Abstract:
In one embodiment, the present invention provides a sensory testing system. In another embodiment, the present invention provides a method of using a sensory testing system to determine sensory pressure thresholds. In a further embodiment, the present invention provides a method of diagnosing a condition characterized by impaired neural function by using a sensory testing system to determine sensory pressure thresholds.

Description:
RELATED APPLICATIONS  
       [0001]     This application claims benefit of U.S. Provisional Patent Application 60/646,770 filed Jan. 25, 2005, the entire contents of which are incorporated by reference for all purposes. 
     
    
     GOVERNMENT SUPPORT  
       [0002]     This invention was supported, in whole or in part, by grants NS-10783 and AR-48925 from the National Institutes of Health. The United States government has certain rights in the invention. 
     
    
     BACKGROUND OF THE INVENTION  
       [0003]     Sensory testing of the skin is done to investigate possible compromised touch or pain sensation. Such testing can be used to detect peripheral neuropathies of various origins, such as diabetes mellitus.  
         [0004]     Sensory testing of the skin is commonly performed by applying filament stimulators, such as von Frey hairs or Symmes-Weinstein filaments, to the skin of the patient or test subject. The filament is advanced past the point of contact to compress the skin until the filament buckles. The patient or subject reports whether or not the resulting compression is detected and whether the sensation is painful. When the filament buckles, the compression force that the filament exerts on the skin is approximately independent of the degree of buckling, and is dependent on the material composition and the structure of the filament, i.e., its diameter, length and composition. Thus, the physician sequentially applies filaments of increasing stiffness and consequently exerting greater compressive force, during the course of testing the sensibility at a given point on the skin&#39;s surface. The force required to produce a criterion response, such as a report of pain, is recorded and the process repeated at another point within the test area on the skin.  
       SUMMARY OF THE INVENTION  
       [0005]     In one embodiment, the present invention provides a sensory testing system. In another embodiment, the present invention provides a method of using a sensory testing system to determine sensory pressure thresholds. In a further embodiment, the present invention provides a method of diagnosing a condition characterized by impaired neural function by using a sensory testing system to determine sensory pressure thresholds. The method of the present invention facilitates rapid and accurate sensory testing by eliminating the time consuming use of manually operated von Frey hairs.  
         [0006]     In preferred embodiments, the invention provides a sensory testing system including a test filament having a proximal end and a distal end, the proximal end for engaging a test subject, the test filament further associated with an axis substantially parallel to the probe, a motor having a shaft moveable along the axis, the shaft further coupled to the distal end of the filament, the motor further capable of moving the shaft at a constant force without requiring a force measuring device in communication with the test filament; and a controller for controlling the operation of the motor. Preferably the test filament remains substantially rigid over a determined range of applied forces and the motor is a linear motor.  
         [0007]     Generally, the system further includes a displacement sensor for measuring a displacement of the shaft. In preferred embodiments, the controller is a digital computer processing machine-readable instructions. The system can be used for testing human subjects, such patients suspected of suffering from conditions such as peripheral neuropathy or diabetes. The system also can be used for testing nonhuman subjects such as veterinary patients or laboratory test animals.  
         [0008]     In preferred embodiments, the present invention provides a method for performing sensory measurements on a subject, the method comprising the steps of receiving an initialization instruction from a controller; receiving an advancement instruction for causing a shaft to increment (“ramp up”) the operating force until a detection signal is received; receiving the detection signal; stopping advancement of the shaft in response to the detection signal; and recording the force applied at the time of the detection signal.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]     The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.  
         [0010]      FIG. 1  is a schematic illustration of an embodiment  100  of the method of the present invention, showing the steps of selecting a test area on the subject  102 , entering selected parameters into a sensory testing system  104 , applying a probe of the sensory testing system to the test area  106 , receiving a stop signal  108  and recording the pressure exerted by the probe on the test area.  
         [0011]      FIG. 2A  is a diagrammatic illustration of an embodiment of the sensory test system of the present invention suitable for use with non-human subject.  
         [0012]      FIG. 2B  is a diagrammatic illustration of the relationship of linear motor  206 , filament retainer  204 , displacement sensor  210 , movable base  212  and cable  216  in one embodiment of the sensory test system of the present invention.  
         [0013]      FIG. 3A  and  FIG. 3B  are graphic representations of results obtained using an embodiment of the sensory test system of the present invention, showing in  FIG. 3A  a plot of load versus time, and in  FIG. 3B  a plot of displacement versus time.  
         [0014]      FIG. 4  is a diagrammatic illustration of another embodiment of the sensory test system of the present invention suitable for use with human subject.  
         [0015]      FIG. 5  is a diagrammatic representation of an embodiment of a suitable computer  400  for use in the sensory testing system of the present invention.  
         [0016]      FIG. 6A  is a schematic illustration of a high level flow diagram showing four phases associated with an exemplary embodiment of the method of the present invention for using an embodiment of a sensory testing system  239  to perform sensory testing on a subject.  
         [0017]      FIG. 6B  and  FIG. 6C  are schematic illustrations that together illustrate the steps of  FIG. 6A  in detail.  
         [0018]      FIG. 7  is a schematic illustration of a networked embodiment of a sensory testing system  239 . 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0019]     In preferred embodiments, the present invention provides a sensory testing system for determining thresholds for tactile, or haptic, sensation in human or animal subjects. In preferred embodiments, the sensory testing system includes a linear DC motor having a shaft and a single test filament mounted on the end of the shaft that is positioned toward the subject during testing. The linear DC motor is operatively linked to a length encoder and to a digital motor controller, which are both operatively linked to a computer that executes a program that controls the movement of the motor shaft and detects its position. During testing the system advances the test filament under program control. The force applied by the motor is increased according to a defined function, preferably a ramp function. The applied force and the displacement of the motor shaft are monitored and stored under program control.  
         [0020]     Human subjects communicate the chosen sensory endpoint, e.g., detectible touch or pain, by generating a detection signal that stops the motor and causes the current producing the compression force of the motor to be recorded. Alternatively, especially in studies of nonhuman subjects, the chosen sensory endpoint is communicated by withdrawal of the body part, such as a foot, that is being tested. Withdrawal of the body part can be detected by the sensory testing system using a displacement transducer. The force that was applied just prior to the communication that the chosen sensory endpoint has been reached is taken as the threshold force. Values of threshold forces are stored in data files, and can be used to create a map of threshold forces superimposed on an image (schematic diagram or video image) of the particular body part being tested.  
         [0021]     The linear motor is operated in a mode that simulates force control. In this mode, the computer moves the motor shaft and attached test filament to maintain a selected force that is determined by the control program. The force exerted by the test filament is independent of how the probe is held by the operator because the motor is operated in a force control mode.  
         [0022]     As used herein, “computer” refers to a digital computer capable of executing programs, and having a processor, memory and input and output devices. Preferably the computer is capable of sensing and manipulating its surroundings by detecting signals and generating signals using the input and output devices. Suitable computers are portable general purpose computers such as laptops and tablet computers, as well as personal digital assistants such as Pocket PCs, Palm and the like. “Subject” means mammals and non-mammals. “Mammals” means any member of the class Mammalia including, but not limited to, humans, non-human primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, and swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, and guinea pigs; and the like. Examples of non-mammals include, but are not limited to, birds, and the like. The term “subject” does not denote a particular age or sex.  
         [0023]      FIG. 1  illustrates an exemplary method for performing sensory measurements using embodiments of the invention. A test area is identified on the surface of a subject (per step  102 ). For example, the skin on the lateral surface of a subject&#39;s arm may be identified as the test area for performing sensory measurements. Next, test parameters are identified and entered into the sensory testing system using an input device (per step  104 ). In one preferred embodiment, the test parameters are entered using a keyboard as an input device. In other embodiments, test parameters are entered using a keypad in response to prompts or chosen from choices provided on a responsive display, such as a touch sensitive screen.  
         [0024]     In preferred embodiments, the measurement of sensory function is performed using a linear motor having an extendable shaft with a probe attached thereto at the end of the shaft nearer the subject (see step  106 ). The probe is attached to the end of the shaft that extends toward the subject at an increasing force, suitably increasing as a ramp function. When a subject senses pressure, preferably a criterion level of pressure, such as painful pressure, the subject reports the sensation using a device that produces a signal that can be detected by the sensory testing system. In a preferred embodiment, the signal is an electrical signal produced by closing a switch, e.g. a human subject depressing a hand-held stop button. In other embodiments, a non-human subject can be trained to report a criterion level of pressure using an appropriate device.  
         [0025]     The signal is received by the sensory test system and directly or indirectly acts to stop the travel of the shaft and probe combination toward the subject (per step  108 ). When the stop signal is received by the system, the pressure exerted by the probe&#39;is recorded by the sensory test system (per step  110 ). In certain embodiments, the sensory test system further measures and records the distance traveled by the shaft.  
         [0026]      FIG. 2A  contains a schematic representation of a preferred embodiment of a system  200  for making measurements of sensory function of a subject in a laboratory environment, such as a non-human subject, e.g., a rat. System  200  includes a test filament  202 , a retainer  204 , a motor shaft  205 , a motor  206 , a mirror  208 , a displacement sensor  210 , a base  212 , a supporting surface  214 , control electronics  218 , a computer  220  and a stop switch  222 .  FIG. 2A  also illustrates a rat  226  as a subject and mesh supporting screen  224 .  
         [0027]     The subject  226  can be placed in a containment enclosure, such as a box, having a mesh screen  224  as a floor surface. Mesh screen  224  contains openings large enough to allow the tip of test filament  202  to pass there through while preventing the foot, or paw, of test animal  226  from passing through the screen  224 . In a preferred embodiment, the enclosure is positioned so test filament  202  can push upward from beneath screen  224  to contact a test area on the surface of a paw of test animal  226 .  
         [0028]     System  200  uses a test filament  202  having a proximal end and a distal end. The distal end of test filament  202  is used to exert a force on a test area of the surface of a foot pad of test animal  226 , while the proximal end is inserted into retainer  204 . Retainer  204  operates to securely retain the proximal end of test filament  202 . In addition, retainer  204  acts as an adapter allowing a transition from test filament  202  to motor shaft  205 . Retainer  204  may include a tapered inner volume having a proximal end and a distal end with the proximal end being larger in diameter than the distal end. The proximal end of test filament  202  is inserted into the proximal end of the tapered inner volume and pushed toward the distal, or narrow, end of retainer  204 . The tapered volume is designed so that test filament  202  is retained at a desired pressure somewhere between the large end and narrow end. Alternatively, retainer  204  may use a plurality of internal fingers that exert substantially equal pressure on the outer surface of the proximate end of test filament  202  when a collar is rotated, or otherwise closed.  
         [0029]     Motor  206  is a linear motor that extends or retracts shaft  205  in response to signals received by way of data cable  216  from motor controller  218 . In a preferred embodiment, the motor  206  is model H2W NCC02-05-005-4JBAT (H2W Technologies, Inc., Valencia, Calif.). Suitable motor controllers can be obtained from Galil Motion Control (Rocklin, Calif.). System  200  may also include a displacement measuring device for determining the amount, or length, of shaft  205  extending beyond motor  206 . In the embodiment of  FIG. 2A , the displacement sensor  210  is a linear variable differential transformer (LVDT, Trans-Tek model 0241-0000). Alternatively, the displacement sensor can be a linear encoder or a linear potentiometer. The longitudinal axes of motor  206 , shaft  205  and test filament  202  are aligned parallel to axis  201 .  
         [0030]     A moveable base  212  is coupled to the lower end of displacement transducer  210  for facilitating movement of test filament  202  from one test location to another. While the embodiment of  FIG. 2A  employs a manually positioned base  212 , alternative embodiments may employ bases that are moved by way of automated positioning devices such as, for example, robotic arms, actuators for positioning test filament  202  using a grid oriented coordinate system, etc. Surface  214  may be any surface capable of supporting manually positioned base  212  such as a bench top or desk top. A mirror  208  may be oriented substantially perpendicular to shaft  205  to facilitate positioning of filament  202  beneath animal  226 . Alternatively, if the operator is located to the side of the containment enclosure, mirror  208  is oriented at an oblique angle to positioning of filament  202  with respect to the selected test location. Mirror  208  may also be used to facilitate observation of when animal  226  lifts a paw in response to filament  202 .  
         [0031]     Motor controller  218  operates under the control of a computer  220  and provides signals to motor  208  for causing shaft  205  to extend outward toward a test subject and to retract into the housing of motor  206 , away from a test subject. An operator initializes system  200  when the distal end of test filament  202  is at a desired position with respect to a test animal  226 . System  200 , using computer  220 , instructs motor controller  218  to cause shaft  202  to move towards animal  226 . While shaft  202  moves, displacement sensor  210  measures the distance shaft  202  has traversed.  
         [0032]     In the embodiment of  FIG. 2A , encoder units are used to monitor the displacement of shaft  202 . Motors having force outputs proportional to motor input currents are used so that force exerted by the motor can be determined from the supplied current. The force exerted by motor  206  is linearly increased by changing a torque limit setting. This causes motor  206  to exert a maximum allowable force through out the travel range of shaft  202 . Shaft  202  may be extended to its maximum allowed limit by way of the current torque limit setting. Shaft  202  is displaced toward test animal  226  using this technique until the test animal  226  signals that it has sensed pain by lifting its paw in response to pressure applied by the distal end of test filament  202 . System  200  is preferably also configured so as to facilitate rapid re-initialization for repetition of an experiment.  
         [0033]     In use, manually positioned base  212  is placed on surface  214  and moved until position under a foot of the subject  226  with the foot in the path of filament  202 . Closing foot switch  222  initiates a single trial in which the motor current is increased under control of the system  200  according to a pre-determined function, such as a linearly increasing ramp. Eventually the subject  226  lifts the foot, resulting in a sharp upward displacement of the filament  202 . The data from such a trial is presented graphically in  FIG. 3A  and  FIG. 3B . The sensory threshold is determined as the force (which is proportional to motor current) that was applied at the time that the foot was lifted, indicated by the dashed line in  FIG. 3A  and  FIG. 3B .  
         [0034]      FIG. 2B  is a diagrammatic illustration of the relationship of linear motor  206 , test filament retainer  204 , displacement sensor  210 , movable base  212  and cable  216  in one embodiment of the sensory test system of the present invention.  
         [0035]      FIG. 3A  and  FIG. 3B  illustrate, respectively, plots of load and displacement versus time for the embodiment used to gather data using a subject  226 , here a laboratory animal such as a rat as shown in  FIG. 2A .  FIG. 3A  shows the exerted load in motor current (which is proportional to load in grams) versus time. As seen from  FIG. 3A , subject  226  lifted its paw in response to the distal end of test filament  202  shortly after two seconds.  FIG. 3B  shows that displacement of shaft  202  rapidly increased at about two seconds. The data shown in the lower plot corresponds to the data shown in the upper plot. The point at which a subject responds to stimuli applied by system  200  is referred to as a lift threshold  302 .  
         [0036]      FIG. 4  illustrates a second preferred embodiment that employs a handheld probe  240  for performing sensory testing on human subjects. One embodiment of a system  239  is shown in  FIG. 4 , being used to make sensory measurements on, for example, a foot  242 . System  239  includes a test filament  244 , retainer  246 , motor  248 , motor controller  250 , push button  252 , foot switch  254 , and computer  256 . In other embodiments, the probe includes test filament  244 , retainer  246 , motor  248 , motor controller  250 , and computer  256  configured as a single handheld device.  
         [0037]     An operator positions the handheld probe  240  at a desired location relative to foot  242 . After initializing system  239 , the operator activates foot switch  254  to begin advancement of test filament  244  toward foot  242 . In preferred embodiments, test filament  244  is made of a naturally occurring or synthetic polymer. In other embodiments, test filament  240  can made of stainless steel or composite. Material, length and diameter of test filament  240  are selected to transmit force to produce accurate measurements. Test filament  240  is attached to the shaft of motor  248  by way of retainer  246 . Motor controller  250  causes test filament  244  to advance in response to closure of foot switch  254  by increasing the motor current, and thus the force exerted by the filament, according to a pre-determined function, such as a linearly increasing ramp. Test filament  244  advances until the subject depresses push button  252 . When push button  252  is closed by the subject, computer  256  ceases advancement of test filament  244  and records the applied force, ending the single trial.  
         [0038]     Test filament  244  can be positioned at another location with respect to foot  242  and the measurement sequence repeated. With human subjects, or test subjects, instructions can be given with respect to when the push button  252  should be pressed relative to a perceived sensation. For example, a subject can be instructed to press the button as soon as any tactile sensation is perceived, or the subject can be instructed to push the button only when a certain level of pain is perceived.  
         [0039]     Prior to performing testing, an image of test locations can be generated and displayed using computer  256 . The image may be a standard template or may be generated using an overlay of a video image and the numerical results. When force measurements are obtained at test locations, the results can be numerically or graphically displayed at the corresponding location on computer  256 . Using computer  256  in conjunction with handheld probe  240  thus lets an operator generate a real-time map of a subject&#39;s extremity using measured data. The mapped results can then be used to coordinate additional testing or to aid in diagnosis. In addition, the mapped results can be shown to the subject to facilitate his/her understanding of diagnosed conditions.  
         [0040]      FIG. 5  illustrates an embodiment of computer  220 ,  256  in more detail as an exemplary computer  400 . The exemplary computer  400  includes a processor  402 , main memory  404 , read only memory (ROM)  406 , storage device  408 , bus  410 , display  412 , keyboard  414 , cursor control  416 , and communication interface  418 .  
         [0041]     Processor  402  may be any type of conventional processing device that interprets and executes instructions. Main memory  404  may be a random access memory (RAM) or a similar dynamic storage device. Main memory  404  stores information and instructions to be executed by processor  402 . Main memory  404  may also be used for storing temporary variables or other intermediate information during execution of instructions by processor  402 . Main memory  404  may also be used for storing temporary variables or other intermediate information during execution of instructions by processor  402 . ROM  406  may be replaced with some other type of static storage device. Data storage device  408  may include any type of magnetic or optical media and its. corresponding interfaces and operational hardware. Data storage device  408  stores information and instructions for use by processor  402 . Bus  410  includes a set of hardware lines (conductors, optical fibers, or the like) that allow for data transfer among the components of computer  400 .  
         [0042]     Display device  412  may be a cathode ray tube (CRT), liquid crystal display (LCD) or the like, for displaying information to a user. Keyboard  414  and cursor control  416  allow the user to interact with computer  400 . Cursor control  416  may be, for example, a mouse. In an alternative configuration, keyboard  414  and cursor control  416  can be replaced with a microphone and voice recognition software to enable the user to interact with computer  400 .  
         [0043]     Communication interface  418  enables computer  400  to communicate with other devices/systems via any communications medium. For example, communication interface  418  may be a modem, an Ethernet interface to a LAN, or a printer interface. Alternatively, communication interface  418  can be any other interface that enables communication between computer  400  and other devices or systems.  
         [0044]     By way of example, a computer  400  suitable for use in an embodiment of the present invention provides control to a motor driven cutaneous indentation sensory testing device described elsewhere in this disclosure. Computer  400  performs operations necessary to complete desired actions in response to processor  402  executing sequences of instructions contained in, for example, memory  404 . Such instructions may be read into memory  404  from another computer-readable medium, such as a data storage device  408 , or from another device via communication interface  418 . Execution of the sequences of instructions contained in memory  404  causes processor  402  to perform a method for extending a testing sensor until a determined pressure is exerted on a subject&#39;s skin and for recording the exerted pressure when a subject provides notification to an operator. For example, processor  402  may execute instructions to perform the functions of measuring cutaneous sensory activity. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement the present invention. Thus, the present invention is not limited to any specific combination of hardware circuitry and software.  
         [0045]      FIG. 6A  provides a high level flow diagram showing four phases associated with an exemplary method for using system  239  to perform sensory testing on a subject. The method begins with an initialization phase which involves supplying power to components such as motor controller  250  (per step  502 ). Next software is set up (per step  504 ) and then one or more sensory tests are performed (per step  506 ). When testing is complete, results may be transferred to other devices and systems (per step  508 ).  
         [0046]      FIGS. 6B and 6C  together illustrate the steps of  FIG. 6A  in detail. Communication with motor controller  250  is opened (per step  510 ). Test parameters are then entered into computer  256  using keyboard  414  (per step  512 ). Examples of test parameters are, but are not limited to, date and time of test, name of ID of test subject, area of body being tested, upper limit of force to be used, insurance provider information, operator&#39;s name and ramping rate for the motor drive signal. Then probe  244  is adjusted in or out with respect to motor  248  (per step  514 ).  
         [0047]     Footswitch  254  is then operated to start the experiment (per step  516 ). In response to the signal from footswitch  254 , the ramp signal for driving motor  248  is generated (per step  518 ) with a number of step values, determined in step  512 . Next, the appropriate control protocol for motor  248  is assembled (per step  520 ) and uploaded to motor controller  250  (per step  522 ). A minimum torque threshold for shaft  205  is set (per step  524 ). Next, the control protocol is executed by setting the iteration count value (ICV) to zero (per step  526 ). Then the torque limit is set to an element equal to the ramp signal value (SV), whose step value corresponds to the current iteration count value (per step  528 ). Movement of probe  244  is then delayed by a determined increment (per step  530 ). For example, advancement of probe  244  may be delayed by 100 milliseconds (ms), 500 ms, or 1000 ms. The position of probe  244  is measured along with the applied current and the present time (per step  532 ).  
         [0048]     Now referring to  FIG. 6C , the iteration count value is advanced incrementally, (per step  534 ). If a subject senses the distal end of probe  244  in response to its advancement (per step  536 ), the subject depresses push button switch  252  (per step  538 ). In contrast, if the subject does not sense probe  244 , the method returns back to step  528  ( FIG. 6B ) from step  536 . A safety measure is built in for unresponsive subjects wherein the system stops if the iteration count value exceeds the number of step values in the ramp signal.  
         [0049]     When the subject closes push button switch  252 , or if the ramp is ended, a signal is received at computer  256 . Receipt of the signal causes computer  256  to generate a force vs. time plot. The force vs. time plot is then displayed on display  412  (per step  544 ), and the threshold is taken as the force at the time the push button switch  252  was closed.  
         [0050]     Computer  256  then creates a header for the data generated during the experiment and stores the acquired data and header as a file in memory (per step  552 ). The header contains information about the gathered data such as the date, subject&#39;s name, system settings and the like. The above sequence can repeated at at one or more additional locations. Then the motor communications channel is closed (per step  554 ). After storing the acquired data and ceasing communication with motor controller  250 , computer  256  may transfer the file to another device or system using a data network (per step  556 ). If a map is being plotted, another position is selected and the above sequence is repeated. When the desired number of sites have been tested, the threshold data are displayed superimposed on the graphic representation of the test area, such as the sole of a foot.  
         [0051]      FIG. 7  illustrates a networked embodiment of the sensory testing system. Networked system  600  may include computer  256  and probe  240 , an insurance provider server  606 , a specialists&#39; workstation  610  and a data network  602 . After completing an experiment, an operator can instruct computer  256  to transmit acquired data to an insurance provider&#39;s server  606  using network  602 . The insurance provider may use the data for authorizing additional treatment, for compiling statistics on its insured population, and for performing its own analysis. Computer  256  may also transmit acquired data to a hospital database  604  for permanent storage and to provide access to other departments within the hospital. Computer  256  may also transmit data to a research database  608 .  
         [0052]     Research database  608  may be used to support one or more ongoing studies involving the sensory perception of animals and/or human subjects. Research database  608  may be coupled to a specialist&#39;s computer  610 . Specialist&#39;s computer  610  may be operated by a person having a high level of expertise in a field that is pertinent to the acquired data. For example, the specialist may be responsible for running and overseeing experiments or he/she may be skilled at making diagnoses based on the data.  
         [0053]     Network  602  may be any type of communications network employing any type of networking protocol. For example, network  602  may be an internet protocol (IP) network, an asynchronous transfer mode (ATM) network, or conventional telephone network such as a plain old telephone system (POTS) network.  
         [0054]     The claims should not be read as limited to the described order or elements unless stated to that effect. Therefore, all embodiments that come within the scope and spirit of the following claims and equivalents thereto are claimed as the invention.