WO2012089221A1 - Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue - Google Patents
Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue Download PDFInfo
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- WO2012089221A1 WO2012089221A1 PCT/EE2011/000009 EE2011000009W WO2012089221A1 WO 2012089221 A1 WO2012089221 A1 WO 2012089221A1 EE 2011000009 W EE2011000009 W EE 2011000009W WO 2012089221 A1 WO2012089221 A1 WO 2012089221A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0048—Detecting, measuring or recording by applying mechanical forces or stimuli
- A61B5/0051—Detecting, measuring or recording by applying mechanical forces or stimuli by applying vibrations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0048—Detecting, measuring or recording by applying mechanical forces or stimuli
- A61B5/0053—Detecting, measuring or recording by applying mechanical forces or stimuli by applying pressure, e.g. compression, indentation, palpation, grasping, gauging
-
- 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
- A61B5/4519—Muscles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B9/00—Instruments for examination by percussion; Pleximeters
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01D—MEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
- G01D5/00—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable
- G01D5/12—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means
- G01D5/14—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage
- G01D5/20—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage by varying inductance, e.g. by a movable armature
- G01D5/2006—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage by varying inductance, e.g. by a movable armature by influencing the self-induction of one or more coils
- G01D5/2033—Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage by varying inductance, e.g. by a movable armature by influencing the self-induction of one or more coils controlling the saturation of a magnetic circuit by means of a movable element, e.g. a magnet
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F7/00—Magnets
- H01F7/06—Electromagnets; Actuators including electromagnets
- H01F7/08—Electromagnets; Actuators including electromagnets with armatures
- H01F7/121—Guiding or setting position of armatures, e.g. retaining armatures in their end position
- H01F7/122—Guiding or setting position of armatures, e.g. retaining armatures in their end position by permanent magnets
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F7/00—Magnets
- H01F7/06—Electromagnets; Actuators including electromagnets
- H01F7/08—Electromagnets; Actuators including electromagnets with armatures
- H01F7/16—Rectilinearly-movable armatures
- H01F7/1607—Armatures entering the winding
- H01F7/1615—Armatures or stationary parts of magnetic circuit having permanent magnet
Definitions
- This invention belongs to the realm of medical technology, it is designed to measure the mechanical stress and biomechanical properties of the parameters of soft biological tissues and to statistically assess their state in real time.
- biomechanical properties of soft biological tissue involve its elasticity, dynamical stiffness, creepability, and mechanical stress relaxation time.
- both the parameters characterising the stress of superficial soft biological tissues, for example of skeletal muscle, and its biomechanical properties are used as a supplementary source of information.
- the said parameters allow specialists to quantitatively determine the extent of pathological processes, and the efficiency of various massage techniques, physiotherapeutic procedures, medication and training programmes, as well as ascertaining the tone of tissues during an operation, and fixing the time of death in forensics .
- Tone is defined as the mechanical stress of skeletal muscle with no voluntary contraction of the muscle. If we multiply the numerical value of the skeletal muscle stress by its cross-section area, we get the value of the force by which the tendon of skeletal muscle is pulling the periosteum of the bone.
- the passive resting tone a state of skeletal muscle with no contraction in the muscle when the muscle is not balancing force torques on the observed joint axis caused by the force of gravity with its mechanical tension. There is no electomyographic (EMG) signal.
- EMG electomyographic
- the resting tone (relaxation) a state of mechanical stress (or tension) of skeletal muscle without voluntary contraction with EMG activity due to, for instance, an emotional or pathological condition. Such a state is more variable than the passive resting tone.
- the muscle force torques in antagonist muscles are balanced.
- the postural tone is a state of skeletal muscle in which the muscle is balancing the force torques of body segments caused by the force of gravity in order to maintain the equilibrium position.
- the muscle tension and stiffness are changing persistently, the variability of which is several times greater than in passive relaxed tone.
- the state of mechanical tension and stiffness level are also significantly higher.
- the tone of the skeletal muscle cannot be decreased at will.
- the level of the tone depends on intramuscular pressure - the higher the intramuscular pressure, the greater the mechanical tensile stress in the muscle (Vain A. 2006 The Phenomenon of Mechanical Stress Transmission in Skeletal Muscles. Acta Academiae Olympiquae Estoniae, Vol 14, No. 1/2 pp. 38-48). If the intramuscular pressure is high, the outflow of venous blood from the muscle will slow down because the veins have no substantial internal blood pressure and when the intramuscle pressure rises, then the veins' cross-section area will decrease. In the case of passive rest, this causes the situation that skeletal muscles' ability to work is restored slowly.
- the amount of work A done when stretching the antagonist muscles can be calculated by the following formula:
- the logarithmic decrement of a muscle' s natural oscillation shows how much mechanical energy dissipates during one period of the muscle's natural oscillation.
- the elasticity of skeletal muscle one of the biomechanical qualities of the muscle
- Elasticity of soft biological tissue means its ability to restore its former shape after the deforming force is removed.
- the opposite term to elasticity is plasticity. If an elastic body changes its shape as a result of an impulse transmitted by external forces, then simultaneously mechanical energy of elasticity is stored in the morphological structures of skeletal muscle which possess elasticity properties.
- contraction and relaxation alternate.
- the duration of each may vary. Sometimes it may last only a split of a second. If the relaxation period is short and the muscle's logarithmic decrement is big, then the initial shape of skeletal muscle fails to be completely restored, the muscle's internal pressure falls insufficiently and, as a result, the outflow of venous blood from the muscle is slowed down. The time taken for the muscle's work capacity to be restored increases, its fatigue also increases, and the danger of a muscle overload trauma becomes a reality.
- Stiffness is a biomechanical property of skeletal muscle which consists in its resistance to any force changing its shape. The property inversely proportional to stiffness is compliance. The unit of measurement of both is N/m. How economical and how accurately co-ordinated a person' s movements are depends on the stiffness of his/her skeletal muscles. Creepability is a biomechanical property of soft biological tissue to deform permanently under constant stress. The creepability property of liquids has been quantitatively measured (US4534211, Molina 0. G. 1985) .
- the creepability property of soft biological tissue might be characterised, for example, by the Deborah number D e .
- the Deborah number is a quantity whose dimension is 1; this number is used to characterise the viscoelasticity of tissues (or creepability of materials) .
- the latter is expressed as the ratio of relaxation time, t mat eriai, representing the intrinsic properties of tissue, and the characteristic time scale of an experiment, or deformation time, t pr0 cess'
- the relaxation property of skeletal muscle tissue is defined as the tissue' s ability to relieve itself of mechanical stress in the case of constant length.
- the principal problem is how to evaluate the state of a person' s skeletal muscles on the basis of measurement data, while the parameters characterising this state are constantly changing due to their involvement in biological processes. Therefore, it is insufficient to represent the state of soft biological tissue by one parameter only, which reflects the level of measurable quantities; considering the aspect of diagnostic information, it is relevant that a characteristic describing the variation of levels be added. For assessment of variety, it is important that the reading of the measuring device be repeated in short-term measuring scales (e.g. measuring after every 1 second) . In this case, measuring should be carried out and monitored by measuring software (firmware), in order to collect in short term a sufficient amount of measurement data for statistical assessment. No such methods of measurement are known as yet in the diagnostics of soft biological tissues.
- the method closest to the present invention is the myometer, a device and method for recording of mechanical oscillations in soft biological tissues (EE03374B1, Vain A. 2001) .
- the essence of the myometer lies in causing a short-term effect on soft biological tissue by giving it a mechanical impulse and subsequently recording the tissue' s mechanical response by means of an electromechanical sensor (acceleration sensor) .
- the impulse may be followed by resonance oscillations of the parts exerting impact. If the size of the device is reduced, then the shoulder of the lever will become so short that it will cause a ' scraping' impact, which may yield incorrect results as the direction of the tissue' s deformation changes during stimulation.
- Another shortcoming is the constructional solution of the above prior art device, in which bending of the signal cable attached to the acceleration sensor during oscillation will bring about dissipation of the energy of impact.
- a shortcoming of the cited prior art device is also the feature that the construction of the measuring apparatus involves rotating details, which need fine tuning to minimise resistance caused by mechanical friction. But the greater the resistance, the less sensitive the device.
- the aim of the present invention is to provide a universal device and method for simultaneous measuring, in real time, of parameters characterising the state of mechanical stress, elasticity, dynamic stiffness, creepability and mechanical stress relaxation time of soft biological tissues.
- a device comprises the body (1) , the processor and controller for governing the measuring process and for calculating parameters (a control means) (2) , a recorder, e.g. acceleration sensor (3), the testing end (4) , the drive, of the testing end position sensors (6, 7) of a moving frame (9), and a shutter (8) of the said position sensors, whereas the drive of the testing end is operable in translational motion, without mechanical friction, and is having the same direction as the testing end, and where in the drive of the testing end comprises a testing end mechanism including a moving frame (9) and elastic elements, e.g.
- the device is operated by a computer program product stored in the processor memory and comprising portions of the software code adapted to perform the method by stages when the program is running in the processor.
- the device's construction and software enable the user to achieve repeatability and reliability of the measuring results, allowing simultaneous measurement of the parameters and processing of data as well as making statistically significant judgements in real time.
- the technical solution of the construction elements of the current invention makes it easy to assemble the device. Nor will the device need any fine tuning once it has been assembled. There is no need for tuning joints, e.g. the measuring mechanism.
- the method for simultaneous measurement of the parameters characterising the biological tissue' s state of mechanical pressure, elasticity, dynamic stiffness, creepability and mechanical stress relaxation time involves the following stages :
- a means for marking the area to be investigated and for facilitating the contact between the testing end and tissue without damaging the latter' s integrity and function is attached either to the testing end or the surface of the tissue ;
- the device disclosed above (myometer) is moved close to the surface being measured, in the course of which, irrespectively of the positioning of the device, the gravitation field and the user, the device causes between the tissue under investigation and the testing end a constant external influence (pre-pressure) with force equalling the gravity of the mass of the testing end mechanism.
- pre-pressure is maintained in stages B-D throughout the series of measurement;
- the placing of the device is stopped when either the light or sound signal of the device changes, indicating that the necessary pre-pressure has been achieved and the elastic element is stress-free, i.e. the preconditions for starting a series of measurements have been met;
- the device described above exerts on soft biological tissue external single impact for a prescribed number of times by a single impulse of the solenoid' s constant electrical power, each impact ends with a quick release. At the start of the impact, the elastic element is stress-free. Throughout the series of measurements, during the prescribed time, the device is kept in the same position until a change of either the light or sound signal indicates the end of the series.
- the parameters of a single external mechanical impulse are chosen, depending on the aims of the diagnostic information, from the following ranges: specific power from the range 0.01-0.2 /mm 2 , the quick release from the range 0.1-15 ms, and the time for achieving the maximum impulse from the range 1-5 ms .
- the mechanical change in the tissue' s shape and the tissue' s subsequent mechanical response are recorded, in real time, as graphs of the tissue's natural oscillations, for instance, as graphs of acceleration following each impulse in stage B.
- the parameters characterising the tissue's creepability and relaxation time of mechanical stress together with statistical assessment of all the calculated parameters are computed in real time; for calculating the parameters characterising soft biological tissue' s state of mechanical stress, elasticity, dynamic stiffness, creepability and relaxation time of mechanical stress, the time range from the measured tissue' s natural oscillations graph is used, for instance, the time range shown by the accelerations graph, which involves the period from the start to the end of the impact and 1.5 oscillation periods of the tissue's subsequent natural oscillations.
- the measuring series consists of single measurements in which the first measurement starts with stage A and is followed by stages B, C, and D. The next measurement in the series proceeds with repetition of stages B, C, and D until completion of the prescribed number of measurements.
- stage A to D To perform stages A to D and calculate the parameters, specially designed software (firmware) is used, which has been stored in the device's processor, comprises portions of software code, and has been adapted to perform stages A to D when the device's firmware is used in the processor. Measuring will be repeated in minimum 1-second intervals for as many times as required for statistical assessment.
- Fig. 1 Principal schematic representation of the device.
- the device for recording the state of mechanical stress and biomechanical properties of soft biological tissues comprises the body 1, with a means at its top holding a processor and controller for monitoring the measuring process and for calculating the parameters (a control means 2), a recorder 3 and a moving frame 9 fastened to an inflexibly base 13 by an elastic element, such as elastic plates 10 and 11.
- the moving frame 9 incorporates a sleeve 14 containing two permanent magnets 15 and 16, whose same-name poles are oriented face to face, while the testing end 4 has been attached to the permanent magnet 16 by means of a cone-shaped end 17 made of either electrical steel or some other suitable material.
- a acceleration sensor 3 has been inflexibly fastened and to the middle of the frame, a shutter 8.
- the position sensors 6 and 7, respectively, have been inflexibly fastened to the body 1.
- the arresting system of the moving frame 9 comprises a drive 20, an actuating screw 21, a slider 22 with a shutter 23 and a means 24 for preventing mechanical damage to the arresting system.
- position sensors 27 (upper) , 28 (middle) and 29 (lower) are inflexibly connected with the body 1.
- a solenoid 5 has been inflexibly fastened to the body 1, lying in the middle of the moving frame 9.
- the solenoid 5 When the measuring process is triggered by turn of the switch 31, the solenoid 5 is activated by electric current directed by the signal picked up from the axis of the acceleration sensor 3, depending on how the body 1 is oriented in the gravitation field. Constant current in the solenoid 5 gives rise to a constant force affecting the two permanent magnets 15 and 16 located in its magnetic field, as a result of which constant pressure is exerted on the slider 22 by the stopper 25 of the moving frame 9. This pressure is then conveyed by the testing end 4 to the biological tissue being measured. Subsequently, the position sensors 6 and 7 of the moving frame 9 are activated, and the slider 22 is positioned by means of the drive 20 and actuating screw 21 from the topmost to the middle position determined by the position sensor 28.
- the shutter 8 of the moving frame 9 will expose the light beam proceeding from the position sensor 6 (in the measuring position vis-a-vis the body 1), and cover the light beam proceeding from the position sensor 7 (vis-a-vis the body 1) ; the testing end 4 will emerge from the opening in the body and the signal lights surrounding the aperture 19 in the testing end will be switched on.
- the device is ready to perform measurements.
- the method applied when using the device comprises the following.
- the testing end 4 is placed on the tissue 30 under investigation, causing a deformation AS (Fig.2) .
- the body 1 of the device is moved towards the tissue until the discontinued beam of light from the position sensor 7 (in the measuring position vis-avis the body 1 is exposed by the shutter 8, whereas the shutter 8 has not yet covered the light beam proceeding from the sensor 6 (in the measuring position) .
- the colour of the light proceeding from the aperture 19 changes, indicating the position of the moving frame 9 in which the elastic plates 10 and 11 are stress-free.
- impulses of current with a fixed shape, duration and frequency are transmitted to the solenoid 5.
- the soft biological tissue undergoes a dynamic transformation ⁇ 1 (Fig.2), which ends with a quick release, after which the biological tissue 30, in accordance with its elasticity properties, undergoes a series of free damping co-oscillations along with the testing end 4, the moving frame 9, and the recorder 3.
- the tissue's natural oscillation is registered by the recorder 3, and the processor will calculate, in real time, the parameters characterising the tissue' s mechanical stress and biomechanical properties, as well as the criteria required for assessment.
- the control means 2 of the device will stop the measuring process and the colour of the light will change.
- the initial colour of the light source will not be restored, unless the position of the moving frame 9 with respect to the sensors 6 and 7 of the measuring position is restored and the measuring session can resume from where it stopped.
- the arresting system will fix the moving frame 9 in its upper limiting position.
- the device was held in the same position (for a prescribed time period) until the light or sound signal changed.
- the mechanical transformation of the tissue was recorded together with the tissue's subsequent mechanical response in the form of a acceleration graph of the tissue' s natural oscillation.
- the recordings were performed a certain prescribed number of times within intervals less than 1 sec (Fig.2) .
- the parameters of the measured tissue's mechanical stress, elasticity, dynamic stiffness and mechanical stress relaxation time were calculated, using the time span on the natural oscillations acceleration graph which consisted of the oscillation period starting with the impact and lasting until its end plus subsequent 1.5 periods of the tissue's first natural oscillation.
- the natural oscillation diagram, results of measurement and the orientation of the device were stored by means of a computer program in the memory of the device.
- the repeated measurements were carried out after min. 1- second intervals for a sufficient number of times for making statistical estimations.
- the results were displayed on the LCD screen of the recorder.
- Table 1 The results of the measurement are given in Table 1 below.
- Table 1 Measurements of the muscle tone and biomechanical properties of a 24-year-old male athlete at rest.
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Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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CA2823054A CA2823054C (en) | 2010-12-31 | 2011-07-07 | Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
ES11749721.4T ES2650162T3 (en) | 2010-12-31 | 2011-07-07 | Device for real-time measurement of parameters of a state of mechanical stress and biomechanical properties of soft biological tissue |
PL11749721T PL2658442T3 (en) | 2010-12-31 | 2011-07-07 | Device for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
NO11749721A NO2658442T3 (en) | 2010-12-31 | 2011-07-07 | |
AU2011351911A AU2011351911B2 (en) | 2010-12-31 | 2011-07-07 | Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
EP11749721.4A EP2658442B1 (en) | 2010-12-31 | 2011-07-07 | Device for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
US13/977,873 US9808183B2 (en) | 2010-12-31 | 2011-07-07 | Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
JP2013546591A JP5981449B2 (en) | 2010-12-31 | 2011-07-07 | Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of living soft tissue |
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EEP201000094 | 2010-12-31 | ||
EEP201000094 | 2010-12-31 |
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WO2012089221A1 true WO2012089221A1 (en) | 2012-07-05 |
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PCT/EE2011/000009 WO2012089221A1 (en) | 2010-12-31 | 2011-07-07 | Device and method for real-time measurement of parameters of mechanical stress state and biomechanical properties of soft biological tissue |
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US (1) | US9808183B2 (en) |
EP (1) | EP2658442B1 (en) |
JP (1) | JP5981449B2 (en) |
AU (1) | AU2011351911B2 (en) |
CA (1) | CA2823054C (en) |
EE (1) | EE05601B2 (en) |
ES (1) | ES2650162T3 (en) |
NO (1) | NO2658442T3 (en) |
PL (1) | PL2658442T3 (en) |
WO (1) | WO2012089221A1 (en) |
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WO2014122011A1 (en) | 2013-02-06 | 2014-08-14 | Myoton As | System and method for non-invasive measurement of soft biological tissue |
WO2014169217A3 (en) * | 2013-04-11 | 2015-11-05 | Ohio University | Systems and methods for establishing the stiffness of a bone using mechanical response tissue analysis |
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- 2011-07-07 WO PCT/EE2011/000009 patent/WO2012089221A1/en active Application Filing
- 2011-07-07 CA CA2823054A patent/CA2823054C/en active Active
- 2011-07-07 EP EP11749721.4A patent/EP2658442B1/en active Active
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- 2011-07-07 ES ES11749721.4T patent/ES2650162T3/en active Active
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WO2014122011A1 (en) | 2013-02-06 | 2014-08-14 | Myoton As | System and method for non-invasive measurement of soft biological tissue |
JP2016506802A (en) * | 2013-02-06 | 2016-03-07 | マイオトーン エイエスMyoton As | System and method for non-invasive measurement of living soft tissue |
AU2014214237B2 (en) * | 2013-02-06 | 2017-09-28 | Myoton As | System and method for non-invasive measurement of soft biological tissue |
US10568561B2 (en) | 2013-02-06 | 2020-02-25 | Myoton As | System and method for non-invasive measurement of soft biological tissue |
WO2014169217A3 (en) * | 2013-04-11 | 2015-11-05 | Ohio University | Systems and methods for establishing the stiffness of a bone using mechanical response tissue analysis |
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Also Published As
Publication number | Publication date |
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CA2823054C (en) | 2019-01-15 |
US20130289365A1 (en) | 2013-10-31 |
EE05601B2 (en) | 2015-06-15 |
US9808183B2 (en) | 2017-11-07 |
ES2650162T3 (en) | 2018-01-17 |
EE201000094A (en) | 2012-08-15 |
EP2658442B1 (en) | 2017-09-06 |
CA2823054A1 (en) | 2012-07-05 |
JP2014505530A (en) | 2014-03-06 |
EP2658442A1 (en) | 2013-11-06 |
NO2658442T3 (en) | 2018-02-03 |
PL2658442T3 (en) | 2018-02-28 |
AU2011351911A1 (en) | 2013-08-15 |
EE05601B1 (en) | 2012-12-17 |
JP5981449B2 (en) | 2016-08-31 |
AU2011351911B2 (en) | 2016-12-22 |
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