Abstract:
A method and apparatus for reshaping cartilage using radiofrequency heating. The cartilage temperature is raised sufficiently for stress relaxation to occur in the cartilage, but low enough so that significant denaturation of the cartilage does not occur. The RF electrodes may be designed to also function as molds, preses, clamps, or mandrills to deform the cartilage tissue. Changes in various properties of the cartilage associated with stress relaxation in the cartilage may be measured in order to provide the control signal to provide effective reshaping without denaturation.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 60/177,543, filed Jan. 21, 2000, entitled “Method and Apparatus for Cartilage Reshaping by Radiofrequency Heating” which is incorporated herein by this reference. 
    
    
     STATEMENT OF GOVERNMENT INTEREST 
     The United States Government has rights in this invention pursuant to contracts between the University of California, and the Department of Energy (95-3800459); the Office of Naval Research (N00014-94-0874); and the National Institutes of Health (1 K08 DC 00170-01, AR-43419, RR-01192, and HL-59472). 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to a method and apparatus for reshaping cartilage tissue, by raising the temperature of the cartilage sufficient for relaxation of stress in the cartilage while maintaining the temperature below that at which significant denaturation of the cartilage occurs. The invention particularly relates to a method and apparatus that utilizes radiofrequency heating to induce the stress relaxation. 
     2. Description of Related Art 
     Cartilage has long been recognized as an almost ideal autologous grafting material for reconstruction of the anatomy of the upper airway and the head and neck. Conventional reconstructive techniques have involved carving, cutting, suturing and/or morselizing the tissue to alter shape. The limitations of these approaches have been donor site morbidity, depletion of viable donor tissue requiring more radical operative techniques, and the unpredictable outcome of the procedure as a function of the stresses present in the transplanted cartilage or native tissue. The advances made in understanding cartilage at the molecular level have led to an interest in predictably altering its morphology for reconstructive purposes for both grafts and in situ. 
     Cartilage is a complex macromolecular tissue composed of 80% water, 13% collagen (Type II), and 7% protein-polysaccharide (proteoglycans). The collagen and proteoglycan molecules are synthesized by the chondrocyte, the constitutive cell of cartilage tissue. The collagen forms a rigid framework that encases large meshes of proteoglycan macromolecules containing copious numbers of charged species, chiefly COO −  and SO 3  moieties. In the matrix, the proteoglycans are compressed and the surrounding collagen framework resists their expansion. Cations (Ca ++  and Na + ) also permeate the matrix, providing electrical neutrality (charge balance). 
     Prior to being used in reconstructive or aesthetic procedures, cartilage must often be reshaped because of differences in shape and morphology between the tissue and the constraints of the recipient site. Traditional methods include reshaping by carving, suturing or morselizing. These methods can result in damage to the tissue and decreased viability. In addition, cartilage has a tendency to return to its original shape after mechanical means of reshaping, due to internal stresses present in the cartilage. These points are also valid for operations which alter cartilage shape in situ such as rhinoplasty, tracheoplasty, and otoplasty. The screened Coulomb potential between the negatively charged moieties residing on adjacent proteoglycan molecules resists mechanical deformation of the cartilage. Without intervention, relaxation of stresses normally takes a prohibitively long period of time, which is impractical in the operating room. 
     Heat can be used to alter the shape of cartilage and create mechanically stable new morphologies. Stress relaxation can result from changes in tissue structure caused by heating of the cartilage, which redistributes tissue water entrapped in the matrix mesh. However, overheating of biological tissue leads to changes in their structure by the processes of denaturation, melting and carbonization connected with chemical bond rupture. There exists a temperature region (60-75 degrees C.) within which molecular bonds are broken resulting in an increase in plasticity of the cartilage, with minimal or no denaturation, melting, carbonization or the boiling of tissue water. Within this region, bound water undergoes the transition to a free state. Upon cooling, this water becomes bound in place, resulting in permanence of shape. 
     An alternate approach to traditional reconstructive techniques was proposed in 1993 by Helidonis and Sobol, which involved the use of photo-thermal heating to accelerate stress relaxation in deformed cartilage grafts. While numerous studies have focused on the biophysical basis of cartilage shape change during laser irradiation, there are other methods of heating cartilage which include contact heating, ultrasound, and radiofrequency (RF). 
     Radiofrequency generators are in widespread use in surgery and used commonly to cut or ‘fulgurate’ tissue or cauterize and coagulate. A newer application is in radiofrequency tissue ablation. Applications of this technique are in the fields of neurosurgery, cardiology, urology, and head and neck surgery, and have been used to treat vertebral disorders such as disc herniation, ablate ectopic cardiac pacemakers, reduce the volume of the prostate, and stiffen the palate to eliminate snoring. These microprocessor controlled devices can maintain tissue temperatures in the 60-90° C. range and heat a controlled volume of tissue surrounding the electrode. U.S. Pat. No. 5,569,242 (Lax et al) discloses the use of RF energy to contract (shrink) collagen tissue. 
     Unlike tissue ablation or contraction which results in protein denaturation, cartilage reshaping involves thermally mediated stress relaxation preferably without denaturation of the tissue. 
     SUMMARY OF THE INVENTION 
     An object of this invention is a method and apparatus for reshaping cartilage via thermally mediated stress relaxation in the cartilage. 
     A further object of this invention is a method and apparatus for reshaping cartilage which utilizes radiofrequency heating to raise the cartilage temperature to the point where stress relaxation occurs but below that at which significant denaturation of the cartilage occurs. 
     In the present invention, cartilage is heated by radiofrequency energy via electrodes in contact (inserted or on the surface) with the cartilage. The cartilage is heated until the stress relaxation temperature is reached in the tissue or stress relaxation is determined through other measurement techniques including optical monitoring and acoustic monitoring. Further aspects of the invention include electrodes shaped to the final desired cartilage shape, and wherein the electrodes are integrated with clamps, jigs or scissors to perform the additional roles of holding and deforming both cartilage grafts and cartilage tissue in situ (e.g. tracheal rings in the airway). In other embodiments of the present invention, an array of electrodes are used to heat the cartilage, wherein the array electrodes may be activated either sequentially or in parallel depending upon the desired thermal field. Monitoring of the stress relaxation temperature may occur by various means, including direct measurement of the temperature, measurement of the changes in the light scattering properties of the cartilage as stress relaxation occurs, and measurement of changes in cartilage physical properties (density, electrical resistance and acoustic properties). 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIGS. 1A and 1B illustrate aspects of the present invention utilizing electrodes that are inserted and placed on the cartilage respectively. 
     FIGS. 2A and 2B illustrate aspects of the present invention wherein the electrodes may be simple (e.g. arcs) or complex shapes. 
     FIGS. 3A and 3B illustrate aspects of the present invention wherein surface mounted electrodes provide additional functions of holding and deforming as part of a clamp, jig or scissors. 
     FIGS. 4A and 4B illustrate further aspects of the present invention wherein the electrodes may comprise an array of electrodes either embedded or on the surface of the RF heating element. 
     FIG. 5 illustrates an exemplary configuration of the present invention with a cartilage bending jig, cartilage specimen, grounding electrode, and RF electrode. 
     FIG. 6 provides photographs of exemplary cartilage before and after shaping by RF heating 
     FIG. 7 illustrates an exemplary configuration of the present invention which includes light scatter measurement to provide a feedback mechanism. 
     FIG. 8 illustrates diffuse transmittance vs. time for a exemplary cartilage specimen undergoing two cycles of RF heating. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 Abbreviations 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 ADC 
                 analog to digital converter 
               
               
                   
                 IR 
                 infrared 
               
               
                   
                 mm 
                 millimeter 
               
               
                   
                 nm 
                 nanometer 
               
               
                   
                 pc 
                 personal computer 
               
               
                   
                 RF 
                 radiofrequency 
               
               
                   
                 Si 
                 silicon 
               
               
                   
                   
               
             
          
         
       
     
     As described herein for various embodiments of the present invention, various types of RF devices may be used to heat and reshape cartilage. 
     Advantages of RF Generated Stress Relaxation/Reshaping 
     To achieve stress relaxation, it is preferred that the cartilage be heated to a temperature in the range of 60 to 75 degrees C., most preferably 70 degrees C., however the precise temperature range is dependent on the heating rate. Distinct advantages exist in using RF generated heating for thermally accelerated stress relaxation of cartilage. The technology is inexpensive and already available in most operating rooms. It requires no additional protective equipment for the operator, in contrast to laser procedures which require eye protection for the surgeon, operating room personnel, and the patient. Because contact heating is used, electrodes may be designed which also function as molds, presses, clamps, or mandrills to deform the cartilage graft or restore/alter the shape of native tissue in situ. Anatomic specimens could then be straightened (as in the case of deformed nasal septal cartilage,) or reshaped into curves of predetermined radii (for applications such as reconstruction of the trachea or nasal ala.) The ability to produce cartilage of a precise shape will minimize the invasiveness of the surgical approach, thereby reducing the morbidity for the patient. 
     RF Heating of Cartilage 
     Conduction of electrical currents within the tissue will depend on the dielectric properties of the tissue as well as the frequency, waveform and amplitude of the source and electrode design. Transmission (or application) of RF energy in biological tissue results in generation of heat due to the vibration of water molecules. The spatial distribution of heat is dependent upon the space-dependent electric field intensity and the thermal diffusivity of the cartilage specimen. The temporal characteristics of any RF generated heat source in tissue depends also upon the duration of RF heating. Lower frequencies (on the order of ½ MHz) in general result in a more volumetric, bulk heating effect due to a larger more uniform electric field. Higher frequencies (on the order of several MHz) confine the electromagnetic energy to a smaller region of space. The requirements for the specific surgical procedure (bulk heating of the entire tissue sample, or localized spot heating) will dictate the power spectrum of frequencies applied to the RF generator. 
     Radiofrequency (RF) Generators 
     In general, bipolar RF heating is preferred, but there may be some applications (such as inside the trachea) where this geometry would not be accommodated, in which case monopolar RF heating may be used. 
     RF Energy Modulation 
     RF energy input (frequency, voltage, current, power, time duration and waveform) to the cartilage affects the temperature profile in the cartilage. Since denaturation of proteoglycans and collagen takes more time than that required for stress relaxation, the time dependent nature of the temperature profile in the cartilage needs to be considered. If the energy is deposited largely at the cartilage surface and interior heating occurs primarily by heat conduction, then modulation of the energy input with time is preferred in order to prevent overheating of the surface prior to stress relaxation occurring in the interior of the cartilage. One means of accomplishing this is modification of the waveform (e.g., cycling the RF energy input on and off, altering frequency etc.). The frequencies may be selected dynamically according to the feedback control signal(s). This can provide real-time variation of the depth distribution of thermal energy deposition. In laser procedures, energy fluence on the order of 25-40 W/cm 2  raises tissue temperatures in 1-3 mm thick cartilage specifimens to 60-70 deg. C in 2-4 seconds. If significant energy is deposited largely at the surface, various cooling means as are well known in the art may be preferred including cooling of the electrodes or handpiece. 
     RF Electrodes and Reshaping Clamps/Jigs 
     The RF electrodes may vary in size and shape, as required for the desired reshaping, and appropriate for the cartilage size and shape, and may be monopolar or bipolar. The RF electrodes are placed in contact with the cartilage either on the surface or inserted into the tissue. Electrodes to be inserted may be of various shapes, preferably needle or knife-blade shaped. Preferred electrode material is stainless steel (medical grade) though other materials including shape memory alloys may also be useful. FIG. 1A shows needle shaped electrodes  13  that are inserted into cartilage  11  which is held by a jig (not shown). Referring to FIG. 1B, RF electrode  13  contacts the surface of unshaped cartilage  15   a  (e.g. nasal tip) to provide RF heating resulting in reshaped cartilage  15   b.  Surface contact electrodes  23 , may be simple shapes, such as in a spatula or arc shape FIG. 2A, or complex shapes (FIG.  2 B). 
     Standard medical jigs, clamps and scissors for reshaping cartilage are well known in the art. A further embodiment of the present invention is where the electrodes themselves are part of the jig, clamps or scissors, not only heating, but also serving to clamp and/or shape the tissue. The electrodes may also be designed to function as molds, presses and mandrills. Referring to FIG. 3A, unshaped cartilage  31   a  is heated, clamped and deformed by surface contact RF electrodes  33  resulting in reshaped cartilage  31   b.  The electrodes are preferably incorporated as part of a jig, clamp or scissors  35  (FIG.  3 B). The electrodes may themselves be shaped into the desired shape, or coupled with (embedded into, or placed on the surface) a non-conductive, biocompatible material such as plastic. It is also possible to construct these type of electrodes from malleable materials in order to provide the use with more shape change options. 
     In the present invention, the electrodes may be placed and repositioned to different places on the cartilage as required for the desired temperature profile in the tissue. In a further embodiment the electrodes may be an array of electrodes, that are either simultaneously or sequentially activated. Referring to FIG. 4A, metal expandable stent  45  is placed inside the cartilage specimen  41  (e.g. tracheal ring), wherein array of electrodes  43  are positioned on the surface of stent  45 . It is to be equally understood that electrode array  43  may be embedded in stent  45 , which may be constructed from using plastic, metal and shape memory alloys. Stents may be of the shape memory type (inserted then heated to expand), or inflatable (balloon-bladder) type. The incorporation of RF technology into current available stents is also feasible. 
     Saline Solution 
     Use of a saline or similar electrolyte solution between the RF electrode(s) and the cartilage may be used to improve contact between the element and the tissue. The solution may also serve to provide cooling to the tissue, mitigating potential situations wherein a vapor bubble develops between the electrode(s) and tissue in dry environments. Active irrigation may improve this process by allowing for modulation of surface temperatures. 
     Rehydration 
     The cartilage may be held in position during the reshaping process, in-vitro or in-vivo. If the cartilage is heated in-vitro outside of a saline solution, the cartilage is preferably rehydrated following such heating, but while mechanically deformed. A rehydration time of approximately 15 minutes has been found to be suitable for maintenance of the new shape following laser heating, and should be equally suitable following RF heating. In-vivo, the re-shaped cartilage is often surrounded by hydrated soft cartilage and hence is an aqueous environment obviating the need for application of external solutions for rehydration, but the need for maintaining deformation will likely still be necessary (15 minutes). 
     Monitoring of Cartilage Stress Relaxation 
     As mentioned previously, stress relaxation occurs within a discrete temperature range, and therefore it is preferred that there be a means to detect the onset of stress relaxation in order to provide feedback control over the temporal and spatial characteristics of the RF heating and hence minimize thermal injury to the chondrocytes. If the RF source is manually operated, the feedback control means could serve to provide visual and/or auditory cues to the operator. If the RF source is automatically controlled, such as by a computer, the feedback control means could be linked directly to the RF source. 
     Temperature Measurements 
     Onset of stress relaxation may be detected by directly measuring temperature, either by contact methods or radiometric. If contact methods are used, it is preferred that a RF generator device with integrated micro-thermocouples be used, to monitor tissue temperature during heating. 
     Measurement of Changes in Cartilage Optical Properties 
     It has been found that thermally mediated stress relaxation in cartilage is also accompanied by changes in light scattering properties in the cartilage. Thus, observed changes in the intensity of diffusely transmitted light during RF generated heating can be used to provide feedback control over the RF power delivery. It is preferred that the wavelength of the illuminating light be in the visible to near IR range. Optical fibers can be used to deliver light to the tissue and also be used to detect backscattered light. Fibers can be incorporated into electrode, jig, clamp etc. design, and one fiber may be use to deliver light and collect the reflected or transmitted optical signal. A variety of signal processing techniques can be used to improve signal quality. Multi-wavelength probing of the tissue may also be of value, providing different qualitative changes in the reflected light curve. 
     Measurement of Cartilage Physical Properties 
     It is known that biological tissue undergoes changes in density and electrical resistance as the tissue is heated. Monitoring of changes in cartilage density or electrical resistance by means well known in the art, during RF heating may also be used to provide feedback control over the RF heating. Other easily measured physical characteristic include tissue acoustic properties which can be detected and evaluated using a variety of acoustic techniques, in general based on piezo-electric technology. This art is well known and commonly used for non-destructive testing applications. 
     EXAMPLES 
     Cartilage Preparation 
     For the following examples, porcine nasal septal cartilage from freshly euthanized animals was obtained from a local abattoir. (Lizzy&#39;s Custom Processing, Chino, Calif.) The specimens were cut into 20 mm×10 mm sections and then cut to a uniform thickness (2 mm) using a custom guillotine microtome. These were stored in normal saline solution at 4° C. and used within 24 hours. 
     Example 1 
     In this example, the Stortz RF generator (Stortz Surgitron #S 2100, 2.8 MHz. Elmed Inc, Addison, Ill.) used was designed primarily for tissue fulguration, coagulation and cauterization, and had an adjustable power control (uncalibrated scale from 1 to 10.) It was thus necessary to estimate the tissue effect at each power setting. This was accomplished by observing the denaturation of albumin (egg white.). 
     To determine approximate power settings on the Stortz RF generator for our application, albumin from fresh egg whites was used as a gross surrogate for protein coagulation and cartilage matrix denaturation. Albumin denatures at 61° C. and provides a clear visual end point for monitoring. The generator was used in bipolar mode and copper tape electrodes (6 mm×6 mm) separated by 2 mm (the thickness of the cartilage slabs) were immersed in the egg whites. Working in a well lighted room, the time required to denature the albumin (clear to white transition) was recorded across the range of power settings on the device yielding denaturation in the range of 3 to 30 seconds. 
     Albumin Coagulation/Denaturation 
     Table 1. is a tabulation of the albumin denaturation data. This allowed selection of approximate power settings of the RF generator for cartilage bending (without denaturation) and diffuse transmittance experiments. Note that the data are for 2 mm electrode separation. 
     
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Time to denature egg white albumin at various power settings of 
               
               
                 the Stortz RF generator (bipolar electrodes separated by 2 mm.) 
               
             
          
           
               
                   
                 power 
                   
                   
                   
                   
                   
               
               
                   
                 setting 
                 1.5 
                 2.0 
                 2.5 
                 3.0 
                 3.5 
               
               
                   
                   
               
               
                   
                 time (s) 
                 30 
                 14 
                 12  
                 6 
                 3 
               
               
                   
                   
                 30 
                 13 
                 6 
                 6 
                 3 
               
               
                   
                   
                   
                 17 
                 6 
                 6 
               
               
                   
                   
                   
                 11 
               
               
                   
                   
                   
                 16 
               
               
                   
                 average 
                 30 
                 14 
                 8 
                 6 
                 3 
               
               
                   
                 time 
               
               
                   
                   
               
             
          
         
       
     
     This process provided approximate power settings and times for the Stortz RF generator so that the proteins of the cartilage matrix could be heated without undergoing denaturation. 
     Reshaping (Bending) Jig 
     The cartilage slab  51  was placed in a wooden bending jig  57  (see FIG.  5 ). A grounding electrode  55  of sheet aluminum with applied conducting gel (produced for application of electrocardiogram electrodes) was placed in contact with the cartilage  51  in the jig  57 . Multiple stab insertions of a needlepoint electrode  53  were made, and the device was turned on for 8 seconds at a power setting of 2 on the power scale, for each insertion. The deformed specimen was then rehydrated in normal saline for 15 minutes. 
     FIG. 6 shows photographs of the cartilage specimen before and after reshaping via RF generated heating with the Stortz RF generator. 
     Example 2 
     In this example, the Somnus RF generator used (a Somnus™ model #215 Radiofrequency Generator, 460 kHz. Somnus Medical Technologies, Inc, Sunnyvale, Calif.) was originally designed for use in palatal, tongue-base and turbinate surgical procedures, and incorporates an internal microprocessor that controls heating to a user-specified temperature. The needle shaped electrode contained a series of integrated micro-thermocouples which were used to monitor the temperature of the surrounding tissue. 
     The cartilage was manually deformed into a curved shape with a standard surgical grounding pad applied. Multiple stab insertions of the electrode were made over the length of the cartilage slabs. At each position, the cartilage was heated to 70° C. The deformed cartilage specimens were then rehydrated in normal saline for 15 minutes. The specimens were photographed before and after reshaping. 
     Example 3 
     In this example, laser light scattered from the specimen may be measured to monitor the degree of RF cartilage heating and stress relaxation during RF heating. Referring to FIG. 7, a diode laser  78  (λ=650 nm, 5 mW) (MWK Industries, Corona, Calif.) is directed co-linear to the surface normal of the cartilage  71  heated by needle RF electrode  73 ; cartilage  71  being held in jig  72 . A mechanical chopper  76  and controller  78  (SR540, Stanford Research Systems, Sunnyvale, Calif.) is used to modulate the intensity of the diode laser. The intensity of the diffusely transmitted laser light I is measured using an integrating sphere  74  (LPM-040-IG, Labsphere, North Sutton, N.H.) positioned on the opposite side of the cartilage from the incident laser light. The signal is synchronously detected using a silicon photoreceiver  75  (Model 2001; New Focus, Mountain View, Calif.) and a lock-in amplifier  79  (time, 300 ms)(Model SR 850 DSP; Stanford Research Systems.) Data is acquired using a 16-bit AD converter (not shown) (AT-MIO-16XE-50; National Instruments, Austin, Tex.) and a personal computer (not shown) running software written in LabView (National Instruments.). I(t) is recorded during RF heating with the Stortz generator at a power setting of 1.25 over 30 seconds. 
     Exemplary diffuse transmittance I(t) during RF generated heating is depicted in FIG.  8 . Two heating cycles in the same specimen are represented. A five-minute cooling interval elapsed between cycles. It is noted that the slope of the ΔI(t)/I 0  vs. time plot reaches zero at approximately 4 s with the 1 st  heating and at approximately 10 s with the 2 nd  heating (I(t)=intensity at time t; I 0 =initial intensity). 
     The correlation between tissue optical properties and accelerated stress relaxation in mechanically deformed cartilage during laser heating has previously been documented. In particular, the slope of I(t) been shown to be zero at the onset of stress relaxation. In this study, the intensity of diffusely transmitted light through the tissue was measured during RF heating. As expected, a gradual decrease in the intensity of the transmitted laser light was observed as the tissue was heated, and the slope of the I(t) was zero after 4 to 10 s. This is within the time interval demonstrated to maintain tissue viability in previous studies. 
     As can be seen, thermally accelerated stress relaxation of cartilage is achievable with RF generated heating. Obviously, numerous modifications and variations of the present invention are possible in the light of the above teachings. It is therefore to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described therein.