Abstract:
The invention pertains to an analysis device for measuring physical, chemical and/or biological parameters in an intervertebral disc. It comprises a probe adapted to be inserted in the intervertebral disc; the probe including at its distal end at least three different sensors. The intervertebral disc analysis system and method is useful for measuring physical, chemical and/or biochemical parameters in the intervertebral disc, the data generated by these sensors providing an effigy of the physiological status of the intervertebral disc. The invention further pertains to a method for obtaining physical, chemical and/or biological data of the intervertebral disc, the data being useful for matters in relation to diseases of the intervertebral disc, in particularly for diagnostics and therapies of diseases of the intervertebral disc.

Description:
PRIORITY 
       [0001]    The present application is a §371 nationalization of PCT/EP2008/052551, filed Mar. 3, 2008, which is herein incorporated by reference in its entirety, and claims the benefit thereof. 
     
    
     THE FIELD OF THE INVENTION 
       [0002]    The present invention refers to an analysis device and method for the evaluation of the physiological status of the intervertebral disc. 
       BACKGROUND 
       [0003]    Diseases of the muscular skeletal system particularly of the intervertebral disc are one of the most frequent diseases in Western territory. Lack of exercise, sedentary work and lifestyle, as well as un-physiological movements result in dysfunction of the spine. Thereby, the intervertebral disc is that part of the spine which is mostly affected. 
         [0004]    For diagnosis and evaluation and determination of therapy of diseased intervertebral discs the physician can make use of various imaging techniques. A popular method is discography; it is accepted as the intervertebral disc evaluation “procedure-of-choice”. By discography the role of the intervertebral disc in causing the patient&#39;s pain is investigated and established. Among experts usefulness of discography is discussed with regard to its indications, value, interpretation of its findings and its safety. Particularly of relevance is the use of fluoroscopic substances which are injected into the intervertebral disc to make lesions and injuries visible. Patients show sometimes allergic reactions towards these fluoroscopic agents. Further, betimes doubtful results of discography are obtained. Discography, like all other imaging techniques, provides the physician with an image of the structures which can be made visible by the specific technique. Physiological conditions are neither shown by discography nor by any other of the imaging techniques applied. Consequently, to properly diagnose a disease of the intervertebral disc as well as for the establishment of precise, tailored and, consequently, effective therapies and treatment plans the knowledge of the physiological status of the intervertebral disc would be of great advantage. Up to date no method or device is known with which the physiological status of the intervertebral disc can be evaluated. 
         [0005]    For therapy U.S. Pat. No. 5,433,739 and US 2006/0224223 A1 disclose heating technique whereby a stylet is inserted via a cannula into the intervertebral disc. For monitoring therapy procedure U.S. Pat. No. 5,433,739 discloses use of a temperature sensor, and US 2006/0224223 A1 discloses use of a pressure sensor, and a combination of pressure and temperature sensors, each being integral part of the stylet. 
       SUMMARY OF THE INVENTION 
       [0006]    Object of the present invention is the provision of a device and method which provides the physician with knowledge of the physiological conditions prevailing in a diseased intervertebral disc. 
         [0007]    This object is accomplished by the device of claim  1 , the method of claim  11  and the use of claim  13 . Preferred embodiments are subject matter of the depending claims. 
         [0008]    The analysis device of the invention is for measuring physical, chemical and/or biological parameters in an intervertebral disc. It comprises a probe adapted to be inserted in an intervertebral disc. The probe includes at its distal end at least three different sensors for measuring physical, chemical and/or biochemical parameters in the intervertebral disc. The data generated by these sensors provide an effigy of the physiological status of the intervertebral disc. Preferably there are at least three different sensors selected from the group consisting of a pressure sensor to measure the pressure of the intervertebral disc, a humidity sensor to measure hygrometry of the intervertebral disc, a pH sensor to measure the pH value of the intervertebral disc, a temperature sensor to measure the temperature in the intervertebral disc, a pO2 sensor to measure partial pressure of oxygen, and sensors to measure cytokines&#39;s levels, levels of degradation products of proteoglycans, contents of debris and particles accumulated in the intervertebral disc. A presently preferred analysis device includes at least a pressure sensor, a pH sensor, and a humidity sensor. Even more preferred is a combination of pressure sensor, pH sensor, humidity sensor, and temperature sensor. 
         [0009]    The invention provides a method for obtaining physical, chemical and/or biological data of the intervertebral disc, the data being useful for matters in relation to diseases of the intervertebral disc, in particularly for diagnostics and therapies of diseases of the intervertebral disc. A probe is inserted into the intervertebral disc, the probe including at least three different sensors for measuring physical, chemical and/or biological parameters in the intervertebral disc, and the data generated by these sensors provide an effigy of the physiological status of the intervertebral disc. Preferably, a cannula is inserted into the intervertebral disc, particularly into the nucleus pulposus. The cannula is adapted to house the probe and the probe is inserted into the intervertebral disc by inserting the probe into the cannula and advancing it to the intervertebral disc, particularly the nucleus pulposus, thereafter the cannula is retracted until the distal end of the probe, including the at least three different sensors, is exposed and measurement of the sensors is commenced. 
         [0010]    Finally, use of physical, chemical and/or biological data, generated by at least three different sensors located in the intervertebral disc for evaluation of the physiological status of an intervertebral disc, is disclosed. The sensors are combined in a single probe that is insertable into the intervertebral disc. 
         [0011]    The analysis device can be used to retrieve the statistical chemical and physical compounds of intervertebral discs. With the different options available for the correction of the intervertebral disc on the market, these decisions are currently being made of visual determinations only. In the future, analyzing the chemistry of the intervertebral disc prior to diagnosis for correction, will lead to increased success for patients and physicians. This will ensure the recommendation suggested by the physician will equal the successful result expected and desired by patients. Of particular relevance is that the effigy of the physiological status obtained by using the inventive device will lead to better tailored therapy and will reduce the therapeutic burden. It will now be possible to precisely medicate diseases of the intervertebral disc and will help avoiding unnecessary surgery. 
         [0012]    The information obtained with the use of the present analysis device will strengthen industry and physicians by allowing worldwide networking, diagnoses, recommendations, research and development for future implants and medications, and ensure success rates for manufacturers of implants and medications, giving them the ability to set their parameters to data received by physicians, and patients. 
         [0013]    The probe of the analysis device of the invention is preferably sterilizable or disposable. 
         [0014]    Examples of the sensors which can be used are the following. However, other technology is also encompassed by the present invention. The examples following are only for illustration and have been proved useful in practice. 
         [0015]    Examples of a temperature sensor are resistance thermometers and thermocouples. Resistance thermometers are constructed in a number of forms and offer great stability, accuracy and repeatability, in some cases they have been proved superior to thermocouples. Resistance thermometers use electrical resistance and require a small power source to operate. The resistance ideally varies linearly with temperature. 
         [0016]    An example of a pH sensor is an ion-selective electrode (ISE). ISE is a transducer (sensor) which converts the activity of a specific ion dissolved in a solution into an electrical potential which can be measured by a voltmeter or pH meter. The voltage is theoretically dependent on the logarithm of the ionic activity, according to the Nernst equation. The sensing part of the electrode is usually made as an ion-specific membrane, along with a reference electrode. Ion-selective electrodes are used in biochemical and biophysical research, where measurements of ionic concentration in an aqueous solution are required, usually on a real time basis. 
         [0017]    An embodiment of a pressure sensor is a piezoresistive pressure sensor. The sensing material in a piezoresistive pressure sensor is a diaphragm formed on a silicon substrate, which bends with applied pressure. Deformation occurs in the crystal lattice of the diaphragm because of that bending. This deformation effects a change in the band structure of the piezoresistors that are placed on the diaphragm, leading to a change in the resistivity of the material. This change may be an increase or a decrease according to the orientation of the resistors. 
         [0018]    Capacitors are examples of humidity sensors. Most capacitors are designed to maintain a fixed physical structure. However, various factors can change the structure of the capacitor; the resulting change in capacitance can be used to sense those factors. The effects of varying the physical and/or electrical characteristics of the dielectric can also be of use. Capacitors with an exposed and porous dielectric can be used to measure humidity in air/fluids. 
         [0019]    As briefly discussed, the probe is preferably inserted and housed in a cannula to be inserted into the intervertebral disc. The cannula can be one which is used for discography, also. This has the advantage that the physician can make use of the same cannula for determining the physiological status and for discography. If, for example, the physiological data are not sufficient to allow definite diagnosis the physician can immediately proceed with discography, without need of a second aditus, and vice versa. For that reason, the size of the analysis device is preferably adapted to cannula sizes used in discography. A range of 14 to 17 Gauge, equivalent to 2.03-1.42 mm, is preferred. Miniaturization is aimed at, when technology permits the use of smaller sensors. 
         [0020]    An embodiment of the inventive method is as follows: The physician places a needle (14 to 17 Gauge) into the intervertebral disc, particularly its nucleus pulposus, of the patient who is fixed in one position. The present analysis device is inserted into the cannula and advanced until it reaches end of the cannula. In order for the surgeon to uncover sensors of the device for proper measurement, the needle will be retracted a certain distance, e.g. 2 cm, exposing the analysis device to the environment, and measurement of the sensors takes place. 
         [0021]    The analysis device is preferably connected to an interface which is in turn connected to a computer. The measurement can be started and stopped by data logging software at anytime by the surgeon. The gathered data will be retained in log file which can be analyzed for example by Windows Excel. 
         [0022]    Examples of measurement ranges of a preferred embodiment of the analysis device of the invention are as follows: 
         [0023]    pH: 0 to 12 
         [0024]    Pressure: 0 to 1333 kPa; burst range: 5332 kPa 
         [0025]    Temperature: 0-70° C. 
         [0026]    Humidity: 0-100% 
         [0027]    Calibration of the sensors is preferred. Sensors can be calibrated before or after measurement. Because sterilization of the probe might considered necessary, calibration of sensors after measurement is preferred. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0028]    In the following embodiments of the invention will be described. The preferred embodiments are not to be construed as limiting the invention. The attached drawings show: 
           [0029]      FIG. 1  an analysis device of the invention in use; 
           [0030]      FIG. 2  an embodiment of a probe of the analysis device; 
           [0031]      FIG. 3  another embodiment of a probe; 
           [0032]      FIG. 4  a further embodiment of a probe; 
           [0033]      FIG. 5  a still further embodiment of a probe; 
           [0034]      FIG. 6  a still further embodiment of a probe; 
           [0035]      FIG. 7  a detail of the analysis device of the invention according to  FIG. 1 ; and 
           [0036]      FIG. 8  a still further embodiment of a probe in a sectional view. 
       
    
    
     DETAILED DESCRIPTION 
       [0037]    In  FIG. 1  a section of a spine is shown schematically. Reference numeral  6  denotes the vertebral body. Reference numeral  20  identifies the intervertebral disc consisting of an outer annulus fibrosus  5 , which surrounds the inner nucleus pulposus  4 . The analysis device  50  of the embodiment shown in  FIG. 1  comprises a probe  1  connected via line  7  with an evaluation unit  8  where data are analyzed, e.g. a computer. The probe  1  is inserted into the intervertebral disc  20  via a cannula  2 . Details of a preferred embodiment of cannula  2  and the inserted probe are shown in  FIG. 7 . As can be seen by reflecting  FIGS. 1 and 7  cannula  2  is introduced into the intervertebral disc whereupon probe  1  is advanced through the inner bore of cannula  2  until it reaches the tip  15  of cannula  2 . As can be seen from  FIG. 7A , after insertion and advance of the probe  1  in cannula  2  the sensors (designated by reference numerals  9  to  13 ) are still located within the lumen of cannula  2 . To expose the sensors to the surrounding intervertebral disc, particularly the nucleus pulposus, cannula  2  is retracted. For this purpose, handle  14  is provided at the distal end of cannula  2 , i.e. at the end opposite to the tip  15 . Probe  1  carries a distance ring  3 . The distance ring  3  is arranged proximally to the sensors which are located at the lateral probe shell  17  near the tip  16  of the probe  1 . Distance ring  3  provides a stop position to cannula  2  which bears against distance ring  3  when it is retracted. Consequently, distance ring  3  is positioned on probe  1  in such distance to probe tip  16  that after retraction of the cannula  2  sensors  9  to  13  are exposed to the intervertebral disc in a sufficient manner to perform measurement. Preferably, the cannula is only retracted to such an extent that it still provides a guide and sheath to the probe  1 . In other words, after retraction of cannula  2  all sensors  9  to  13  located at the distal end of probe  1  should be exposed to the circumjacent tissue. However, the remaining, proximally located parts of probe  1  should still be housed in the interior of cannula  2 . Consequently, depending on location and arrangement of the sensors on probe  1  and the overall length of probe  1 , the distance ring  3  is to be spaced accordingly. 
         [0038]      FIGS. 2 to 6 , each, show different arrangements of sensors included in analysis device  50 . It is to be noted that only a detail is shown, namely the distal parts of the probes, where sensors are arranged.  FIG. 2  shows a three-sensor model, whereas  FIGS. 3 to 6  each show four-sensor options. As can be seen from all  FIGS. 2 to 6  sensor elements are preferably arranged at the distal end of the probe, i.e. the end of the probe which is inserted into the intervertebral disc, opposing that end which is connected via line  7  with the evaluation unit  8 . 
         [0039]    In  FIG. 2  a three-sensor model is depicted. Probe  101  includes pressure sensor  109 , humidity sensor  110 , and pH sensor  111 . Reference electrodes for the pH sensor  111  are also arranged at the probe; they are marked with reference numerals  112 . All sensors, as such, are arranged around the distal end of the probe  101 . One can also say they are arranged on the lateral probe shell  117 . Equivalent to the term “lateral probe shell” can be regarded the terms “mantle” or “surface of the probe  101 ”. Reference electrodes  112  of the pH sensor  111  are disposed on the tip  116  of the probe  101 , whereby the reference electrodes  112  reach into the lateral probe shell  117 . Pressure sensor  109  and pH sensor  111  are arranged in line, one after the other, seen from the one end of the probe  101  to the other end, whereas humidity sensor  110  is arranged across from pressure sensor  109  and pH sensor  111 . 
         [0040]    In the embodiment of FIG.  3 —a four-sensor model—pressure sensor  209 , humidity sensor  210  and pH sensor  211  are located in a row on the lateral probe shell  217 . Further included is a combined temperature and pO2 sensor  213 . This combined sensor  213  is placed on the tip  216  of the probe  201 . Again, reference electrodes  212  of the pH sensor  211  are included in probe  201 . 
         [0041]      FIG. 4  shows a further embodiment of a probe  301  where pressure sensor  309 , humidity sensor  310  and pH sensor  311  are arranged consecutively, one after the other, with a certain distance to each other at the lateral probe shell  317 . The distance between the individual sensors is to be chosen that not any interference between the sensors  309  to  311  occurs. Reference electrodes  312  are again provided at the tip  316  of the probe. The tip  316  of the probe  301  according to the embodiment shown in  FIG. 4  is rounded to ensure that probe  301  does not harm the intervertebral disc when advancing and positioning the probe in the intervertebral disc. A combination of temperature and pO2 sensor  313  is located opposite to pH sensor  311 . 
         [0042]      FIGS. 5 and 6 , each show still further embodiments of the inventive probe. At the tip  416  and  516  of the probe  401  and  501  combined sensors  413  and  513  to measure temperature and pO2 level, pressure sensor  409  and  509 , and humidity sensor  410  and  510 , respectively, are arranged. PH sensor  411  and  511  and its reference electrode  412  and  512  are placed on the lateral probe shell  417  and  517 , respectively. In  FIG. 5 , the reference electrode  412  is arranged parallel to, in line with the pH sensor  411 , whereas in  FIG. 6  reference electrode  512  is arranged opposite to the pH sensor  511 . 
         [0043]      FIG. 8  shows a longitudinal section of an embodiment of probe  601  in a graphical representation. At the tip  616  of the probe  601  sensor  613 , combining temperature and pO2 measurement, is located. The combined sensor  613  is flanked by reference electrodes  612  of the pH sensor  611 . The tip  616  has rounded edges to present the combined sensor  613  to environment optimally. As can be seen, combined sensor  613  protrudes over the tip  616 . PH sensor  611  is arranged close to its reference electrodes  612 . By this measure reliability of measurements of the pH sensor is ensured. Humidity sensor  610  is located in an aperture  622  of the probe  601 . Pressure sensor  609  is also located in an aperture of the probe. It is covered by a silicone membrane  619 . Pressure sensor  609 , humidity sensor  610  and pH sensor  611  are spatially separated from each other, but are arranged in a row. Electrical wires  618  of all sensors are bundled in the centre of the probe  601  and are passed towards evaluation unit  8 , as shown in  FIG. 1 . 
         [0044]      FIG. 8  also shows a preferred construction of the probe  601 . A flexible plastics tube  623  has apertures  622  at those locations where sensors are to be mounted. Mounting of the sensors is performed in that the individual sensors are placed in its assigned apertures  622 , carrying electrical wires  618 , each. Adhesive  621  (hatched), e.g. epoxy resin or UV curable resin, is filled in for fixation of the sensors  609 ,  610 ,  611 ,  612 ,  613 . As can be seen in  FIG. 8 , the head  626  of the probe  601  is built up of sensor  613 , reference electrodes  612  and adhesive  621 . Following thereafter is tube  623 , filled with adhesive  621  and carrying further sensors, sensors  611 ,  610  and  609 . Adhesive  621  is only applied as far as sensors reach and as it is necessary for fixation purposes. In the probe  601  of  FIG. 8  adhesive  621  reaches from the front end  625  of the probe  601  to the pressure sensor  609 , but pressure sensor  609  is not completely embedded in adhesive  621 . By this construction, the head  626  and those parts of the probe  601  carrying sensors is solid due to adhesive  621 . Thereafter, due to flexibility of the tube  623 , the probe  601  is flexible. The tip  616  is particularly firm, this supports advance of the probe  601  in cannula  2 . The described construction of probe  601  is of advantage for its insertion into the intervertebral disc  20 . The probe  601  can be constructed in any length desired due to the material used, flexible tube  623 , which has no fixed length. Apertures  622  for insertion of various sensors are prepared in the near of the front end  625  of tube  623 , whereas at its rear end  624  the electrical wires  618  leave the probe  601 . Preferably, probe  601  has minimum length of approximately 20 cm, as typically used cannulas for discography and for the purposes of this invention have a length of 20 cm. Even more preferred probe  601  is longer than 20 cm. At its end a plug can be mounted for connecting it to the evaluation unit  8  or any other apparatus.