This document discusses elastography, a new method for quantitatively measuring tissue elasticity using ultrasound. Elastography can provide information about tissue properties that overcome limitations of conventional sonography. It has applications in imaging breast tissue, prostate, liver lesions, and detecting vulnerable plaque. Radiofrequency analysis of ultrasound signals may help characterize plaque components compared to conventional IVUS. Higher frequency ultrasound biomicroscopy around 40-60MHz can provide resolution of 50um needed to image thin vessel layers.

1. Thermo-Elastography
Susan Sanati, MD
Jonathan Ophir, Ph.D
Faouzi Kallel, Ph.D
Ward Casscells, MD
James T. Willerson, MD
Morteza Naghavi, MD

2. Elastography is a new method for
quantitative measurement of tissue elasticity
based on ultrasound.
The elastic properties of soft tissues depend
on the high level of tissue organization, their
molecular building blocks, and on the
microscopic and macroscopic structural
organization of these blocks. It does not
depend on the geometry or the boundary
conditions surrounding the material.

3. Pathological changes are generally
correlated with changes in elastic
modulus.
Young’s Modulus or Elastic Modulus is a
constant that measures the stiffness of the
material and whose value varies with the
material. It is calculated from the following
equation:
Local YM= Local stress / Local strain

4. Method for elastography:
A quasi-static compression is applied to the tissue, then
local tissue displacements are estimated from the time
delays between the gated pre and post compression echo
signals; whose axial gradient is then computed to estimate
and display the local strain. Strain is utilized as an indicator
of local compliance of tissue under the assumption of
constant stress.
This is accomplished by acquiring a set of digitized
radiofrequency echo lines from the tissue region of interest,
by compressing the tissue for example with the ultrasonic
transducer, along the ultrasonic radiation axis by a small
amount (about 1% or less of tissue depth), and by acquiring
a second, post-compression set of echo lines from the same
region of interest.

5. When an elastic medium , such as tissue is
compressed by a constant uniaxial stress, all points
in the medium experience a resulting level of
longitudinal strain whose principal components are
along the axis of compression.
If one or more of tissue elements have a higher
stiffness parameter than the others, that element
will generally experience less strain than a softer
one.

7.  It is expected that elastography may
convey new information that
overcomes the limitation of
conventional sonography in the
visualization of isoechoic regions.
 For identical object contrasts,
elastography was found to have
significantly higher detectability than
echography at all lesion diameters
considered.

8. Longitudinal (a) Sonogram, (b) elastogram and (C)
pathology photograph of an ovine kidney in vitro. Black
corresponds to low strain and white to high strain.
elastogram Pathology photographsonogram

9. Applications of Elastography

10. Elastographic Imaging of Breast Tissue
 Normal glandular breast tissue has an elastic
modulus similar to that of fat at low strain levels, but it
increases by an order of magnitude above fat at high
strain levels. The average shear moduli of normal
breast tissue is approximately four times softer than
fibroadenoma and fibroadenomas are approximately
eight times softer than carcinomas.
 Cancers seem to be larger on elastograms than
sonograms.

11. Sonogram, elastogram and strain profile of an invasive ductal
carcinoma. An irregular mass is seen on the sonogram where only
an echogenic band and shadow are seen. The lesion is clearly
visible as a dark area on the elastogram.
sonogram elastogram Strain profile

12. Elastographic Imaging of
Prostate
 Most of the prostate cancers appear
hypoechoic by ultrasound, but only 20%
of hypoechoic lesions are malignant.
 Transrectal ultrasound fails to detect 8-
30% of the prostate cancers that are
palpable on digital rectal exam.
 Elastography can produce consistent
images of the normal anatomy of
prostate.

13. sonogram elastogram
Gross pathology
photograph
Matching sonogram, elastogram and gross pathology
photograph of an anterior-posterior transverse cross-
section of a canine prostate gland in vitro

14. Elastographic detection of
HIFU-Induced lesions
 The primary mechanism of damage associated with
the formation of a HIFU lesion is a thermal one. The
energy deposition from heat treatment can result in
protein denaturation (coagulation and blanching),
vaporization (dehydration and shrinkage), or
carbonization (disintegration and blanching) of the
tissues.
 Protein denaturation elevates the elastic modulus of
proteins and of soft tissues.

15.  Standard ultrasonic methods are not accurate
enough for the detection of purely thermal
lesions. Only some of the lesions appear as
hyperechoic lesions which is related to the
formation of gas bubbles due to vaporization
and /or cavitation.
 The increased echogenicity of the treated
areas tend to fade with time, presumably due
to resorption of gas bubbles.

16. Sonogram
Elastogram of HIFU-induced lesions in liver. The lesion is
not clearly depicted in the corresponding sonograms.
Elastogram

17. Matching elastogram, sonogram and tissue photograph of a pair of
two lesions. The estimated areas of the lesions from elastogram and
tissue photograph are 33.84 mm2
and 31.6 mm2
for the left lesion
and 29.03 mm2
and 33.86 mm2
for the right lesion. The evaluation of
hyperechoic area visible in the sonogram for the right lesion
corresponds for 12.5 mm2
.
elastogram sonogram
Tissue
photograph

18. Tissue
photograph
elastogram
T2-weighted
MR
sonogram

19. elastogram
sonogram
Elastogram
using color
scale
Tissue
photograph
Elastographic visualization in color enhances the border of
the lesion.

20. Intravascular Ultrasound
 IVUS has the unique advantage of allowing
the study of vessel wall morphology and
pathology beneath the endothelial surface at
the same time.
 It also has the unique capability to
characterize arterial wall structure in cross-
sectional images instead of luminography that
is done in angiography.

21. Contemporary
array
Rotating element
scanner
Rotating mirror
scanner

22. Advantages of IVUS
 1. Detection of wall pathology in apparently normal
angiographic segments.
 In angiography there is no change until at least 40%
reduction of the area circumscribed by internal
elastic lamina happens.
 2. Detection of plaque eccentricity:
 Angiography requires angiogram perpendicular to
maximum plaque thickness and it compares the
thickness to proximal and distal segments, and
involvement of these proximal and distal parts
causes misinterpretation.
 IVUS measures directly maximal and minimal
thickness of plaque, so there is no misreading.

23.  3. Study of plaque composition: Study of
plaque composition may be helpful in
deciding which lesions are more suitable for
which specific treatment modality.
 IVUS has the capacity of identifying plaque
rupture and vulnerable plaques. Plaques
seem to be prone to rupture when the
echolucent area is larger than 1 mm2
, the
echolucent area/plaque ratio greater than
20% and the fibrous cap thinner than
0.7 mm (?). IVUS has resolution of up to
200µm.

24. Soft plaque
with small
calcification
at 9 o’clock
Eccentric
non-calcific
hard
plaque
Mixed plaque
suggestive of
an area of
lipid
deposition
enclosed in a
fibrous cap.
Diffuse
subendothelial
calcification

25.  IVUS can be used for three
dimensional reconstruction image of
the artery that is used for
measurement of plaque size and
volume.

26. Schematic illustration of 3D reconstruction for deriving volumetric
information on lumen and plaque.

27. Longitudinal and transverse cross-sectional planes with resulting
volumetric information.

28. IVUS Limitations
 1. Poor resolution for studying plaque with
thin cap
 Miniaturization (micro-packaging of
transducer) still is not enough for detection
of stenosis in distal small coronary arteries.
 2. The catheter still is not flexible enough for
an easy coronary application.

29.  3. The image quality currently available is not
enough for complete evaluation of vascular
dimensions and morphological changes.
 4. Limited steerability precludes correction of
non-coaxial or eccentric intravascular position
which influences the intensity with which the
structure is visualized.
 5. It is an expensive technology.
 6. It is time consuming.
 7. Lack of familiarity and/or training for the
system.

30.  Ultrasonic distinction between the plaque types is
difficult and may lead to problems of interpretation
particularly in the real time in vivo situation.
 Calcifications which are easily recognized from
ultrasonic images, occur in both lipid and fibrous
plaques; dense fibrous plaque or microcalcification
may induce marked attenuation and mimic the bright
echoes with posterior shadowing which are
indicative of microcalcification.
 Both thrombus and soft plaque lesions produce
relatively soft echoes and therefore can not be
identified based on their ultrasound appearance
alone.

31.  What can be added to IVUS to increase
its value in detection of vulnerable
plaque

32. IVUS + RF Analysis
 Quantitative IVUS characterization of the
biophysical components of the vessel wall in
vivo has been limited to date because the
currently available systems provide only a
qualitative visual rendering of the acoustic
properties of the vessel layers.
 Radiofrequency analysis of the unprocessed
ultrasound signal allows a more detailed
interrogation of various vessel components.

33. Histological cross-sections of host aorta and allograft.
Intimal proliferation and adventitial infiltration apparent in
allograft.

34. IVUS RF-derived attenuation is significantly different for host
aorta and allograft. In corresponding IVUS images, no

35.  This method reflects attenuation of the
entire ROI, so small heterogeneities of
the tissue may remain undetected.
 Native atherosclerosis , which is more
heterogeneous in nature, may be
difficult to distinguish by this technique.

36. Ultrasound Biomicroscory
 Normal intimal thickness ranges from 50 to
150 µm and medial thickness is in the order
of 200-300 µm thickness. Therefore systems
with higher lateral and axial resolution are
needed.
 In ultrasound biomicroscopy the majority of
applications appear to be developing in the
40-60 MHz frequency range, where resolution
on the order of 50µm can be achieved.

37.  Because of the difficulties with practical
IVUS catheter fabrication with a size as
small as 250-300µm current application
of this method for intravascular imaging
in vivo is not possible and study is
confined to phantom studies

38. Figure 31: (a) 30-MHz and (c) 50-MHz IVUS images; and (b) corresponding
histology of a stenosed femoral artery ex vivo. The 30-MHz image shows
pronounced lateral streaking that impairs visualization of the plaque. At
50 MHz, the plaque and vessel structure are significantly improved.

39. Figure 32: (a) and (b) 40-MHz IVUS imaging in human coronary arteries in vivo,
compared to (c) and (d) which are 30 MHz IVUS imaging. Images of asymmetric
plaque and stents show much tighter speckle and improved definition in the
higher frequency images.

40. Intravascular Elastography
 Since the outcome of an interventional procedure is
determined not only by morphology of a diseased
vessel but also by the tissue components of the
atheroma, knowledge of these properties is useful.
 Intravascular elastography is a new technique to
obtain the local mechanical properties of the vessel
wall and its pathology using IVUS. Knowledge of
these mechanical properties may be useful for
guiding interventional procedures and further
characterization of vulnerable plaque. Regions of
elevated strain are ascribed to propensity to rupture,
characterizing the lesion as a vulnerable plaque.

41.  For intravascular elastography we need pre-
and post-compression images of the artery.
For pre-compression image we can use basal
IVUS.
 For compressing the artery, two sources of
mechanical excitation are feasible in the
intravascular application: 1)the expansion of a
compliant angioplasty balloon and 2) the
arterial pulse pressure.

42. .
 Balloons offer a more controllable
deformation of the artery at the expense of
interruption of blood flow.
 Minimal duration of vessel occlusion is
warranted by the ability to perform the
elastographic data acquisition in less than a
second.

45. Transverse cross-section of IVUS catheter combined
with balloon designed by Endosonics that has been used
for intravascular elastography before.

46.  2) The arterial pressure offers a source of
biomechanical, differential deformation,
which can be controlled by time acquisition
of data frames. The ability and requirement
to assess elasticity from very small strains
(less than 1%) provides the opportunity to
complete the measurement within a short
time interval during which tissue can be
considered stationary.

47.  The real time IVUS is capable of
providing information about the dynamic
contraction of the arterial wall during a
cardiac cycle. Its potential clinical
application is to study wall compliance
through a sequential measurement of
the changes in the luminal dimensions
in relation to blood pressure.

48. Dimensional change of (a) lumen area and (b) corresponding pressure over
two cardiac cycles.

49.  Under the effect of an intraluminal pressure
hard, noncompliant tissue areas will deform
less than soft compliant tissue areas.
Compliance is estimated locally within the
vessel wall at all points within the cross-
section.
 Special processing of radiofrequency
signals enables the assessment of
micrometric displacements and minute
(subpercent) strains that are practically
undetectable from analysis of echograms.

50. Plaque is detected
by both echogram
and elastogram
(phantom)
Plaque is detected
only by elastogram
(phantom)
sonogram elastogram

51.  Problems with Intravascular elastography:
 The pulsation of the arterial system
introduces a noncontrolled movement of the
catheter in the lumen resulting in
misalignment of successive frames.
 Nonintegrated catheter consisting of an
imaging device and a compliant balloon is
another possibility to advance to in vivo
elastography. Motion artifacts are minimized
with this combined catheter, but blood flow is
interrupted.

52.  Vessel mimicking phantoms were scanned in
a water tank at two states of intraluminal
pressure.
 These intraluminal pressures can be
interpreted as specific time intervals during
arterial pulsations or as the state at different
pressure of a balloon.
Works Done by Others

53. Experiments were performed in a water tank, filled with
saline solution and equipped with two insertion sheaths at
either side. The IVUS catheter was inserted via the proximal
sheath . Intraluminal pressure was applied by means of a
water column system.Two scans were acquired at two
intraluminal pressure levels.

54. Corresponding echogram, elastogram and histologic
counterparts with hematoxylin-eosin and Verhoeff’s
elastic Van Gieson stain of a human femoral artery. (I) a
severe calcified lesion. (II) a small calcified deposit.
echogram
elastogram
Hematoxylin-
eosin
Verhoeff’s

55.  A group of scientists in Biomedical
Ultrasonics Lab at the University of Michigan
have used a combined IVUS 64 element
phased array system operating at 20 MHz
and balloon catheter designed by
Endosonics for compressing and at the
same time imaging vessel wall. Using this
technique internal motion of the arterial wall
can be tracked to produce elasticity images
of the artery.
 The maximum radial strain produced was
about 1.5-4%.

56. The histology reveals that the region between 4 and
11 o’clock is fibrous material and the region
between 2 and 4 o’clock is fatty material.
Strain imageechogram

57.  Recently a group in Georgia obtained
elastography images of rabbit carotid
artery by external compression of
carotid artery by a probe touching neck.

58. Strain values of carotid artery shown as color data

59. Arterial Ultrasound Palpation
 Cespedes et al presented a one-dimensional
method to measure and display local
deformation of the inner layer of arterial wall.
 They identified regions of different stiffness by
this method independantly of the ability to
visualize the same lesion on the echo image.
 They identified regions of stress
concentration at the shoulders of the plaque
and areas of stress concentrations in plaques
with lipid contents, which is an indicator of
plaque vulnerability.

60. IVUS image and strain palpogram of an iliac artery specimen with
a stiff plaque. The plaque is clearly visible in the echo image. A
small region of increased strain is shown at the edge of the
plaque (at 3 o’clock) in the three strain palpograms. Strain
increases with increased intraluminal pressure, particularly in the
plaque free region of the wall.

61. Stress-strain modulus palpogram of the iliac artery specimen at
three levels of intraluminal pressure.

62. Palpogram of diseased human femoral artery. It shows soft areas
between 3 and 6 o’clock and between 8 and 10 o’clock. The
remaining areas seem to be harder. The histology reveals that
main plaque component in the soft region is the fatty material
and the hard regions contain a large amount of collagen.

63.  Primary results suggest that the
average aggregate elastic properties of
soft and hard plaques are significantly
different, and vulnerable plaques can
be characterized by elasticity imaging.

64. Intravascular
Thermo-Elastography
Catheter

65. Our Proposal
1. Intravascular Basket Thermo-
Elastography for characterizing
atherosclerotic plaques using an
IVUS+Basket catheter:
We propose to add a piezoelectric
transducer to our thermosensor catheter
enabling simultaneous measurement of the
temperature at each location and receiving
the reflected ultrasound waves that are then
transformed to strain images.

66.  Shape memory expandable wires of the
Basket Catheter that can be controlled
from outside makes it quite possible to
induce scalable compression on the
plaque.
 In comparison to balloon catheter
Basket catheter has the privilege of not
interrupting blood flow and can function
much easier.

67. Basket Catheter
Basket Catheter

68. media
intima
media
intima

69. Calcified atherosclerotic
plaque
Our designed
Basket+IVUS
catheter
intima
media
media

70. 2) Intravascular
Microbolometer
Thermo-Elastography
Catheter

71.  2. Intravascular Thermo-Elastography
using balloon catheter combined with
piezoelectric transducer and built-in
microbolometer:
We can measure temperature and elasticity of
different parts of vessel wall at the same time
by using a specialized elongated balloon on
this catheter.
 The problem with this technique is temporary
occlusion of blood flow.

72. Balloon
Ultrasound transducerBolometer
IVUS+Balloon +Bolometer
(catheter tip)

73.  3. Elastographic detection of aortic plaque
using transesophageal elastography based
on pulse compression technique:
 With each pulse arterial wall is compressed.
By a transesophageal ultrasound probe and
use of software we can transfer received
waves to strain image of the artery.
 Normal aorta, calcified plaque and lipid-rich
plaque are expected to respond differently
against the pulse pressure and can be
identified based on different strain patterns
in elastographic images.

74.  4. Non-invasive elastocardiographic
detection of vulnerable carotid plaques
by pulse-compression or external
compression of carotid arteries by
ultrasound probe:

75. Our proposal is all about marriage!
Ms. Infrared with Mr. Ultrasound
Lets think about the name of the kid


76. This is a prototype lateral viewing IVUS catheter using
a micromotor which was designed about four years ago.

77.  In this catheter an ultrasound beam is
scanned radially by a micromotor instead of
a rotation transmitting wire. The rotation of
micromotor is performed and controlled by
an external magnetic field.
 The magnet part of micromotor having two
poles can be rotated by an external sinous
magnetic field. The rotation can be
controlled by the same external magnetic
field. The frequency range of micromotor
increases in proportional to the magnitude of
the external magnetic field.

78. Insertion of Thermo-Elastography catheter into coronary
arteries

79. Megasonics Angioplasty Catheter combined with
built-in IVUS

80. Transverse Cross-Section of Megasonics Catheter

81. IVUSMicrobolometerBalloon
IVUS WireMicrobolometer
Wire
Guide Wire
Lumen
Thermo-Elastography Catheter Tip
Rolling access

82. Unexpanded balloon in the artery
intima
media
IVUS
transducer
Balloon
Axis
Microbolometer

83. intima
media
Atherosclerotic
Plaque
Balloon
Microbolometer
IVUS
IR
Camera
Stage 0
Pressure A
Compression a
Expanded Thermo-Elastography Catheter

84. intima
media
Atherosclerotic
Plaque
Microbolometer
IVUS
IR Camera
Stage 1
Pressure B
Compression b= a + 1%

85. Pre-compression image in stage 0 is
measured with the balloon expanded to a
point to produce compression a.
Post-compression image in Stage 1 is
measured with balloon expanded to a point to
produce compression (a + 1%).
For comparability of these images they should
be gated.

86. Relative changes of balloon diameter and inflation
pressure

87. Problems with Thermo-
Elastography
 1. Motion of object:
 - Respiratory motion
 - Cardiac motion: - Systolic
- Diastolic
 - Coronary motion
 Possible solution: Pressure and
Electrocardiographic gated imaging.

88.  2. Motion of Sensor:
- Coronary flow
 Possible solution: Completion of
Imaging in a fraction of second and
pressure gating.

89.  3. Unequal compression of the artery:
 - Lengthwise: because of unequal diameter of
the artery in proximal and distal segments.
 - Circumferential due to asymmetric plaque.
 Possible solution: Using small diameter
elastic balloon

90.  4. Interruption of blood flow
 Possible solution: completion of
measurement in a fraction of second or
continuous perfusion

91. Megasonics
Catheter
Thermo-
Elastography
Catheter
Balloon Length 20 mm 40-50 mm
Balloon
Diameter(8 atm)
2.5-4 mm 2.5-4 mm
Length of
transducer
4 mm 4 mm
Diameter of
transducer
3.5 F 2 F
Inflation
Pressure
8 atm Multi-steps
Used Material Extendable,
unfoldable