Abstract:
An MR-guided biopsy, for example, prostate biopsy, is performed by a mechanical tool for stabilizing the patient in prone position and for guiding the biopsy needle into defined targeted lesions in the prostate gland. The patient can lay prone in the MRI. The apparatus can guide an MR-visible, sterile needle sleeve, which can have a hollow tube filled with contrast media, through the anus onto the inner wall of the colon. Due to the visibility of the contrast media in the sleeve, the apparatus can be guided to the exact position. The sleeve can incorporate a tube within the contrast media filled sleeve to insert the biopsy needle and to push this needle forward into the prostate. The apparatus can utilize various mechanical mechanisms to stereotactically move the needle or needle sleeve in various directions.

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     The present application is a continuation-in-part of U.S. application Ser. No. 10/366,831, filed Feb. 14, 2003 now abandoned, which claims the benefit of U.S. Provisional Application Ser. No. 60/357,205, filed Feb. 14, 2002, the present application also claims priority of U.S. Provisional Application Ser. No. 61/016,300, filed Dec. 21, 2007, which are hereby incorporated by reference herein in their entirety, including any figures, tables, or drawings. 
    
    
     FIELD OF INVENTION 
     The subject invention pertains to a method and apparatus for MR-guided biopsy. The subject invention can be applied to prostate biopsy. In a specific embodiment, the subject invention relates to a stereotactic positioning device for MR-guided interventions, such as biopsies of suspicious areas of the prostate gland. MRI (magnetic resonance imaging) is a current radiological imaging modality to view soft tissue lesions of the human body. MR can be used to guide the subject positioning device to directly puncture lesions in the prostate and/or to biopsy these. 
     BACKGROUND OF THE INVENTION 
     Prostate cancer is the most common cancer, excluding skin cancers, in American men. The American Cancer Society estimates that during 2002 about 189,000 new cases of prostate cancer will be diagnosed in the United States. Accurate determination of the extent of local disease in the prostate is difficult. Current imaging techniques include, for example, transrectal ultrasound (TRUS), endorectal coil magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopic imaging (MRSI). The reported accuracy of TRUS for determining if prostate cancer is confined within the capsule varies widely from 58% to 90%. However, preliminary data from recent studies of endorectal MRI show higher accuracy (75-90%) than TRUS, and better consistency. 
     In addition to morphologic extent, directed biopsy and assessment of tumor aggressiveness are important for accurate staging and treatment for prostate cancer when there is an elevated PSA. Current biopsy techniques are based on random spatial sampling and have a lower than desired sensitivity (60-70%) for identification of carcinoma of the prostate. Early preliminary studies of combined MRI/MRSI demonstrated localization of cancer to a sextant of the prostate with sensitivity up to 95% and specificity up to 91%. However, more specifically localized biopsies, rather than randomly taken biopsies, would be desirable. 
     MRI is presently regarded as the best imaging modality for assessing soft-tissue tumors like prostate cancer. This is confirmed by numerous reports in the literature. In an early study, carried out from December 1987 to April 1989, Rifkin et al [7] report on the collaborative effort of five institutions that are part of the Radiological Diagnostic Oncology Group. More than 200 patients who were thought clinically to have localized cancer of the prostate were studied preoperatively with both MRI and transrectal ultrasonography to evaluate the ability of these techniques to determine the exterit (stage) of the tumor. They underwent radical prostatectomy, and radiologic and pathological findings were correlated. The overall staging accuracy of ultrasonography was 58% (126 of 219 patients), with a standard error of 3%. The overall staging accuracy of MRI was 69% (133 of 194 patients), with a standard error of 3%. The subject invention can increase the diagnostic accuracy of MRI when combining MRI scans with interventional biopsy techniques. 
     Prostate cancer is the second most common cause of cancer death in US men. Its incidence is on the rise because more cancers are detected due to wide-ranging screening programs using either digital rectal exams or serum prostate-specific antigen (PSA). Whenever abnormalities crop up in these examinations, the patient is traditionally referred for ultrasound-guided biopsy, which has a low sensitivity and a specificity of only 60% for cancer detection [3]. This is why ultrasound is often used just to guide biopsies. However, MRI performs much better at cancer detection. 
     Typical prostate biopsies are performed by palpation (whether or not a nodule is present) or using ultrasound guidance (when a visible lesion is present). However, endorectal ultrasound is not sensitive enough for a screening tool. The visibility of the anterior capsule is poor as is visualization of seminal vesicle and lymph node involvement. Extracapsular disease and lymph node involvement is better picked up with MR, although interobserver variability is quite high (positive predictive value ˜70%). PSA and proton MR spectroscopy get higher ratings for predicting the Gleason grade. Patients with incompatible PSA and biopsy results or MR spectroscopy results or with MR visible lesions would thus benefit from an MR guided prostate biopsy. 
     BRIEF SUMMARY OF INVENTION 
     The subject invention pertains to a method and apparatus for MR-guided biopsy. The subject invention can be applied to, for example, prostate biopsy. In a specific embodiment, the subject invention can provide a mechanical tool for stabilizing the patient in prone position and to guide a biopsy needle into defined targeted lesions in the prostate gland. The patient can lay prone in the MRI. The subject apparatus can guide an MR-visible, sterile needle sleeve, which can have a hollow tube filled with contrast media, through the anus onto the inner wall of the colon. Due to the visibility of the contrast media in the sleeve, the apparatus can be guided to the exact position. The sleeve can incorporate a tube within the contrast media filled sleeve to insert the biopsy needle and to push this needle forward into the prostate. The subject apparatus can utilize various mechanical means to stereotactically move the needle or needle sleeve in various directions. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a prostate biopsy system in accordance with the subject invention, patient lying prone. 
         FIG. 2  illustrates a stick to remotely operate the embodiment of  FIGS. 3A-4D  and others of the subject device from outside the MR magnet. 
         FIG. 3A  illustrates a three dimensional view of an embodiment of the subject invention, from a more frontal point of view. 
         FIG. 3B  illustrates a three dimensional view of the embodiment of  FIG. 3A  of the subject invention, from a more back point of view. 
         FIG. 4A  illustrates a cross-sectional view of disposable needle-sleeve and needle-sleeve-block of  FIGS. 3A and 3B . 
         FIG. 4B  illustrates a super-side view of a disposable needle-sleeve and needle-sleeve-block of  FIGS. 3A ,  3 B, and  4 A. 
         FIGS. 4C and 4D  illustrate a the snap-in mechanism of the disposable needle block of  FIGS. 4A and 4B . 
         FIG. 5A  illustrates a disposable biopsy needle which can be used with an embodiment of the subject invention. 
         FIG. 5B  illustrates a needle guide with depth control which can be incorporated with an embodiment of the subject invention. 
         FIG. 5C  illustrates a hub-tube and stopper located at a different position with respect to needle block  51  than shown in  FIG. 5B  and shows a hub-tube  45  and stopper  46  outside of the needle block  51  for illustration purposes. 
         FIG. 6  illustrates a cross-sectional view of a straight biopsy device in accordance with the subject invention, which is attached to a patient&#39;s body. 
         FIG. 7  illustrates a cross-sectional view of a curved biopsy device in accordance with the subject invention, which is attached to the patient&#39;s body. 
         FIG. 8  illustrates the different biopsy locations in the prostate gland. 
         FIG. 9  illustrates a three dimensional view of another specific embodiment of the subject invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The subject invention pertains to a method and apparatus for MR-guided biopsy. In a specific embodiment, the subject invention can be utilized for prostate biopsy. In a specific embodiment, the subject invention relates to a positioning device for prostate interventions, which can incorporate many parts, such as a biopsy needle, a needle sleeve, various positioning and adjustment parts, coils, and more. 
       FIG. 1  illustrates a specific embodiment of the subject prostate biopsy system in use with a patient. The patient  1  is lying in a prone position and the biopsy needle  2  is introduced endorectally through the anus  3 . A specially shaped positioning device  4  is positioned under the patient&#39;s hips to stabilize the patient as needed for the procedure. Positioning device  4  can provide cushion to the patient. In this position the patient&#39;s back side is lifted up a little, so that the physician has better access through the patient&#39;s anus  3 . In  FIG. 1  the biopsy needle  2  is directly inserted through the anus  3  of the patient through the intestine wall of the rectum directly into the prostate. Here no special introducer device, as described is used. On the positioning device  4  is mounted a holding arm  6 , which is movable around an axis  7  and is adjustable in height. Attached to the holding arm  6  is the needle holder  8  through which the biopsy needle  2  will slide. 
     There are two ways to operate this embodiment, and later described prostate biopsy embodiments, in conjunction with magnetic resonance imaging (MRI). In a first technique the patient is pulled out from the MR magnet to operate the device, pushed back in the magnet to control the position of the needle guide, and pulled out from the magnet for further needle adjustments if needed. The dimensions for the necessary corrections can be taken from the image and transferred to the scales of the device. In a second technique, the patient stays in the magnet and images are taken during the needle repositioning procedure. The device will appear in the image and is operated from the outside by simply reaching in with the arm of the operator or by remotely operated tools. These tools can be, for example, long plastic sticks  9 . Sticks  9  can be between 50 cm and 150 cm long, and 5 mm to 20 mm in diameter. Sticks  9  can have a grip  10  on the proximal end and a tool  11  at the distal end to attach to a particular part of the prostate biopsy device. The attachment tool  11  can, for instance, attach directly to the grip of the biopsy needle  2  for the purpose of adjusting the position and pushing the needle  2  into the tissue. The attachment tool  11  can be changed to attach to different parts. The stick  9  can be extended in length during the operation or there can be sticks of various defined preset lengths. 
       FIG. 3  shows another embodiment of the subject invention.  FIG. 3A  shows the device from a frontal view, while  FIG. 3B  shows the device from a rear view. Positioning device  13  is mounted on the base plate  14 . Positioning device  13  can also provide cushion for the patient. The arm of the device, including lower arm  16  and upper arm  17 , is locked in the arm-mounting-track  15  of the base plate  14  by arm-mounting-lock-bolt  18 . Operating the adjustment-screw  19  allows the lower arm  16  to lengthen or shorten itself by means of a spiral-drive, not further shown here, within the lower arm  16 . The spiral-drive moves the sliding-part  20  of the lower arm  16  against the fixed base-part  21  of the lower arm  16 . The upper arm  17  is fixed on the distal end of the sliding-part  20  of the lower arm  16  and is designed to be a curved track for the needle-sleeve-holder  22 . The needle-sleeve-holder  22  slides up and down the curved upper arm  17  and locks in the desired position via a locking mechanism, operated with lock-bolt  23 . The curved upper arm  17  allows the movement of the needle-sleeve around a pivot point. In a specific embodiment, the pivot point is the anus  3 , such that the patient can be positioned and the subject device adjusted so that as the needle-sleeve-holder  22  slides up and down the curved upper arm  17  the needle-sleeve moves about a pivot point, with the pivot point being the patient&#39;s anus. The needle sleeve  24  with needle-sleeve-block  25  can be a disposable device and can be changed via the needle-sleeve-lock-in mechanism  26 , not further shown here. The needle sleeve  24  and needle-sleeve-block  25  can be moved forward and backwards via a spiral-drive mechanism, not further shown in detail here, by operating screw  50 . This whole prostate-biopsy-device can be a reusable, and at least a cleanable, but most likely a sterilizeable unit. Screws, such as adjustment screw  19  or operating screw  50 , can be reached and operated with a stick  9 , as shown in  FIG. 2 . Special adapting tools  11  are designed, but not further described here. In another embodiment of the invention, which is not further shown here, these screws are not manually operated, but motor operated with MR compatible motors such as piezo electric motors described in U.S. Pat. No. 6,274,965. 
     A specific embodiment of a needle-sleeve  24  and needle-sleeve-block  25  is shown in  FIGS. 4A-4D .  FIG. 4A  illustrates the disposable needle-sleeve and needle-sleeve-block in cross sectional view and  FIG. 4B  illustrates a super side view of the disposable needle-sleeve and needle-sleeve-block. The needle-sleeve  24  incorporates an outer tube  27 , which is sealed on its distal end by a seal-stop  29 , or a molded plastic ending, not further shown here. On the proximal side of the needle-sleeve  24  the needle-sleeve-block  25  seals the outer tube  27 . An inner tube  28  penetrated through the entire length of the needle-sleeve  24 . The hollow space  30  within the outer tube  27  is therefore sealed. This hollow space  30  can be filled with any contrast giving agent. In a specific embodiment, hollow space  30  can be filled with a MR positive contrast producing media with short T 1 , T 2  or T 2 * relaxation time. Examples of such media include Gd-DTPA (Gadolinium-diethylene-triaminepentacetic acid) and vitamin E. This contrast producing agent can allow the needle-sleeve  24  to be located easily under MR imaging. Very fast sequences can be used to show the needle guide. The section plane in which the biopsy should take place can be defined such that real time imaging in this plane can allow movement of the needle guide until it is perfectly lined up with the lesion. The needle guide can be fixed in this position and the biopsy can be taken outside the magnet. 
     The needle-sleeve-lock-in mechanism  26  allows a fast, safe and easy connection of the needle holder in the positioning device. Mechanical fixation  41  allows a precise lock-in in the longitudinal axis of the needle-sleeve-block  25 . The mechanical fixation mechanism  42  has a squared cross section to prevent rotation of the needle-sleeve-block  25 . The locking lever  43  fits into the mechanical fixation  41  at the opposite site. 
     The subject invention also relates to other techniques to make the needle sleeve visible for the MRI scanner. Fiducial markers, or other markers that use for example overhauser or electron spin can be incorporated. Two or three of these markers can exactly define the position of the needle sleeve and the way the needle will go. To save time it is possible to take a high resolution 3-D-image first and use the needle guide only to navigate. This has the advantage of fast nice pictures of the lesion in real time. For safety reasons it might be desirable to take at least one image with the needle guide in place. 
     The biopsy needle can slide through inner tube  28 , which can be aligned parallel to the outer tube  27 . The inner diameter and length of tube  28  can match the outer diameter of the biopsy needle used. Typically the inner diameter is 8 to 16 G (gauge) or 1.7 to 3.0 mm. The needle-sleeve-block  25  with needle-sleeve  24  can be adapted to the needle-sleeve-holder  22  of the reusable prostate-biopsy system by, for example, a snap-on mechanism  31 . For better orientation, the needle sleeve block can be filled with material which can produce contrast to show up in the image and indicate the axis of rotation of screw  50 . In a specific embodiment, the needle sleeve can be made of materials substantially invisible to magnetic resonance imaging and a needle which is visible can be used. 
     The system incorporating the needle-sleeve  24  and its sub-parts, the needle-sleeve-block  25 , and the snap-on mechanism  31  can be made as one disposable part. This system can utilize plastic parts. Examples of plastic which can be utilized include but are not limited to, PE, PP, PU, PEEK or TEFLON (i.e. polytetrafluoroethylene (PTFE)). Ceramic or low artifact giving metals, such as titanium and titanium-alloys can also be used. 
       FIG. 5A  shows a typical, disposable, fully automatic biopsy needle as used for this prostate biopsy device. The needle itself can be made out of a MR visible titanium alloy as described for instance in U.S. Pat. Nos. 6,120,517 or 5,895,401. Other surgical tools like the one in U.S. Pat. No. 6,238,355 can be inserted as well. 
       FIG. 5B  shows a needle guide with depth control. The hub-tube  45  is coaxial and penetrates through the needle-sleeve  51  and has a stopper  46  on its proximal end. This hub-tube  45  shortens or lengthens the inner tube  28  of the needle-sleeve  51 . Hence, if a needle, such as shown in  FIG. 5A , penetrates through the inner-tube  28  it will have to stop at the stopper  46  and therefore can penetrate to a defined depth. This hub-tube  45  can be locked in position by a lock-in mechanism not shown herein. 
       FIG. 5C  shows the hub-tube  45  and stopper  46  located at a different position with respect to needle sleeve  51  than shown in  FIG. 5B  and shows a hub-tube  45  and stopper  46  outside of the needle sleeve  51  for illustration purposes. 
     Another specific embodiment of the subject invention is shown in  FIG. 6 . The biopsy needle  2  is penetrating through the positioning system  32 , which itself is only mounted to the patient  33  by clamping in the anus  3 . The positioning system  32  comprises a ball-and-socket-joint  34 , which allows a full angulated movement of the biopsy needle  2 , as shown by curved arrows in  FIG. 6 . This positioning system  32  can be a disposable device, and can be made of MR compatible materials, such as PE, PP, PU, PEEK or TEFLON (PTFE). Ceramic or low artifact giving metals, such as titanium and titanium-alloys can also be used.  FIG. 7  shows the same device with a needle  35 , which is pre-bent and curves in a given direction when pushed out of a straight rigid needle  36 . The curved needle  35  can be made out of, for example, super-elastic nickel-titanium (NiTi), the rigid and straight needle  36  can be made out of a titanium alloy, such as described in U.S. Pat. No. 6,238,355. Outer needle  36  is attached to grip  37 , and needle  35  is attached to grip  38 . By grasping grip  38  with one hand and grip  37  with the other hand and pushing the one hand, and therefore grip  38 , against the other hand, and therefore grip  37 , needle  35  will be pushed out of needle  36  and will bend, as shown with the arrows. 
       FIG. 9  shows an alternative version of the prostate biopsy system. The needle plate  47  holds the biopsy device, which can be automated and driven by an MR compatible piezoelectric motor, for instance as shown in U.S. Pat. No. 6,274,965. This mechanism is posted on an upper arm  55 , lower arm  54  and a base plate  53 , all to be locked in defined positions by locking mechanism  49 . 
     EXAMPLE 1 
     This example describes a method for affecting a biopsy in accordance with the subject invention. In a specific embodiment, the subject prostate-biopsy-device can be operated in conjunction with a body faced array coil taking 6 to 8 samples, for example, by implementing the following:
         Position the patient and the subject prostate-biopsy-device. Lay the patient prone on the stabilization pillow.   Install the body faced array coil, and the arm of the prostate biopsy device.   Insert the needle-sleeve through the anus onto the inner wall of the intestine posterior to the prostate (left apical corner of the prostate a).   Move the patient with device in the MR magnet and perform a first control scan (axial through prostate and needle sleeve).   Reposition the needle-sleeve if needed by moving the arm of the device from outside by using the sticks or move the patient out of the magnet and reposition manually the appropriate screws.   Measure the depth of the lesion in the prostate via another MR scan. If position is right move the patient out of magnet, introduce the biopsy needle through the needle sleeve into the prostate, and fire the biopsy needle to do the biopsy, or move the patient out of the magnet, introduce the biopsy through the needle sleeve into the prostate, fire the needle, and take a control image with the needle in place. Push out the needle notch, move the patient back into the MR magnet to make a controlling scan, and move the patient out of the magnet, to fire the biopsy needle to do the biopsy. (Or move the patient out of the magnet, introduce the biopsy needle through the needle sleeve into the prostate, drive the patient back into the MR magnet, and fire the biopsy needle to do the biopsy by using a stick from outside to operate the needle.) Alternatively, the hub-tube  45  of the device can be repositioned, so that the needle only penetrates to a certain depth.   Take out the first sample. Move the sliding part of the lower arm  20  by turning adjustment screw  19  to position the needle sleeve in the middle b (referring to  FIG. 8 ) of the left half of prostate  5  and to the end c (referring to  FIG. 8 ) of the prostate  5  to take a biopsy from each position.   Position the needle guide at the right side of the prostate  5  d (referring to  FIG. 8 ) and take a control image. If the position is correct the patient is moved out of the magnet again and the next tree biopsies d, e, f, (referring to  FIG. 8 ) can be taken from the right side of the prostate in the same way as the left. For biopsies of special regions or additional lateral biopsies, the needle guide has to be positioned new and a control image has to be taken.
 
The procedure described in this example allows a caregiver to take only two to four images to perform safe and fast biopsies with good control of the needle position. T 2  weighted sequences can be used to view the prostate  5 . After giving contrast media T 1 , weighted FLASH 3D sequences (SIEMENS 1.5T) can be used. For the intervention itself, a HASTE sequence or a T 1  weighted Spin Echo sequence can be used. In a 0.2 T SIEMENS MR tomographer, imaging was accomplished using a FLASH 2D-Sequence (TR/TE=100/9: 70Grad), T 2 -SE (TR/TE=100/9; 70Grad), and a FISP-Rotated-Keyhole-Sequence (TR/TE=18/8; 90Grad).
       

     EXAMPLE 2 
     Embodiments of the subject invention can use the KM-filled needle guide to be detected under MRI and to be used to guide instruments under MRI. The needle guide can have different sizes and shapes that allow better detection or better recognition under MRI. The shape of the cavity that is filled can have, for example, a round shape, a cylindrical shape with a central aperture to put the needle through, or an irregular shape that can allow detection of all three degrees of freedom, as well as rotation. The use of different shapes can allow differentiation of needle guides from each other if there is more than one needle guide used at the same a time. In addition, software can be used to automatically detect the position of the needle sleeve and to use this information to control the MRI scanner. Transfer of this information to the scanner to acquire the MR-signal of the needle sleeve can be enhanced by adding self-resonating LC-circuits or small active coils. Both techniques can help to detect the needle guide with the MR-scanner and automatically detect the instrument track. Resonating or active coils of different size and shape can help differentiate the needle sleeves and make localization faster and more accurate. 
     To position an instrument in a moving organ such as a liver or a lung, a more flexible holding arm can be utilized and a connector for interconnection with sterile positioning units can be incorporated. 
     An embodiment of the subject invention has a base that can be a base plate or a fixation on the MR-table. Further, there is a flexible positioning arm with two rotating ball-joints at the ends, one joint in the middle, and a central clamping mechanism. The distal end has a connector to allow connection to different sterile positioning units. This connection can be designed so that a plastic drape can be placed over the holding arm so that the conical part of the connector can be pushed through the plastic drape. This allows a sterile drape holding arm to be connected with a sterile positioning arm. 
     In this case, the positioning unit carries an adjustable ball-shaped needle guide that is pushed against the skin and can allow insertion and guiding of an instrument. The S-shaped fixation arms allow the ball to be placed directly on the skin and to have area for a loop-coil to improve images in the region of interest. This imaging coil can also be integrated in the fixation arms or connected to them. This coil can also be used as a positioning coil as it is close to the needle guide and can detect the position and direction of the needle sleeve by using a special sequence that correlates with the filling and configuration of the needle guide to give clear signals. 
     An embodiment of the subject invention can allow clamping of the bass-shaped needle guide, which can contain KM filling or can be connected to a needle guide of, for example, a cylindrical or other shape. The screw allows free rotation and clamping of the ball. If the screw is opened further, the ball can be released completely to allow free motion by an easy-release mechanism. For example, the ball can take disposable needle sleeves that are currently used for breast biopsies with integrated clamping, and can also take bone biopsy devices or instruments such as endoscopes. 
     It is possible to steer the MR-imaging plane by the needle guide with real time imaging. The needle guide is detected by an automated detection software, as known in the art, which can provide the MR scanner the direction and position of the imaging plane. If the instrument is in the correct position, the MR scanner can automatically generate a control scan that shows the instrument and the surrounding anatomy. 
     It is also possible to use the MR scanner as a navigation system to detect the needle guide and to overlay the theoretical position from a prior detected dataset. This can allow pre-adjustment and the ability to take a confirmation scan to see if the instrument can be inserted safely. 
     MR-detectable markers can be integrated in the holding arm, the connector, the positioning unit, in the needle guide, or integrated in the Instrument. Techniques for connecting markers with the instruments is well known in the art and can be utilized in accordance with the subject invention. 
     The holding arm can carry different positioning systems, such as one for a prostate or one with the ball-shaped needle guide for a liver as described above. The holding arm can also carry a y-x positioning unit or a grid-plate. The conical connector can carry a frame that may have an integrated coil and can carry the grid-plate or can carry the plates for y-x positioning. 
     The frame can carry fiducial markers that can be recognized by software, such as DynaCad™, to determine the exact needle position or needle guide position, which can be used to adjust and to visualize the needle track before the needle is inserted. 
     The fast connector allows the exchange of positioning units as well as the use of marker-plates to form different navigation systems, and allow the combination of these solutions. In this way, it is possible to define the position with an optical or other navigation system outside the magnet or to reference the arm position and to make adjustments with the positioning unit. 
     In addition, to make these positioning capabilities more effective, it is often desirable to have very little patient movement. This can be achieved by using a vacuum mattress to fix the extremities, for example. This mattress can be connected to the base of the holding arm. 
     All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification. 
     It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.