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SUMMARY Structural heterogeneity is a hallmark of living cells that drives local mechanical properties and dynamic cellular responses. However, the robust quantification of intracellular mechanics is lacking from conventional methods. Here, we describe the development of deformation microscopy, which leverages conventional imaging and an automated hyperelastic warping algorithm to investigate strain history, deformation dynamics, and changes in structural heterogeneity within the interior of cells and cell nuclei. Using deformation microscopy, we found that partial or complete disruption of LINC complexes in cardiomyocytes in vitro and lamin A/C deficiency in myocytes in vivo abrogate dominant tensile loading in the nuclear interior. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries at interchromatin regions, which are associated with active transcription. Deformation microscopy represents a foundational approach toward intracellular elastography, with the potential utility to provide mechanistic and quantitative insights in diverse mechanobiological applications., Graphical Abstract, In Brief Ghosh et al. show that deformation microscopy, a technique based on image analysis and mechanics, reveals deformation dynamics and structural heterogeneity changes for several applications and at multiple scales, including tissues, cells, and nuclei. They reveal how the disruption of nuclear proteins and pathological conditions abrogate mechanical strain in the nuclear interior.

In several nuclear cardiac imaging applications (SPECT and PET), images are formed by reconstructing tomographic data using an iterative reconstruction algorithm with corrections for physical factors involved in the imaging detection process and with corrections for cardiac and respiratory motion. The physical factors are modeled as coefficients in the matrix of a system of linear equations and include attenuation, scatter, and spatially varying geometric response. The solution to the tomographic problem involves solving the inverse of this system matrix. This requires the design of an iterative reconstruction algorithm with a statistical model that best fits the data acquisition. The most appropriate model is based on a Poisson distribution. Using Bayes Theorem, an iterative reconstruction algorithm is designed to determine the maximum a posteriori estimate of the reconstructed image with constraints that maximizes the Bayesian likelihood function for the Poisson statistical model. The a priori distribution is formulated as the joint entropy (JE) to measure the similarity between the gated cardiac PET image and the cardiac MRI cine image modeled as a FE mechanical model. The developed algorithm shows the potential of using a FE mechanical model of the heart derived from a cardiac MRI cine scan to constrain solutions of gated cardiac PET images.

The 4-D extended cardiac-torso (XCAT) phantom has provided a valuable tool to study the effects of anatomy and motion on medical images, especially cardiac motion. One limitation of the XCAT was that it did not have a physiological basis which to realistically simulate variations in cardiac function. In this paper, we incorporate into the XCAT anatomy the four-chamber finite element (FE) living heart model (LHM) developed by the living heart project. The LHM represents the state of the art in cardiac FE simulation because of its ability to accurately replicate the biomechanical motion of the entire heart and its variations. We create a new series of 4-D phantoms capable of simulating patients with varying body sizes and shapes; cardiac positions, orientations, and dynamics. While extendable to other imaging modalities and technologies, our goal is to use the FE-enhanced XCAT models to investigate the optimal use of computed tomography for the evaluation of coronary artery disease. With the ability to simulate realistic, predictive, patient quality 4-D imaging data, the enhanced XCAT models will enable optimization studies to identify the most promising systems or system parameters for further clinical validation.

Structural heterogeneity is a hallmark of living cells and nuclei that drives local mechanical properties and dynamic cellular responses, including adhesion, gene expression, and differentiation. However, robust quantification of intracellular or intranuclear mechanics are lacking from conventional methods. Here, we describe new development of deformation microscopy that leverages conventional imaging and an automated hyperelastic warping algorithm to investigate strain history, deformation dynamics, and changes in structural heterogeneity within the interior of cells and nuclei. Using deformation microscopy, we found that tensile loading modes dominated intranuclear architectural dynamics in cardiomyocytes in vitro or myocytes in vivo, which was compromised by disruption of LINC complex molecule nesprin-3 or Lamin A/C, respectively. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries compared to controls at interchromatin regions where active translation was expected. Deformation microscopy represents a foundational approach toward intracellular elastography, with potential utility to provide new mechanistic and quantitative insights in diverse mechanobiological applications.

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.

Biological tissues have a complex hierarchical architecture that spans organ to subcellular scales and comprises interconnected biophysical and biochemical machinery. Mechanotransduction, gene regulation, gene protection, and structure-function relationships in tissues depend on how force and strain are modulated from macro to micro scales, and vice versa. Traditionally, computational and experimental techniques have been used in common model systems (e.g., embryos) and simple strain measures were applied. But the hierarchical transfer of mechanical parameters like strain in mammalian systems is largely unexplored in vivo. Here, we experimentally probed complex strain transfer processes in mammalian skeletal muscle tissue over multiple biological scales using complementary in vivo ultrasound and optical imaging approaches. An iterative hyperelastic warping technique quantified the spatially-dependent strain distributions in tissue, matrix, and subcellular (nuclear) structures, and revealed a surprising increase in strain magnitude and heterogeneity in active muscle as the spatial scale also increased. The multiscale strain heterogeneity indicates tight regulation of mechanical signals to the nuclei of individual cells in active muscle, and an emergent behavior appearing at larger (e.g. tissue) scales characterized by dramatically increased strain complexity.

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.

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.

The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping the template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R 2 = 0.96), circumferential strain (R 2 = 0.96), radial strain (R 2 = 0.93), and longitudinal strain (R 2 = 0.76) (p

This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18–59 ml. and ejection fraction (EF) values by 14–50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17–54 ml. and 14–45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R2 = 0.99).

The four-dimensional (4-D) NURBS-based cardiac-torso (NCAT) phantom, which provides a realistic model of the normal human anatomy and cardiac and respiratory motions, is used in medical imaging research to evaluate and improve imaging devices and techniques, especially dynamic cardiac applications. One limitation of the phantom is that it lacks the ability to accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). The goal of this work was to enhance the 4-D NCAT phantom by incorporating a physiologically based, finite-element (FE) mechanical model of the left ventricle (LV) to simulate both normal and abnormal cardiac motions. The geometry of the FE mechanical model was based on gated high-resolution X-ray multislice computed tomography (MSCT) data of a healthy male subject. The myocardial wall was represented as a transversely isotropic hyperelastic material, with the fiber angle varying from -90 degrees at the epicardial surface, through 0 degrees at the midwall, to 90 degrees at the endocardial surface. A time-varying elastance model was used to simulate fiber contraction, and physiological intraventricular systolic pressure-time curves were applied to simulate the cardiac motion over the entire cardiac cycle. To demonstrate the ability of the FE mechanical model to accurately simulate the normal cardiac motion as well as the abnormal motions indicative of CAD, a normal case and two pathologic cases were simulated and analyzed. In the first pathologic model, a subendocardial anterior ischemic region was defined. A second model was created with a transmural ischemic region defined in the same location. The FE-based deformations were incorporated into the 4-D NCAT cardiac model through the control points that define the cardiac structures in the phantom which were set to move according to the predictions of the mechanical model. A simulation study was performed using the FE-NCAT combination to investigate how the differences in contractile function between the subendocardial and transmural infarcts manifest themselves in myocardial Single photon emission computed tomography (SPECT) images. The normal FE model produced strain distributions that were consistent with those reported in the literature and a motion consistent with that defined in the normal 4-D NCAT beating heart model based on tagged magnetic resonance imaging (MRI) data. The addition of a subendocardial ischemic region changed the average transmural circumferential strain from a contractile value of -0.09 to a tensile value of 0.02. The addition of a transmural ischemic region changed average circumferential strain to a value of 0.13, which is consistent with data reported in the literature. Model results demonstrated differences in contractile function between subendocardial and transmural infarcts and how these differences in function are documented in simulated myocardial SPECT images produced using the 4-D NCAT phantom. Compared with the original NCAT beating heart model, the FE mechanical model produced a more accurate simulation for the cardiac motion abnormalities. Such a model, when incorporated into the 4-D NCAT phantom, has great potential for use in cardiac imaging research. With its enhanced physiologically based cardiac model, the 4-D NCAT phantom can be used to simulate realistic, predictive imaging data of a patient population with varying whole-body anatomy and with varying healthy and diseased states of the heart that will provide a known truth from which to evaluate and improve existing and emerging 4-D imaging techniques used in the diagnosis of cardiac disease.

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 (ΔR2=−0.023 fiber stretch, ΔR2=−0.020 circumferential strain, ΔR2=−0.005 radial strain, and ΔR2=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 (ΔR2=−0.032 fiber stretch, ΔR2=−0.023 circumferential strain, ΔR2=−0.04 radial strain, and ΔR2=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.

A series of models were developed in which a circulatory system model was coupled to an existing series of finite element (FE) models of the left ventricle (LV). The circulatory models were used to provide realistic boundary conditions for the LV models. This was developed for the JSim analysis package and was composed of a systemic arterial, capillary, and venous system in a closed loop with a varying elastance LV and left atria to provide the driving pressures and flows matching those of the FE model. Three coupled models were developed, a normal LV under normotensive aortic loading (116/80mm Hg), a mild hypertension (137/89mm Hg) model, and a moderate hypertension model (165/100mm Hg). The initial step in the modeling analysis was that the circulation was optimized to the enddiastolic pressure and volume values of the LV model. The cardiac FE models were then optimized to the systolic pressure/volume characteristics of the steady-state JSim circulatory model solution. Comparison of the stress predictions for the three models indicated that the mild hypertensive case produced a 21% increase in the average fiber stress levels, and the moderate hypertension case had a 36% increase in average stress. The circulatory work increased by 18% and 43% over that of the control for the mild and moderate hypertensive cases, respectively. [DOI: 10.1115/1.4023697]

The objectives of the following research were to evaluate the utility of a deformable image registration technique known as hyperelastic warping for the measurement of local strains in the left ventricle through the analysis of clinical, gated PET image datasets. Two normal human male subjects were sequentially imaged with PET and tagged MRI imaging. Strain predictions were made for systolic contraction using warping analyses of the PET images and HARP based strain analyses of the MRI images. Coefficient of determinationR2values were computed for the comparison of circumferential and radial strain predictions produced by each methodology. There was good correspondence between the methodologies, withR2values of 0.78 for the radial strains of both hearts and from anR2=0.81andR2=0.83for the circumferential strains. The strain predictions were not statistically different(P≤0.01). A series of sensitivity results indicated that the methodology was relatively insensitive to alterations in image intensity, random image noise, and alterations in fiber structure. This study demonstrated that warping was able to provide strain predictions of systolic contraction of the LV consistent with those provided by tagged MRI Warping.

International audience; Left ventricular hypertrophy induced by systemic hypertension is generally regarded a morphological precursor of unfortunate cardiovascular events. Myocardial fiber disarray has been long recognized as a prevalent hallmark of this pathology. In this chapter, ex vivo diffusion tensor magnetic resonance imaging is employed to delineate the regional loss of myocardial organization that is present in the excised heart of a spontaneously hypertensive rat, as opposed to a control. Fiber tracking results are provided that illustrate in great detail the alterations in the integrity of cardiac muscle microstructure due to the disease. A quantitative analysis is also performed. Another contribution of this chapter is the model-based assessment of the role of the myofiber disarray in modulating the mechanical properties of the myocardium. The results of this study improve our understanding of the structural remodeling mechanisms that are associated with hypetensive left ventricular hypertrophy and their role.

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.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.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.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.

The current 3D XCAT phantom allows users to manually define the regional myocardial perfusion defect (MPD) as a simple pie-shaped wedge region with reduced activity level in the myocardium of left ventricle. To more accurately and realistically model the MPD, we have developed a new regional MPD model for the 3D XCAT phantom for myocardial perfusion SPECT (MP-SPECT) studies based on the location and the severity of the stenosis in a computer generated coronary arterial tree. First, we generated a detailed coronary arterial tree by extending the large proximal branches segmented from patient CT images to cover the whole heart using an iterative rule-based algorithm. Second, we determined the affected downstream vascular segments of a given stenosis. Third, we computed the activity of each myocardial region as a function of the inverse-distance-weighted average of the flow of the neighboring vascular segments. Fourth, we generated a series of bull’s-eye maps of MP-SPECT images of different coronary artery stenosis scenarios. Fifth, we had expert physician readers to qualitatively assess the bull’s-eye maps based on their similarity to typical clinical cases in terms of the shape, the extent, and the severity of the MPDs. Their input was used to iteratively revise the coronary artery tree model so that the MPDs were closely matched to those found in bull’s-eye maps from patient studies. Finally, from our simulated MP-SPECT images, we observed that (1) the locations of the MPDs caused by stenoses at different main arteries were different largely according to their vascular territories, (2) a stenosis at a proximal branch produced a larger MPD than the one at a distal branch, and (3) a more severe stenosis produced a larger MPD than the less severe one. These observations were consistent to those found in clinical cases. Therefore, this new regional MPD model has enhanced the generation of realistic pathological MP-SPECT images using the XCAT phantom. When combining with the mechanical model of the myocardium, the new model can be extended for the simulation of 4D gated MP-SPECT simulation of a pathological heart with both perfusion and motion defects.

The goal of this work is to create a detailed three-dimensional (3D) digital breast phantom based on empirical data and to incorporate it into the four-dimensional (4D) NCAT phantom, a computerized model of the human anatomy widely used in imaging research. Twenty sets of high-resolution breast CT data were used to create anatomically diverse models. The datasets were segmented using techniques developed in our laboratory and the breast structures will be defined using a combination of non-uniform rational b-splines (NURBS) and subdivision surfaces (SD). Imaging data from various modalities (x-ray and nuclear medicine) were simulated to demonstrate the utility of the new breast phantoms. As a proof of concept, a simple compression technique was used to deform the breast models while maintaining a constant volume to simulate modalities (mammography and tomosynthesis) that involve compression. Initial studies using one CT dataset indicate that the simulated breast phantom is capable of providing a realistic and flexible representation of breast tissue and can be used with different acquisition methods to test varying imaging parameters such as dose, resolution, and patient motion. The final model will have a more accurate depiction of the internal breast structures and will be scaleable in terms of size and density. Also, more realistic finite-element techniques will be used to simulate compression. With the ability to simulate realistic, predictive patient imaging data, we believe the phantom will provide a vital tool to investigate current and emerging breast imaging methods and techniques.

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.

A search for baryonia with negative and positive strangeness decaying respectively into\(\Lambda + \bar p + pions\) and\(\bar \Lambda + p + pions\) has been carried out in a neutron beam with a mean momentum of ≅40 GeV/c in an experiment performed at the Serpukhov accelerator. There is a strong indication of the existence of these baryonia. The following four charge states are observed for negative and positive strangeness: neutral, negative, positive and doubly charged. Their mean mass is 3055±25 MeV/c2 and the width Γ≦36±15 MeV/c2. The data show that the isotopic spin of the baryonia is ≧3/2. The baryonia production cross sections in the acceptable kinematic regionXF≧0.2 andPT≦1 GeV/c times the branching ratios of the observed decays are of the order of 1 μb per nucleon.

The accurate determination of strain in deforming biological tissues is a necessary and important part of experimental investigations in biomechanics. We have developed a method, referred to as Hyperelastic Warping, to combine medical image data with a solid mechanics analysis approach to allow estimation of tissue strains in the absence of detailed information about boundary conditions and in some cases constitutive information. The method makes use of medical image data to provide information about the deforming tissue and thus the strain and stress fields. The mathematical problem is to search through all admissible configurations for the one that minimizes the difference between a transformed template image and a target image collected experimentally. The resulting deformation map is used to determine the strain field. This technique has been applied successfully to determine strain in several biological soft tissues. This paper describes the theory, implementation and validation of the technique for measurement of transmural strains in the left ventricle.

Purpose: The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n = 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Methods: Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the “base” and “target” for morphing. Several combinations of transformations were applied to morph between the “base’ and “target” datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms, generated from morphing three human subject datasets, were used in a preliminary observer evaluation where four board certified breast radiologists with varying amounts of experience ranked the level of realism (from 1 = “fake” to 10 = “real”) of the simulated images. Results: The morphing technique was able to successfully generate new and unique morphed datasets from the original human subject data. The radiologists evaluated the realism of simulated mammograms generated from the morphed and unmorphed human subject datasets and scored the realism with an average ranking of 5.87 ± 1.99, confirming that overall the phantom image datasets appeared more “real” than “fake.” Moreover, there was not a significant difference (p > 0.1) between the realism of the unmorphed datasets (6.0 ± 1.95) compared to the morphed datasets (5.86 ± 1.99). Three of the four observers had overall average rankings of 6.89 ± 0.89, 6.9 ± 1.24, 6.76 ± 1.22, whereas the fourth observer ranked them noticeably lower at 2.94 ± 0.7. Conclusions: This work presents a technique that can be used to generate a suite of realistic computerized breast phantoms from a limited number of human subjects. This suite of flexible breast phantoms can be used for multimodality imaging research to provide a known truth while concurrently producing realistic simulated imaging data.

Cardiovascular disease is the leading cause of morbidity and mortality in diabetic individuals. Diabetes mellitus is associated with a two- to four-fold increase in risk of coronary heart disease. This risk is independent of other classical risk factors including age, smoking, elevated serum cholesterol levels, and hypertension, and the overall risk of cardiovascular disease increases proportionally with the number of risk factors. Many groups are currently investigating the aetiology of diabetic vascular disease, with particular interesting being paid to the processes involved in the formation of highly cross-linked carbohydrate-protein complexes known as melanoids. These complexes appear to be formed by glycation arising from reactions between glucose and the amino groups on proteins, and their formation within the vessel wall resqlts in a decrease in vascular elasticity. This decrease in elasticity has been implicated in the increased incidence of atherosclerosis in diabetic individuals. Previous testing modalities could not test in the radial direction and required assumptions based on incompressibility in order to determine the radial behavior of the artery.

New data is presented on the ratios of structure functions F 2 ( x , Q 2 ) measured in deep inelastic muon scattering with deuterium, nitrogen, and iron targets. The existence of nuclear effects at large Q 2 is confirmed with improved systematic accuracy. The ratio F 2 Fe ( x ) F 2 D 2 ( x ) covers the range 0.20 ⩽ x ⩽ 0.70 and is in agreement with earlier measurements. The ratio F 2 N 2 ( x )/ F 2 D 2 ( x ) is measured over the range 0.08 ⩽ x ⩽ 0.70 and is compatible with unity below x = 0.3.

New Results are presented on nuclear effects in deep inelastic muon scattering on deuterium and iron targets at large Q 2 . The ratio F Fe 2 (x) F D 2 2 (x) measured in the kinematic range 0.06⩽ x ⩽0.70, 14GeV 2 ⩽ Q 2 ⩽70 GeV 2 is in good agreement with earlier measurements in the region of x > 0.25. At lower x , the structure function ratio exhibits an enhancement of ≈5%.

A large toroidal iron spectrometer for the study of deep-inelastic muon scattering at the CERN SPS has been upgraded to extend the accessible kinematic range and to reduce the systematic errors on absolute cross-section measurements. The layout of the improved apparatus, the construction of new detectors and associated electronics, and the structure of a new data-acquisition system are described in detail.