U.S. patent application number 11/117067 was filed with the patent office on 2005-12-22 for ultrasound measurement techniques for bone analysis.
This patent application is currently assigned to Odetech AS. Invention is credited to Hoff, Lars, Oygarden, Kjell.
Application Number | 20050283073 11/117067 |
Document ID | / |
Family ID | 21886453 |
Filed Date | 2005-12-22 |
United States Patent
Application |
20050283073 |
Kind Code |
A1 |
Hoff, Lars ; et al. |
December 22, 2005 |
Ultrasound measurement techniques for bone analysis
Abstract
Ultrasound measurement of bone quality using nonlinear analysis
in combination with or alternatively using shear waves provide
improved information about human bone conditions. Surface waves
also provide a novel method to estimate shear wave velocity.
Inventors: |
Hoff, Lars; (Bekkestua,
NO) ; Oygarden, Kjell; (Skarer, NO) |
Correspondence
Address: |
INTELLECTUAL PROPERTY GROUP
FREDRIKSON & BYRON, P.A.
200 SOUTH SIXTH STREET
SUITE 4000
MINNEAPOLIS
MN
55402
US
|
Assignee: |
Odetech AS
|
Family ID: |
21886453 |
Appl. No.: |
11/117067 |
Filed: |
April 28, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11117067 |
Apr 28, 2005 |
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10036072 |
Oct 19, 2001 |
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6899680 |
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60241609 |
Oct 19, 2000 |
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Current U.S.
Class: |
600/437 |
Current CPC
Class: |
A61B 8/485 20130101;
A61B 8/0875 20130101 |
Class at
Publication: |
600/437 |
International
Class: |
A61B 008/00 |
Claims
What is claimed is:
1. A method of measuring bone condition using ultrasound waves,
comprising the steps of: a) transmitting a signal sequence of
ultrasound waves for impingement on a bone being measured; b)
arranging a detection transducer configuration for receiving a
portion of the transmitted signal sequence of ultrasound waves
after impingement on the bone being measured; and c) determining
the degree of acoustic nonlinearity of the bone to estimate the
material conditions of the bone.
2. The method of claim 1 used for detecting bone reduction and
conditions related thereto.
3. The method of claim 1 used to estimate whether the bone is
changing from a homogenous to a more heterogeneous structure.
4. The method of claim 1 wherein the nonlinearity of the bone is
measured with harmonic frequency detection comprising the steps of:
a) transmitting a sound pulse through the bone; and b) measuring
the harmonic distortion.
5. The method of claim 4 wherein the second harmonic is sensed.
6. The method of claim 4 wherein a harmonic higher than the second
harmonic is sensed.
7. The method of claim 4 wherein combinations of harmonics are
sensed.
8. The method of claim 1 wherein the nonlinearity of the bone is
measured with nonlinear frequency mixing detection comprising the
steps of: a) transmitting two frequencies through the bone; b)
receiving the transmitted signals; and c) measuring the sum and/or
difference frequencies in the received signal.
9. The method of claim 8 wherein the two frequencies transmitted
are transmitted by two separate transducers.
10. The method of claim 8 wherein the two frequencies are
transmitted by exciting one transducer with both frequencies.
11. The method claim 9 wherein the transmitted signals are received
by one of the transducers that transmitted a frequency.
12. The method of claim 9 wherein the transmitted signals are
received by a third transducer.
13. The method of claim 10 wherein the transmitted signals are
received by the transducer that transmitted the frequencies.
14. The method of claim 10 wherein the transmitted signals are
received by a second transducer.
15. The method of claim 1 wherein the nonlinearity of the bone is
measured with a combination of harmonic detection and nonlinear
frequency mixing detection.
16. The method of claim 15 further comprising the steps of: a)
transmitting a plurality of signals at different frequencies
through the bone; b) receiving a portion of the transmitted
signals; c) measuring the sum and/or difference frequencies of a
first transmit frequency combined with the harmonics of a second
transmit frequency.
17. The method of claim 15 further comprising the steps of: a)
transmitting two frequencies through the bone; b) receiving the
transmitted signals; c) measuring the sum and/or difference
frequencies of the harmonics of the transmit frequencies.
18. The method of claim 1 used in conjunction with other
measurement techniques.
19. The method of claim 18 where the other measurement technique
measures at least one of reflection of sound and scatter of
sound.
20. The method of claim 18 where the other measurement technique
measures attenuation of sound.
21. The method of claim 18 where the other measurement technique
measures speed of sound.
22. The method of claim 1 used in conjunction with estimates for
elastic properties.
23. The method of claim 1 used in conjunction with measurements of
shape.
24. The method of claim 1 used in conjunction with measurements of
geometrical dimensions.
25. A method for diagnosing osteoporosis comprising the steps of:
a) transmitting a signal sequence of ultrasound waves for
impingement on a bone being measured; b) arranging a detection
transducer configuration for receiving a portion of the transmitted
signal sequence of ultrasound waves after impingement on the bone
being measured; and c) measuring the degree of acoustic
nonlinearity of the bone to estimate the material conditions of the
bone indicative of the onset of osteoporosis.
26. The method of claim 25 further comprising the step of assigning
the measured bone portion a bone strength index.
27. The method of claim 26 further comprising the step of
repeatedly comparing sequential time spaced measurements of the
same bone structure to identify onset or susceptibility to bone
disease.
28. The method of claim 25 in which the step of measuring the
degree of acoustic nonlinearity of the bone comprises: a)
transmission to achieve a two frequency mixing by transmitting two
frequencies f.sub.1 and f.sub.2; and b) receipt of f.sub.1 and
f.sub.2 at the difference and/or sum frequencies f.sub.1-f.sub.2
and f.sub.1+f.sub.2.
29. The method of claim 25 in which the step of measuring the
degree of acoustic nonlinearity of the bone comprises: a)
transmission of an amplitude modulated signal by transmitting a
signal p=(1+A sin 2.pi.f.sub.mt) sin 2.pi.f.sub.0t; and b)
receiving the signal at a modulation frequency f.sub.m and a
selected second or higher harmonic of that frequency.
30. The method of claim 25 in which the step of measuring the
degree of acoustic nonlinearity of the bone comprises: a)
transmission of signals comprising one high imaging frequency
f.sub.i and one low pumping frequency f.sub.p; and b) receiving the
signals at sum and/or difference frequencies f.sub.i-f.sub.p and
f.sub.i+f.sub.p.
31. The method of claim 25 in which the step of measuring the
degree of acoustic nonlinearity of the bone comprises: a)
transmission of a signal comprising one transmit frequency f.sub.0;
and b) receiving the signal at a harmonic of the transmit
frequency.
32. A method of measuring bone strength comprising the steps of: a)
measuring the shear wave velocity (c.sub.s); b) estimating the Lame
coefficient shear modulus (.mu.) of the bone by use of the formula:
5 C s = and c) assigning a bone strength index of measure based on
the estimate of shear modulus.
33. The method of claim 32 further comprising the additional step
of measuring bone strength by measuring the degree of nonlinearity
of the bone to estimate the material conditions of the bone.
34. The method of claim 32 used in conjunction with other
measurement techniques.
35. The method of claim 34 where the other measurement technique
measures reflection of sound.
36. The method of claim 34 where the other measurement technique
measures scatter of sound.
37. The method of claim 34 where the other measurement technique
measures attenuation of sound.
38. The method of claim 34 where the other measurement technique
measures speed of sound.
39. The method of claim 34 used in conjunction with estimates for
elastic properties.
40. The method of claim 34 used in conjunction with measurements of
shape.
41. The method of claim 34 used in conjunction with measurements of
geometrical dimensions.
42. A method for diagnosing osteoporosis comprising the steps of:
a) measuring the pressure wave velocity through a patient's bone;
b) measuring the shear wave velocity through a patient's bone; c)
calculating the ratio of shear wave velocity to the pressure wave
velocity to determine whether the bone is degraded.
43. The method of claim 42 further including calculating the speed
of sound in the bone by transmitting ultrasonic waves using a
transmitter placed on the surface of a patient's skin, through the
tissue to the bone at a predetermined angle, receiving ultrasonic
waves refracted from the bone at a receiver positioned on the
surface of a patient's skin a known distance from the transmitter,
and measuring the time of the first arrival of refracted ultrasonic
wave at the receiver.
44. A device for measuring bone density comprising a means for
measuring the shear wave velocity through a patient's bone.
45. The device of claim 44 wherein a first transducer transmits a
wave into the patient's bone and a second transducer receives the
wave.
46. The device of claim 45 wherein the first and second transducers
are the same transducer.
47. The device of claim 44 further comprising a means for measuring
the pressure wave velocity through a patient's bone.
48. A system for measuring bone density by measuring the shear wave
velocity through a patient's bone.
49. A method of measuring bone density comprising the step of
measuring the phase velocity as a function of frequency.
50. The method of claim 49 further comprising the step of measuring
the frequency dependant attenuation.
51. The method of claim 49 further comprising the steps of a)
measuring the degree of nonlinearity of the bone to estimate the
material conditions of the bone; and b) measuring the shear wave
velocity and estimating the shear modulus (.mu.) of the bone.
52. The method of claim 49 used in conjunction with other
measurement techniques.
53. The method of claim 52 where the other measurement technique
measures reflection of sound.
54. The method of claim 52 where the other measurement technique
measures scatter of sound.
55. The method of claim 52 where the other measurement technique
measures attenuation of sound.
56. The method of claim 52 where the other measurement technique
measures speed of sound.
57. The method of claim 49 used in conjunction with estimates for
elastic properties.
58. The method of claim 49 used in conjunction with measurements of
shape.
59. The method of claim 49 used in conjunction with measurements of
geometrical dimensions.
60. A device for measuring bone density comprising a means for
measuring the phase velocity as a function of frequency.
61. A system for measuring bone density comprising a means for
measuring the phase velocity as a function of frequency.
62. A method for diagnosing osteoporosis comprising the steps of:
1) placing a transmitter of ultrasonic waves on a predetermined
area on the surface of a patient's skin; 2) placing a receiver of
ultrasonic waves on an area on the surface of the patient's skin a
known distance from the transmitter; 3) transmitting ultrasonic
waves through the tissue to the bone at a predetermined angle; 4)
measuring the time of the arrival of the first ultrasonic wave by
the receiver; and 5) calculating the speed of sound in the bone
using the time of arrival of the first ultrasonic wave.
63. A system for diagnosing osteoporosis comprising: 1) a
transmitter configured for transmitting ultrasonic waves onto a
predetermined area on the surface of a patient's skin and through
the tissue to the bone so as to create a surface wave at a
bone-tissue interface region that is measurable by a receiver of
the ultrasonic surface wave; 2) at least one receiver of ultrasonic
waves on an area on the surface of the patient's skin a known
distance from the transmitter; and 3) analysis circuitry for
measuring the surface wave velocity and translating the measured
velocity into an indicator of bone health status.
64. The system of claim 63 in which the transmitter is configured
so that the tissue-bone interface is in the acoustic near field of
the transmitter.
65. The system of claim 63 comprising means for selectively either
vertically polarizing or horizontally polarizing the surface wave
that is generated.
Description
FIELD OF THE INVENTION
[0001] The invention relates to improved sensing and analysis of
ultrasound measurement signals for use as a diagnostic tool in bone
analysis.
BACKGROUND OF THE INVENTION
[0002] The field of ultrasound imaging of mammalian physiology is
well known and well established. However, the methodology is
dominated by certain techniques which have known limitations that
are susceptible to improvement or alteration. This technology is
known to be used in the imaging of various sites, such as spinal,
wrist, knee, cartilaginous areas, and other musculoskeletal
locations in mammals, particularly humans. The use of ultrasound
for these sites generally is referred to as Quantitative Ultrasound
(QUS), and is often in a competitive role with other imaging
modalities.
[0003] However, there has recently been some interest in using
ultrasound in a predictive role for the disease known as
osteoporosis. Osteoporosis is a disease of the skeleton in which
the amount of calcium present in the bones slowly decreases to the
point where the bones become brittle and prone to fracture. In
other words, the bone loses density. It is estimated that over 10
million people in the United States suffer from this disease, and
18 million more have low bone mass, placing them at increased risk
for this disorder. Osteoporosis is no longer considered a solely
age or gender-dependent, and when diagnosed early it can often be
treated successfully.
[0004] In summary, osteoporosis is a major public health problem
characterized by significant morbidity, mortality, and economic
burden. Bone mass measurements, using ultrasound technologies,
appears to be one of the best ways to make the diagnosis of
osteoporosis. However, certain improvements are needed in this
emerging area of medical technology to overcome reliability and
availability of imaging systems.
SUMMARY OF THE INVENTION
[0005] A system and method is disclosed for diagnosing osteoporosis
comprising the components and software implemented steps of
transmitting a signal sequence of ultrasound waves for impingement
on a bone being measured; arranging a detection transducer
configuration for receiving a portion of the transmitted signal
sequence of ultrasound waves after impingement on the bone being
measured; and measuring the degree of acoustic nonlinearity of the
bone to estimate the material conditions of the bone indicative of
the onset of osteoporosis.
[0006] There is also disclosed a system and method for measuring
bone strength comprising components and software implemented steps
of measuring the shear wave velocity (c.sub.s); estimating the Lam
coefficient shear modulus (.mu.) of the bone by use of the formula:
1 C s =
[0007] and assigning a bone strength index of measure based on the
estimate of shear modulus.
[0008] There is further disclosed a system and method for
diagnosing osteoporosis comprising components and software
implemented steps of measuring the pressure wave velocity through a
patient's bone; measuring the shear wave velocity through a
patient's bone; calculating the ratio of shear wave velocity to the
pressure wave velocity to determine whether the bone is
degraded.
[0009] A still further disclosure includes a system for diagnosing
osteoporosis comprising a transmitter configured for transmitting
ultrasonic waves onto a predetermined area on the surface of a
patient's skin and through the tissue to the bone so as to create a
surface wave at a bone-tissue interface region that is measurable
by a receiver of the ultrasonic surface wave; at least one receiver
of ultrasonic waves on an area on the surface of the patient's skin
a known distance from the transmitter; and analysis circuitry for
measuring the surface wave velocity and translating the measured
velocity into an indicator of bone health status.
DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a schematic of ultrasound wave propagations in
tissue and bone media.
[0011] FIG. 2 is a graph of measured P waves in human samples.
[0012] FIG. 3 is a graph of measured S waves in human samples.
[0013] FIG. 4 is a graph of the ratio of measured S and P waves in
human samples.
[0014] FIG. 5 is a block diagram of a pulse propagation measuring
setup.
[0015] FIG. 6 is a block diagram of a backscatter or reflection
measuring setup.
[0016] FIG. 7 is a block diagram of a reflection at an angle
measuring setup.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0017] Osteoporosis is also defined as a skeletal disorder
characterized by compromised bone strength predisposing to an
increased risk of fracture. Bone strength reflects the integration
of two main features: bone density and bone quality. Bone density
is expressed as grams of mineral per area or volume and in any
given individual is determined by peak bone mass and amount of bone
loss. Bone quality refers to architecture, turnover, damage
accumulation (e.g., microfractures) and mineralization.
Osteoporosis is well established as a significant risk factor for
fracture.
[0018] Osteoporosis can be further characterized as either primary
or secondary. Primary osteoporosis can occur in both genders at all
ages but often follows menopause in women and occurs later in life
in men. In contrast, secondary osteoporosis is a result of
medications, other conditions, or diseases. Osteoporosis is
diagnosed when bone density has decreased to the point where
fractures will happen with mild stress, its so-called fracture
threshold. This is defined by the World Health Organizations as
bone mass density (BMD) that is a 2.5 standard deviation (SD) or
more below the average BMD for young adults. (One standard
deviation below the norm in a measurement of hip bone density is
equivalent to adding 14 years to a person's risk for fracture.)
Measurements of between 1 and 2.5 SD below normal are defined as
osteopenia.
[0019] The consequences of osteoporosis include the financial,
physical, and psychosocial, which significantly affect the
individual as well as the family and community. An osteoporotic
fracture is a tragic outcome of a traumatic event in the presence
of compromised bone strength, and its incidence is increased by
various other risk factors. Traumatic events can range from
high-impact falls to normal lifting and bending. The incidence of
fracture is high in individuals with osteoporosis and increases
with age. Osteoporotic fractures, particularly vertebral fractures,
can be associated with chronic disabling pain. Nearly one-third of
patients with hip fractures are discharged to nursing homes within
the year following a fracture. Notably, one in five patients is no
longer living 1 year after sustaining an osteoporotic hip fracture.
Hip and vertebral fractures are a problem for women in their late
70s and 80s, wrist fractures are a problem in the late 50s to early
70s, and all other fractures (e.g., pelvic and rib) are a problem
throughout postmenopausal years. Indeed, the National Osteoporosis
Foundation (United States) estimates that there are more than 1.5
million fractures reported each year.
[0020] By way of example, hip fracture alone has a profound impact
on quality of life, as evidenced by findings that 80 percent of
women older than 75 years preferred death to a bad hip fracture
resulting in nursing home placement. However, little data exist on
the relationship between fractures and psychological and social
well-being. Other quality-of-life issues include adverse effects on
physical health (impact of skeletal deformity) and financial
resources. An osteoporotic fracture is associated with increased
difficulty in activities of daily life, as only one-third of
fracture patients regain pre-fracture level of function and
one-third require nursing home placement. Fear, anxiety, and
depression are frequently reported in women with established
osteoporosis and such consequences are likely under-addressed when
considering the overall impact of this condition. Direct financial
expenditures for treatment of osteoporotic fracture are estimated
at $10 to $15 billion annually. A majority of these estimated costs
are due to in-patient care but do not include the costs of
treatment for individuals without a history of fractures, nor do
they include the indirect costs of lost wages or productivity of
either the individual or the caregiver.
[0021] Currently, the most popular technique for determining bone
density is dual-energy x-ray absorptiometry (DEXA), which measures
bone density throughout the body within two to four minutes. The
measurements are made by detecting the extent to which bones absorb
photons that are generated by very low-level x-rays. Physicians use
a formula based on the results of these procedures to determine if
bone density has deteriorated to the fracture threshold.
[0022] Unfortunately, DEXA is not widely available and may be
inappropriate for many patients. Other techniques that measure
density may also result in accurate measures of overall bone loss
and be less expensive and may not expose the patient to the
radiation inherent to DEXA and its analogs. These are examples of
the opportunities for ultrasound, subject to basic improvements in
its accuracy, sensitivity, and overall predictive value.
[0023] Use of ultrasound in relation to monitoring of bone growth
is also well documented. With respect to bone healing, one study
reports that callus (i.e., the hard bonelike substance thrown out
between and around the ends of a fractured bone) is easily
visualized with ultrasound. Moreover, callus as seen on ultrasound
predates its appearance on radiographs. It has also been suggested
that fracture union on ultrasound precedes radiographic union.
Thus, it is believed that ultrasound may provide important
prognostic information concerning fracture healing as well as
valuable information of regenerate bone during the process of limb
lengthening.
[0024] Ultrasound has been used for many years to investigate the
mechanical properties of various engineering materials. It offers
the theoretic advantage of measuring material properties other than
density. As noted above, this technique is termed quantitative
ultrasound (QUS). This offers the advantages of small size,
relatively quick and simple measurements, and no radiation. QUS
measurements are generally considered as much easier to perform at
skeletal sites with minimal soft tissue covering. However, to date,
most QUS devices measure the peripheral skeleton, including the
heel, shin, knee cap, and fingers only, due to certain
limitations.
[0025] Regardless, several different QUS devices and methods have
been shown to be predictive of hip fracture, independent of
radiograph-based bone density measurements. QUS has enjoyed
widespread use around the world and has recently been approved for
clinical use in the United States. Indeed, certain changes in
government reimbursement schemes may even accelerate the
introduction and use of QUS technologies in order to avail lower
cost high quality methodologies to a greater population. Although
apparently the QUS technologies are exciting, there are still
concerns and room for improvements. For example, researchers are
still not certain exactly which mechanical or structural parameters
of the bone are being measured with QUS. It has been speculated
that QUS may be related to trabecular size, trabecular spacing, and
parameters of bone mineralization such as crystal size and
orientation.
[0026] In yet another analysis, it has been found that broadband
ultrasound attenuation (BUA) also predicts the occurrence of
fractures in older women and is a useful diagnostic test for
osteoporosis. The strength of the association between BUA and
fracture is similar to that observed with bone mineral density.
Broad-band acoustic attenuation and speed-of-sound have also been
shown to display a quantitative relationship to mineralization.
Further, in another study, measurements of the attenuation and
velocity of ultrasound from 0.3 to 0.8 MHz have been performed on a
number of bovine cancellous bone samples. The influence of bone
mineral content was isolated by measuring the acoustic properties
of the samples at various stages of demineralization resulting from
controlled nitric acid attack. The correlation coefficient r,
between the attenuation at different frequencies and bone density
was found to be in the range 0.68-0.97. Broadband ultrasonic
attenuation (BUA) was also calculated and produced r values between
0.84 and 0.99. The velocity measurements indicated a correlation
greater than 0.97 in all cases. Thus velocity appears to be the
parameter most sensitive to changes in bone mineral density alone.
Attenuation and BUA are less well correlated presumably because of
a sensitivity to minor structural change. Accordingly, further
advances in research are required and encouraged.
[0027] Yet another study determined that each standard deviation
decrease in calcaneal broadband ultrasound attenuation was
associated with a doubling of the risk for hip fractures after
adjustment for age and clinic. The relationship was similar for
bone mineral density of the calcaneus and femoral neck. Decreased
broadband ultrasound attenuation was associated with an increased
risk for hip fracture. A low broadband ultrasound attenuation value
was particularly strongly correlated with intertrochanteric
fractures, i.e., fractures at the proximal femur. The conclusion
reached was that decreased broadband ultrasound attenuation
predicts the occurrence of fracture in elderly women and that this
may also provide a useful diagnostic test for osteoporosis. Thus,
the need to accurately account for attenuation and sound velocity
profiles of bone in patients at various sites is quite important in
this fight against osteoporosis.
[0028] In summary, osteoporosis is a major public health problem
characterized by significant morbidity, mortality, and economic
burden. Osteoporotic fractures in older women are related, for the
most part, to the women's BMD. Ultrasound does not measure bone
density but rather measures two parameters called speed of sound
(SOS) and broadband ultrasound attenuation (BUA) that are related
to the structural properties of bone. Studies have shown that QUS
measures have the ability to distinguish fracture patients from
controls and to predict future fracture. The advantage for
ultrasound devices is that they are small, portable, use no
ionizing radiation, and may provide an attractive alternative to
radiation-based densitometry. Bone mass measurement appears to be
one of the best ways to make the diagnosis of osteoporosis.
However, considerable improvements are needed in this emerging area
of medical technology.
[0029] The methods in use for the measurement of bone density by
ultrasound are generally limited to measurement of direct
transmission and scatter measurements, sending sound through a
bone, and measuring acoustic transmission and speed of sound,
including reflection. The velocity of sound in bone can be measured
using a technique analogous to that used in the field of refraction
seismics, which involves investigations of the sea floor for
various purposes. As applied to physiological testing, the method
consists of a first transducer transmitting an ultrasonic wave from
a point external of the tissue into an inner bone at a critical
angle. This generates pressure, shear and/or surface waves that
propagate along the interface between the bone and the soft tissue.
The wave radiated from these waves is then received by a second
transducer, also positioned external to the tissue. The speed of
sound in the bone is calculated from the first time of arrival of
the sound pulse at the receiving transducer. This method requires
the velocity of sound in bone to be greater than in the surrounding
soft tissue, which is true for pressure waves, but may not be
fulfilled for shear waves.
[0030] The method is illustrated in FIG. 1, and is summarized as
follows. An acoustic wave is emitted from the transmitter T into
the body of the patient and received with the receiver R. T and R
are placed on the skin of the patient at a distance x. The emitted
wave may follow three paths from T to R:
[0031] (1) Direct wave. This wave follows a straight line parallel
to the skin surface and is denoted by line 13.
[0032] (2) Reflected wave. This wave is reflected at the boundary
between the soft tissue and the bone, and is denoted by line
15.
[0033] (3) Refracted wave. This wave, denoted by line 17, hits the
bone at critical angle .theta..sub.c, propagates along the
interface between soft tissue and bone, while radiating acoustic
energy back to the tissue at critical angle .theta..sub.c. Some of
the radiated sound is received by the receiver R. The critical
angle .theta..sub.c is given by 2 c = v o v 1 ( 1 )
[0034] where v.sub.o is the speed of sound in the tissue and
v.sub.1 is the speed of sound in the bone.
[0035] The time of flight from T to R for these three waves are
t.sub.1, t.sub.2 and t.sub.3. The arrival time t.sub.3 of the
refracted wave can be found from FIG. 1 to be 3 t 3 = x / v 1 + 2 d
o v 1 2 - v o 2 v o v 1 ( 2 )
[0036] where x is the distance between transmitter T and receiver R
and d.sub.o is the distance from the skin surface to the bone, as
shown in FIG. 1.
[0037] The wave velocity v.sub.1 of the bone is larger than the
wave velocity v.sub.0 of the soft tissue. If, in addition, the
distance x between T and R exceeds a minimum value x.sub.min, the
refracted wave 17 may arrive on R before the other waves 13, 15,
that is
v.sub.1>v.sub.o and x>x.sub.min=>t.sub.3<t.sub.1,
t.sub.2 (3)
[0038] Hence, the time t.sub.3 can be found from the first arrival
of a signal at R after transmitting from T. When the time of first
arrival t.sub.3 is measured, the speed of sound in the bone v.sub.1
is calculated from (Eq. 2). The speed of sound in the soft tissue
v.sub.0 and the distances x and d.sub.o must be measured
independently. This may be done from ultrasound time-of-flight
measurements. This technique allows accurate measurements of sound
velocity independent of geometric dimensions. This technique may be
combined by one or more of the principles below to increase the
accuracy of the estimates of sound velocity.
[0039] U.S. Pat. No. 5,197,475 illustrates ultrasound measurement
setups using such basic principles of ultrasound pressure wave
transmission and/or reflection, particularly as a function of
angle. The reference provides very broad but useful description of
measurement systems and techniques, and also briefly addresses the
concept known as shear wave measurements. Elaborating on that
latter concept, and other unknown combinations of techniques, is
one of the goals of the present invention.
[0040] Shear waves do not propagate far in tissue, but will
propagate in solid structures like bone. Moreover, the shear wave
velocity is more sensitive to material structure than the pressure
wave velocity, in that it differs more strongly between various
materials. Hence, the shear wave velocity is a more sensitive
parameter than pressure wave velocity for detecting the state of
the measured bone.
[0041] The pressure c.sub.p and shear c.sub.s wave velocities of an
elastic solid are given by the expressions 4 Cp = + 2 and Cs = ( 4
)
[0042] where .rho. is the density and .lambda. and .mu. are the
Lame coefficients of the material.
[0043] Measurement of the shear wave velocity includes an estimate
for the second Lame coefficient .mu., which is the shear modulus of
the material. Degradation of a material typically causes a
reduction in its density .rho. and a reduction in material
rigidity, that is, lower values of .lambda. and .mu.. Measurements
of both c.sub.p and c.sub.s in (Eq. 4) gives more information about
the underlying material properties than measurements of c.sub.p
alone.
[0044] If a material undergoes a transition from an elastic solid
to a looser porous structure, this causes a larger reduction in the
shear modulus .mu. than in the bulk modulus K=.lambda.+2/3.mu..
Hence, independent measurements of c.sub.p and c.sub.s, calculating
e.g. the ratio c.sub.s/c.sub.p, will provide information about the
relation between the shear and bulk moduli of the material. This
gives information about whether the material is changed from an
homogeneous solid into a looser porous structure.
[0045] Velocity dispersion is a characteristic property of
heterogenous media, especially porous materials. If the bone
undergoes a transition from homogeneous to porous, it can also
change from non-dispersive to dispersive. Hence, sound velocity
dispersion can be used as an indicator of altered tissue material
structure. In addition, this technique can reduce the need for an
accurate measurement of sound velocity, as it only requires
relative measurement of phase velocity as function of frequency,
and the technique does not depend on accurate measurements of
geometric dimensions. In the case of a heterogenous medium, the
phase velocity typically undergoes a change where the wavelength is
of the same magnitude as the grain size. This transition may be
used as an estimate for "grain size" in a porous material. Velocity
dispersion measurements can be combined with measurement of
frequency dependent attenuation, to further increase the accuracy
of the estimates.
[0046] Another aspect of ultrasound imaging relates to
nonlinearity. All sound propagation is nonlinear, and will generate
harmonics at sufficiently high amplitudes over sufficiently long
distances. Small voids or other inhomogeneities can act as
nonlinear sources in solid materials, and increase the acoustic
nonlinearity parameter. Hence, measurements of the degree of
nonlinearity in a material can be used to estimate material
conditions. Especially, it may be used to estimate whether the
material is changing from a homogeneous to a more heterogenous
structure.
[0047] There are several ways to measure the degree of
nonlinearity. The most obvious is to transmit a sound pulse through
the material and measure the harmonic distortion, i.e. the level at
harmonics of the transmitted frequency. Here, the second harmonic
is the most natural choice, but also higher harmonics, or
combinations of harmonics can be used. Harmonic detection is
summarized as
Transmit frequency f.sub.T (5)
Receive one or more of the harmonics 2f.sub.T, 3f.sub.T, 4f.sub.T,
. . .
[0048] Nonlinear frequency mixing may be an even better method. Two
frequencies are transmitted through the sample. This can be done
either by two separate transducers, or by exciting one transducer
with both frequencies. The transmitted or scattered signals from
the material is picked up by another, or the same, transducer.
Nonlinear mixing will cause sum- and difference frequencies in the
received signals. The level at these sum and/or difference
frequencies is an indicator of the condition of the material.
Nonlinear frequency mixing is summarized as
Transmit frequencies f.sub.1 and f.sub.2
Receive at sum and/or difference frequencies f.sub.1+f.sub.2,
f.sub.1-f.sub.2 (6)
[0049] The harmonic and nonlinear frequency mixing techniques may
also be combined, i.e. receive at sum and difference frequencies of
the harmonics. An example would be
Transmit frequencies f.sub.1 and f.sub.2 (7)
[0050] Receive at sums and/or differences around harmonics, e.g.
2f.sub.1-f.sub.2, 2f.sub.1+f.sub.2, 3f.sub.1+f.sub.2 . . . .
[0051] The methods mentioned above may be combined in various
measuring or display techniques to increase the quality of the
outcomes. Further, these techniques may be combined with other
measurement techniques, such as measurements of reflection,
scatter, attenuation and speed of sound. They may also be combined
with estimates for elastic properties, and with measurements of
shape and geometrical dimensions.
[0052] In addition to the possible combinations noted above, the
invention also includes a recognition of technical know how across
diverse industries. For example, as is well known in the petroleum
industry, porosity of materials is one of the parameters that
influences acoustic velocity and attenuation. In the case of
increasing porosity, a decrease in the acoustic velocities and an
increase of the attenuation are expected. Moreover, it is now
appreciated that compressional and shear waves can be affected
differently from an increase in porosity. Past studies on acoustic
P wave velocity measurements in bones were made primarily for
porosity monitoring. A more efficient and suitable method for
clinical use may be to measure the shear or S-wave velocity, and a
combination of petroleum and medical research knowledge may be
useful in that regard, as well as certain breakthrough realizations
of the inventor.
[0053] Preliminary acoustic velocity measurements on bovine bones
were made in order to test the possibility of measuring P-wave
velocity, S-wave velocity and attenuation in bones using the
equipment available in the Formation Physics Laboratory at SINTEF
Petroleum Research in Trondheim, Norway. A sample description and
preparation of samples in a representative bone structure comprises
a compact outer layer, a cancellous bone, and inner bone marrow.
Pieces of the cow bones were obtained from a butcher's shop and
were preserved in a supposed best condition, but which included
partially frozen matter which later caused some concern as to
certain readings.
[0054] The bone to be examined is a structural bio composite of ca.
70% (by weight) inorganic calcium salts embedded in collagen
fibres. Most of the inorganic phase consists of hydroxyapatite
(calcium phosphate) but a large amount of carbonate, citrate and
fluoride amines are also present. Long bones such as the femur or
thigh bones are composed of a harder, compact composite outer
layer, which improves the stiffness and strength-to-weight indices
for the material, surrounding a spongy interior (cancellous bone)
and the marrow. Bones exhibit viscoelastic properties and are
sensitive to rate of loading.
[0055] Suitable results of the testing on the bovine samples
validate the equipment and methodology suitable for advancement to
tests on human bone samples. Pulse wave transmission (PWT)
techniques and continuous wave techniques (CWT) were then used in
order to measure compressional (Pw) and shear (Sw) wave velocities
on the bovine samples TI 1-TI 5 and on the human samples TIU 1-TIU
6. The transducers used in the experiments were broadband P-wave
and S-wave Panametric 500 kHz transducers for the PWT and 5 MHz for
the CWT. Generally, two oppositely parallel, smooth sides were made
on the samples to allow for mounting of the acoustic
transducers.
[0056] The PWT equipment consisted of a WAVETEK model 278 12 MHz
Programmable Synthesized Function Wave Generator, an ENI model
2100L RF 10 kHz-12 MHz amplifier, a YOKOGAWA model DL 1300A 4
Channels 100 MHz digital oscilloscope, a Physical Acoustic
Corporation model 220b 40-60 dB preamplifier and filter between 100
and 1200 kHz, a computer to control the system, and a sample holder
mechanism.
[0057] The continuous wave equipment consisted of a Hewlett Packard
33120A 15 MHz Function Arbitrary Waveform wave generator, a wave
detector (containing) an amplifier and a modulator, a computer to
control the system, and a sample holder mechanism. Measurements
were made at 100, 250, 500, 750 kHz emitting frequencies, when
possible. Measurements were made by CWT, both for P and S wave. The
amplitude of the output signal was also recorded.
[0058] In the pulse wave techniques, the signal was sinusoidal and
was generated at 230 mV and amplified by 50 dB. Corrections were
made for the system delay, and the velocities were calculated using
the first break criterion. For each position, 5 measurements were
taken and the average value of those measurements was calculated.
Acoustic velocity, amplitude and wavelength were reported. The
error in the measurements was estimated to +/-2%.
[0059] Sample TI 1
[0060] P wave and S wave measurements were performed at three
different positions on the bone by pulse wave technique and by
using 500 kHz transducers at 100 kHz excitation frequencies. The P
wave velocity was also measured at 250 kHz. It was not possible to
record the output signal at 250 kHz for S-wave. Measurements were
made on all three different bone structures. The measurements
performed on the sample TI 1 were made in three different positions
on the bone, in order to detect the velocities of the marrow,
cancellous and hard zones as accurately as possible.
1TABLE 1A TI 1 Typical P- Typical S- Frequency P wave vel wave
length S wave vel wave length Typical A Material (kHz) (km/s) (m)
(km/s) (m) Pw Sw (v) Marrow 100 2.278 0.022 1.004 0.01 4 *
10.sup.-4 5 * 10.sup.-4 Cancellous 100 2.456 0.024 1.111 0.011 1.5
* 10.sup.-3 zone 3 * 10.sup.-4 Hard zone 100 2.691 0.024 5 *
10.sup.-4
[0061]
2TABLE 1B TI 1 Typical P- Typical S- Frequency P wave vel wave
length S wave vel wave length Typical A Material (kHz) (m/s) (m)
(m/s) (m) (v) Pw Marrow 250 2.446 0.009 3 * 10.sup.-4 Cancellous
250 2.529 0.010 4.7 * 10.sup.-4 zone Hard zone 250 2.618 0.010
[0062] Sample TI 2
[0063] P wave and S wave measurements were performed by using the
pulse wave technique with 500 kHz transducers at 100, 250, 500 and
750 kHz excitation frequencies. It was not possible to record the
output signal at 100 kHz for S wave. Measurements were made on the
cancellous zone.
3TABLE 2 TI 2 Typical P- Typical S- Frequency P wave vel wave
length S wave vel wave length Typical A Material (kHz) (km/s) (m)
(km/s) (m) (v) Pw Sw Cancellous 100 2.291 0.022 2.5 * 10.sup.-3
zone -- Cancellous 250 2.395 0.009 1.552 0.006 2 * 10.sup.-3 zone 2
* 10.sup.-4 Cancellous 500 2.566 1.460 0.0029 1 * 10.sup.-3 zone
0.005 4 * 10.sup.-4 Cancellous 750 2.751 0.003 2.013 0.0026 5 *
10.sup.-4 zone --
[0064] Sample TI 3
[0065] P wave and S wave measurements were performed by using the
pulse wave technique with 500 kHz transducers at an excitation
frequency of 100 kHz. It was not possible to record output signals
at higher frequencies. The measurements were made on the cancellous
zone.
4TABLE 3 TI 3 Typical P- Typical S- Frequency P wave vel wave
length S wave vel wave length Typical Material (kHz) (km/s) (m)
(km/s) (m) A (v) Cancellous 100 3.120 0.031 1.408 0.015 zone or (?)
1.722
[0066] Sample TI 4
[0067] P wave and S wave velocity measurements were made by using
the CWT technique on a small sample (millimeter or cutting
dimension). In this case, 5 MHz transducers were used in a range of
frequencies from 3 to 10 MHz. The results reported are average
values of the velocities measured at all those frequencies. The
measurements were made on a selected piece of the hard outer
zone.
5TABLE 4 TI 4 Frequency P wave vel S wave vel Material (MHz) (km/s)
(km/s) Cancellous 3-10 3.83 .+-. (0.05) 1.80 .+-. (0.04) hard
zone
[0068] Since one of the objectives of the bovine study was to
validate the measuring of P and S wave acoustic velocities on bone
samples and to achieve some experience with this material, the
experiments were considered to be successful and indicative. Also,
acoustic velocity in this bone was validated as being frequency
dependent, with the velocities increasing with frequency.
[0069] Measurements on the human bone samples then occurred. The
samples were already prepared at the arrival in the laboratory, and
were in natural condition in plastic envelopes. Occasional grinding
was necessary to enhance proper contact. A summary of the human
bone sample sources is shown below in Table 5 below.
6 TABLE 5 Sample Age Gender TIU 1 77 Female TIU 2 91 Male* TIU 3 91
Male* TIU 4 95 Female** TIU 5 95 Female** TIU 6 76 Female *from the
same person **from the same person
[0070] The human bone sample measurements were performed with only
pulse wave techniques. Measurements were done systematically at
100, 250, 500, and 750 kHz both for P wave and S wave.
[0071] Sample TIU 1
[0072] The P wave and S wave measurements were performed by pulse
wave technique and by using 500 kHz transducers at 100, 250, 500,
and 750 kHz excitation frequencies. The P wave signal was clear at
all frequencies even if the resolution at 750 was quite poor. The S
wave signal was best defined at 250 kHz. At this frequency the two
modes separated.
7TABLE 6 TIU 1 Typical P Typical S Frequency P wave vel wave length
S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 3.18 0.03
1.45 0.014 250 3.28 0.01 1.52 0.006 500 3.40 0.006 1.57 0.003 750
3.43 0.004 -- --
[0073] Sample TIU 2
[0074] P wave and S wave measurements were performed by pulse wave
technique and by using 500 kHz transducers at 100, 250, 500 and 750
kHz excitation frequencies. The P wave signal was clear at all
frequencies. The S wave signal was well defined at frequencies
higher than 250 Khz, after that the sample was grounded.
8TABLE 7 TIU 2 Typical P Typical S Frequency P wave vel wave length
S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 2.86 0.02
1.27 0.012 250 2.94 0.01 1.44 0.005 500 3.01 0.006 1.47 0.0029 750
3.16 0.004 1.53 .002
[0075] Sample TIU 3
[0076] P wave and S wave measurements were performed by pulse wave
technique and by using 500 kHz transducers at 100, 250, 500 and 750
kHz excitation frequencies. The P wave signal was clear at all
frequencies even though the resolution at 750 kHz was poor. The S
wave signal was readable only at 250 kHz and was recognized at 100
kHz.
9TABLE 8 TIU 3 Typical P Typical S Frequency P wave vel wave length
S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 2.71 0.03
1.24 0.012 250 2.88 0.01 1.48 0.006 500 2.98 0.006 -- -- 750 3.03
0.004 -- --
[0077] Sample TIU 4
[0078] P wave and S wave measurements were performed by pulse wave
technique and by using 500 kHz transducers at 100, 250, 500 and 750
kHz excitation frequencies. The P wave signal was clear at all
frequencies even though the resolution at 750 kHz was poor. The S
wave signal was readable only at 250 kHz, but that result may be
suspect.
10TABLE 9 TIU 4 Typical P Typical S Frequency P wave vel wave
length S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 2.36
0.02 -- -- 250 2.42 0.01 1.55 0.006 500 2.52 0.005 -- -- 750 2.61
0.003 -- --
[0079] Sample TIU 5
[0080] P wave and S wave measurements were performed by pulse wave
technique and by using 500 kHz transducers at 100, 250, 500 and 750
kHz excitation frequencies. The P wave signal was clear at all
frequencies even though the resolution at 750 kHz was poor. The S
wave signal was readable only at 250, 500, and 750 kHz, but the
signal was poor.
11TABLE 10 TIU 5 Typical P Typical S Frequency P wave vel wave
length S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 2.37
0.02 -- -- 250 2.50 0.01 1.34 0.005 500 2.53 0.005 1.40 0.003 750
2.61 0.003 1.43 0.0019
[0081] Sample TIU 6
[0082] P wave and S wave measurements were performed by pulse wave
technique and by using 500 kHz transducers at 100, 250, 500 and 750
kHz excitation frequencies. The P wave signal was clear at all
frequencies even though the resolution at 750 kHz was poor. The S
wave signal was readable only at 250 and 500 kHz.
12TABLE 11 TIU 6 Typical P Typical S Frequency P wave vel wave
length S wave vel wave length (kHz) (km/s) (m) (km/s) (m) 100 2.68
0.03 -- -- 250 2.74 0.01 1.18 0.005 500 2.93 0.006 1.20 0.002 750
2.96 0.004 -- --
[0083] FIGS. 2-4 are plots of the recorded human sample P wave
velocities (V.sub.p), S wave velocities (V.sub.s), and a ratio of
the velocities (V.sub.s/V.sub.p). In these Figures, line 21
represents human sample TIU 1, line 22 represents human sample TIU
2, line 23 represents human sample TIU 3, line 24 represents human
sample TIU 4, line 25 represents human sample TIU 5, and line 26 as
human sample TIU 6. Again, the main interest was in the trabecular
part of the bone, where the effect of osteoporosis is generally
first seen.
[0084] These findings suggest that although S wave measurements
were more difficult to measure than P wave measurements, the
existence of a shear wave in human trabecular bone is verified. The
shear wave in trabecular bone is heavily attenuated, i.e. more
attenuated than the P wave. In these samples the shear wave
velocity in the trabecular bone was measured at between about 1200
and 1600 m/s, depending on sample and frequency.
[0085] These results support the inventors' analysis that shear
waves may be a useful measure of bone condition, including possible
degradation. The shear wave velocity and/or attenuation is believed
to be a more sensitive indicator of bone condition than the P wave
parameters widely used in present instruments, particularly for the
trabecular bone in which a marked change in shear wave velocity may
indicate that normal lattice bridges and connections are no longer
competent. Improved means of determining shear wave, or S wave,
velocity v.sub.s and possibly attenuation .alpha..sub.s, at one or
more frequencies, or as a function of frequency, v.sub.s(f),
.alpha..sub.s(f), are all viable techniques included herein. For
example, surface waves at the bone-tissue interface provides a
novel method to estimate the shear wave velocity in the bone.
Surface waves at a fluid-solid interface typically have a velocity
of about 0.87 and 0.95 times the shear velocity. Hence, the surface
wave velocity provides a method to estimate the shear wave velocity
in the bone. This is somewhat analogous to methods used to estimate
the shear wave velocity in the sea floor from surface waves
propagating along the water-sea floor interface.
[0086] Of particular interest are the nonlinear methods identified
herein for detection of micro-cracks or micro-fractures in the
human bone. These cracks may act as sources for nonlinear acoustic
generation, and therefore the methods identified herein may be
considered somewhat analogous to recently developed methods for
detecting micro-cracks and other defects in nondestructive
testing/evaluation of materials known generally as nonlinear
acoustic nondestructive evaluation (NANDE) or nonlinear wave
modulation spectroscopy. Measurement of acoustic nonlinearity can
therefore be used as an indicator of bone condition.
[0087] Several of the disclosed measurement methods are considered
part of this novel technique. The transmitted signal may either be
a continuous wave, CW, or a pulsed wave, PW. The measurements can
be accomplished as through-transmission (as shown in FIG. 5),
pulse-echo backscatter (as shown in FIG. 6), or scatter at an angle
(as shown in FIG. 7). In FIG. 5, there is shown representatively
configured components of a control unit 52, signal generator 54,
amplifier 59, transmitter 61, the object being measured 64,
receiver 72, amplifier 79, analog to digital converter, and
registration unit 86. The configuration of FIG. 6 includes most of
the similar components but also that of transmit/receive switch 60
and transmit/receive transducer 62. In FIG. 7, the configuration is
similar to that depicted in FIG. 5 but with and angled reflection
setup. The detection of nonlinearity can be done by any of the
following methods:
[0088] 1. Two frequency mixing by transmitting two frequencies
f.sub.1 and f.sub.2. These may then be received at the difference
and/or sum frequencies f.sub.1-f.sub.2 and f.sub.1+f.sub.2;
[0089] 2. Amplitude modulated signal by transmitting a signal
p=(1+A sin 2.pi.f.sub.mt) sin 2f.sub.0t and then receiving at the
modulation frequency f.sub.m and/or its harmonic, e.g.,
2f.sub.m;
[0090] 3. Transmit one high imaging frequency f.sub.i and one low
pumping frequency f.sub.p and then receive at the sum and/or
difference frequencies f.sub.i-f.sub.p and f.sub.i+f.sub.p; and
[0091] 4. Transmit at one frequency f.sub.0 and receive at the
harmonics of the transmit frequency, such as 2f.sub.0, 3f.sub.0,
4f.sub.0, . . . or xf.sub.0.
[0092] The invention thus recognizes alternate methods and
techniques to improve the quality and availability of ultrasound
quantitative measurement modalities for various bone conditions. It
is recognized that the various techniques may be combined with or
substituted for known techniques and systems to achieve an overall
improvement in this measurement capability.
* * * * *