Patent Document

FIELD OF THE INVENTION 
     This invention relates generally to injection devices, and more particularly to injection devices guided by heat dissipation characteristics of the body tissue through which the device is being inserted. 
     BACKGROUND 
     It is increasingly important that a physician or surgeon delivering substances, such as drugs, is able to efficiently and accurately locate the desired target tissue for effective delivery of the substance. This is particularly true when the concentration of the substance required at the target site cannot be safely or effectively achieved by introduction of the substance to a location remote from the target site. Currently, it is difficult to determine injection depth and/or tissue type without visually guiding the needle of an injection device or having some other indication of the needle location within a patient&#39;s body. 
     For example, fluoroscopy can be used to guide the injection device, but fluoroscopy lacks the resolution and sensitivity needed to accurately guide the injection device into the desired tissue location. Alternatively, electrocardiograph signals have been used when delivering substances to ventricular tissues of the heart, but this technique cannot be used throughout the entire body. In addition, the use of imaging systems (e.g., ultrasonic, magnetic resonance, and optical) to view the injection device and surrounding tissue has been proposed, but the barriers to usage of such systems are large (e.g., including large capital investment, large space requirements, and ownership of intellectual property by others). 
     SUMMARY 
     A method and apparatus are disclosed for determining injection depth and/or tissue type based on the heat dissipation characteristics of body tissue. In various embodiments, an elongate member such as a needle has at least one thermally conductive heating element mounted thereon. The heating element comprises material whose electrical resistance changes in response to a change in temperature. In addition, the apparatus includes an anemometry circuitry interface electrically coupled to the heating element so that the anemometry circuitry can measure the heat dissipation characteristics of the tissue environment in which the heating element is disposed. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
       Various embodiments are illustrated by way of example and not by way of limitation in the figures of the accompanying drawings in which like references indicate similar elements. It should be noted that references to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references mean at least one. 
         FIG. 1  is an embodiment of a heating element coupled to a needle. 
         FIG. 2  is an electrical schematic of anemometry circuitry according to an embodiment. 
         FIG. 3  shows the needle structure of  FIG. 1  disposed within a blood stream. 
         FIG. 4  shows the embodiment of  FIG. 3  disposed partially in a vessel wall and partly in the blood stream. 
         FIG. 5  shows the device of  FIG. 4  disposed almost entirely within the vessel wall. 
         FIG. 6  is a graph which shows the voltage output of an embodiment as it varies over time during the insertion shown in  FIGS. 3-5 . 
         FIG. 7  shows an embodiment having multiple heating elements disposed on a needle such that one sensor is within the vessel wall and one sensor is disposed within the blood stream. 
     
    
    
     DETAILED DESCRIPTION 
     The various embodiments described herein use heat dissipation characteristics of tissue to determine injection depth and/or tissue type. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the various embodiments. It will be apparent, however, to one skilled in the art that the various embodiments may be practiced without some of these specific details. The following description and the accompanying drawings provide examples for the purposes of illustration only. However, these examples should not be construed in a limiting sense as they are merely intended to provide exemplary embodiments, rather than to provide an exhaustive list of all possible implementations. 
     Referring now to  FIG. 1 , device  10  is shown which comprises cylindrical needle  12  having a lumen therethrough with opening  14  at a distal end to access a desired area within the body. Among other functions, needle  12  can be used to deliver a substance, extract a substance, or otherwise used to puncture tissue. Examples of substances that may be delivered include drugs, pharmaceutical agents, fluids, proteins, polypeptides, gene therapy material, cell therapy material, and deoxyribonucleic acid (“DNA”). 
     The dimensions of needle  12  will vary depending on the application. For instance, needle  12  can be designed for use with an intracardiac catheter to access a patient&#39;s atria or ventricles of the heart via a patient&#39;s vascular system, for use with an intravascular catheter to access a patient&#39;s vascular system, for percutaneous use (e.g., puncturing the skin), and for generally accessing blood-filled cavities and vessels (e.g., blood volumes). 
     Specifically, if needle  12  is to be used with an intracardiac catheter, the outer diameter of needle  12  is preferably between 0.065 inches (16 gage) and 0.013 inches (29 gage). In this regard, the gage sizes of hypodermic needle stock are relatively standard in the industry and refer to the outer diameter of the needle. The inner diameter will vary depending on the wall type. For intravascular catheter use, needle  12  will preferably have an outer diameter between 0.032 inches (21 gage) and 0.010 inches (31 gage). For percutaneous use, needle  12  can be any size suitable for a particular insertion location and the type of material to be injected or withdrawn. However, the most useful size range of needle  12  for percutaneous use would have an outer diameter between 0.134 inches (10 gage) and 0.009 inches (32 gage). Despite the given size ranges for each application, it is contemplated that sizes outside of the given ranges can be used. 
     In addition, device  10  includes heating element  16  coupled to an exterior portion of needle  12 . Heating element  16  will have approximately the same diameter size constraints as needle  12  listed above for each application. This is due to the fact that a heating element which has an outer diameter substantially larger than the outer diameter of the needle could create problems when inserting and extracting device  10 . Regarding the length of heating element  16 , it is preferred that the length be between 0.010 inches and 0.400 inches. However, lengths outside of this range could also be used. 
     In various embodiments, heating element  16  comprises material whose electrical resistance changes in response to a change in temperature. Specifically, heating element  16  is constructed with a controlled temperature/resistance relationship. In various embodiments, heating element  16  is constructed of tungsten or platinum wire or a thin metallic film. These materials have a resistance which increases as the temperature increases. However, heating element  16  may be constructed of other materials such as those used in thermistors and other devices that exhibit changes in electrical resistance in response to a change in temperature. 
     Device  10  additionally includes first electrically conductive lead  20  electrically coupled to a first end of heating element  16  and second electrically conductive lead  22  electrically coupled to a second end of heating element  16  to serve as an interface with anemometry circuitry. In other embodiments, an alternative anemometry circuitry interface could be used. Although anemometry circuits are generally used to measure flow rates of fluids, the various embodiments disclosed herein use anemometry circuitry to measure heat dissipation (e.g., flow of thermal energy) from heating element  16 . 
     Although the embodiment shown utilizes cylindrical needle  12  to mount heating element  16 , other embodiments contemplate other elongate members (that may be non-cylindrical) so long as they are suitable for insertion into a body. For example, the elongate member could be a thin rod (with or without opening  14  and with or without a sharpened distal end). Furthermore, opening  14 , if present, could be disposed more proximally on needle  12 , which would allow for heating element  16  to be disposed distal to opening  14 . Such a configuration would advantageously provide for heat dissipation measurement in situations in which tissue just distal of the desired injection depth provides a more reliable or larger signal change/reading. 
       FIG. 1  depicts heating element  16  as a wire. The wire should be large enough to conduct a sufficient amount of current but small enough to be effectively mounted on needle  12 . It is worth noting that in various embodiments, heating element  16  can comprise at least one of a wire, a film, and a thermistor material. 
     In one embodiment, heating element  16  has a length that is approximately equal to or less than the known thickness of a targeted tissue (accounting for the tissue penetration angle of device  10 ) whose heat dissipation characteristics are to be measured by device  10 . Embodiments which include this feature are able to more discretely measure heat dissipation characteristics and detect differences in such characteristics than embodiments with heating elements  16  which are longer and, therefore, have no penetration depth at which heating element  16  is surrounded by only the targeted tissue. 
     In the embodiment shown in  FIG. 1 , heating element  16  is shown having a coil portion  18  wrapped around needle  12  with covering  24  disposed over coil portion  18 . Covering  24  is adhered to needle  12  or formed as an integral part of needle  12 . Covering  24  protects heating element  16  and provides for a smooth transition with the surface of needle  12  to make insertion of needle  12  into tissue easier and less traumatic. 
     Covering  24  can be made of a non-conductive material to insulate the patient from electrical current flowing through coil portion  18 . Moreover, the wire that forms coil portion  18  may also be coated with an electrical insulator. Thus, either or both methods of providing electrical insulation described herein may be used. 
       FIG. 1  shows heating element  16  as a coiled wire. Other wire configurations are also suitable. For example, heating element  16  can be formed by placing the center of the wire near the distal end of heating element  16  and winding each end  20  and  22  in opposite directions around needle  12  towards the proximal end of needle  12 . Alternatively, the wire may be wound in a zigzag pattern, proximally and distally, back and forth in a desired area. Alternatively, heating element  16  can be formed by mounting the wire within a groove or a plurality of grooves formed within the surface of needle  12 . 
     In addition to wire configurations, heating element  16  can be formed by sputtering a thin film of metal over a masked insulator (masked to lay down the desired heating element metal configuration), removing the mask, attaching the conductors, and coating the remaining metal connections with an insulator (e.g., a dielectric material). Moreover, a photo-etching process, similar to that used in the microelectronics industry, could be used to remove metal from needle  12  in the desired configuration. 
     Heating element  16  can be mounted on needle  12  such that distance  26  (from the distal end of opening  14  to the proximal end of heating element  16 ) is substantially equivalent to a desired injection depth. Heating element  16  may be enclosed or mounted on or in a suitable assembly, syringe, or catheter to aid in the insertion, advancement, orientation, and delivery of device  10  to the desired position within the body prior to injection. 
     In addition, the proximal end of device  10  may be provided with suitable electrical connections to external circuitry and/or instrumentation (not shown) as well as fluid connections to force the injectant through device  10 . Common catheter assemblies provide such connections. 
     In various embodiments, needle  12  can be comprised of material which is not electrically conductive (e.g., ceramic) or material which is electrically conductive (e.g., stainless steel). It is worth noting that ceramic needles advantageously increase response time and sensitivity of heating element  16  due to the reduced thermal mass and thermal conductivity of ceramic. However, electrically conductive materials have electrical connection advantages, which can simplify device design. For instance, in embodiments in which a portion of needle  12  is electrically conductive, heating element  16  can be connected to anemometry circuitry by (i) first electrically conductive lead  20  electrically coupled to a first end of heating element  16  and (ii) a conductive portion of needle  12  coupled to a second end of heating element  16 . 
     If a high thermal mass needle (e.g., stainless steel) is used, a thermal insulator can be disposed between heating element  16  and needle  12  to minimize any reduction in response time and sensitivity of heating element  16  caused by needle  12 . 
     Regardless of the construction and materials used to construct heating element  16 , device  10  can have more than just a single heating element  16 , as shown in  FIG. 1 . For instance, if a plurality of heating elements  16  are mounted on needle  12  and operated separately and/or in groups, multiple penetration depths/tissue types can be controlled/identified. In addition, a single penetration depth can be more effectively controlled with an embodiment which utilizes a plurality of heating elements  16 . 
     Turning now to  FIG. 2 , an embodiment of anemometry circuitry is shown. In the embodiment shown, the anemometry circuitry is configured to measure the heat dissipation characteristics of an environment in which heating element  16  is disposed. The anemometry circuitry is electrically coupled to heating element  16  shown in  FIG. 1 . Specifically, a first end of heating element  16  is electrically coupled to first junction  42  of bridge circuit  28 , and a second end of heating element  16  is electrically coupled to node  41  of bridge circuit  28 . 
       FIG. 2  is a simplified representation of a temperature controlled hot wire or hot film anemometer system. Although there are many ways to operate an anemometer system (e.g., constant current or constant voltage), temperature controlled is preferred because the various embodiments are intended to be used within the body. Control over the temperature of heating element  16  can advantageously avoid tissue damage caused by temperature. In addition, signal level changes in response to the heat dissipation characteristics of the environment in which heating element  16  is disposed will be maximized. 
     The anemometry circuitry shown in  FIG. 2  includes balancing bridge circuit  28 , controlled amplifier  30 , and signal amplifier  32 . Although other designs and configurations for the circuitry could be used, this simplified representation is included for ease of discussion. Bridge circuit  28  is comprised of heating element  16 , a system controlled variable resistor  34  and two fixed resistors  36  and  38 . Heating element  16  acts as a resistor within bridge circuit  28 . 
     Bottom node  41  of bridge  28  is connected to ground (e.g. 0 volts). Thus, when a voltage is applied at top node  40  of bridge  28 , current will flow through heating element  16 , causing a dissipation of power. Due to the material and construction of heating element  16 , the dissipated power is dissipated as heat. The heat will raise the temperature of heating element  16  such that the temperature change will cause a change in the resistance of heating element  16 . 
     For the sake of simplicity, it is assumed that fixed resistors  36  and  38  have the same resistance value. Although this is not required, this assumption makes explanation of the anemometry circuitry easier to understand. As heating element  16  increases in temperature, the resistance of heating element  16  also increases, causing the voltage at first junction  42  (between heating element  16  and resistor  36 ) to increase. 
     Thus, if variable resistor  34  has a resistance value adjusted by the circuitry to be equal to that of heating element  16 , then the voltage at second junction  44  (between fixed resistor  38  and variable resistor  34 ) will be the same as at first junction  42 . When the voltages are equivalent, bridge circuit  28  is understood to be “balanced”. Thus, once variable resistor  34  has been adjusted to have a resistance value equal to that of heating element  16 , any changes to the resistance of heating element  16  (e.g., caused by changes in temperature) will cause the voltage at junction  42  to change in the direction of and roughly in proportion to the temperature change of heating element  16 . Thus, the voltage at first junction  42  would be either higher or lower than the voltage at second junction  44 . 
     Amplifier  30  is electrically coupled to bridge circuit  28  to sense the difference in voltage drop across heating element  16  and variable resistor  34  caused by the difference between the resistance of heating element  16  and the resistance of variable resistor  34 . Amplifier  30  receives power, from positive Vsupply and is also coupled to ground. Amplifier  30  compares the voltages of positive input  46  and negative input  48 . If positive input  46  is a higher voltage than negative input  48 , the positive difference between input  46  and input  48  is amplified and output through line  50 . 
     It is worth noting that no voltage higher than positive Vsupply will be seen at output  50 . If negative input  48  is equal to or higher than positive input  46 , then the voltage present at output  50  will be a low positive value (e.g., too low to cause significant heating of heating element  16 ). Amplifier  30  is able to compare the input voltages since positive input  46  is connected to second junction  44 , and negative input  48  is connected to first junction  42 . Output  50  of amplifier  30  is connected to top node  40  of bridge circuit  28 . 
     Focusing now on the interaction between amplifier  30  and bridge circuit  28 , it is assumed that bridge circuit  28  is initially in a balanced condition. Thus, the voltage applied to top node  40  of bridge circuit  28  by output  50  of amplifier  30  is low, and heating element  16  is not being heated. Also, the resistance of heating element  16  is equal to that of variable resistor  34 . 
     If the anemometry circuitry system raises the resistance of variable resistor  34 , the voltage at junction  44  will exceed the voltage at junction  42 . This, in turn, creates a positive voltage difference between positive input  46  and negative input  48 . This positive voltage difference causes output  50  to dramatically rise in voltage. 
     Output  50  is applied to top node  40  of bridge circuit  28 , raising the current through heating element  16 , which causes the power (e.g., heat) dissipated by heating element  16  to increase dramatically. The increase in heat dissipated by heating element  16  results in an increase in the temperature of heating element  16 . 
     When the temperature of heating element  16  nearly reaches the temperature at which the resistance of heating element  16  is the same as that of variable resistor  34 , the voltages at junctions  42  and  44  will be very close to equal. In addition, output  50  applied to top node  40  of bridge circuit  28  will begin to drop until an equilibrium is reached. Upon reaching this equilibrium, heating element  16  will be heated to a temperature that correlates to a resistance that is very close to that of variable resistor  34 . With high amplification factors in amplifier  30 , this resistance difference can be made to be negligible. 
     Since the resistance/temperature relationship of heating element  16  is known and heating element  16  now has the same resistance as variable resistor  34 , the temperature of heating element  16  is also known. Thus, this interaction allows the temperature of heating element  16  to be set by adjusting the value of variable resistor  34  so long as positive Vsupply can supply enough voltage/current to top node  40  of bridge circuit  28  to sufficiently heat heating element  16  to the desired temperature. It is worth noting that the desired temperature is above ambient temperature of heating element  16  and that output  50  is at some intermediate voltage value between the maximum and minimum values for which amplifier  30  is configured when heating element  16  is heated above the ambient temperature. 
     Thus, output  50  is directly related to the heat transfer environment of heating element  16 . If that environment carries heat away from heating element  16  rapidly, then output  50  will be a higher value than if that environment carries heat away more slowly. 
     It is expected that these changes in output  50  may be small. Thus, signal amplifier  32  is employed to increase the size of the change to a level suitable for an associated instrument (not shown) to sample, process, and display the measurements in a suitable manner. Signal amplifier  32  operates similarly to controlled amplifier  30 . However, signal amplifier  32  is supplied with negative Vsupply, instead of power supply ground. Thus, output  56  may vary between the values of positive Vsupply and negative Vsupply in response to the voltage difference of inputs  52  and  54 . 
     If positive input  52  is a higher voltage than negative input  54 , then the positive difference between the two inputs is amplified, and the amplified voltage is presented at output  56 . If positive input  52  is a lower voltage than negative input  54 , then the negative difference between the two inputs is amplified, and the amplified negative voltage is presented at output  56 . It is worth noting that the amplification factor for negative and positive differences is the same. 
     Negative input  54  is connected to wiper  58  of system controlled potentiometer  60 . Potentiometer  60  is also connected to positive Vsupply and power supply ground such that, as wiper  58  is adjusted, the voltage at wiper  58  will vary between zero and the voltage of positive Vsupply. 
     Assuming that heating element  16  is maintained at a higher than ambient temperature, amplifier  32  behaves in the following manner. Since voltage output  50  is connected to positive input  52  of amplifier  32 , input  52  is at some intermediate positive voltage level. The anemometry circuitry may then adjust wiper  58  such that negative input  54  is at or nearly at the same voltage as input  52 . Thus, voltage output  56  of amplifier  32  will be approximately zero. 
     However, if heating element  16  is moved to an environment that transfers heat more rapidly, positive input  52  (from output  50 ) will exceed negative input  54  (from wiper  58 ), and output  56  of amplifier  32  will increase a multiple of the actual increase seen at input  52  due to an amplification factor of amplifier  32 . If heating element  16  is moved to an environment that transfers heat less rapidly, positive input  52  will be less than negative input  54 , and output  56  of amplifier  32  will have a negative value which is a multiple of the actual decrease seen at input  52 . 
     Although anemometry circuitry is generally used to measure the flow velocity of fluid or gas, or, where the dimensions of the flow conduit are known or constant, to calculate flow rates, various embodiments described herein use the detected differences in the heat dissipation characteristics of different body tissues to determine injection depth and/or tissue type. It is worth noting that the embodiments disclosed herein should not be limited to measuring the heat dissipation characteristics of tissues since there are other materials within the body which are not generally considered tissues but will still have measurable heat dissipation characteristics. For instance, spinal fluid and amniotic fluid are not considered tissues but could have their respective heat dissipation characteristics measured to determine injection depth or material type. 
     Focusing now on exemplary heat dissipation characteristics of different materials, atheroma is a degenerative accumulation of lipid-containing plaque on the innermost layer of a wall of an artery. For heat dissipation purposes, atheroma is generally a waxy substance with no blood flow. If device  10  were inserted into a layer of atheroma, heating element  16  would only dissipate a negligible amount of heat. 
     Similarly, fat tissue does not have much blood flow, and therefore, heating element  16  inserted into fat tissue would experience a low heat dissipation rate. However, the same heating element  16  inserted into muscle tissue, which has substantial blood flow, would experience a high heat dissipation rate, and if heating element  16  were inserted into a moving blood stream, the heat dissipation rate experienced by heating element  16  would be extremely high. 
       FIGS. 3-6  demonstrate how device  10  with a single heating element  16  can be used to control the depth of penetration of needle  12  into the wall of a coronary artery to desired penetration depth  26 . It is assumed that device  10  is inside a suitable catheter (not shown) at the desired location, that the catheter is a relatively good thermal insulator, that heating element  16  is being driven at a temperature above blood temperature, and that the anemometry circuitry which drives heating element  16  is connected to heating element  16  and properly configured. 
       FIG. 6  shows a graph of voltage output  56  of amplifier  32  versus time. Before T 1 , heating element  16  is inside the catheter (not shown). Since the catheter is assumed to be a relatively good thermal insulator, the drive voltage or current required to keep heating element  16  at a stable temperature is low. Thus, output  56  of amplifier  32  is very negative. At time T 1 , device  10  is rapidly moved out of the catheter and into blood stream  62  of the artery ( FIG. 3 ). 
     Blood stream  62  carries away heat at an extremely high rate, which cools heating element  16  mounted on device  10  rapidly. Thus, output  56  rises rapidly to a maximum value and remains at the maximum value until T 2 , when heating element  16  has almost reached the set temperature (or resistance) again. At T 3 , bridge circuit  28  reaches equilibrium with the new heat dissipation environment of blood stream  62 . The line segment between T 3  and T 4  represents the new equilibrium level. This line segment is shown as a straight line for simplicity, but in reality, this line segment would have oscillations due to changes in the velocity of blood stream  62  relative to heating element  16  during the cardiac cycle. 
     The line segment between T 4  and T 5  represents the smooth continuous insertion of heating element  16  into artery wall  64  ( FIG. 4 ). Since artery wall  64  will be composed of atheroma, muscle tissue, connective tissue, and other surrounding tissues with low heat flow characteristics, artery wall  64  will be a better thermal insulator than blood stream  62 . Thus, output  56  will change in a negative direction until heating element  16  is completely within artery wall  64  at T 5 .  FIG. 5  shows device  10  inserted into artery wall  64  to desired penetration depth  26 . 
     As discussed above, the line segment between T 4  and T 5  is, shown as a straight line for simplicity, but in fact, the line segment will have the same cardiac cycle bumps as the line segment between T 3  and T 4 . However, as more of heating element  16  is inserted into artery wall  64 , the amplitude of these cardiac bumps will decrease until heating element  16  is no longer in blood stream  62 . 
     One drawback of the single heating element design is that if needle  12  were inserted further into artery wall  64 , there would be little change in output  56  to alert the user of the change in position. However, if second heating element  17  were mounted just proximal to first heating element  16  ( FIG. 7 ), then desired penetration depth  26  could be more easily determined. Assuming heating elements  16  and  17  are constructed in the same manner, desired penetration depth  26  would be located when the greatest difference in outputs  56  of each of the respective heating elements was observed. 
     If needle  12  were further inserted into artery wall  64 , output  56  of heating element  17  would decline toward the value of output  56  for heating element  16 . Conversely, if needle  12  were withdrawn from artery wall  64 , then output  56  of heating element  16  would increase toward the output  56  of heating element  17 . Thus, multiple heating elements allow for monitoring the depth of penetration of needle  12  within relatively close limits relative to any tissue interface where the two interfacing tissues have sufficient difference in heat dissipation characteristics and thickness relative to the length of heating elements  16  and  17  to be detectable. 
     As shown in  FIG. 7 , multiple heating elements can be constructed within a single heating element assembly. For example, in the embodiment shown, heating element  16  and heating element  17  are both disposed in covering  24 . In addition, only three electrical leads are required since each heating element has a separate bridge circuit  28  (not shown) connecting the heating element to ground (node  41  in  FIG. 2 ). Thus, heating element  16  and heating element  17  share a lead to ground. In embodiments which use needle  12  as a conductive lead, needle  12  can be used as the ground connection for all heating elements. 
     The embodiments disclosed herein can be operated by much more complex and sophisticated circuitry and instrumentation to filter, process, and detect the differences in the heat dissipation characteristics of different tissue types. For example, the temperature of heating element  16  could be stepped in increments small enough to avoid saturating amplifier  30  toward or away from body temperature, using the rate of equilibrium establishment to differentiate tissue types or boundaries in a more rapid manner. 
     It is to be understood that even though numerous characteristics and advantages of various embodiments have been set forth in the foregoing description together with details of structure and function of the various embodiments, this disclosure is illustrative only. Changes may be made in detail, especially matters of structure and management of parts, without departing from the scope of the various embodiments as expressed by the broad general meaning of the terms of the appended claims.

Technology Category: 1