VISUALIZATION OF 4D ULTRASOUND MAPS
20220409167 · 2022-12-29
Inventors
Cpc classification
A61B8/12
HUMAN NECESSITIES
A61B8/463
HUMAN NECESSITIES
A61B8/5223
HUMAN NECESSITIES
A61B8/485
HUMAN NECESSITIES
A61B8/5261
HUMAN NECESSITIES
G01S15/8925
PHYSICS
G01S7/52071
PHYSICS
A61B8/085
HUMAN NECESSITIES
A61B8/483
HUMAN NECESSITIES
G06T7/30
PHYSICS
International classification
A61B8/00
HUMAN NECESSITIES
A61B8/12
HUMAN NECESSITIES
Abstract
A medical system includes an ultrasound probe for insertion into an organ of a body and a processor. The ultrasound probe includes (i) a two-dimensional (2D) ultrasound transducer array, and (ii) a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ. The processor is configured to (a) using the signals output by the sensor, register multiple ultrasound images of a tissue region, acquired over a given time duration by the 2D ultrasound transducer array, with one another, and (b) generate a map of the tissue region indicative of respective amounts of motion of tissue locations in the tissue region.
Claims
1. A medical system, comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; and a processor, which is configured to: using the signals output by the sensor, register multiple ultrasound images of a tissue region, acquired over a given time duration by the 2D ultrasound transducer array, with one another; and generate a map of the tissue region indicative of respective amounts of motion of tissue locations in the tissue region.
2. The medical system according to claim 1, wherein the processor is further configured to: identify, based on the amounts of motion of the tissue locations, that tissue at one or more of the tissue locations comprises scar tissue; and present the map to a user, with an indication of the identified scar tissue.
3. The medical system according to claim 2, wherein the processor is configured to indicate the identified scar tissue using a graphically encoded level of motion of the tissue.
4. The medical system according to claim 3, wherein the graphically encoded level of motion comprises a color-coded level of motion.
5. The medical system according to claim 2, wherein the processor is configured to identify the scar tissue by comparing the amounts of tissue motion to a threshold value.
6. A medical system, comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; and a processor, which is configured to: using the signals output by the sensor, register multiple ultrasound images of a region of the organ, acquired by the 2D ultrasound transducer array, with one another; isolate inner wall images and outer wall images of the region one from the other; apply different graphical encodings to the inner wall images and the outer wall images; overlay the inner wall images and the outer wall images to generate a combined image; display the combined image to a user; and adjust a transparency of one or both of the overlaid inner wall images and outer wall images.
7. The medical system according to claim 6, wherein the different graphical encodings are different color palettes.
8. The medical system according to claim 6, wherein the inner wall images and outer wall images of the region are an endocardium image and a respective epicardium image of a same portion of a heart.
9. A medical system, comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: an ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; and a processor, which is configured to: using the signals output by the sensor, register multiple ultrasound images of a tissue region, acquired by the ultrasound transducer array, with one another; generate a map of the tissue region, and incorporate in the map an icon indicative of a type of the ultrasound probe used for acquiring the ultrasound images; and present the map to a user with an indication of the type of the ultrasound probe.
10. The medical system according to claim 9, wherein the type of the ultrasound probe is one of an ultrasound probe comprising a one-dimensional (1D) array and an ultrasound probe comprising a two-dimensional (2D) array of transducers.
11. A medical system, comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; and a processor, which is configured to: using the signals output by the sensor, register multiple ultrasound images of a tissue region, acquired by the 2D ultrasound transducer array, with one another; generate an ultrasound image of the tissue region; upload, to a graphical user interface, (i) the generated ultrasound image and (ii) one or more additional images of the tissue region acquired by one or more respective non-ultrasound medical imaging modalities; generate a combined image by weighting respective contributions of the ultrasound image and of the or more additional images; and display the combined image to a user.
12. The medical system according to claim 11, wherein the processor is further configured to adjust the combined image by adjusting the weighting.
13. A medical system, comprising: a display, configured to display images to a user; and a processor, which is configured to: register two or more different representations of a tissue region, acquired in accordance with a medical modality, with one another; generate a combined image by weighting respective contributions of the representations; and display the combined representation to the user using the display.
14. The medical system according to claim 13, wherein the representations comprise electrophysiological maps.
15. The medical system according to claim 14, wherein the electrophysiological maps comprise local activation time (LAT) or bipolar voltage maps.
16. A method, comprising: inserting an ultrasound probe into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; using the signals output by the sensor, registering multiple ultrasound images of a tissue region, acquired over a given time duration by the 2D ultrasound transducer array, with one another; and generating a map of the tissue region indicative of respective amounts of motion of tissue locations in the tissue region.
17. The method according to claim 16, and comprising: identifying, based on the amounts of motion of the tissue locations, that tissue at one or more of the tissue locations comprises scar tissue; and presenting the map to a user, with an indication of the identified scar tissue.
18. The method according to claim 17, wherein indicating the identified scar tissue comprises indicating the identified scar tissue using a graphically encoded level of motion of the tissue.
19. The method according to claim 18, wherein the graphically encoded level of motion comprises a color-coded level of motion.
20. The method according to claim 17, wherein identifying the scar tissue comprises comparing the amounts of tissue motion to a threshold value.
21. A method, comprising: inserting an ultrasound probe into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; using the signals output by the sensor, registering multiple ultrasound images of a region of the organ, acquired by the 2D ultrasound transducer array, with one another; isolating inner wall images and outer wall images of the region one from the other; applying different graphical encodings to the inner wall images and the outer wall images; overlaying the inner wall images and the outer wall images to generate a combined image; displaying the combined image to a user; and adjusting a transparency of one or both of the overlaid inner wall images and outer wall images.
22. The method according to claim 21, wherein the different graphical encodings are different color palettes.
23. The method according to claim 21, wherein the inner wall images and outer wall images of the region are an endocardium image and a respective epicardium image of a same portion of a heart.
24. A method, comprising: inserting an ultrasound probe into an organ of a body, the ultrasound probe comprising: an ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; using the signals output by the sensor, registering multiple ultrasound images of a tissue region, acquired by the ultrasound transducer array, with one another; generating a map of the tissue region, and incorporate in the map an icon indicative of a type of the ultrasound probe used for acquiring the ultrasound images; and presenting the map to a user with an indication of the type of the ultrasound probe.
25. The method according to claim 24, wherein the type of the ultrasound probe is one of an ultrasound probe comprising a one-dimensional (1D) array and an ultrasound probe comprising a two-dimensional (2D) array of transducers.
26. A method, comprising: inserting an ultrasound probe into an organ of a body, the ultrasound probe comprising: an ultrasound probe for insertion into an organ of a body, the ultrasound probe comprising: a two-dimensional (2D) ultrasound transducer array; and a sensor configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array inside the organ; using the signals output by the sensor, registering multiple ultrasound images of a tissue region, acquired by the 2D ultrasound transducer array, with one another; generating an ultrasound image of the tissue region; uploading, to a graphical user interface, (i) the generated ultrasound image and (ii) one or more additional images of the tissue region acquired by one or more respective non-ultrasound medical imaging modalities; generating a combined image by weighting respective contributions of the ultrasound image and of the or more additional images; and displaying the combined image to a user.
27. The method according to claim 26, and comprising adjusting the combined image by adjusting the weighting.
28. A method, comprising: registering two or more different representations of a tissue region, acquired in accordance with a medical modality, with one another; generating a combined image by weighting respective contributions of the representations; and displaying the combined representation to the user.
29. The method to claim 28, wherein the representations comprise electrophysiological maps.
30. The method according to claim 29, wherein the electrophysiological maps comprise local activation time (LAT) or bipolar voltage maps.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0027]
[0028]
[0029]
[0030]
[0031]
[0032]
[0033]
[0034]
[0035]
DETAILED DESCRIPTION OF EMBODIMENTS
Overview
[0036] Embodiments of the present invention that are described hereinafter provide methods and systems that use a probe, such as a catheter, having a two-dimensional (2D) array of ultrasound transducers for producing three-dimensional (3D) or four-dimensional (4D) ultrasound images. In the present context, the term “3D ultrasound image” refers to an ultrasound image that represents a certain volume in three dimensions. The term “4D ultrasound catheter” refers to a catheter incorporating a 2D array of ultrasound transducers. The term “4D ultrasound image” refers to a time series of 3D ultrasound images of a certain volume acquired by the 2D array. A 4D image can be regarded as a 3D movie, the fourth dimension being time. Another way of describing a 4D image (or rendering) is as a time-dependent 3D image (or rendering). Where used in the heart, a 4D ultrasound catheter may be referred to as “4D Intracardiac Echocardiography (ICE)” catheter.
[0037] In the disclosed embodiments, the catheter also comprises an integral location sensor, such as a magnetic position sensor, that is pre-registered with the 2D array. The 2D array produces a 3D sector-shaped ultrasound beam occupying a defined solid angle; (such a beam is referred to herein as a “wedge,” as opposed to a 1D array “fan”). The 2D array is thus able to image a 2D section of an inner wall of an organ, such as of a cardiac chamber. Because of the integral location sensor, the spatial coordinates of every voxel in the imaged section is known based on the known relative position and orientation on the catheter shaft between the location sensor and the 2D array.
[0038] It may be possible to generate a 4D ultrasound rendering, and, at the same time, an electrophysiological (EP) rendering, of a portion of the heart. However, it is difficult for a physician to correlate the two separate renderings.
[0039] Some embodiments of the present invention overlay EP data, such as local activation times (LATs) or bipolar voltages, on a 4D ultrasound image or 3D rendering, the 3D/4D representation generated by a 4D ultrasound catheter. Because the 4D catheter has an integral location sensor and its pre-registration with the 2D array, the two entities, i.e., the EP values and the ultrasound image, are automatically registered in the combined image so that registration of the EP parameters with the ultrasound image is not required.
[0040] For example, the 4D ultrasound image may show 3D details of a wall of a heart chamber, as well as movement of the wall, so that the combined image shows these details as well as the electrical activity (e.g., the EP data). This will be apparent, for example, in a wall tissue region of a scar, where the mechanical movement of the tissue is different from that of surrounding unscarred tissue, and the electrical propagation in the region of the scar is different from that of unscarred tissue. The combined image may enhance a capability of a clinician to diagnose and decide on a treatment of a cardiac problem related to scars. In another embodiment, a user may import strain information from the ultrasound images and use a processor to compare and/or display the imported strain information with the electrical activity. This enables correlation between mechanical and electrical heart functionality.
[0041] Standard ultrasound images of surfaces of the walls of a heart chamber, i.e., the endocardium and the epicardium images, can be acquired. However, the different surfaces are hard to comprehend, even though the images are somewhat displaced in an ultrasound image, as both surfaces depicted in grayscale means it is impossible to clearly see the two surfaces. Typically, the endocardium and epicardium images are obtained by a processor segmenting the volume data acquired by the ultrasound probe. If an anatomical map exists, the processor may use the map to identify the different surfaces.
[0042] Some embodiments of the present invention allow a user of the 4D ultrasound catheter to apply different color palettes to the two images of the surfaces of the chamber wall. This renders the two surfaces clearly differentiable, by, for example, a processor overlaying a colored endocardium image on an epicardium image that is colored differently. The user may also adjust the transparency of the overlay to further enhance the combined image displayed.
[0043] As the ultrasound catheter is registered to the mapping location system, the system can use this pre-acquired knowledge to color the multiple structures (e.g., the endocardium and the epicardium) in the ultrasound image with different color scales.
[0044] Moreover, each area in each of the ultrasound images can be colored with a unique color scale according to its functionality, or used definition, such as using different color palette comprising, for example, warm colors or cold colors. For example, after mapping the right atrium, the ultrasound image area of the right atrium can be colored differently (with different color scales, such as red with different intensity according to the gray levels, or different color palettes, such as warm colors vs. cold colors for the endocardium and the epicardium images).
[0045] Icons for ultrasound catheters do not differentiate between the types of ultrasound catheter used. For example, in contrast to a 1D catheter which produces an ultrasound fan, 2D catheters produce an ultrasound wedge. In an embodiment, to inform a reviewer how ultrasound data was acquired, a processor selects a specific icon to incorporate into an existing 3D surface ultrasound rendering. In this embodiment the processor may display an icon of a 2D catheter producing 4D images, by incorporating a wedge icon in a 3D/4D rendering.
[0046] In many medical procedures, images having different functionalities may be acquired, e.g., using different imaging modalities, and, for comparison purposes, these images may be registered. Since they are registered, the images may be combined with each other so that the different elements on the images may be viewed simultaneously. However, each image typically carries much visual information, so that combining the images may quickly lead to information overload.
[0047] Some embodiments of the present invention provide a graphical user interface (GUI) that allows a reviewer to generate and adjust a combined image by weighting the contributions of the separate images to the combined image. In an example, three available images are to be considered that are all registered one with other (e.g., to a coordinate system of a tracking system): a computerized tomography (CT) image, a magnetic resonance imaging (MRI) image, and an ultrasound (US) image. Using the GUI to weight the CT, MRI and US images, the reviewer combines the three images into one. One disclosed image weighting model, which a GUI may apply using a processor, is based on the assumption that the images are positioned at the apices of a triangle, where the triangle is used as a weighting selector. To this end, the reviewer can move a cursor within the triangle to select the weight applied to each image.
[0048] Note that the different images to be weighted and combined do not necessarily have to be of different modalities. Rather, these images can be different representations of a tissue region acquired by a same medical modality. For example, an EP mapping modality can generate a first representation of LATs in a color map, and a second representation of a bipolar voltages map provided in gray scales. Such a combined EP representation may possess enhanced clinical significance.
SYSTEM DESCRIPTION
[0049]
[0050] Specifically, sensor 52 is configured to output signals indicative of a position, direction and orientation of the 2D ultrasound transducer array 52 inside the organ. A processor of the system is configured to register multiple ultrasound image sections using the signal output by the sensor acquired by the 2D ultrasound transducer array 50, one with the other.
[0051] As seen, distal end assembly 40 is fitted at the distal end of a shaft 22 of the catheter. Catheter 21 is inserted through a sheath 23 into a heart 26 of a patient 28 lying on a surgical table 29. The proximal end of catheter 21 is connected to a control console 24. In the embodiment described herein, catheter 21 is used for ultrasound-based diagnostic purposes, although the catheter may be further used to perform therapy, such as electrical sensing and/or ablation of tissue in heart 26, using, for example, a tip electrode 56.
[0052] Physician 30 navigates distal end assembly 40 of catheter 21 to a target location in heart 26 by manipulating shaft 22 using a manipulator 32 near the proximal end of the catheter.
[0053] In an embodiment, 2D ultrasound-array 50, shown in detail in an inset 25, is configured to image a left atrium of heart 26.
[0054] As seen in an inset 45, ultrasound array 50 comprises a 2D array 50 of multiple ultrasound transducers 53. Inset 45 shows ultrasound array 50 navigated to an ostium 54 of a pulmonary vein of the left atrium. In this embodiment, 2D array 50 is an array of 32×64 US transducers. The 2D array is able to image a section of the inner wall of the ostium. Because of the integral location sensor, and its pre-registration with the 2D array, the spatial coordinates of every pixel in the imaged section are known by the system. An example of a suitable 2D array is described in D. Wildes et al., “4-D ICE: A 2-D Array Transducer With Integrated ASIC in a 10-Fr Catheter for Real-Time 3-D Intracardiac Echocardiography,” in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 63, no. 12, pp. 2159-2173, December 2016, doi: 10.1109/TUFFC.2016.2615602, which is incorporated herein by reference in its entirety.
[0055] Control console 24 comprises a processor 39, typically a general-purpose computer, with suitable front end and interface circuits 38 for receiving signals from catheter 21, as well as for, optionally, applying treatment via catheter 21 in heart 26 and for controlling the other components of system 20. Console 24 also comprises a driver circuit 34, configured to drive magnetic field generators 36.
[0056] During the navigation of distal end 22 in heart 26, console 24 receives position and direction signals from location sensor 52 in response to magnetic fields from external field generators 36. Magnetic field generators 36 are placed at known positions external to patient 28, e.g., below table 29 upon which the patient is lying. These position and direction signals are indicative of the position and direction of 2D ultrasound-array 50 in a coordinate system of the position tracking system.
[0057] The method of position and direction sensing using external magnetic fields is implemented in various medical applications, for example, in the CARTO™ system, produced by Biosense Webster, and is described in detail in U.S. Pat. Nos. 6,618,612 and 6,332,089, in PCT Patent Publication WO 96/05768, and in U.S. Patent Application Publications 2002/0065455, 2003/0120150, and 2004/0068178, whose disclosures are all incorporated herein by reference.
[0058] Exemplary catheters and imaging assemblies that enable deflection and rotation are described in detail in U.S. Pat. Nos. 9,980,786; 10,537,306; and U.S. Patent Publication No. 2020-0061340 A1, whose disclosures are all incorporated herein by reference.
[0059] In some embodiments, processor 39 may be configured to operate array 52 in a “sweeping mode” to image a whole cardiac camber, as described below. In an embodiment, the imaged cardiac chamber (e.g., a left atrium) is presented to physician 30 by processor 39 on a monitor 27, e.g., in as a volume rendering 55.
[0060] Processor 39 typically comprises a general-purpose computer, which is programmed in software to carry out the functions described herein. The software may be downloaded to the computer in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory.
[0061] The example configuration shown in
[0062] Rendering and Visualization of 4D Ultrasound Maps
[0063]
[0064] Using the registration, processor 39 derives a tissue color-coded motion map 244 from the acquisition, comprising a color-coded visualized scarred region 233. The processor distinguishes a scar by estimating that the mechanical movement of the tissue therein is different (typically lower or absent) from that of surrounding non-scarred tissue. In an embodiment, the processor graphically encodes (e.g., marks, or color codes), also in real time, e.g., on the video image that is displayed, the amounts of motion, to distinguish immobile areas that may be scarred tissue.
[0065] In an embodiment, the processor is configured to identify scarred tissue by comparing the level of tissue motion to a threshold value of expected amount of motion of a healthy tissue.
[0066]
[0067] In an embodiment, using location information from sensor 52, endocardium image 270 and its respective epicardium image 272 are extracted from an ultrasound acquisition/conventional image (e.g., the cardiac surfaces shown by images 270 and 272 are isolated from one another using an algorithm). Consider, for example, a scenario in which the catheter is in a cardiac chamber, or a user has selected a point in the chamber, or an anatomical Carto map already exists, and its center mass can be used. In an embodiment, the processor may apply an algorithm that extends a simulated beam ray from the selected point, such that the ray intersects the first surface and then the second border. Existing algorithms that are used today for segmentation of CT and MRI 3D scans can be also utilized, for example multi-thresholding based on statistical local and global parameters, mathematical morphology, and image filtering.
[0068] Subsequently, imaged section 360 is color coded in each of the ultrasound images with a unique color scale according to its functionality (e.g., amount of movement). The color code can be correlated to velocity, strain, voltage, thickness, local activation time and/or using another definition, for example by using different color scales, e.g., warm colors vs. cold colors.
[0069] In the shown example, the user may also adjust the transparency of the overlay 270 to further enhance the combined displayed image.
[0070]
[0071] In the shown embodiment, a region 403 of the surface rendering is made transparent by processor 39, which further incorporates therein icon 404, to show a wedge beam of 2D catheter 21 that was used for the intracardiac acquisition.
[0072]
[0073] In the shown embodiment, GUI 500 allows a reviewer of combined image 508 to select the display weighting that is applied to three images, a computerized tomography (CT) image 504, a magnetic resonance imaging (MRI) 506, and an ultrasound (US) image 502 that are all registered one with the other.
[0074] A disclosed image weighting algorithm 505 used with GUI 500 assumes the images are positioned at the apices of a triangle 507, and a reviewer can move a cursor 509 within the triangle area to select the relative weights w applied to each image. In one embodiment the weights are normalized by the sum of weights that is kept equal to one, ω.sub.CT+ω.sub.MRI+ω.sub.U/S=1. In another embodiment, the weights are normalized by the sum of squares of the weights and kept equal to one, ω.sup.2.sub.CT+ω.sup.2.sub.MRI+ω.sup.2.sub.U/S=1.
[0075] GUI 500 and method of weighting using a triangle area are shown by way of example. Other implementations are possible, for example, using a circle or a polygon to represent the image-weighting space.
[0076] Methods of Visualization of 4D Ultrasound Maps
[0077]
[0078] Next, at a tissue motion map derivation step 604, processor 39 derives a color-coded tissue-motion map that is indicative of scarred tissue regions, such as rendering 244 described in
[0079] At a rendering displaying step 606, processor 39 displays a cardiac tissue motion rendering of step 602 to a user, such as shown with rendering 55 on monitor 27 of
[0080] The flow chart of
[0081]
[0082] Next, processor 39 isolates endocardium and respective epicardium images of a same imaged section, such as images 270 and 272 of imaged section 360, shown in
[0083] In a color-coding step 706, processor 39 applies different color palettes (e.g., red-based and blue-based) to images 270 and 272, for example, to indicate amounts of motion.
[0084] At image overlaying step 708, processor 39 overlays endocardium image 270 on epicardium image 272 to generate a combined image 275.
[0085] Processor 39 displays combined image 275 to a user at a displaying step 710. Finally, at an adjustment step 712, the user adjusts a level of transparency of image 270 to make combined image 275 more visible.
[0086]
[0087] Next, processor 39 derives color coded 3D rendering of cardiac chamber 402, shown in
[0088] At icon incorporation step 806, processor 39 incorporates icon 404 that shows a wedge ultrasound beam, indicating that a 2D ultrasound catheter, such as catheter 21, was used for acquiring the data at step 802.
[0089] Finally, at a displaying step 808, processor 39 displays the icon-incorporated rendering to a user.
[0090]
[0091] Next, processor 39 derives a color-coded US image, such as image 502, of a cardiac region, at an ultrasound imaging step 904.
[0092] At images uploading step 906, processor 39 uploads to GUI 500 US image 502, CT image 504, and MRI image 506. The images comprise a same cardiac region and are registered one with other by processor 39.
[0093] At a combined image generation step 908, processor 39 generates combined image 508 by weighing US image 502, CT image 504, and MRI image 506, using one of the normalizing weighting methods described above.
[0094] At a displaying step 910, processor 39 displays combined image 508 to a user.
[0095] Finally, at an adjustment step 912, the user adjusts the relative weights (e.g., contributions) of images 502 using GUI 500, 504, and 506, ω.sub.U/S, ω.sub.CT, and ω.sub.MRI, respectively, by moving a cursor in GUI 500, as described above, to make combined image 508 more informative.
[0096] Although the embodiments described herein mainly address cardiac applications, the methods and systems described herein can also be used in other body organs. For example, the disclosed technique can be used with transesophageal ultrasound (TEE) devices visualizing the heart. As another example, the disclosed technique may be used for invasive ultrasound lung imaging, and for visualizing liver and kidney.
[0097] It will thus be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and sub-combinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art. Documents incorporated by reference in the present patent application are to be considered an integral part of the application except that to the extent any terms are defined in these incorporated documents in a manner that conflicts with the definitions made explicitly or implicitly in the present specification, only the definitions in the present specification should be considered.