Abstract:
A measuring system may provide quantitative information relating to condition of cartilage. Negative pressure may be applied to cartilage to induce flow of fluid from or through the cartilage. A level of negative pressure needed to induce a particular flow of the fluid may be employed to provide a quantitative indicia of cartilage condition. An averaged level of negative pressure measured over a period of time may be used to calculate hydraulic resistance of the cartilage.

Description:
RELATED APPLICATIONS 
       [0001]    This application claims the priority date of U.S. Provisional Application No. 61/249,339 filed Oct. 7, 2009. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
       [0002]    This invention was made with Government support under AR044058 awarded by NIH. The Government has certain rights in the invention. 
     
    
     BACKGROUND OF THE INVENTION 
       [0003]    The present invention relates to diagnosis and repair of defects and damage of cartilage tissue. 
         [0004]    Articular cartilage is a load-bearing connective tissue at the ends of long bones in synovial joints that facilitates low-friction, low-wear joint articulation. The load-bearing ability of cartilage is dependent on the presence of a large aggregating proteoglycan, aggrecan, in a matrix structure. Aggrecan is highly negatively charged due to its numerous glycosaminoglycan (GAG) side chains, and the charge density of these GAG molecules creates a swelling pressure in the interstitial fluid of cartilage that resists compression. 
         [0005]    It is known that hydraulic permeability of osteochondral tissue, especially articular cartilage, may increase with degeneration and erosion. Progressive degeneration and erosion of articular cartilage that can occur with osteoarthritis (OA) has been correlated with increased hydraulic permeability. In addition, focal defects, which are commonly observed in the knees of symptomatic patients during arthroscopy, are discrete areas of cartilage erosion that also likely have increased hydraulic permeability. Increase in hydraulic permeability may diminish the ability of cartilage to maintain fluid pressurization, leading to larger strains on the cartilage matrix and further degeneration, as well as abnormal fluid flow and communication between the intraarticular space and the subchondral bone. 
         [0006]    Repair strategies for cartilage defects may include arthroscopic procedures, such as microfracture; soft tissue grafts; osteochondral grafts of autogenic or allogenic source material; cell transplantation with or without a scaffold, including autologous cell implantation and mesenchymal stem cells; and synthetic and natural scaffolds. Interstitial fluid pressurization, and load-bearing capacity, may be typically restored with osteochondral graft techniques. 
         [0007]    Determination of the possible presence and extent of cartilage defects is a critical factor in formulating a repair strategy. Clinically useful measures to diagnose the extent of cartilage degeneration and efficacy of repair strategies are limited, especially with regard to pressure maintenance within the cartilage tissue. Presently used techniques may include visual observation during arthroscopy and/or imaging modalities such as plain film x-ray attenuation, magnetic resonance imaging (MRI) and computed tomography (CT). These methods alone may produce only limited quantitative results. 
         [0008]    While a determination of hydraulic permeability may be a valuable indicator of condition of cartilage, a direct measurement of this parameter has been performed only by experimental perfusion techniques on isolated samples of tissue in a laboratory setting. A typical ex vivo permeability measurement must be performed for a number of hours before yielding meaningful results. Indirect measurements of hydraulic permeability, extrapolated from mechanical indentation testers, have been performed, but require tissue deformation and assumptions about matrix composition that may not be applicable in damaged tissues. Direct measurement of hydraulic permeability, in situ, has heretofore not been practicable. 
         [0009]    As can be seen, there is a need for a system that may produce quantitative information indicative of cartilage condition. In particular there is a need for a system in which a quantitative indicator of hydraulic permeability may be determined in situ. 
       SUMMARY OF THE INVENTION 
       [0010]    In one aspect of the present invention, a system for assessing condition of cartilage may comprise: a contact device; a flow inducer; a fluid circuit interconnecting the contact device and the flow inducer; and a pressure sensor for determining negative pressure (−P) in the fluid circuit. 
         [0011]    In another aspect of the present invention, a contact device for a system for assessing condition of cartilage may comprise: a flexible cap; and a flexible tube attached to the cap through which negative pressure can be applied to the cartilage when the cap is in contact with the cartilage. 
         [0012]    In still another aspect of the present invention, a method for evaluating condition of cartilage may comprise the steps of: inducing flow of fluid from or through the cartilage; measuring negative pressure required to produce a particular flow rate of the fluid; and employing the measured negative pressure to produce a quantitative assessment of condition of the cartilage. 
         [0013]    These and other features, aspects and advantages of the present invention will become better understood with reference to the following drawings, description and claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0014]      FIG. 1  is a schematic diagram of system for assessing condition of cartilage in accordance with an embodiment of the invention; 
           [0015]      FIG. 2  is set of graph curves that illustrate, comparatively, data from healthy and defective cartilage in accordance with an embodiment of the invention; 
           [0016]      FIG. 3  is set of bar graphs that illustrate, comparatively, hydraulic resistance of healthy and defective cartilage in accordance with an embodiment of the invention; 
           [0017]      FIG. 4  is a perspective top view of a contact device in accordance with the invention; 
           [0018]      FIG. 5  is a perspective bottom view of the contact device of  FIG. 4  in accordance with the invention; and 
           [0019]      FIG. 6  is a flow chart of a method for assessing condition of cartilage in accordance with an embodiment of the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0020]    The following detailed description is of the best currently contemplated modes of carrying out the invention. The description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the invention is best defined by the appended claims. 
         [0021]    Various inventive features are described below that can each be used independently of one another or in combination with other features. 
         [0022]    The present invention generally provides a system that allows for in situ determination of hydraulic resistance to assess if a defect or damage to cartilage is present. In a particular application, the measurement system may be used in an arthroscopic setting. 
         [0023]    Referring now to  FIG. 1 , an exemplary embodiment of the present invention is shown. A measurement system, designated generally by the numeral  10 , may comprise a contact device  12 , a flow inducer  14 , a pressure sensor  16 , a processor  18  and a display unit  20 . The contact device  12 , the flow inducer  14  and the pressure sensor  16  may be interconnected with each other on a fluid circuit  22 . In an exemplary embodiment of the system  10 , the processor  18  may be electrically connected to the pressure sensor  16 . In another embodiment of the system  10 , the processor  18  may be electrically connected to both the pressure sensor  16  and the flow inducer  14 . 
         [0024]    In operation, the contact device  12  is in contact with a region of osteochondral tissue  24  such as cartilage, which may be referred to hereinafter as cartilage  24 . The flow inducer  14  may be employed to produce negative pressure in the fluid circuit  22 . The contact device  12  may apply this negative pressure to the cartilage  24 . In response to the negative pressure, fluid  26  may flow through or out of the cartilage. The fluid  26  may comprise any one of various fluids (e.g., cartilage interstitial fluid, synovial fluid, and/or the fluid component of bone marrow) which may be present in or adjacent to the cartilage  24 . 
         [0025]    As the fluid  26  may flow out of or through the cartilage  24 , it may increase overall volume of fluid in the fluid circuit  22 . A rate at which this volume increases (Q) may be a function of magnitude of negative pressure (−P) in the fluid circuit  22 . In other words a flow rate (i.e., Q) of the fluid  26  may be interrelated to −P. It must be noted, however, that the rate Q is not exclusively determined by the pressure level P. One factor that affects rate Q is cartilage hydraulic pressure. If the cartilage  24  has a high hydraulic resistance (i.e., low permeability), then a particular rate of flow Q may require a high magnitude of −P. Conversely, if the cartilage  24  has a low hydraulic resistance (i.e., high permeability), then the same Q may be attainable with a lower magnitude of −P. It may be seen that, by operation of the system  10 , a value of hydraulic resistance (R) of a particular portion of the cartilage  24  may be quantified with a determination of two measurable parameters, −P and Q. 
         [0026]    Referring now to  FIG. 2 , a series of graph curves were prepared to illustrate comparatively how the system  10  responded while being applied to healthy cartilage and defective cartilage. A curve  202  was prepared to illustrate how −P varied over time when the contact device  12  was applied to a healthy portion of the cartilage  24 . A curve  201  was prepared to illustrate how −P may varied over time when the contact device  12  was applied to a defective portion of the cartilage  24 . Both of the curves  201  and  202  represent operation of the system  10  when Q was held constant and equal for both curves. It may be seen that with progressive time lapse, the curve  202  (i.e., healthy cartilage) shows a higher magnitude of negative pressure than the curve  201  (i.e., defective cartilage). It may also be seen that with increasing time, a pressure difference (ΔP) between curves  201  and  201  became larger. For example, at a time of about 4 seconds ΔP was about 2 kilopascals (kPa) to about 3 kPa. At a time of about 20 seconds ΔP was about 30 kPa. Thus at 20 seconds, ΔP was more readily discernible than at 4 seconds. 
         [0027]    It has been found that data relating to −P may be reduced and fit to a model equation to determine R of cartilage  24  in various states of health or degeneration. Pressure values may be normalized to a baseline average pressure recorded over 5 seconds before initiation of flow. A zero time point may be set as a point at which the pressure may increase over standard deviations from the baseline average. The system  10  may be modeled in accordance with the expression: 
         [0000]    
       
         
           
             
               
                 
                   
                     - 
                     P 
                   
                   = 
                   
                     QR 
                      
                     
                       ( 
                       
                         1 
                         - 
                         
                           exp 
                            
                           
                             [ 
                             
                               - 
                               
                                 t 
                                 RC 
                               
                             
                             ] 
                           
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   Equation 
                    
                   
                       
                   
                    
                   1 
                 
               
             
           
         
       
     
         [0000]    where: 
         [0028]    −P is averaged measured pressure over a time t; 
         [0029]    R is hydraulic resistance of the cartilage; 
         [0030]    C is a predetermined compliance of the system  10 ; and 
         [0031]    Q is the flow rate. 
         [0032]    In a typical measurement of cartilage condition, the time t may be selected to be consistent with a time constant of the system  10  in its operational mode. In other words, the time t may be selected to be equal to R*C. In such a case, the exponential term of Equation 1 may be exp (−1) or about 0.36. This may correspond to a time t at which −P may be at about 64% of its final value. When the time t is selected to be equal to the time constant, the system  10  may be operated in a manner that may clinically optimized. In other words, values of −P may be readily discernible for comparative purposes but time lapse for performing a measurement may remain desirably low. For example, it has been found that an optimum time for performing a particular measurement sequence with an exemplary embodiment of the system  10  may be about 20 seconds. 
         [0033]    Referring now to  FIG. 3 , a bar graph shows a comparative set of R values that were determined from the data of  FIG. 2 . A bar graph  301  represents a value of R that was determined by applying the contact device  12  to defective cartilage. A bar graph  302  represents a value of R that was determined by applying the contact device  12  to healthy cartilage. 
         [0034]    In operation, the contact device  12  may be applied to cartilage in any one of numerous clinical settings, such as open-joint surgery or arthroscopic surgery. The system  10  may be employed during a procedure to determine, in “real time” whether a patient&#39;s cartilage is healthy or defective. The contact device may be applied to a particular portion of the patient&#39;s cartilage and, within about 20 seconds, a clinician may be able to see a quantitative display of R on the display unit  20 . In this context, the system  10  may be employed as an adjunct to a cartilage repair procedure. Because cartilage condition may be determined in “real-time”, repair strategy decisions may be made based on quantitative assessment of cartilage conditions. 
         [0035]    Referring now to  FIGS. 4 and 5 , an exemplary embodiment of the contact device  12  is illustrated. In the exemplary embodiment of  FIGS. 4 and 5  the contact device  12  may be constructed so that it may be arthroscopically-deliverable. The contact device  12  may comprise a cylindrical silicone rubber cap  12 - 1 , having exemplary dimensions of about 8 millimeters (mm) height by 15 mm inner diameter by 1.4 mm thickness. The cap  12 - 1  may be glued on a flat silicone toroidal ring  12 - 2  having exemplary dimensions of about 18 mm outer diameter, 10 mm inner diameter by 1.0 mm thickness. A silicone rubber disc  12 - 3  having exemplary dimensions of about 23 mm diameter by 2.0 mm thick may be glued to the closed end. A hole  12 - 4 , having an exemplary dimension of about 3 mm diameter, may be in a side of the cap  12 - 1 . A stainless steel tube  12 - 5  (e.g., 4.5 mm outer diameter by 0.13 mm thick) may be adhered inside silicone tubing  12 - 6  (e.g., 3.8 mm inner diameter by 1.0 mm thick) and secured to the hole  12 - 4 . The contact device  12 , constructed with dimensions and materials described above, may be suitable for insertion through a standard arthroscopic cannula with an inner diameter of about 8 mm. While the contact device  12  may be compressed to pass through the cannula, the device  12  may be rigid enough to resist deformation when exposed to negative pressure, for example as high as 80 kPa, when in contact with the cartilage  24 . 
         [0036]    Referring now to  FIG. 6 , a flow chart may illustrate an exemplary method  600  which may be employed to evaluate condition of cartilage. In a step  602  a measurement system may be calibrated for a particular clinical session wherein a particular length and volume of the fluid circuit may be employed. (For example, calibration may be performed to quantify compliance (C) of the system  10 . The fluid circuit  22  may be filled with fluid such as saline. The contact device  12  may be placed on a rigid surface and a compliance value, in units kPa/mm 3 , may be determined. The processor  18  may be programmed to apply the determined C to all R determinations for the particular clinical session). 
         [0037]    In a step  604 , the contact device may be placed in contact with a portion of cartilage of a patient (e.g., the contact device  12  may be inserted through an arthroscopic cannula and into contact with the cartilage  24  during an arthroscopic diagnostic and repair procedure). In a step  606 , flow may be induced in the fluid circuit (e.g., the flow inducer  14  may be operated to induce a volume change of the system  10  at a rate Q; the rate Q may be predetermined and constant. Alternatively, the rate Q may be variable in which case the variable rate Q may be continuously transmitted to the processor  18 ). In a step  608 , negative pressure in the system may be measured for a time t (e.g., the pressure sensor  16  may sense −P over a time period that corresponds to a time constant of the system  10 ). In a step  610 , −P data may be processed to produce an R value (e.g., average −P collected over the time t may be processed in accordance with the Equation 1 in the processor  18  to yield an R value for a particular portion of the cartilage  24 ). In step  612 , the R value may be displayed (e.g., the processor  18  may produce a signal to the display unit  20  so that the display unit  20  may display the R value to a clinician). 
         [0038]    It should be understood, of course, that the foregoing relates to exemplary embodiments of the invention and that modifications may be made without departing from the spirit and scope of the invention as set forth in the following claims.