Alexander I. Veress

Measurement of strain in the left ventricle during diastole with cine-MRI and deformable image registration.

The assessment of regional heart wall motion (local strain) can localize ischemic myocardial disease, evaluate myocardial viability, and identify impaired cardiac function due to hypertrophic or dilated cardiomyopathies. The objectives of this research were to develop and validate a technique known as hyperelastic warping for the measurement of local strains in the left ventricle from clinical cine-magnetic resonance imaging (MRI) image datasets. The technique uses differences in image intensities between template (reference) and target (loaded) image datasets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target image. To validate the technique, MRI image datasets representing two deformation states of a left ventricle were created such that the deformation map between the states represented in the images was known. A beginning diastolic cine-MRI image dataset from a normal human subject was defined as the template. A second image dataset (target) was created by mapping the template image using the deformation results obtained from a forward FE model of diastolic filling. Fiber stretch and strain predictions from hyperelastic warping showed good agreement with those of the forward solution (R2=0.67 stretch, R2=0.76 circumferential strain, R2=0.75 radial strain, and R2=0.70 in-plane shear). The technique had low sensitivity to changes in material parameters (deltaR2= -0.023 fiber stretch, deltaR2=-0.020 circumferential strain, deltaR2=-0.005 radial strain, and deltaR2=0.0125 shear strain with little or no change in rms error), with the exception of changes in bulk modulus of the material. The use of an isotropic hyperelastic constitutive model in the warping analyses degraded the predictions of fiber stretch. Results were unaffected by simulated noise down to a signal-to-noise ratio (SNR) of 4.0 (deltaR2= -0.032 fiber stretch, deltaR2=-0.023 circumferential strain, deltaR2=-0.04 radial strain, and deltaAR2=0.0211 shear strain with little or no increase in rms error). This study demonstrates that warping in conjunction with cine-MRI imaging can be used to determine local ventricular strains during diastole.

Vascular mechanics of the coronary artery

This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. Methods: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. Results: The arteris exhibited non-linear elastic behavior. The total tissue creep strain was ɛcreep = 0.082±0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. Conclusions: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.

Strain Measurement in Coronary Arteries Using Intravascular Ultrasound and Deformable Images

Atherosclerotic plaque rupture is responsible for the majority of myocardial infarctions and acute coronary syndromes. Rupture is initiated by mechanical failure of the plaque cap, and thus study of the deformation of the plaque in the artery can elucidate the events that lead to myocardial infarction. Intravascular ultrasound (IVUS) provides high resolution in vitro and in vivo cross-sectional images of blood vessels. To extract the deformation field from sequences of IVUS images, a registration process must be performed to correlate material points between image pairs. The objective of this study was to determine the efficacy of an image registration technique termed Warping to determine strains in plaques and coronary arteries from paired IVUS images representing two different states of deformation. The Warping technique uses pointwise differences in pixel intensities between image pairs to generate a distributed body force that acts to deform a finite element model. The strain distribution estimated by image-based Warping showed excellent agreement with a known forward finite element solution, representing the gold standard, from which the displaced image was created. The Warping technique had a low sensitivity to changes in material parameters or material model and had a low dependency on the noise present in the images. The Warping analysis was also able to produce accurate strain distributions when the constitutive model used for the Warping analysis and the forward analysis was different. The results of this study demonstrate that Warping in conjunction with in vivo IVUS imaging will determine the change in the strain distribution resulting from physiological loading and may be useful as a diagnostic tool for predicting the likelihood of plaque rupture through the determination of the relative stiffness of the plaque constituents.

Strain measurement in the left ventricle during systole with deformable image registration

The objective of this study was to validate a deformable image registration technique, termed Hyperelastic Warping, for left ventricular strain measurement during systole using cine-gated, non-tagged MR images with strains measured from tagged MRI. The technique combines deformation from high resolution, non-tagged MR image data with a detailed computational model, including estimated myocardial material properties, fiber direction, and active fiber contraction, to provide a comprehensive description of myocardial contractile function. A normal volunteer (male, age 30) with no history of cardiac pathology was imaged with a 1.5 T Siemens Avanto clinical scanner using a TrueFISP imaging sequence and a 32-channel cardiac coil. Both tagged and non-tagged cine MR images were obtained. The Hyperelastic Warping solution was evolved using a series of non-tagged images in ten intermediate phases from end-diastole to end-systole. The solution may be considered as ten separate warping problems with multiple templates and targets. At each stage, an active contraction was initially applied to a finite element model, and then image-based warping penalty forces were utilized to generate the final registration. Warping results for circumferential strain (R(2)=0.75) and radial strain (R(2)=0.78) were strongly correlated with results obtained from tagged MR images analyzed with a Harmonic Phase (HARP) algorithm. Results for fiber stretch, LV twist, and transmural strain distributions were in good agreement with experimental values in the literature. In conclusion, Hyperelastic Warping provides a unique alternative for quantifying regional LV deformation during systole without the need for tags.

An analysis of the mechanical parameters used for finite element compression of a high‐resolution 3D breast phantom

PURPOSE The authors previously introduced a methodology to generate a realistic three-dimensional (3D), high-resolution, computer-simulated breast phantom based on empirical data. One of the key components of such a phantom is that it provides a means to produce a realistic simulation of clinical breast compression. In the current study, they have evaluated a finite element (FE) model of compression and have demonstrated the effect of a variety of mechanical properties on the model using a dense mesh generated from empirical breast data. While several groups have demonstrated an effective compression simulation with lower density finite element meshes, the presented study offers a mesh density that is able to model the morphology of the inner breast structures more realistically than lower density meshes. This approach may prove beneficial for multimodality breast imaging research, since it provides a high level of anatomical detail throughout the simulation study. METHODS In this paper, the authors describe methods to improve the high-resolution performance of a FE compression model. In order to create the compressible breast phantom, dedicated breast CT data was segmented and a mesh was generated with 4-noded tetrahedral elements. Using an explicit FE solver to simulate breast compression, several properties were analyzed to evaluate their effect on the compression model including: mesh density, element type, density, and stiffness of various tissue types, friction between the skin and the compression plates, and breast density. Following compression, a simulated projection was generated to demonstrate the ability of the compressible breast phantom to produce realistic simulated mammographic images. RESULTS Small alterations in the properties of the breast model can change the final distribution of the tissue under compression by more than 1 cm; which ultimately results in different representations of the breast model in the simulated images. The model properties that impact displacement the most are mesh density, friction between the skin and the plates, and the relative stiffness of the different tissue types. CONCLUSIONS The authors have developed a 3D, FE breast model that can yield high spatial resolution breast deformations under uniaxial compression for imaging research purposes and demonstrated that small changes in the mechanical properties can affect images generated using the phantom.

Age related development of atherosclerotic plaque stress: A population-based finite-element analysis

BackgroundIn order to identify those age-related factors in the development of coronary atherosclerosis that would affect the stability of the plaque system, we have developed idealized, finite-element, cross-sectional models of the arterial wall and associated lesions, derived from population-based data. MethodsThe physical development and morphology of coronary plaques was documented in the Pathobiological Determinants of Atherosclerosis in Youth histological study. Using this database, finite-element analysis models were created for five age groups (15–19, 20–24, 25–29 and 30–34 years) and for the 25 largest lesions. Cosmos (Structural Research, Inc., Los Angeles, California, USA) was used to create and analyze the models. ResultsThe area of greatest stress shifted from the intima opposite the lesion in the 15–19 years age group to the edge of the cap and adjacent healthy tissue in the later age groups. Increasing age had a strong positive correlation with the shoulder stress level (r = 0.95) and the per cent stenosis correlated well with shoulder stress (r = 0.99, P < 0.002). Increasing the cap stiffness from a soft cap to a fibrous cap in the 30–34 year age group model resulted in a localized increase in shoulder surface stress by 10%. A calcified cap increased this shoulder surface stress by 30%. ConclusionsThis finite-element analysis of the population-based data shows that the increase in stress appears to be closely related to the impaired load-bearing capability of the lipid pool that develops with age. The shoulder area of the lesion has been shown to be the location of most of the plaque fractures. Coronary Artery Dis 9:13–19

Incorporation of a Left Ventricle Finite Element Model Defining Infarction Into the XCAT Imaging Phantom

The 4D extended cardiac-torso (XCAT) phantom was developed to provide a realistic and flexible model of the human anatomy and cardiac and respiratory motions for use in medical imaging research. A prior limitation to the phantom was that it did not accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). We overcame this limitation in a previous study by combining the phantom with a finite-element (FE) mechanical model of the left ventricle (LV) capable of more realistically simulating regional defects caused by ischemia. In the present work, we extend this model giving it the ability to accurately simulate motion abnormalities caused by myocardial infarction (MI), a far more complex situation in terms of altered mechanics compared with the modeling of acute ischemia. The FE model geometry is based on high resolution CT images of a normal male subject. An anterior region was defined as infarcted and the material properties and fiber distribution were altered, according to the bio-physiological properties of two types of infarction, i.e., fibrous and remodeled infarction (30% thinner wall than fibrous case). Compared with the original, surface-based 4D beating heart model of the XCAT, where regional abnormalities are modeled by simply scaling down the motion in those regions, the FE model was found to provide a more accurate representation of the abnormal motion of the LV due to the effects of fibrous infarction as well as depicting the motion of remodeled infarction. In particular, the FE models allow for the accurate depiction of dyskinetic motion. The average circumferential strain results were found to be consistent with measured dyskinetic experimental results. Combined with the 4D XCAT phantom, the FE model can be used to produce realistic multimodality sets of imaging data from a variety of patients in which the normal or abnormal cardiac function is accurately represented.

Direct measurement of intranuclear strain distributions and RNA synthesis in single cells embedded within native tissue.

Nuclear structure and mechanics play a critical role in diverse cellular functions, such as organizing direct access of chromatin to transcriptional regulators. Here, we use a new, to our knowledge, hybrid method, based on microscopy and hyperelastic warping, to determine three-dimensional strain distributions inside the nuclei of single living cells embedded within their native extracellular matrix. During physiologically relevant mechanical loading to tissue samples, strain was transferred to individual nuclei, resulting in submicron distributions of displacements, with compressive and tensile strain patterns approaching a fivefold magnitude increase in some locations compared to tissue-scale stimuli. Moreover, nascent RNA synthesis was observed in the interchromatin regions of the cells studied and spatially corresponded to strain patterns. Our ability to measure large strains in the interchromatin space, which reveals that movement of chromatin in the nucleus may not be due to random or biochemical mechanisms alone, but may result from the transfer of mechanical force applied at a distant tissue surface.

Deformable Image Registration with Hyperelastic Warping

The extraction of quantitative information regarding growth and deformation from series of image data is of significant importance in many fields of science and medicine. Imaging techniques such as MRI, CT and ultrasound provide a means to examine the morphology and in some cases metabolism of tissues. The registration of this image data between different time points after external loading, treatment, disease or other pathologies is performed using methods known as deformable image registration. The goal of deformable image registration is to find a transformation that best aligns the features of a “template” and “target” image (Fig. 12.1). In the ideal case, the quantity and quality of the image texture present in the template and target images, as well as the similarity in underlying anatomical structure, would yield a unique “best” transformation. In real problems, however, this is not the case. Deformable image registration is most often ill-posed in the sense of Hadamard [2–3]. No perfect transformation exists, and the solution depends on the choice of the cost function and associated solution methods. Deformable image registration grew primarily out of the pattern recognition field where significant effort has been devoted to the representation of image ensembles (e.g., [4–13]). The approaches that are used are usually classified as either model-based or pixel-based. Model-based approaches typically require

Population of 100 Realistic, Patient-Based Computerized Breast Phantoms for Multi-modality Imaging Research

Breast imaging is an important area of research with many new techniques being investigated to further reduce the morbidity and mortality of breast cancer through early detection. Computerized phantoms can provide an essential tool to quantitatively compare new imaging systems and techniques. Current phantoms, however, lack sufficient realism in depicting the complex 3D anatomy of the breast. In this work, we created one-hundred realistic and detailed 3D computational breast phantoms based on high-resolution CT datasets from normal patients. We also developed a finiteelement application to simulate different compression states of the breast, making the phantoms applicable to multimodality imaging research. The breast phantoms and tools developed in this work were packaged into user-friendly software applications to distribute for breast imaging research.