Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
  • A61B10/02—Instruments for taking cell samples or for biopsy
  • A61B10/0233—Pointed or sharp biopsy instruments
  • A61B10/025—Pointed or sharp biopsy instruments for taking bone, bone marrow or cartilage samples
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
  • A61B5/4504—Bones
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
  • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
  • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
  • A61B5/6848—Needles
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N3/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N3/40—Investigating hardness or rebound hardness
  • G01N3/42—Investigating hardness or rebound hardness by performing impressions under a steady load by indentors, e.g. sphere, pyramid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
  • A61B5/4504—Bones
  • A61B5/4509—Bone density determination
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2203/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N2203/0001—Type of application of the stress
  • G01N2203/0003—Steady
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2203/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N2203/0014—Type of force applied
  • G01N2203/0016—Tensile or compressive
  • G01N2203/0019—Compressive
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2203/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N2203/0058—Kind of property studied
  • G01N2203/006—Crack, flaws, fracture or rupture
  • G01N2203/0062—Crack or flaws
  • G01N2203/0064—Initiation of crack
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2203/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N2203/0058—Kind of property studied
  • G01N2203/0076—Hardness, compressibility or resistance to crushing
  • G01N2203/0078—Hardness, compressibility or resistance to crushing using indentation
  • G01N2203/0082—Indentation characteristics measured during load
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2203/00—Investigating strength properties of solid materials by application of mechanical stress
  • G01N2203/0058—Kind of property studied
  • G01N2203/0089—Biorheological properties

Definitions

• the invention relates to novel methods and instruments for evaluating the strength of human and animal bones.
• BMD bone mineral density
• Other techniques including dual energy x-ray absorptiometry, quantitative ultrasound and others. These techniques all measure properties of bone without inducing fracture at any length scale. They are generally believed to be incomplete measures of fracture resistance. This is especially true for young, healthy people, such as Army recruits, for whom these conventional measures of bone fracture risk have been found to be ineffective in assessing fracture risk during basic training [12]. Further, it is known that these measurements, though valuable, do not fully characterize fracture risk in elderly patients or in patients with osteoarthritis, osteoporosis or other bone disease.
• Osteoporosis is a major public health concern according to the World Health Organization (WHO) [13]. While 50 million women worldwide suffer from the disease, osteoporosis and osteopenia (low bone mass) are frequently associated with increased age, but both diseases affect people in every stage of life, having a huge impact on people in the workforce. The economic burden of osteoporosis is expected to reach $131.5 billion by 2050 [14]. Healthcare costs in the United States currently exceed $15 billion annually for osteoporosis related treatment [15].
• Osteopenia and osteoporosis are frequently asymptomatic and diagnosis is often not ascertained until a fracture has occurred or until a low bone mineral density (BMD) has been determined.
• BMD bone mineral density
• the most significant complication of osteoporosis is fracture, often induced by trauma of a very low magnitude [16].
• a fracture may mean loss of mobility along with life quality and increased risk of mortality.
• Numerous interventions have been shown to reduce the risk of fracture in this population; however, despite the overwhelming number of patients falling into the fracture risk categories, facilities for evaluations are inadequate and only those evaluated as the highest risk are adequately tested and treated. The vast majority of those at risk are unevaluated, due to costs considerations [17].
• a plethora of diagnostic Instruments are currently in use for assessing fracture risk in patients, focusing on decrease in bone mineral density and deterioration of micro architecture. Dual-energy x-ray absorptiometry (DEXA) has been used to clinically measure these factors. Bone mineral density currently remains the most widely accepted indicator of fracture risk and is also used for true diagnosis of osteoporosis. DEXA is most commonly accepted as the instrument of choice and is used as the main determinant in evaluating risk, but numerous drawbacks and limitations have been observed. Discrepancies between instruments may have a serious effect on the diagnosis and treatment of patients [19]. Additionally, patients with normal BMD may experience fractures while those with low BMD may be at low risk [18].
• Peripheral quantitative computed tomography has also been studied in hopes of finding a useful tool for establishing bone fracture risk and was found to be less sensitive than DEXA and determined as a poor assessment tool for discriminating those with fractures [26]. In another investigation, pQCT does seem to be a reliable tool for calculating bone Calcium concentrations [27].
• Development of morphometric X-ray Absorptiometry was investigated for determining vertebral deformities. High variability in analysis was determined with inter- operator assessment and the precision of analysis declined relative to complexity of the vertebral shape [28].
• Blood tests are sometimes prescribed to evaluate other conditions that influence bone strength. These cover a wide range of activities from alkaline phosphatase and thyroid stimulating hormone to vitamin D and calcium levels. Many of these tests may be beneficial in diagnostics and in determining treatment protocols [32].
• Intrinsic toughness characterizes the resistance of mineralized tissues to cracking and fracture. Indentation protocols offer a means to quantify both the toughness and hardness of the biomaterials [1]. Examinations of the dentin-enamel junction of teeth further confirm the value of indentation protocols for understanding crack propagation and fracture mechanics. Using a Vickers indentation instrument, lmbeni et al. were able to characterize how cracks propagate and where crack-arrest barriers appear. Toughness and hardness factors for the enamel, dentin and the interface between the two were quantified [43].
• Indentation instruments also currently exist that are designed for use under surgical conditions.
• One such instrument has been designed to measure the stiffness of cartilage through arthroscopic surgical control [44, 45].
• Biomechanical property changes in articular cartilage are early indicators of degeneration in the tissues.
• a reduction in compressive stiffness of articular cartilage is related primarily to the reduction of proteoglycan content and early detection offers possibilities for treatment to arrest the conditions leading to the degenerative process [44].
• Osteopenetrometer was designed for in vivo testing of trabecular bone during surgical procedures. This instrument was developed to characterize the mechanical properties of trabecular bone to obtain information relevant to reducing the problem of implant loosening following total knee arthroplasty [48].
• the Osteopenetrometer involved penetrations of lengths of order 8 millimeters and widths of order millimeters in diameter at implant sites during surgery. The goal was to have large enough penetrations to average over many trabeculae inside the trabecular bone.
• the present invention overcomes the foregoing disadvantages by evaluating material properties of the bone through contact with a test probe. In particular embodiments, one can thereby measure the actual resistance of bone to fracture.
• a novel instrument is provided that assesses macroscopic bone fracture risk by measuring how resistant the bone is to microscopic fractures caused by a test probe inserted through the skin or other soft tissue and periosteum down to the bone.
• the microscopic fractures are so small that they pose negligible health risks: the volume of damaged bone can be on the order 0.01 cubic millimeter or smaller in current embodiments.
• the resistance of the bone to these microscopic fractures is a good indication of the resistance of the bone to macroscopic fracture.
• bone fracture risk is assessed by creating microscopic fractures in bone.
• the advantage of such an instrument is that it gives, with a very quick and inexpensive test, information about bone fracture risk that is not available from any existing instrumentation. This new diagnostic information can be used alone or to supplement the results from conventional diagnostics, such as bone mineral density.
• the invention provides methods and instrumentation to assess bone fracture risk in a subject, comprising inserting a test probe through the periosteum and/or soft tissue of the subject so that the test probe contacts the subject's bone, and determining the resistance of the test bone to microscopic fracture by the test probe.
• the subject can be a living person or animal in a clinical setting where the test probe is inserted through overlying skin, or directly through the periosteum during an operation where the periosteum is exposed, or into a cadaver bone through both skin and periosteum or through soft tissue or only the periosteum, depending on the nature of the experiment.
• the instrument could penetrate the endosteum if an interior surface of bone were surgically exposed.
• the instrument can also measure directly on bone surfaces that have been surgically exposed.
• the instrument can also measure directly on bone pieces that have been cut out of subjects, whether or not they are still covered with periosteum or endosteum.
• the test probe is inserted a microscopic distance into the bone to create one or more microscopic fractures in the bone. Bone fracture risk can be assessed by determining the extent of penetration, or it can be assessed by determining the resistance of the bone to penetration of the test probe.
• the method further includes similarly inserting a reference probe so as to contact the subject's bone without the reference probe significantly penetrating the bone, to serve as a reference for determining the extent of insertion of the tip of the test probe.
• the test probe can be formed as a rod and the reference probe can be in the form of a sheath in which the test probe is disposed, the end of the sheath proximal the test probe tip serving as the reference.
• the test probe and reference probe can be sharpened asymmetrically to minimize lateral offset between the tip of the test probe and the tip of the reference probe.
• the test probe is sufficiently sturdy to resist deformation when penetrating the bone, while in still other embodiments, the test probe resists deformation when penetrating weak bone but is deformed by healthy bone. High deformation indicates bone that is fracture resistant, low deformation indicating bone that is at risk for fracture.
• the test probe can contain a stop surface to prevent penetration into the bone beyond a predetermined distance, facilitating quantification of the deformation.
• the test probe can be a single use test probe that can be discarded after use by a patient, or by a physician, as can the reference probe.
• the test probe can be sterilized as can the reference probe.
• a manufacturer could supply single use combinations consisting of sterilized test probes with sterilized reference probes in a sterile package.
• rearward motion of the test probe is resisted as the test probe is pulled out of the bone and the extent of resisting force is determined as a measure of resistance of the bone to fracture.
• bone fracture risk is assessed by determining the force needed to insert the test probe into the bone, and a force versus distance parameter can be generated and correlated with fracture risk.
• a diagnostic instrument for assessing bone fracture risk in a subject comprising a housing supporting a test probe constructed for insertion through the periosteum on a bone of a subject, whether or not through soft tissue or other overlying skin, for contacting the subject's bone, and means for evaluating a material property of the bone through contact with the test probe.
• the material property evaluated by the diagnostic instrument is one or more of:
• test probe is inserted a microscopic distance into the bone to create one or more microscopic fractures in the bone to enable the determination of one or more of:
• the diagnostic instrument can include a reference probe constructed for insertion through the periosteum, and any overlying skin or other soft tissue, to contact the bone without the reference probe significantly penetrating the bone, to serve as a reference for determining the extent of insertion of the tip of the test probe.
• the reference probe can be in the form of a sheath in which the test probe is disposed, the end of the reference probe being proximal the test probe tip serving as a reference.
• the test probe can be formed as a rod with its tip disposed to extend a maximum predetermined distance beyond the end of the reference probe.
• the test probe which can be formed of tool steel or stainless steel (with the tip of the test probe formed of the same material as the shaft of the test probe, or of another material such as diamond, silicon carbide, or hardened steel), and the reference probe, which can be formed from a hypodermic needle, can each be tapered asymmetrically whereby to minimize lateral offset between the test probe tip and the reference probe tip, and are sufficiently sharp to penetrate the periosteum of the bone and any overlying skin or other soft tissue.
• the diagnostic instrument can apply a fixed force of a first magnitude to the test probe to determine a starting position of the test probe relative to the reference probe, apply a fixed force of a second magnitude to the test probe, measure a change in position of the test probe relative to the reference probe, reduce the fixed force to the first magnitude, and record the change in the position of the test probe relative to the reference probe.
• the diagnostic instrument can further determine a force versus distance parameter for the inserted test probe by determining the force needed to insert the test probe a predetermined distance into the bone, and/or the distance the test probe inserts into the bone under predetermined force.
• the diagnostic instrument can include a load cell connected to the test probe for determining the force needed to insert the test probe said predetermined distance.
• a solenoid can be electromagnetically connected to a mounting pin, with the test probe connected to an end of the mounting pin, for generating the force.
• One or more springs can be disposed to oppose action of the solenoid.
• the diagnostic instrument can include a linear variable inductance transducer having a core connected to the test probe for determining the distance the test probe inserts into the bone under a predetermined force.
• Other distance sensors can also be used.
• the distance sensor it is desirable for the distance sensor to have: 1) sensitivity down to roughly 1 micron, 2) range up to about 1 mm and 3) response time preferably a few milliseconds or faster.
• Distance sensors with these characteristics include optical distance sensors and capacitance sensors.
• a rotating cam and a follower pin can be included, the cam having a surface operating on the follower pin, one end of the follower pin being in sliding contact with the cam surface, the other end of the follower pin being connected to the test probe.
• Other mechanisms to insert the test probe with a rotary motor include a motor-driven, ball screw or Acme screw to convert the rotary motion of the motor to linear motion.
• the Acme screw has the advantage that it can hold a load in a power off situation enabling measurements of force relaxation vs. time after an indentation to fixed depth.
• rotary to linear motion mechanisms such as piston mechanisms can be used.
• Other linear motion generators may also be used.
• the linear motion generator should supply forces up to 10 Newtons with a range of motion up to 1 mm. Sharper or smaller diameter test probes could use less force. Measurements of some pre-yield mechanical parameters such as elastic modulus could use much less force, down to the milliNewton range.. A disadvantage, however, of going to much smaller forces and indentation depths is that the properties of a smaller volume of bone is probed. Our tests to date have shown that it is desirable to have enough volume to average over at least several osteons, which have typical diameters of order 0.2 mm, to reduce scatter in the measured data.
• a guide for the test probe and reference probe can be mounted at the lower end of the housing, the guide and the reference probe being formed to removably connect to each other with aligned passageways through which the test probe extends.
• the reference probe itself can be removably mounted to the guide.
• the guide can be formed with an externally threaded neck extending from its lower end, the reference probe being formed with an internally threaded opening about its passageway for threadably mounting to the neck of the guide.
• the test probe is a single use, replaceable probe.
• the test probe and reference probe are both single use, replaceable probes [0033]
• the combination of test probe and reference probe can be provided as disposable, replaceable and, optionally, sterile, parts, as can the probe guide.
• the diagnostic instrument of the present invention is distinct from previous instruments. It is designed to be used without the need to surgically expose the bone surface.
• the small diameter probe assembly is inserted through the periosteum and any overlying skin or other soft tissue, down to the bone. It is not necessary to expose or visualize the bone surface.
• the diagnostic instrument of the present invention is designed to probe not only pre-yield parameters like elastic modulus, but also post-yield parameters like toughness by actually creating yield in a small probed volume of the bone.
• the diagnostic instrument of the present invention can also be operated with an oscillating force in addition to a slowly varying or static force. This can be accomplished, for example, by feeding a solenoid, a moveable coil in a permanent magnetic field such as used for loudspeakers or other devices for converting electrical current to mechanical force with an oscillating current plus a slowly varying current or static current.
• the resultant oscillating force can be read from a force sensor such as a load cell.
• the oscillating distance can be read from a distance sensor such as an LVDT.
• a faster distance sensor such as an optical sensor like the MTI - 2000 Fotonic sensor can be used.
• the optical fiber probe of the sensor can be attached to the body of the instrument and can read the distance to a tab which is connected to the test probe.
• the amplitude or phase of the oscillating distance as a function of frequency and as a function of slowly varying or static force can be explored to increase diagnostic differentiation.
• the slope of the distance vs. time plot just after the impact has distinguished baked from unbaked bone in some tests.
• the slope of the distance vs. time plot in the 10s of milliseconds after the impact was significantly less for the unbaked bone: by more than a factor of 5. This indicates that the unbaked bone impeded the repetitive insertion of the probe better than the baked bone in these tests.
• an optical sensor the MTI - 2000 Fotonic sensor, in our tests.
• any other fast distance sensors with the required 1) sensitivity, down to roughly 1 micron, 2) range, up to about 1 mm and 3) response time, preferably a few milliseconds or faster, could be used.
• Other examples of such sensors include optical lever sensors and capacitance sensors.
• the instrument that we describe here could be used to characterize materials other than bone. It could be used to characterize other tissues such as cartilage and skin. It could be used to measure materials properties of metals such as aluminum alloys and copper alloys, plastics such as polymethylmethalcrylate and Teflon, wood, and ceramics. It has the advantage that it can be used as a hand held instrument to measure materials properties outside of testing labs. For example, it could be used to measure materials properties of aircraft wings to check for fatigue or welds on pipelines to check for embrittlement. Its narrow combination of test probe and reference probe would allow it to measure on surfaces inaccessible to other testing instruments such as durometers.
• test probe and reference probe it could penetrate soft coatings such as rust or dirt or polymer coatings or corrosion layers or marine organic deposits to measure the properties of the underlying material. It could test pipes buried underground.
• Figures 1a, b and c depict an assembly of test probe and reference probe as it is used in three stages of an embodiment of the invention
• Figure 2 schematically depicts a generalized diagnostic instrument for a preferred embodiment of the invention
• Figures 3a, b and c depict respectively front, side and rear views of a specific embodiment of the generalized diagnostic instrument of Figure 2;
• Figures 4a - e depict (a and b) force versus distance curves obtained respectively on samples of unbaked and baked bovine bone, (c and d) distance versus time curves respectively on samples of unbaked and baked bovine bone, and (e) distance versus number of cycles on samples of unbaked and baked bovine bone, all using the diagnostic instrument of Figure 3;
• Figures 5a and b depict (a and b) force versus distance curves obtained respectively on samples of age 19 human bone and age 59 human bone, using the diagnostic instrument of Figure 3;
• Figures 6a - d depict (a and b) multiple force versus distance curves obtained respectively on samples of baked bovine bone and unbaked bovine bone through soft tissue, and (c and d) force versus number of cycles to a fixed distance obtained again respectively on samples of baked bovine bone and unbaked bovine bone through soft tissue, using the diagnostic instrument of Figure 3;
• Figure 7 is a cross-sectional view of a combination of a test probe and a reference probe of this invention in accordance with another embodiment
• Figure 8 is a cross-sectional view of a diagnostic instrument used in an embodiment of Figure 2;
• Figures 9a - 9g depict the penetrating ends of a variety of test probes that can be used in the invention.
• Figures 10a and b depict the penetrating ends of other test probes that can be used in the invention.
• Figure 11 depicts the penetrating end of still another test probe that can be used in the invention.
• Figures 12a - d depict various supports for diagnostic instrument embodiments that can be used in the invention.
• Figures 13a - d depict embodiments of the force generator that can be used in diagnostic instruments of this invention.
• Figure 14 depicts another embodiment of the invention.
• Figure 15 depicts top views of the slide rail and interconnecting flange used in the embodiment of Figure 14;
• Figure 16 is a plan view of the test probe vice used in the embodiment of Figure 14.
• Figure 17 shows electronics used for operation of some diagnostic instruments of Figure 2.
• the essential feature of the invention is a test probe, which is inserted through the periosteum and through any overlying skin or other soft tissue to contact a bone surface.
• the design concept for the diagnostic Instrument of this invention is that a probe assembly, consisting of a test probe 100 and a reference probe 102 is inserted through the periosteum of a bone and any overlying skin or other soft tissue of a living person, animal or cadaver so that it comes to rest on the surface of the bone.
• Three stages for an exemplary assembly of test probe 100 and reference probe 102 are shown in Figures 1a - c.
• the test probe is inserted into the bone to measure material properties.
• the force vs. distance curves can be processed to give parameters such as: 1) maximum insertion distance, 2) maximum force reached and 3) change of these values after multiple cycles of insertion.
• test probe and reference probe can optionally be sharpened asymmetrically, as shown in Figures 1a - c, to minimize the lateral offset between the tip of the test probe 100 and the tip of the reference probe 102. This minimizes the zero offsets in force vs. distance curves that result from bone surfaces that are not completely perpendicular to the axis of the probe assembly.
• the test probe 100 can be formed from a rod of tool steel that is 0.5 mm in diameter tipped with a 5 degree to 90 degree cone. It slips inside a #21 syringe, with a specially sharpened end, that acts as the reference probe 102.
• An exemplary assembly consists of a sharpened high speed steel rod as the test probe 100 and a sharpened hypodermic needle, 22 gauge as the reference probe 102.
• Figure 1a shows the probe assembly on the surface of the bone just before test probe insertion. Note that the tip of the reference probe 102 has been ground to have its tip close to the tip of the test probe 100.
• test probe 100 The distance the test probe 100 is inserted into the bone is measured relative to the position of the reference probe 102 on the surface of the bone. The force to insert and withdraw the test probe 100 is also measured. If the test probe is cycled deeply enough into the bone, typically over a few microns, there will be post-yield damage that can be sampled in subsequent cycles, which is shown in Figure 1c as a hole 104 remaining in the bone after the test probe is withdrawn.
• Figure 2 shows a generalized diagnostic instrument for the currently preferred embodiment.
• the test probe 200 is connected through a shaft 206 to an optional torque and angular displacement sensor 208 then to an optional torque generator 210, then to an optional linear displacement sensor 212, then to an optional force sensor 214, and finally to an optional force generator 216.
• the optional reference probe 202 is connected to the housing 218 that holds the sensors and generators.
• the housing 218 could be supported and positioned on the sample under test by a support. This does not exhaust the possibilities for measurement or actuation.
• a solenoid plus a fixed stop could be used to insert the test probe 200 to a fixed distance.
• the force vs. time after the insertion would have information about how the bone relaxed after the insertion.
• the solenoid would generate a force, but as long as the force was larger than needed to insert the test probe 200 to the fixed distance, then it would act like a displacement generator: generating a fixed displacement.
• This functionality also exists in Figure 3. Thus the separation between force generator and distance generator is not always clear.
• Other additions could include a heater to heat the probe that could be wound around the shaft 206.
• Figure 3 shows an enhanced example of the generalized diagnostic instrument shown in Figure 2.
• an optional displacement generator 320 consisting of a motor 322, a rotating horizontal cam 324 and a follower pin 326 held in contact with the cam 324 with two springs 328.
• the motor can be translated laterally with a screw 344 and locked down with screws 346 to adjust the range of motion: the closer the axis of the motor 322 is to the axis of the follower pin 326, the smaller the range of motion.
• Other embodiments can be constructed without the use of springs.
• a ball screw or Acme screw can be used to convert the rotary motion of a motor to linear motion.
• the Acme screw has the advantage that it can hold a load in a power off situation enabling measurements of force relaxation vs. time after an indentation to fixed depth.
• rotary to linear motion mechanisms such as piston mechanisms can be used.
• the diagnostic Instrument also has an optional force generator that cycles the test probe 300 into and out of the bone with forces generated by a solenoid 334 in combination with the two springs 328.
• This combination provides positive forces for insertion, when the force from the solenoid 334 exceeds the force from the two springs 328 and it provides negative forces to pull the test probe out of the bone when the force from the solenoid is less than the force from the two springs.
• the two adjustable stops 348 which are screws, prevent the solenoid from inserting the test probe too far into the bone. If it is desired to study the response of the bone to forces, then these screws 348 act only as safety devices - they are adjusted to stop the test probe 300 only well beyond the range that is actually probed.
• these screws can be adjusted to give a fixed indentation depth and 2) the current to the solenoid adjusted to be sufficient to insert the test probe 300 all the way until the stops 348 stop the indentation for all samples being tested. Then the response of all the samples to the same indentation can be monitored.
• the optional displacement generator 320 consisting of a motor 322, a rotating horizontal cam 324 and a follower pin 326 held in contact with the cam 324 with two springs 328 can also serve another purpose.
• the adjustment of the position of the test probe 300 relative to the reference probe 302 can be made with a screw or micrometer that pushes the follower pin 326. This screw or micrometer can be mounted where the motor 322 would have been mounted; it replaces the motor 322 and cam 324.
• the force sensor 330 can be any appropriate commercial force sensor, such as an s-beam load cell connected to the follower pin 326 at its top end and to a connector 335 at its bottom end, which in turn is connected to the test probe 300.
• the LVDT 332 is connected at its top end to the bottom end of the follower pin 326. the bottom end of the LVDT 332 is connected to test probe by a connecting pin 336.
• test probe 300 For the embodiment of Figures 3a - c, in which the force to pull sharpened test probes 300 out of the bone exceeds 1 Newton, one can clamp the test probe 300 to the connecting pin 336 with a collet 338. The test probe 300 then passes through a guide 340 that can be screwed into and out of the body of the instrument to adjust the projection of the test probe 300 relative to the reference probe 302. The reference probe 302 mounts on a mating neck 342 machined on the end of the guide 340.
• the diagnostic Instrument shown in Figure 3 can be used in two different measurement modes: (1) force controlled or (2) distance controlled. In the first, the test probe gets inserted into the bone until a set force is reached and the measured parameter is the resulting insertion distance. In the second mode, the insertion force is increased until the test probe inserts a set distance.
• the diagnostic Instrument can cycle the test probe into and out of the bone with two different actuation systems.
• One system based on a solenoid, is most convenient for cycling to a fixed force. For this a current is supplied to the solenoid by a 0-2A voltage controlled current source. For operation to a fixed force the current source supplies a current that increases to a fixed maximum.
• the other system based on a motor and cam, is most convenient for cycling to fixed distance.
• Figures 4 and 5 demonstrate the use of the solenoid system.
• Figure 6 demonstrates the use of the motor and cam system.
• the diagnostic instrument shown in Figure 3 with an oscillating force in addition to a slowly varying or static force.
• This can be accomplished, for example, by feeding the solenoid 334 with an oscillating current plus a slowly varying current or static current.
• the resultant oscillating force can be read from a force sensor 330 such as a load cell 330.
• the oscillating distance can be read from a distance sensor, 332, such as an LVDT.
• a faster distance sensor such as an optical sensor like the MTI - 2000 Fotonic sensor can be used.
• the optical fiber probe of the sensor 350 can be attached to the body of the instrument and can read the distance to a tab 352 which is connected to the test probe 300.
• the amplitude or phase of the oscillating distance as a function of frequency and as a function of slowly varying or static force can be explored to increase diagnostic differentiation.
• the slope of the distance vs. time plot just after the impact can easily distinguish baked from unbaked bone.
• the slope of the distance vs. time plot in the 10s of milliseconds after the impact is significantly less for the unbaked bone: by more than a factor of 5. This indicates that the unbaked bone impedes the repetitive insertion of the probe better than the baked bone.
• an optical sensor the MTI - 2000 Fotonic sensor, in our tests.
• any other fast distance sensors with the required 1) sensitivity, down to roughly 1 micron, 2) range, up to about 1 mm and 3) response time, preferably a few milliseconds or faster, could be used.
• Examples of such sensors include optical lever sensors and capacitance sensors.
• Figures 4a - e show that the diagnostic instrument of this invention can discriminate between baked bovine bone and unbaked, control, bovine bone.
• This model system of baked vs. unbaked bone is very useful because baking is an easy way to degrade its fracture resistance. Differences in fracture properties become dramatic for bone baked at 250 degrees C. for 2.5 hours [4,49].
• the bones are held in a small machinist's vices in a glass bowl that is resting on a simple spring scale on a lab jack.
• the lab jack is used to raise the scale, bowl, vice and bone until the bone contacts the probe assembly of the diagnostic instrument.
• the applied preloading force with which the reference probe contacts the bone can be set by continued raising of the lab jack until the desired force is read on the scale. This applied force will set the maximum force that can be used during the testing cycles. If the applied force is exceeded, the reference probe will lift off the bone.
• the unbaked, control, bone resists penetration of the test probe better: the distance that the test probe penetrates at fixed force is smaller.
• the unbaked, control, bone also survives cycling better, i.e. repetitive loading to a fixed force.
• the maximum penetration that results from each cycle reaches a limit for the unbaked, control bone, while the maximum penetration continues to increase for the baked bone.
• the maximum force for each cycle increases slightly, especially for the baked bone. This is because we are using open loop electronics that just cycles the current to a fixed maximum.
• the force from the solenoid is, however, dependent on not only the current, but also on the position of the ferromagnetic core in the solenoid coil. As the distance of penetration increases, the position of the core changes to positions that give slightly more force for the same current. Feedback on the measured force in a closed loop system that controls the current can stabilize the force.
• Figures 5a and b demonstrate that the diagnostic instrument can discriminate between the bone material properties of two individual humans that could be expected, based on previous investigations [1,4,50,51] to have different fracture properties because one is young, 19 years old, and one is elderly, 59 years old.
• the bone of the younger individual shows increased recovery upon retraction of the probe and requires more force to penetrate repeatedly to the same depth. Further, the maximum penetration distance that results from each cycle reaches a limit for the bone from the younger individual, while the maximum penetration distance continues to increase for the bone from the older individual even though the bone from the younger individual is cycled to a larger fixed force (7 vs. 5.5 Newton). This suggests that the bone from the older individual is less able to resist damage accumulation. Damage accumulation in the form of microcracks has been associated with increased fracture risk [52-55]. Because of the small number of samples, we cannot, however, statistically conclude that that a significant difference has been demonstrated between the bone material properties of bone from younger vs. older individuals.
• Figures 6a - d demonstrate the use of the diagnostic instrument with the alternate actuation system involving a motor and cam rather than the solenoid used in the experiments of Figures 4 and 5.
• the distance of penetration is controlled with the motor and the force is measured with the load cell.
• the force necessary to insert the test probe to a fixed distance decreases as the bone is damaged.
• Figures 6a - d also demonstrate the ability of the diagnostic instrument to penetrate soft tissue, even the tough periosteum that covers the bone surface, and still make measurements on the bone.
• small indentations are made into the bone with a sharpened test probe that is sturdy enough to not be deformed by penetrating bone.
• this type of test probe include test probes with diamond, silicon carbide, or hardened stainless steel tips.
• the resistance of the bone to the penetration of this sharpened test probe and/or its response, i.e., resistance, as the sharpened test probe is removed, are indicators of the fracture risk of the bone on the microscopic scale, which are in turn related to the fracture risk of bone on the macroscopic scale.
• a force vs. distance curve comparable to those taken with existing macro-mechanical testing, nanoindentation, microindentation or AFM indentation equipment is measured, with the sharpened test probe inserted through the skin to contact the bone.
• hardness and elastic modulus could be evaluated using the well established protocols and standards that have been established for materials testing with the existing macro-mechanical testing, nanoindentation, microindentation or AFM indentation equipment.
• Test probe tips for this purpose have been shown in Figure 9.
• a sheath over the sharpened test probe comes into contact with the bone surface and serves to define a reference position.
• the penetration of the sharpened test probe into the bone is then measured relative to the sheath. From measurements of force vs. penetration distance, parameters can be extracted as for conventional indentation testing of materials. In particular, this method can be used to measure recovery properties of bone to repeated indents. This supplies information pertinent to the fatigue resistance of bone, an aspect currently not measured by other devices.
• a valuable feature of this invention is that it can be done on a living patient with minimal impact and negligible health risks. For pain- sensitive patients, local anesthesia could be injected at the site to be tested.
• disposable single-use test probes can include good vs. bad indicators and can be available for use by individuals outside a doctor's office to assess their own bone fracture risk.
• the test probe tip extends a fixed distance beyond a sheath that stops at the bone surface.
• a spring or elastomer resists the motion of the test probe shaft back into the sheath and an indicator measures the motion of the test probe shaft back into the sheath. As the sheath is pushed until it contacts the bone surface the test probe tip must enter the bone or the test probe shaft must be pushed back into the sheath.
• the amount that the test probe shaft is pushed back into the sheath is a measure of the resistance of the bone to penetration and fracture; more fracture resistant bone will be indicated by more motion of the test probe shaft back into the sheath rather than penetration of the test probe tip into the bone.
• Another embodiment of the instrument uses a special material for a test probe tip that is hard enough to indent weak bone, but not healthy bone.
• a special material for a test probe tip that is hard enough to indent weak bone, but not healthy bone.
• ceramics with controlled porosity or metal alloys or polymers could be used. If such a test probe is inserted to a controlled force - such as in the range of 10 to 1000 milliNewton - then, after it is withdrawn, the deformation of the special material can be quantified: high deformation indicates bone that is fracture resistant; low deformation indicates bone that is at risk for fracture.
• test probe can be inserted up to a stop, for example a broad shoulder on the test probe a fixed distance behind the tip, with the deformation of the special material quantified.
• a test probe 700 is shown, which passes inside a reference probe 702 and is attached to a mounting pin 704, which passes through an alignment plate 705, and adheres to a magnet 706 mounted in a holder 707 that is screwed into a shaft 708 connected to the diagnostic instrument ( Figures 8 and 2).
• the reference probe 702 is mounted in a reference probe holder 710, for example a Luer lock as used in hypodermic needles.
• the reference probe holder 710 locked onto a mating receptacle 712 connected to the diagnostic instrument.
• the probe assembly 714 consisting of the test probe 700, its mounting pin 704, the reference probe 702 and its reference probe holder 710 can be disposable and sterilizable.
• the probe assembly 714 can be quickly mounted and dismounted from the diagnostic instrument. During mounting, the mounting pin snaps into contact with the magnet 706 as the reference probe holder 710 is mounted onto the mating receptacle 712.
• An optional test probe stop 716 in combination with a retaining stop 718 can simplify dismounting by pulling the mounting pin 704 off the magnet 706 as the reference probe holder is dismounted. The entire probe assembly 714 then comes off at once, eliminating the need to remove the test probe 700 and its mounting pin 704 separately after the reference probe 702 and the reference probe holder 710 are removed.
• subcomponents of the probe assembly have been identified with individual numbers. More generally we will use the phrase "combination of test probe and reference probe" to refer to the complete probe assembly ready for mounting on the diagnostic instrument. This combination of the test probe and the reference probe could be supplied sterilized and disposable for single use.
• Figure 8 shows the diagnostic instrument in a preferred embodiment.
• the test probe 800 is connected via the mounting pin 804, the alignment plate 805, the magnet 806 and the holder 807 to the shaft 808 of a distance sensor 813.
• the distance sensor comprises a commercial electronic digital indicator with a range of 0-125 mm and a readout down to 0.001 mm.
• the position of the test probe is measured relative to the reference probe 802, which is connected via components 803 and 809 to the distance sensor 813.
• a force or impact is transmitted through the distance sensor 813 by the shaft 808, which projects above the sensor.
• an impact plate 814 screwed to the top of the shaft 808 is impacted by a mass 815 that accelerates due to gravitational and/or optional spring 816 forces.
• the impacts are made reproducible by an indexing shaft 817 which is connected to the mass 815 with an indexing pin 818 that runs through the top cap 819.
• This top cap is screwed onto the body of the impact device 820 which is, in turn, screwed onto the distance sensor 813.
• the indexing shaft 817 is kept centered by a linear bearing 821.
• the optional torque and angular displacement sensor 208 and the optional torque generator 210 are omitted.
• the optional linear displacement sensor 212 is a digital dial gauge 813.
• the optional force sensor 214 is omitted.
• the optional force generator 216 is an assembly of parts 814-820.
• test probe 900 and reference probe 902 previously shown in Figure 7 as 700 and 702 respectively, in Figure 2 as 200 and 202 respectively and in Figure 1 as 100 and 102 respectively can have various shapes, and be made of various materials.
• Figure 9 shows different possibilities for each.
• Test probe 900d/c is patterned after the indenters used in some Rockwell and Brinell hardness testing, and has a half sphere of tungsten carbide 900b bonded to a steel shank 900c.
• Test probe 900d/e is patterned on the diamond indenter used in Knoop hardness testing.
• Test probe 900f/g has a diamond 90Of in the shape of a square-based pyramid whose opposite sides meet at the apex at an angle of 136° as used in Vickers hardness testing of metals and ceramics, mounted on a ceramic shaft 90Og.
• Test probe 90Oh is a tube that can be rotated for measuring friction on the surface of bone.
• Test probe 90Oj is a screw that can test bone by measuring the torque necessary to screw it into the bone from inside the reference probe 902a.
• Reference probe 902a is designed to penetrate skin and soft tissue before coming to rest on the surface of a bone.
• Reference probes 902b and 902c are designed for use with an optional outer syringe ( Figure 11) so that they do not need to be sharp for tissue penetration.
• Reference probe 902d/e is designed for penetrating soft tissue including tough soft tissue on bone surfaces, with the sharpened end 902d that is made of a material such as a soft aluminum alloy or plastic that can penetrate the soft tissue, but flattens when striking the bone and is mounted on a tube of more rigid material such as stainless steel 902e.
• Other pairings of test probes 900 and reference probes 902 are possible, such as test probe 900b with reference probe 902e/d.
• reference probes need not be cylindrically symmetric tubes.
• the reference probe can be a tube with slits 1002f to allow soft tissue to flow out from between the test probe and reference probe. It can be a rod 1002h terminated with ends 1002g. It can also be a hypodermic syringe with optional reground tip as shown in Figure 1.
• an optional outer syringe 1122 can be reversibly locked to the reference probe 1102 with an adhesive 1123 such as wax or soft plastic that is designed to stay intact through soft tissue, but break when the outer syringe 1122 hits the bone, thus allowing the test probe 1100 and the reference probe 1102 to contact the bone.
• the outer syringe 1122 can be attached to the reference probe 1102 during insertion by a removable pin 1124. After the removable pin 1124 is removed the reference probe 1102 and test probe 1100 can be slid into contact with the bone to be tested. The outer syringe 1122 can optionally be slid back out of the soft tissue before the bone is tested.
• Figures 12a - 12d show various supports for the diagnostic instrument.
• the diagnostic instrument slides through a guide 1225 that rests on the skin 1226.
• the test probe 1201 and reference probe 1202 penetrate the skin 1226 and soft tissue 1227 down to the bone 1228.
• the guide 1225 keeps the test probe approximately normal to the skin and underlying bone.
• the diagnostic instrument is hand-held.
• the indexing pin 1218 is pulled out with a thumb ring 1229 to initiate an impact during a test.
• the bone being tested 1231 is held in a vice 1232 under fluid 1233 contained in a vessel 1234.
• the diagnostic instrument can also be hand-held used for testing bone in regions of the body when the guide 1225 is not used.
• the diagnostic instrument is held in a clamp 1235 that is attached via a rod 1236 to a support plate 1237 - as shown rotated 90° - that rests on a lab jack 1238 which can be raised or lowered to adjust for different height samples such as the bone 1239 inside an arm 1240 that rests in a "V" block support 1241.
• the support plate 1237 moves freely on top of the lab jack 1238 to adjust the lateral position of the test probe.
• the bubble level 1242 on the rod 1236 guides adjustment of the lab jack 1238 to keep the test probe 1200 vertical.
• the diagnostic instrument is attached through an x, y, z force sensor 1242 to an x, y, z translator 1243.
• the translator 1243 controls the lateral positioning of the test probe to directly above the region to be tested and then lowers the test probe at controlled speed.
• the x, y, z force sensor 1242 can be used to monitor the vertical, z, force during insertion of the test probe and stop the lowering of the test probe by the x, y, z translator 1243 when a given set force is reached.
• the x, y, z force sensor 1242 can be used in a feedback system to keep the lateral, x and y, forces below set tolerances by positioning the diagnostic instrument with the x and y axes of the x, y, z translator 1243 during insertion of the test probe.
• Figures 13a - d show various embodiments of the force generator 216 of Figure 2.
• Figure 13a is a schematic version of the force generator shown in Figure 8 without the optional spring 816 or the indexing pin 818.
• the weight 1315 is lifted by shaft 1317 which is graduated so it can be lifted a precise amount. It is dropped, accelerates under gravity, and hits the impact plate 1314 on the shaft 1308.
• a magnetic core 1350 is pulled down by a coil 1351 to apply a force to shaft 1308.
• the gap 1352 is zero from the start: the current through the coil 1351 determines the force.
• a spring 1353 controls the starting position of the core 1350 and returns it to the starting position after an impact or slower varying force is applied by passing current through the coil 1351.
• This force generator is especially well suited to measurements of the resistance of the bone to fatigue fracture because it is easy to use an electronic pulse generator or other repetitive waveform generator to apply a series of impacts or force cycles to measure the indentation depth as a function of the number of impacts or force cycles.
• this type of force generator for applying a fixed force of a first magnitude to the test probe to determine a starting position of the test probe relative to the reference probe; optionally applying an impact to the test probe; applying a fixed force of a second magnitude to the test probe; measuring the change in position of the test probe relative to the reference probe; reducing the fixed force to the first magnitude; and recording the change in the position of the test probe relative to the reference probe.
• the force of a first magnitude is applied by a spring that is included inside the distance sensor 813 (Fig.
• Grizzly Digital Indicator that we used, a Grizzly Digital Indicator, supplemented by an optional external spring (not shown) that surrounds the shaft 807 and, by pushes on a washer (not shown) between the holder 807 and the shaft 808.
• forces of a first magnitude ranging from 0.1 to 0.8 lbs.
• forces of a second magnitude ranging from 1 to 3 lbs by applying currents of 0.42 to 1.25 amps to the coil 1351.
• test probe 800 To insert the test probe 800 and reference probe 802 through the soft tissue down to the bone with the test probe 800 extended approximately 0.02 inches beyond the reference probe 802 and held there by the springs.
• the test probe 800 When the bone is contacted, the test probe 800 is forced back into the reference probe 802 by allowing the full weight of the instrument, approximately 4 lbs. to rest on the bone surface, until the test probe 800 is flush with the end of the reference probe 802 as shown by a reading on the distance sensor 813 of within an acceptable margin of zero (one can generally used an acceptable margin of less than 10 microns).
• the test probe is applying a force of first magnitude to the bone: we have used 0.8 lbs.
• multilayer piezoelectric actuators 1354 such as the Tokin model AE1010D44H40, produce the force. They are shown in a push-pull configuration. To push down on the shaft 1308 the center two are expanded, and the outer four are contracted. They are joined at the top by a coupling plate 1355 which can be glued on with epoxy. In this way, forces up to over 2,00ON can be generated with displacements up to 160 ⁇ m. These are sufficient for bone indentation experiments with the probe assembly shown in Figure 7.
• a motor 1356 such as a digital stepper motor, derives a threaded nut 1358 with a rotating screw 1357.
• This screw can optionally be a ball screw or Acme screw.
• the Acme screw has the advantage that it can hold a load in a power off situation enabling measurements of force relaxation vs. time after an indentation to fixed depth. This compresses the spring 1359 which is constrained not to rotate. The spring 1359 applies a force to the plate 1360 at the top of the shaft 1308.
• FIG. 14 An alternate embodiment of the invention is shown in Figure 14.
• the frame of the device 1410 is connected to a support stand 1407 for immobilizing the limb of a patient on a firm foam cushion 1408 using Velcro straps 1409.
• a slide rail 1412 is attached to the frame.
• a sliding flange 1414 holds the diagnostic instrument, which in this Figure 14 consists of a test probe 1400 connected with a test probe vice 1406 via a shaft 1416 to a force and tension gauge 1403.
• Other examples of diagnostic instruments such as shown in Figures 2, 3 and 8 can alternately be mounted on the sliding flange 1414
• This assembly of sliding flange 1414 and diagnostic instrument can either: 1) be dropped from a fixed height to deliver an fixed impact or 2) gradually lowered to apply a force approximately equal to the weight of the assembly of sliding flange and diagnostic instrument.
• a force and tension gauge 1403 records the force administered at indentation and the tension required to free the test probe 1400 from the bone can both be measured.
• the diagnostic instrument can be attached to the sliding flange via a y, 1404, x, 1405 translator that can be used to move the diagnostic instrument laterally to be correctly positioned over the limb of a patient held on a firm foam cushion 1408 using Velcro straps 1409.
• Figure 15 shows a the top view of slide rail 1510 and interconnecting flange 1512.
• test probe vice 1616 attaches to directly to the force and tension gauge such as shown in Figure 14 and has a tightening collar to tighten the jaws that hold the disposable test probe 1600.
• Figure 17 shows the electronics necessary for operation of some diagnostic instruments ( Figure 2).
• Measurement and control electronics 1710 are needed to read the signals from the optional torque and angular displacement sensor 208, the optional linear displacement sensor 212 and the optional force sensor 214, and to supply signals to drive the optional torque generator 210 and optional force generator 216, as well as the optional x, y, z force sensor 1742 and the optional x, y, z translator 1743.
• An optional Computer 1711 is needed for implementing complex and/or automated test sequences using programs such as Labview or custom software.
• an automated test sequence can include the following steps: the x, y, z translator 1743 is used under computer 1711 control, to position the test probe 200 above a sample 1739, 1740; then the diagnostic instrument is lowered until the reference probe 202 penetrates tissue down to the bone 1739 as sensed by an increased z force on the x, y, z force sensor 1742, as measured by the measurement and control electronics 1710; when a preset value of z force is reached, the computer 1711 stops the x, y, z translator 1743; then the computer 1711 sends a signal via the measurement and control electronics 1710 to generate a specified force sequence with the force generator 216; the resultant displacement of the test probe 200 relative to the reference probe 202 is sensed by the linear displacement sensor 212 measured by the measurement and control electronics 1710 and recorded by the computer 1711 ; and the computer 1711 then sends a signal through the measurement and control electronics 1710 to the x, y, z translator to raise the test probe 200 out of
• the test probe 200 has a screw shape such as 90Oj in Figure 9.
• the optional reference probe is omitted.
• a torque sensor 208 such as the National Instruments RTS series or the S. Himmelstein MCRT series is used together with a torque generator 210 such as a motor.
• the displacement sensor 212 is a linear variable differential transducer (LVDT) such as the P3 America model EDCL, or a linear motion potentiometer such as a P3 America model MM10.
• the force sensor 214 is a load cell such as the National Instruments SLB series or the Sentran ZA series.
• the force generator 216 is a digital stepper motor driving a spring-screw arrangement as shown in Figure 13d.
• the entire diagnostic instrument is supported as shown in Figure 17.
• the torque needed to screw the test probe 90Oj into the bone is measured by torque and angular displacement sensor 208 for fixed force supplied by the force generator 216 as the screw screws into the bone. After the screw is screwed into the bone, the force to pull the screw out is, optionally, measured with the force sensor 216.
• This same diagnostic instrument could be used with test probe 200 and an optional reference probe 202 to measure the rotary friction of test probe 200 with shape 90Oi, 900b, 90Oh or other shapes on the surface of the bone. We have observed that some osteoporotic bone has decreased friction due to fatty deposits on the surface. Thus this rotary friction could be diagnostic for some types of osteoporosis.

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