scispace - formally typeset

Book ChapterDOI

Imaging tumor microenvironment with ultrasound

10 Jul 2005-Vol. 19, pp 516-528

AbstractRecent advances in molecular biology are providing new opportunities for breast cancer imaging. Our approach uses ultrasound to image viscoelastic features of tumors. These features describe microenvironmental factors that stimulate signaling pathways in tumors that ultimately affect metastatic potential and response to traditional therapeutics. This paper explains the motivation for the approach, describes measurements in phantoms and patients, and defines measurement sensitivity using hydrogels with tissue-like features.

...read more

Content maybe subject to copyright    Report

Citations
More filters

Journal ArticleDOI
TL;DR: The focus of this paper is on imaging parameter estimation from ultrasonic echo data, and how jitter from hand-held force applicators used for clinical applications propagate through the imaging chain to generate image noise.
Abstract: Techniques are being developed to image viscoelastic features of soft tissues from time-varying strain. A compress-hold-release stress stimulus commonly used in creep-recovery measurements is applied to samples to form images of elastic strain and strain retardance times. While the intended application is diagnostic breast imaging, results in gelatin hydrogels are presented to demonstrate the techniques. The spatiotemporal behaviour of gelatin is described by linear viscoelastic theory formulated for polymeric solids. Measured creep responses of polymers are frequently modelled as sums of exponentials whose time constants describe the delay or retardation of the full strain response. We found the spectrum of retardation times τ to be continuous and bimodal, where the amplitude at each τ represents the relative number of molecular bonds with a given strength and conformation. Such spectra indicate that the molecular weight of the polymer fibres between bonding points is large. Imaging parameters are found by summarizing these complex spectral distributions at each location in the medium with a second-order Voigt rheological model. This simplification reduces the dimensionality of the data for selecting imaging parameters while preserving essential information on how the creeping deformation describes fluid flow and collagen matrix restructuring in the medium. The focus of this paper is on imaging parameter estimation from ultrasonic echo data, and how jitter from hand-held force applicators used for clinical applications propagate through the imaging chain to generate image noise.

71 citations


Journal ArticleDOI
TL;DR: Variable projection (VP) is proposed, a new technique named variable projection to estimate accurately and robustly the TC and steady-state value of the elastographic parameter of interest from its temporal curve that is robust to noise and capable of estimating the time constant with accuracy higher than that of typically employed curve-fitting techniques.
Abstract: Novel viscoelastic and poroelastic elastography techniques rely on the accurate estimation of the temporal behavior of the axial or lateral strains and related parameters. From the temporal curve of the elastographic parameter of interest, the time constant (TC) is estimated using analytical models and curve-fitting techniques such as Levenberg–Marquardt (LM), Nelder–Mead (NM), and trust-region reflective (TR). In this paper, we propose a new technique named variable projection (VP) to estimate accurately and robustly the TC and steady-state value of the elastographic parameter of interest from its temporal curve. As a testing platform, the method is used with a novel analytical model, which can be used for both poroelastic and viscoelastic tissues and in most practical experimental conditions of clinical interest. Finite element and ultrasound simulations and experimental results demonstrate that VP is robust to noise and capable of estimating the TC of the elastographic parameter with accuracy higher than that of typically employed curve-fitting techniques. The results also demonstrate that the performance of VP is not affected by an incorrect initial TC guess. For example, in simulations, VP can estimate the TC of axial strain and effective Poisson’s ratio accurately for initial guesses ranging from 0.001 to infinite times of the true TC value even in fairly noisy conditions (30-dB signal to noise ratio). In experiments, VP always estimates the axial strain TC reliably, whereas the LM, NM, and TR methods fail to converge or converge to wrong solutions in most of the cases.

5 citations


Journal ArticleDOI
Abstract: Ultrasound poroelastography is a cost-effective and noninvasive imaging technique, which can be used to reconstruct mechanical parameters of tissues such as Young’s modulus, Poisson’s ratio, inters...

1 citations


Proceedings ArticleDOI
01 Oct 2006
Abstract: In elasticity imaging, tissues are stimulated with mechanical forces while spatiotemporal strain responses are observed. The basis for diagnostic imaging is that disease processes characteristically alter the structure of connective tissues that determine viscoelastic properties. Time-varying strains for step-like stress stimuli were measured in gelatin hydrogels and normal breast tissue. The medium's mechanical response function - the retardance-time spectrum - was computed. This spectrum is the continuous distribution of time constants that characterizes viscoelastic behavior. Spectra were parameterized using low order discrete rheological models from linear viscoelastic theory to reduce data dimensionality yielding parameters related to stiffness and viscosity: elastic strain and two retardation time constants. Broadband, continuous, bi-modal spectra was obtained for gelatin samples. Similar spectra with narrow bandwidth were found for breast tissue, both characteristic of lightly cross-linked amorphous polymers. Measured time constants in gelatin indicated fast (1-10 s) fluidic behavior and a slower (50-400 s) matrix restructuring. Corresponding parameters in breast were 3.2 plusmn 0.8 s and 42.0 plusmn 28 s. Phantom imaging studies showed that these parameters provided consistently high target contrast. Although the ultra-structure of collagen within gelatin and breast stroma is different, their mechanical behavior is quite similar. Creep in both media are consistent with the molecular theory of entanglement coupling proposed to explain amorphous polymer behavior

Posted Content
TL;DR: A cubic spline–based interpolation method, which allows to use only good quality strain frames (i.e., frames with sufficiently high signal-to-noise ratio [SNR]) to estimate the strain TC, and is of great help in applications relying on the accurate assessment of the temporal behavior of strain data.
Abstract: Ultrasound poroelastography is a cost-effective non-invasive imaging technique, which is able to reconstruct several mechanical parameters of cancer and normal tissue such as Young's modulus, Poisson's ratio, interstitial permeability and vascular permeability To estimate the permeabilities, estimation of the strain time constant (TC) is required, which is a challenging task because of non-linearity of the exponential strain curve and noise present in the experimental data Moreover, noise in many strain frames becomes very high because of motion artifacts from the sonographer, animal/patient and/or the environment Therefore, using these frames in computation of strain TC can lead to inaccurate estimates of the mechanical parameters In this letter, we introduce a cubic spline based interpolation method, which uses only the good frames (frame of high SNR) to reconstruct the information of the bad frames (frames of low SNR) and estimate the strain TC We prove with finite element simulation that the proposed reconstruction method can improve the estimation accuracy of the strain TC by 46% in comparison to the estimates from noisy data, and 37% in comparison to the estimates from Kalman filtered data at an SNR of 30dB Based on the high accuracy of the proposed method in estimating strain TC from poroelastography data, the proposed method can be preferred technique by the clinicians and researchers interested in non-invasive imaging of tissue mechanical parameters

References
More filters

BookDOI
01 Jan 1989

1,057 citations


Journal ArticleDOI
TL;DR: Experimental results are presented demonstrating that displacements on the order of 10 microm can be generated and detected in soft tissues in vivo using a single transducer on a modified diagnostic US scanner and support the clinical feasibility of a radiation force-based remote palpation imaging system.
Abstract: The clinical viability of a method of acoustic remote palpation, capable of imaging local variations in the mechanical properties of soft tissue using acoustic radiation force impulse (ARFI) imaging, is investigated in vivo. In this method, focused ultrasound (US) is used to apply localized radiation force to small volumes of tissue (2 mm(3)) for short durations (less than 1 ms) and the resulting tissue displacements are mapped using ultrasonic correlation-based methods. The tissue displacements are inversely proportional to the stiffness of the tissue and, thus, a stiffer region of tissue exhibits smaller displacements than a more compliant region. Due to the short duration of the force application, this method provides information about the mechanical impulse response of the tissue, which reflects variations in tissue viscoelastic characteristics. In this paper, experimental results are presented demonstrating that displacements on the order of 10 microm can be generated and detected in soft tissues in vivo using a single transducer on a modified diagnostic US scanner. Differences in the magnitude of displacement and the transient response of tissue are correlated with tissue structures in matched B-mode images. The results comprise the first in vivo ARFI images, and support the clinical feasibility of a radiation force-based remote palpation imaging system.

1,036 citations


Journal ArticleDOI
TL;DR: Solutions for the indentation of the layer by the plane end of a rigid circular cylinder and by a rigid sphere are suggested as useful for the determination of the elastic shear modulus of intact cartilage.
Abstract: A mathematical model is developed for indentation tests of articular cartilage. The cartilage, normally bonded to the subchondral bone, is modeled as an infinite elastic layer bonded to a rigid half space, and the indenter is assumed to be a rigid axisymmetric punch. The problem is formulated as a mixed boundary value problem of the theory of elasticity and solutions are obtained for the indentation of the layer by the plane end of a rigid circular cylinder and by a rigid sphere. Subject to detailed verification with independent tests, the present solutions are suggested as useful for the determination of the elastic shear modulus of intact cartilage.

834 citations


Book
01 Jan 1977

633 citations


Journal ArticleDOI
TL;DR: Fundamental information regarding the 3-D microstructural-mechanical properties of the ECM and its component molecules are important to the overall understanding of cell-ECM interactions and the development of novel strategies for tissue repair and replacement.
Abstract: The importance and priority of specific micro-structural and mechanical design parameters must be established to effectively engineer scaffolds (biomaterials) that mimic the extracellular matrix (ECM) environment of cells and have clinical applications as tissue substitutes. In this study, three-dimensional (3-D) matrices were prepared from type I collagen, the predominant compositional and structural component of connective tissue ECMs, and structural-mechanical relationships were studied. Polymerization conditions, including collagen concentration (0.3-3 mg/mL) and pH (6-9), were varied to obtain matrices of collagen fibrils with different microstructures. Confocal reflection microscopy was used to assess specific micro-structural features (e.g., diameter and length) and organization of component fibrils in 3-D. Microstructural analyses revealed that changes in collagen concentration affected fibril density while maintaining a relatively constant fibril diameter. On the other hand, both fibril length and diameter were affected by the pH of the polymerization reaction. Mechanically, all matrices exhibited a similar stress-strain curve with identifiable "toe," "linear," and "failure" regions. However the linear modulus and failure stress increased with collagen concentration and were correlated with an increase in fibril density. Additionally, both the linear modulus and failure stress showed an increase with pH, which was related to an increasedfibril length and a decreasedfibril diameter. The tensile mechanical properties of the collagen matrices also showed strain rate dependence. Such fundamental information regarding the 3-D microstructural-mechanical properties of the ECM and its component molecules are important to our overall understanding of cell-ECM interactions (e.g., mechanotransduction) and the development of novel strategies for tissue repair and replacement.

580 citations