Thermo-Elastography

Susan Sanati, MDJonathan Ophir, Ph.DFaouzi Kallel, Ph.DWard Casscells, MD

James T. Willerson, MDMorteza Naghavi, MD

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.

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

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.

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.

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.

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

Applications of Elastography

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.

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

Elastographic Imaging of ProstateMost 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.

sonogram elastogramGross pathology photograph

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

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.

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.

Sonogram

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

Elastogram

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

Tissue photograph

elastogram

T2-weighted MR

sonogram

elastogram

sonogram

Elastogram using color scale

Tissue photograph

Elastographic visualization in color enhances the border of the lesion.

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.

Contemporary

array

Rotating element

scanner

Rotating mirror scanner

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.

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.

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

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

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

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

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.

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.

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.

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

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.

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

IVUS RF-derived attenuation is significantly different for host aorta and allograft. In corresponding IVUS images, no distinction is possible in ROIs.

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.

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.

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

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. 

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.  

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.

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.

. 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.

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

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.

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.

Dimensional change of (a) lumen area and (b) corresponding pressure over

two cardiac cycles.

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.

Plaque is detected by both echogram and elastogram

(phantom)

Plaque is detected only by elastogram

(phantom)

sonogram elastogram

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.

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

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.

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.

echogramelastogram

Hematoxylin-eosin

Verhoeff’s

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%.

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

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

Strain values of carotid artery shown as color data

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.

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.

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

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.

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.

Intravascular Thermo-Elastography

Catheter

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.

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.

Basket Catheter Basket Catheter

media

intima

media

intima

Calcified atherosclerotic plaque

Our designed Basket+IVUS catheter

intima

mediamedia

2) Intravascular MicrobolometerThermo-Elastography Catheter

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.

Balloon

Ultrasound transducerBolometer

IVUS+Balloon +Bolometer

(catheter tip)

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.

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

Our proposal is all about marriage!

Ms. Infrared with Mr. Ultrasound

Lets think about the name of the kid

This is a prototype lateral viewing IVUS catheter using

a micromotor which was designed about four years ago.

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.

Insertion of Thermo-Elastography catheter into coronary arteries

Megasonics Angioplasty Catheter combined with

built-in IVUS

Transverse Cross-Section of Megasonics Catheter

IVUSMicrobolometerBalloon

IVUS WireMicrobolometer Wire

Guide Wire Lumen

Thermo-Elastography Catheter Tip

Rolling access

Unexpanded balloon in the artery

intimamedia

IVUS transducer

Balloon

Axis

Microbolometer

intimamedia

Atherosclerotic Plaque

Balloon

Microbolometer

IVUS

IR Camera

Stage 0

Pressure A

Compression a

Expanded Thermo-Elastography Catheter

intima

mediaAtherosclerotic Plaque

Microbolometer

IVUS

IR Camera

Stage 1

Pressure B

Compression b= a + 1%

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.

Relative changes of balloon diameter and inflation pressure

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

Electrocardiographic gated imaging.

2. Motion of Sensor: - Coronary flow

Possible solution: Completion of Imaging in a fraction of second and pressure gating.

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

4. Interruption of blood flow

Possible solution: completion of measurement in a fraction of second or continuous perfusion

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