Abstract:
A method, system and apparatus for manufacturing anatomically and functionally accurate soft tissue phantoms with multimodality characteristics for imaging studies is disclosed. The organ/tissue phantom is constructed by filling a container containing an organ having inner vasculature therein with a molten elastomeric material; inserting a plurality of rods with bumps thereupon through the container and the organ; allowing the molten elastomeric material to harden and cure; removing the organ; replacing the organ with a plurality of elastomeric segments; and removing an elastomeric segment and replacing the void created thereupon with molten PVA to create a PVA segment; allowing the molten PVA segment to harden and cure; and repeating the creation of PVA segments until all the elastomeric segments have been removed, such that each successive molten PVA segment adheres to and fuses with the previous hardened PVA segment so as to form an approximately complete organ phantom cast. The organ/tissue phantom is completed by inserting the approximately complete organ phantom cast inserting upside-down into a fixture made from the bottom-most elastomeric segment, which contains molten PVA; and allowing the molten PVA to harden and cure.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to medical organ phantoms and, more particularly, to a method, apparatus and system for creating and/or generating anatomically and functionally accurate soft tissue phantoms with multimodality characteristics for imaging studies. 
       BACKGROUND OF THE INVENTION 
       [0002]    Researchers working with CT, X-ray, MRI, PET/SPECT, ultrasound, optical imaging, electromagnetic imaging (e.g., RF, microwave, THz) and other imaging technologies require imaging targets. These targets are needed, inter alia, to test and validate imaging hardware and software performance. Imaging studies generally require use of anatomically-accurate and functionally-accurate organ phantoms. These “phantoms” allow for lengthy investigations for validation and testing of imaging equipment without the necessity of human patients or other living models, thereby avoiding unnecessary exposure to X-ray and other risks. Phantoms vary in complexity depending upon a various parameters, e.g., imaging requirements. In some situations, simple cylinders or other rudimentary structures may suffice, but in other situations, anatomically-accurate, functionally-accurate, dynamic, multi-modal imaging characteristics are required. Phantoms with high degrees of functionality can employ materials that closely approximate the mechanical and/or chemical properties of tissue while maintaining MRI, X-ray, CT, PET/SPECT, ultrasound imaging and other imaging qualities. 
         [0003]    Anatomical accuracy for purposes of imaging targets has been difficult to achieve in practice due to the enormous complexity of organ geometry. Commercially-available phantoms generally offer rigid anatomical representations of the organ-of-interest, without dynamic tissue-mimicking biomechanical deformations/functionalities or imaging characteristics that allow for multimodality testing (e.g., MR, CT, X-ray, US, PET/SPECT). 
         [0004]    What is needed, but has heretofore not been achieved, are phantoms that exhibit a range of properties that closely mimic the behaviour of biological tissue in terms of image appearance, mechanics and/or chemical characteristics. The present invention describes a novel phantom technology that addresses the shortcomings of conventional imaging targets, while allowing the creation/generation of high-functionality imaging targets. The imaging targets/phantoms that are created/generated according to the present invention offer a host of significant advantages, particularly in test environments, e.g., environments involving testing of multimodality hardware and software for reconstruction, segmentation, registration, quantification and/or visualization. 
       SUMMARY OF THE INVENTION 
       [0005]    The present invention provides advantageous methods, systems and apparatus for creating/generating an anatomically-correct tissue or organ phantom. Exemplary phantoms generated according to the present invention offer tissue-mimicking mechanical properties that are reproduced directly from an original structure, e.g., a human organ. According to exemplary embodiments, the phantom is constructed by filling a container containing an organ or other tissue structure of interest having inner vasculature with a molten elastomeric material; inserting a plurality of rods through the container and the organ/tissue; allowing the molten elastomeric material to harden and cure; removing the organ/tissue; replacing the organ/tissue with a plurality of elastomeric segments; removing an elastomeric segment; and replacing the void created thereupon with a molten material, e.g., polyvinyl alcohol (PVA), to create a PVA segment. The molten PVA segment is generally allowed to harden and cure, and the foregoing steps are repeated so as to create additional PVA segments until all elastomeric segments have been removed. 
         [0006]    Each successive molten PVA segment generally adheres to and fuses with the previous hardened PVA segment so as to form a substantially complete organ/tissue phantom cast. In exemplary embodiments, organ/tissue phantoms may be formed by positioning the organ/tissue phantom cast in a fixture or other stabilizing structure, e.g., upside-down. A range of elastomeric materials may be used according to the present disclosure. In exemplary embodiments, the elastomeric material is silicone rubber. 
         [0007]    Through the technique disclosed herein, highly accurate and useful organ/tissue phantoms may be created in an efficient and reliable manner. Most organs and anatomical/tissue structures may be effectively replicated for phantom purposes, such organ/tissue phantoms being characterized by properties that closely mimic the anatomical characteristics of the underlying organ/tissue. In a particularly preferred embodiment of the present disclosure, a phantom human heart may be created for use in imaging studies or the like. 
         [0008]    Additional features, functions and benefits of the disclosed systems, methods and apparatus will be apparent from the detailed description which follows, particularly when read in conjunction with the appended figures. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]    For a more complete understanding of the present invention, reference is made to the following detailed description of exemplary embodiments considered in conjunction with the accompanying drawings, in which: 
           [0010]      FIG. 1  is a schematic diagram of a heart phantom produced using a prior art “Lost Wax” method; 
           [0011]      FIG. 2  is an FD10 X-Ray image of a “doped” PVA phantom constructed according to the method of the present invention; 
           [0012]      FIG. 3  is a 3D ultrasound image of a “doped” PVA phantom constructed according to the method of the present invention; 
           [0013]      FIG. 4  is a schematic diagram of an exemplary heart phantom being constructed according to the method of the present invention, wherein a human heart is placed in a container which is then filled with silicone rubber; 
           [0014]      FIG. 5  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein a plurality of rods are thrust through one side of the mould container; 
           [0015]      FIG. 6  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the heart has been removed and the blood volume moulds have lost registration relative to an outer mould; 
           [0016]      FIG. 7  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the plurality of rods are reinserted into their previous locations through the mould container to restore registration; 
           [0017]      FIG. 8A  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the mould container is filled with one segment of silicone rubber; 
           [0018]      FIG. 8B  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the mould container is filled with a second segment of silicone rubber; 
           [0019]      FIG. 8C  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the mould container is filled with a third segment of silicone rubber; 
           [0020]      FIG. 8D  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein the mould container is filled with a fourth segment of silicone rubber; 
           [0021]      FIG. 9  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein segments of silicone rubber are removed and replaced with molten PVA; 
           [0022]      FIG. 10  is a schematic diagram of an exemplary heart phantom being constructed according to the disclosed method, wherein all silicone rubber segments have been removed and replaced with molten and solid PVA (newly added molten PVA fuses with previously added/solid PVA); 
           [0023]      FIG. 11  is a photograph of a top view of an exemplary PVA heart cast which is removed from the registered mould with the hard plastic moulds in registration; 
           [0024]      FIG. 12A  is a photograph of a front side view of the exemplary PVA heart cast of  FIG. 11  with the hard plastic moulds removed; 
           [0025]      FIG. 12B  is a photograph of a top view of the exemplary PVA heart cast of  FIG. 11  with the hard plastic moulds removed; 
           [0026]      FIG. 13  is a schematic diagram showing completion of a PVA heart cast while it is maintained in a mounting fixture; 
           [0027]      FIG. 14  is a photograph of a perspective view of an exemplary mounting fixture; 
           [0028]      FIG. 15A  is a photograph of a perspective view of a completed PVA heart cast in the mounting fixture of  FIG. 14 ; 
           [0029]      FIG. 15B  is a photograph of a side view of a completed PVA heart cast in the mounting fixture of  FIG. 14 ; 
           [0030]      FIG. 16  is a schematic view of a completed phantom heart attached to the mounting arrangement for permitting robust mechanical manipulation by servo motors under the control of an external controller; 
           [0031]      FIG. 17  is a photograph of an exemplary test setup shown schematically in  FIG. 16 , in which the mechanical manipulation of the heart phantom is synchronized to an ECG waveform on the display of a laptop computer; 
           [0032]      FIG. 18  is a photograph of the test setup shown in  FIG. 17  with the addition of ultrasound, X-Ray, and Aurora imaging equipment; and 
           [0033]      FIG. 19  is a photograph of an exemplary test setup used for calibration of the 3D space surrounding a heart phantom for use in the mechanical manipulation test fixtures of  FIGS. 16-18 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0034]    The methods, systems and apparatus of the present invention provide anatomically-correct organ/tissue phantoms with tissue-mimicking mechanical properties. The disclosed phantoms are advantageously reproduced directly from an original organ/tissue, e.g., a human heart. Although the present invention is described in terms of producing an anatomically accurate heart phantom, the present invention can be used to produce phantoms of other internal organs, tissues and anatomical structures, both animal and human. 
         [0035]    With reference to  FIG. 1 , a schematic diagram of a heart phantom produced using the prior art “Lost Wax” method is shown, generally indicated at  10 . The positive replica  10  includes a left segment  12  and a right segment  14  which define heart walls  16 ,  18  and a central septum  20 . The segments  12 ,  14  and the septum  20  are formed from a negative external mould  22  and internal blood volume casts  24 ,  26 . Although the internal casts  24 ,  26  and the external mould  22  are easily made, using these to directly cast a positive replica proves problematic in that the inner casts  24 ,  26  are no longer registered to the external mould  22 . This registration needs to be accurate at the sub-millimeter level in three dimensions due to the large thickness variation in the heart walls  16 ,  18  and the septum  20 . Without a high degree of accuracy, holes can form at locations  28  in the septum  20  or in the external heart walls  30 . 
         [0036]    Another problem to overcome is entrapment of the internal casts  24 ,  26 . Since the positive replica  10  is a shape with internal voids and relatively small outlets to the outside world (not shown), internal blood volume casts  24 ,  26  (the blood volume) would be trapped inside the replica  10  and would need to be removed. Ancient techniques (lost wax) would serve well here. The blood volume casts  24 ,  26  could be poured out when heated. Unfortunately, the material used for the blood volume casts  24 ,  26  would have to melt +/−100° F. to prevent damage to a suitable material for the heart walls  16 ,  18 . The methods, systems and apparatus of the present invention overcome the significant limitations of melt-based techniques through an advantageous segmentation approach. 
         [0037]    A preferable casting material for use as the final phantom cast is polyvinyl alcohol (PVA). PVA is a cryogel which has remarkable tissue-like properties, and by manipulation of temperature, time, and composition, physical properties of organs may be approximated PVA produces phantoms of high anatomical accuracy and texture, while making it possible to attain accurate registration and eliminate entrapment. This material is described in the following references, which are incorporated herein by reference in their entirety: Kenneth C. Chu and Brian K. Rutt, “Polyvinyl Alcohol Cryogel: an Ideal Phantom Material for MR Studies of Arterial Flow and Elasticity,” Departments of Medical Biophysics and Diagnostic Radiology, University of Western Ontario, and Tom Lawson Family Imaging Research Laboratories, John P. Robarts Research Institute, London, Ontario, Canada; R. C. Chan, M. Ferencik, T. Wu, U. Hoffmann, T. J. Brady, and S. Achenbach, “Evaluation of arterial wall imaging with 16-slice multi-detector computed tomography”, Computers in Cardiology 2003, Thessaloniki, Greece, September, Vol. 30:661-4, 2003; A. Chau, R. Chan, S. Nadkarni, N. Iftimia, G. J. Tearney, and B. E. Bouma, “Vascular optical coherence elastography: assessment of conventional velocimetry applied to OCT”, in Biomedical Topical Meetings on CD-ROM (The Optical Society of America Biomedical, Washington, D.C., 2004), FH47; and M. Ferencik, R. C. Chan, S. Achenbach, J. B. Lisauskas, S. L. Houser, U. Hoffmann, S. Abbara, R. C. Cury, B. E. Bouma, G. J. Tearney, and T. J. Brady, “Evaluation of Arterial Wall Imaging with 16-slice Multi-detector Computed Tomography in Vessel Phantoms and Ex Vivo Coronary Arteries,” Radiology 2006 (in press). 
         [0038]    PVA in its natural state is virtually transparent to X-Ray and Ultrasound (depending on frequency used). PVA can be doped, i.e., materials like iodine, graphite, MR contrast (e.g., gadolium, copper sulphate and the like), MR iron-oxide nanoparticles, and/or optical contrast agents (e.g., microspheres, optical nanoshells, intralipid, lipids/oils, optical dyes, ultrasonic microbubbles) can be added to achieve required imaging densities. Representative images of doped PVA phantoms are shown in  FIG. 2  using an FD10 X-Ray and in  FIG. 3  using 3D ultrasound. 
         [0039]    PVA has the additional advantageous property that it can be poured onto a previously cast and cured PVA segment and heated to create a bonded single piece composite cast with no signs of demarcation between segments. As a result, an organ/tissue phantom, e.g., a heart phantom, can be built of a number of slices or segments fused together to yield registered and un-entrapped interior detail. In an exemplary method, system and apparatus of the present invention, registration is achieved by successively casting a plurality of silicone rubber segments vertically, one atop the other, until a nearly complete heart shaped cast is created. These segments are cast such that they do not bond together and are securely registered on both the surface of the blood volume and the inside of the surface cast of the heart exterior. Such method, system and apparatus of the present invention produces blood volume positive casts that are tightly registered to the inside of the external surface of a negative heart (or other organ/tissue/anatomical) mould. 
         [0040]      FIGS. 4-10  and  13  illustrate steps that may be employed according to the present disclosure to create/manufacture a PVA heart phantom. In  FIG. 4 , a human heart  32  is placed in a container  34  filled partially with silicone rubber  36 . Then, the ventricles  38 ,  40  are filled with silicone rubber through the vessel openings  42 ,  44 . In  FIG. 5 , a plurality of rods  46  having a number of (spherical) “bumps”  48  are thrust through one side  33  of the mould container  34 , piercing in succession a heart wall  50 , an inner blood volume 52, the septum  54 , a second blood volume 56, the remaining heart wall  58 , and the remaining container wall  60 . The silicone rubber is then allowed to cure, which creates blood volume moulds  62 ,  64  and an outer mould  66  (see  FIG. 6 ). The heart  32  is then removed from the mould container  34  and dissected to free the internal blood volume (moulds)  62 ,  64 . As shown in  FIG. 6 , the blood volume moulds  62 ,  64  have lost registration to the outer mould  66 . Referring now to  FIG. 7 , registration can be restored by reinserting a plurality of rods  46  with a number of “bumps”  48  in their previous locations through the mould container  34  and the blood volume moulds  62 ,  64 , as shown. 
         [0041]    Referring now to  FIGS. 8A-8D , the mould container  34  (which includes a plurality of inserted rods  46 ) is then filled with successive segments  68 A- 68 D of molten silicone rubber. Each of the segments  68 A- 68 D are allowed to solidify and cure. As a result, the segment  68 B does not adhere to the segments  68 A or  68 C. Likewise, the segment  68 C does not adhere to the segments  68 B or  68 D, etc. None of the segments  68 A- 68 D bond to outer mould  66 . The blood volume moulds  62 ,  64  are removed and negative moulds are made of them. From the negative moulds, positive hard plastic blood volume moulds  78 ,  80  are made. 
         [0042]    Referring now to  FIG. 8D , the hard plastic moulds  78 ,  80  are placed inside the segments  68 A- 68 D that were cast earlier. The segments  68 A- 68 D determine the rigidity and quality of registration. Referring to  FIGS. 9 and 10 , the PVA material  72  is cast in the registered mould. The plurality of rods  46  are all removed. Then, the silicone segments  68 A- 68 D are removed one at a time and the voids are filled with PVA to produce PVA segments  74 A- 74 D. The newly added PVA segments  74 A- 74 D fuse with the previously added/cured PVA segments, e.g., under appropriate temperature conditions. Typically, the fusion process is undertaken sequentially, i.e., adjacent PVA segments are fused one at a time. When all the PVA segments  74 A- 74 D have hardened and cured, there results a nearly complete PVA heart cast  76 . 
         [0043]    Thus, in an exemplary technique for fabricating a phantom according to the present disclosure, e.g., a heart phantom, the following steps are employed:
       A mould of the outside of the heart is formed, as described above.   A silicone replica of the heart is formed using the foregoing mould.   The silicone segment of the heart apex replica is placed in the bottom of the foregoing negative outer silicone mould of the heart.   Rigid implants/hard plastic moulds (e.g., elements  78 ,  80 ) are inserted into the heart apex replica that is positioned at the bottom of the heart mould.   PVA (or other suitable polymeric material) is poured around the plastic moulds and treated/cured to a hard condition.   Remove from mould and separate silicone apex replica from hard plastic moulds/PVA combination. Return the hard plastic moulds/PVA combination to the mould and turn “upside-down”.   Add PVA through opening in bottom of mould; newly added PVA bonds or fuses to the previously hardened PVA (under appropriate temperature conditions), thereby replicating the previously-removed apex.   The structure is removed from the mould and the hard plastic moulds are removed from within the PVA.       
 
         [0052]      FIG. 11  shows a photograph of the PVA heart cast  76  removed from the outer mould  70  but with the hard plastic moulds  78 ,  80  in registration, while  FIGS. 12A-12B  are photographs showing the PVA heart cast  76  with the hard plastic moulds  78 ,  80  removed. Removal of hard plastic moulds  78 ,  80  may be assisted/facilitated by water lubrication. 
         [0053]    Referring now to  FIGS. 13 and 14 , the PVA heart cast  76  is typically completed by employing a mounting arrangement  84 , which includes the silicone mould segment  68 A, a cured PVA flange  86 , a plurality of barbed tube fittings  88 , and a plurality of tubes  90 . The silicone mould segment  68 A is turned upside-down and mounted to the cured PVA flange  86  via the plurality of barbed tube fittings  88  therebetween. The plurality of tubes  90  are then inserted at one end  92  of the barbed tube fittings  88  until the plurality of tubes  90  protrude a predetermined distance from the other end  94  of the barbed tube fittings  88 . A pool of hot PVA  96  of appropriate depth is poured to a level flush with the top  98  of the silicone mould segment  68 A. The hot PVA  96  immediately blends with underlying cured PVA flange  86 . The PVA heart cast  76  is then reinserted into the silicone mould segment  68 A of the mounting arrangement  84  containing the hot PVA  96 . The hot PVA  96  is displaced up into the PVA heart cast  76  forming an overlapping fusion bond. When this composite is cooled and heated to cure the PVA, a completed phantom heart  100  is formed (see  FIGS. 15A and 15B ). 
         [0054]    Thus, from a step-wise standpoint, this second fabrication stage generally involves the following steps:
       Utilizing a second mould of the outside of the heart, a set of fittings are positioned with respect to such second mould and face downwardly. This mould is of limited height (e.g., approximately one inch).   PVA is poured atop the second mould to form a PVA pool within a dam-like structure. The fittings extend above the PVA pool.   The heart mould fabricated in the first series of steps is turned upside down and pressed downward into the PVA pool until it registers with the mould details, thereby defining a complete heart phantom. As before, the newly added PVA bonds or fuses to the previously hardened PVA (under appropriate temperature conditions).       
 
         [0058]    Referring now to  FIG. 16 , the completed phantom heart  100  is shown attached to the mounting arrangement  84  for permitting robust mechanical manipulation. The apex  102  of the phantom heart  100  can be fitted with a coupling  104  which is actuated by servo motors  106  or other actuating units under the control of an external controller  108 , such as a personal computer. The coupling  104  permits compression and rotation of the completed phantom heart  100  using servo motors  106 . A blood surrogate (not shown) may be pumped by external means or, with the addition of appropriate valves, pumped by the completed phantom heart  100 . Software loaded into the controller  108  is generally employed to control required heart movements via the servo motors  106 . This software has the capability, for example, to source ECG signals in synchronization with the servo motors  106 .  FIG. 17  shows a photograph of the completed phantom heart  100  in the mounting arrangement  84  which is driven by a two axis servo motor  110  under software control, outputting a synchronized ECG waveform on the display  112  of a laptop computer  114 .  FIG. 18  is a photograph of the same arrangement complete with ultrasound, X-Ray, and Aurora imaging equipment. 
         [0059]    Referring now to  FIG. 19 , exemplary calibration of the 3D space surrounding a heart phantom is provided by inserting a “U” shaped fixture  114  into a keyway  116  in the mounting arrangement  84 . The fixture  114  contains numbers of stainless steel balls  118  fixed at random locations about the fixture  114 . The positions of the balls  118  are precisely determined with respect to reference marks  120  in the three planes of the fixture  114 . Referring again to  FIGS. 18 and 19 , the 3D space encompassing the completed phantom heart  100  will be “seen” by X-ray, ultrasound, and an Aurora magnetic probe (not shown). While X-ray imaging and an ultrasound probe can satisfactorily resolve the steel balls to define the volume, the image “seen” by the Aurora magnetic probe is distorted by the presence of the steel balls when the probe is placed on them during calibration. To combat this deficiency, additional shallow holes may be drilled adjacent to the steel balls at precisely known offsets. The magnetic probe is placed in these surrogate locations, the offsets are noted in software, and the 3D volume is acquired. 
         [0060]    The present invention is subject to numerous applications. The tissue-mimicking polyvinyl-alcohol material used to construct the completed heart phantom  100  can be “biologically-functionalized” by replacing some or all of the PVA with a tissue-engineering extra-cellular matrix seeded with living cells or chemically-active molecular markers/probes. This approach allows for even closer approximation of the biochemical properties of living tissue, in particular with respect to metabolic processes that are essential to functional imaging techniques such as with PET or SPECT. In addition, fiducial targets such as beads, rubies, contrast-containing PVA-microspheres, capsules, microbubbles, etc., can be embedded in either a targeted or randomized fashion within the phantom tissue to provide additional markers to be used for validation experiments. In another exemplary embodiment, 3D printing techniques can be combined with phantom generation in such a way as to allow the use of patient-specific imaging volumes from which segmented organ surfaces can be extracted. These surfaces can then be fed directly to a 3D printer for construction of a negative mould into which a PVA “tissue” matrix can be poured and formed. Alternately, a novel 3D printing technology could be developed which allows for direct PVA printing in 3D. In this approach, PVA droplets are layered in a manner akin to current inkjet technology in low-cost consumer printers. 
         [0061]    The present invention has several advantages over prior art phantoms and phantom generating techniques. For example, the methods, systems and apparatus of the present invention provide anatomically-accurate and functionally-accurate organ/tissue phantoms which can be used in any experiment intended for testing and validation of multimodality imaging hardware and software platforms. Clinical applications include, but are not limited to, testing of strategies for interventional procedure guidance (e.g., thyroid biopsy, liver biopsy ablation, prostate biopsy/ablation, etc.), cardiac catheterization, electrophysiology procedures, and minimally-invasive surgery. The disclosed methods, systems and apparatus allow for the injection of adjustable multimodality tissue-mimicking contrast for natural or enhanced imaging by X-ray, ultrasound, MRI (this is extensible to nuclear medicine imaging techniques such as PET/SPECT with the introduction of radiotracers within the “tissue” matrix), and other optical and/or electromagnetic imaging modalities (e.g., RF, microwave and THz). Moreover, the present invention provides an adjustable approximation of the physicochemical properties of heart tissue. In addition, the present invention provides for:
       dynamic and programmable heart motion, including but not limited to, torsion/rotation and compression;   attached or imbedded vasculature;   accurate internal and external anatomical details including wall thickness;   ECG (or any arbitrary waveform) output for synchronization to CT, cardiac X-ray and other medical equipment;   tubing fittings incorporated into heart structure;   mechanical mounting appropriate for mechanical operation; and   integrated calibration feature to define the 3D volume of the heart.
 
The present invention can also be housed in a configurable water filled tank with a large ultrasound access port and a dynamic mechanical access port for testing of interventions typical of electrophysiology or cardiac catheterization procedures.
       
 
         [0069]    It will be understood that the embodiments described herein are merely exemplary and that a person skilled in the art may make many variations and modifications without departing from the spirit and scope of the invention. All such variations and modifications are intended to be included within the scope of the invention.