sub.RI+z.sub.LS+z.sub.LI)] (1)
(37) The user may then select a first or initial anatomical location using the software interface 80 (Step 5 of
(x.sub.0,y.sub.0,z.sub.0)=(x.sub.LS,y.sub.LS,z.sub.LS) (2)
and may then estimate a plane abc 108 that defines the direction of blood flow within the LSPV as:
a(x−x.sub.0)+b(y−y.sub.0)+c(z−z.sub.0)=0 (3)
where (a, b, c) is a vector {right arrow over (v)}.sub.0 normal to the plane abc 108, with the initial guess of the LSPV center 104 being:a,b,c
=
(x.sub.C−x.sub.0),(y.sub.C−y.sub.0),(z.sub.C−z.sub.0)
(4)
As the LSPV is at least substantially tubular (that is, defines a lumen), the LSPV center (x.sub.0, y.sub.0, z.sub.0) is located within the LSPV lumen and not on a portion of tissue. The plane abc 108 may span or extend across the lumen or a cross-sectional area of the LSPV (90), as shown in a, b, c
may extend from LSPV center (x.sub.0, y.sub.0, z.sub.0) toward the LA. Thus, at this stage in the method, vector
a, b, c
may represent an initial estimated direction of blood flow through the LA. In the next steps, vector
a, b, c
is further defined such that vector
a, b, c
defines a plane that has a minimum surface area when measured by the boundary where the plane intersects the anatomical feature (defined by contour S.sub.n). For example, the methods described below in Steps 6-15 are one possible approach for determining the direction of flow corresponding to the direction when the plane abc and the anatomical contour S.sub.n comprise a minimum cross-sectional area of the anatomical feature. However, it will be understood that other mathematical algorithms could additionally or alternatively be used to determine the direction of flow, and the methods described in Steps 6-15 may not be the only way to do so.
(38) The processing unit 72 may then identify a vector d, e, f
lying in plane abc 108 (Step 6 in
d, e, f
may be normal to
a, b, c
, as
a, b, c
is normal to plane abc 108. The vector
d, e, f
may be determined by introducing a slight perturbation in two of the directions and calculating the third. For example, the processing unit 72 may select the two directions having the smallest magnitude represented by
a, b, c
such that {circumflex over (x)} and ŷ are selected if c>a, c>b. For example, small perturbations may be selected around (x.sub.0, y.sub.0, z.sub.0) in the selected directions as in (x.sub.0+Δx, y.sub.0+Δy, z.sub.0). Given the plane abc 108 and new points x.sub.0+Δx and y.sub.0+Δy, the processing unit 72 may calculate Δz such that the following expression is satisfied:
(39)
The vector created by the new point (Δx, Δy, Δz) may lie in the plane abc and be perpendicular to the normal vector a, b, c
with a resulting vector
d, e, f
described as:
d,e,f
=(x.sub.0,y.sub.0,z.sub.0)+t(Δx,Δy,Δz) (6)
(40) Starting at (x.sub.0, y.sub.0, z.sub.0), the processing unit 72 may then increase t until the vector d, e, f
intersects the endocardial surface S.sub.n (for example, an inner wall of the LSPV) (Step 7 in
(41) Referring now to d, e, f
around the vector
a, b, c
by a small degree θ (Step 8 of
.sub.rot=
cos θ+(
×
)sin θ+
(
×
)(1−cos θ) (7) where:
=
d, e, f
and
=
a, b, c
and
.sub.rot is the new rotated vector.
(42) The processing unit 72 may repeat this calculation of (r.sub.i).sub.C in this rotated vector .sub.rot in the new direction from the point (x.sub.0, y.sub.0, z.sub.0) (Step 9 in
(43) When θ has been spanned by 2π radians, or 360°, the processing unit 72 may calculate the surface area A of an area defined by the intersection of plane abc 108 and the endocardial surface S.sub.n according to the following equation (Step 10 in
(44)
where n is the number of angular sweeps performed by the processing unit 72 in executing the algorithm and 0≤θ.sub.i≤2π. The surface area A of an area defined by the intersection of plane abc 108 and the endocardial surface of the pulmonary vein. So, performing this calculation may indicate the shape of the lumen of the pulmonary vein, which may be referred to as the contour, and the cross-sectional size of the pulmonary vein lumen.
(45) Referring now to a, b, c
by perturbing the vector in two orthogonal directions (Step 11 in
.sub.n and the second orthogonal direction may be referred to as the yaw direction
.sub.y. Both the pitch and yaw directions may lie in the plane abc and also be orthogonal to each other. The pitch direction may be chosen as the initial vector
d, e, f
calculated previously in the Step 6 of the method. The yaw direction can then be calculated by taking the cross product according to the following equation, or by another equivalent method:
a,b,c
×
d,e,f
=
m,n,p
(9)
This new vector m, n, p
lies in the plane abc and is perpendicular to both
a, b, c
and
d, e, f
.
(46) The processing unit 72 may rotate vector a, b, c
in the pitch direction by an amount+θ.sub.p using equation (7) (Step 12 in
a, b, c
.sup.i+1. The processing unit may repeat the calculation described above, or an equivalent method, to calculate a new area of the adjustment plane (abc).sup.i+1 intersecting the endocardial surface S.sub.n. The processing unit 72 may then rotate vector
a, b, c
in the pitch direction by −θ.sub.p using equation (7) to define a second adjustment plane (abc).sup.i−1 and second adjustment vector
a, b, c
.sup.i−1. The processing unit 72 may then calculate a new area of the second adjustment plane (abc).sup.i−1 intersecting the endocardial surface S.sub.n, as discussed above. The processing unit 72 may then select the first updated vector
a, b, c
from the adjustment vectors
a, b, c
.sup.i (the original vector
a, b, c
),
a, b, c
.sup.i+1, and
a, b, c
.sup.i−1 where the surface area A is minimized (i.e., where the surface area A is smallest). The direction corresponding to the minimum surface area is an estimate for the most likely directly of flow at that point in the anatomical structure.
(47) The processing unit 72 may rotate the updated vector a, b, c
according to equation (7) around the yaw direction by an amount of +φ.sub.y and −φ.sub.y to determine vector
a, b, c
.sup.j+1 and vector
a, b, c
.sup.j−1, respectively (Step 13 in
a, b, c
from vectors
a, b, c
.sup.j,
a, b, c
.sup.j+1, and
a, b, c
j.sup.−1 where the surface area A is minimized.
(48) The processing unit 72 may repeat Steps 12 and 13 iteratively until the surface area A is minimized (Step 14 in a, b, c
.sup.i may now be normal to the plane 108′ that is perpendicular to the most likely direction of blood flow, the plane being defined as follows:
ax+by+cz+d=0 (10)
Plane a, b, c 108 and original vector a, b, c
represented an estimated direction of blood flow through the LSPV. At this stage in the method, however, the direction of blood flow may be more certain and plane a, b, c may be adjusted slightly (the adjusted plane being represented as 108′ in
a, b, c
may also be adjusted slightly (the adjusted or updated vector being represented as
a, b, c
.sup.i in
(49) Referring now to
(50) Referring now to a, b, c
′a, the coordinates of the location being calculated by the following equation:
(x.sub.1,y.sub.1,z.sub.1)=(x.sub.0,y.sub.0,z.sub.0)+ta,b,c
(11)
where t indicates a physical distance from x.sub.0, y.sub.0, z.sub.0 along the vector a, b, c
.
(51) The processing unit 72 may repeat Steps 6 through 16 using the new location 110a (x.sub.1, y.sub.1, z.sub.1) as the initial guess of the LSPV center (Step 17 in a, b, c
′a using coordinates (x.sub.1, y.sub.1, z.sub.1), a new location 110b being defined from location 110a along vector
a, b, c
′b using coordinates (x.sub.2, y.sub.2, z.sub.2), new location 110c being defined from location 110b along vector
a, b, c
′c using coordinates (x.sub.3, y.sub.3, z.sub.3), so on until n locations have been defined.
(52) Using this method, the processing unit 72 may calculate the direction of blood flow in each pulmonary vein (Step 18 in a, b, c
′a−
a, b, c
′n determined from the new starting locations 110a-110n may together show an overall direction of blood flow throughout the pulmonary vein.
(53) Further, the areas centered at each centroid point may be used by the processing unit 72 to estimate the cross-sectional area of the pulmonary vein (Step 19 in
(54) Finally, the processing unit 72 may determine or estimate the ostium or other ablation target for each pulmonary vein (Step 20 in
(55) Additionally, the displayed anatomical features may also be used to determine where a particular treatment device may be used, based on the geometry of the treatment device and the anatomical feature. For example, using the methods described in U.S. Ser. No. 15/259,683, the entirety of which is incorporated herein by reference, one or more target “landing zones” for treatment elements or other parts of the medical device 16 may be determined and displayed to the user. For example, the processing unit 72 may determine a distal target site 116a and a proximal target site 116b to be used as navigation targets when maneuvering the device 16 to a treatment area.
(56) The success of a treatment may depend on delivering the optimal dose of treatment energy to the target tissue site, which may in turn depend on tissue thickness at the target tissue site. With the pulmonary vein ostium 114 identified, the thickness of the pulmonary vein can be determined by calculating the distance between the endocardial surface dS.sub.n, or inner pulmonary vein surface, and the epicardial surface dS.sub.p, or outer pulmonary vein surface, along the pulmonary vein ostium identified using the method described above (Step 21 in a, b, c
using the following formula:
T=dS.sub.p−dS.sub.n (12)
Further, the pulmonary vein contour C may be swept along pulmonary vein and the calculation made at every location, which may provide an estimate of tissue thickness along the length of the pulmonary vein and at the ostium 114. The calculated thicknesses may be used to determine optimum treatment energy dose. As a non-limiting example, if cryoablation is used, the control unit 14 may adjust the temperature of the treatment element(s) 34 and/or treatment time such that thicker tissue is treated at a lower temperature and/or for a longer period of time than thinner tissue.
(57) As will be appreciated by one of skill in the art, certain concepts described herein may be embodied as a method, data processing system, and/or computer program product. Accordingly, these concepts described herein may take the form of an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. Furthermore, the disclosure may take the form of a computer program product on a tangible computer usable storage medium having computer program code embodied in the medium that can be executed by a computer. Any suitable tangible computer readable medium may be utilized including hard disks, CD-ROMs, electronic storage devices, optical storage devices, or magnetic storage devices.
(58) It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described herein above. In addition, unless mention was made above to the contrary, it should be noted that all of the accompanying drawings are not to scale. A variety of modifications and variations are possible in light of the above teachings without departing from the scope and spirit of the invention, which is limited only by the following claims.