A Robust and Accurate Two-Step Auto-Labeling Conditional Iterative Closest Points (TACICP) Algorithm for Three-Dimensional Multi-Modal Carotid Image Registration

Atherosclerosis is among the leading causes of death and disability. Combining information from multi-modal vascular images is an effective and efficient way to diagnose and monitor atherosclerosis, in which image registration is a key technique. In this paper a feature-based registration algorithm, Two-step Auto-labeling Conditional Iterative Closed Points (TACICP) algorithm, is proposed to align three-dimensional carotid image datasets from ultrasound (US) and magnetic resonance (MR). Based on 2D segmented contours, a coarse-to-fine strategy is employed with two steps: rigid initialization step and non-rigid refinement step. Conditional Iterative Closest Points (CICP) algorithm is given in rigid initialization step to obtain the robust rigid transformation and label configurations. Then the labels and CICP algorithm with non-rigid thin-plate-spline (TPS) transformation model is introduced to solve non-rigid carotid deformation between different body positions. The results demonstrate that proposed TACICP algorithm has achieved an average registration error of less than 0.2mm with no failure case, which is superior to the state-of-the-art feature-based methods.     

Exemplar-Based Image Inpainting Using a Modified Priority Definition

Exemplar-based algorithms are a popular technique for image inpainting. They mainly have two important phases: deciding the filling-in order and selecting good exemplars. Traditional exemplar-based algorithms are to search suitable patches from source regions to fill in the missing parts, but they have to face a problem: improper selection of exemplars. To improve the problem, we introduce an independent strategy through investigating the process of patches propagation in this paper. We first define a new separated priority definition to propagate geometry and then synthesize image textures, aiming to well recover image geometry and textures. In addition, an automatic algorithm is designed to estimate steps for the new separated priority definition. Comparing with some competitive approaches, the new priority definition can recover image geometry and textures well.     

Force relaxation and permanent deformation of erythrocyte membrane.

Force relaxation and permanent deformation processes in erythrocyte membrane were investigated with two techniques: micropipette aspiration of a portion of a flaccid cell, and extension of a whole cell between two micropipettes. In both experiments, at surface extension ratios less than 3:1, the extent of residual membrane deformation is negligible when the time of extension is less than several minutes. However, extensions maintained longer result in significant force relaxation and permanent deformation. The magnitude of the permanent deformation is proportional to the total time period of extension and the level of the applied force. Based on these observations, a nonlinear constitutive relation for surface deformation is postulated that serially couples a hyperelastic membrane component to a linear viscous process. In contrast with the viscous dissipation of energy as heat that occurs in rapid extension of a viscoelastic solid, or in plastic flow of a material above yield, the viscous process in this case represents dissipation produced by permanent molecular reorganization through relaxation of structural membrane components. Data from these experiments determine a characteristic time constant for force relaxation, tau, which is the ratio of a surface viscosity, eta to the elastic shear modulus, mu. Because it was found that the concentration of albumin in the cell suspension strongly mediates the rate of force relaxation, values for tau of 10.1, 40.0, 62.8, and 120.7 min are measured at albumin concentrations of 0.0, 0.01, 0.1, and 1.% by weight in grams, respectively. The surface viscosity, eta, is calculated from the product of tau and mu. For albumin concentrations of 0.0, 0.01, 0.1, and 1% by weight in grams, eta is equal to 3.6, 14.8, 25.6, and 51.9 dyn s/cm, respectively.     

2-D Crystallization of theRhodococcus20S Proteasome

The 2D crystallization method using a liquid–liquid interface has been applied to theRhodococcus20S proteasome. Two types of ordered arrays were obtained, both large enough for high-resolution analysis. The first one is a hexagonal close-packed array, whereas the second one has fourfold symmetry. By image analysis based on a real space correlation averaging technique, the close-packed array was found to be hexagonally packed but the molecules had complete rotational freedom. The fourfold array is, however, a true crystal with p4 symmetry. Lattice constants area=b= 20.0 nm and the unit cell of this crystal contains two proteasomes. The diffraction pattern computed from the original picture shows the spots up to (4.5) that correspond to 3.1 nm resolution. After applying an unbending procedure, the diffraction pattern shows spots extending to 1.8 nm resolution.     

Single particle 3D reconstruction for 2D crystal images of membrane proteins

In cases where ultra-flat cryo-preparations of well-ordered two-dimensional (2D) crystals are available, electron crystallography is a powerful method for the determination of the high-resolution structures of membrane and soluble proteins. However, crystal unbending and Fourier-filtering methods in electron crystallography three-dimensional (3D) image processing are generally limited in their performance for 2D crystals that are badly ordered or non-flat. Here we present a single particle image processing approach, which is implemented as an extension of the 2D crystallographic pipeline realized in the 2dx software package, for the determination of high-resolution 3D structures of membrane proteins. The algorithm presented, addresses the low single-to-noise ratio (SNR) of 2D crystal images by exploiting neighborhood correlation between adjacent proteins in the 2D crystal. Compared with conventional single particle processing for randomly oriented particles, the computational costs are greatly reduced due to the crystal-induced limited search space, which allows a much finer search space compared to classical single particle processing. To reduce the considerable computational costs, our software features a hybrid parallelization scheme for multi-CPU clusters and computer with high-end graphic processing units (GPUs). We successfully apply the new refinement method to the structure of the potassium channel MloK1. The calculated 3D reconstruction shows more structural details and contains less noise than the map obtained by conventional Fourier-filtering based processing of the same 2D crystal images.     

Three-dimensional reconstruction of the surface protein of Pyrodictium brockii: Comparing two image processing strategies

The three-dimensional structure of the surface layer protein of the hyperthermophilic archaebacterium Pyrodictium brockii was determined by electron crystallographic techniques to a resolution of approximately 1.6 nm. Two image processing strategies—correlation averaging and lattice unbending—were explored with regard to their potential to compensate for lattice distortions. Reconstructions performed via these two routes did not show any significant difference although the unbending approach might be expected to give superior results since, in principle, it incorporates a correction for unit cell displacement, rotation, and deformation while conventional correlation averaging compensates for displacements only. The discussion furthermore addresses some hitherto ignored problems associated with the correction of lattice disorder at higher tilts.     

A method to obtain surface strains of soft tissues using a laser scanning device

A three-dimensional laser scanning device was developed allowing surface digitization of musculoskeletal and soft tissue structures under different loads. Image-processing algorithms were formulated for image registration. These were used to determine displacement mapping and then surface strains. Various validation experiments were performed. Accuracy was obtained on a test cylinder after rigid rotation and on a silicon cylinder compressed in four loading steps. The system accuracy (including the scanning and the data evaluation) was +/-0.10% strain in vertical and +/-0.16% strain in shear and circumferential direction for the rigid rotation exhibiting the zero-strain situation. Silicon cylinder compression showed that the accuracy was best for small strains, whereas strains >5% evoked a slight underestimation increasing further with higher strains (error of 0.54% for 7.22% vertical strain). It was possible to increase the accuracy by performing the strain measurements via sub-steps. This had a remaining error of 0.41% for 7.22% vertical strain. A further experiment was carried out in order to acquire the surface strain of a human lumbar intervertebral disc while it was forced to flexion and extension. This study introduced a laser-based scanning method to obtain soft tissue surface strains. It is important to know the strain distribution of musculoskeletal structures and soft tissues. This could help to better understand the mechanical loading of biological structures e.g. the processes in fracture healing. These data could also be used to assist in the validation process for finite-element models.     

Computing the direction of heading from affine image flow

Observers moving through a three-dimensional environment can use optic flow to determine their direction of heading. Existing heading algorithms use cartesian flow fields in which image flow is the displacement of image features over time. I explore a heading algorithm that uses affine flow instead. The affine flow at an image feature is its displacement modulo an affine transformation defined by its neighborhood. Modeling the observer's instantaneous motion by a translation and a rotation about an axis through its eye, affine flow is tangent to the translational field lines on the observer's viewing sphere. These field lines form a radial flow field whose center is the direction of heading. The affine flow heading algorithm has characteristics that can be used to determine whether the human visual system relies on it. The algorithm is immune to observer rotation and arbitrary affine transformations of its input images; its accuracy improves with increasing variation in environmental depth; and it cannot recover heading in an environment consisting of a single plane because affine flow vanishes in this case. Translational field lines can also be approximated through differential cartesian motion. I compare the performance of heading algorithms based on affine flow, differential cartesian flow, and least-squares search.     

Regulation of cell adhesion by affinity and conformational unbending of alpha4beta1 integrin

Rapid activation of integrins in response to chemokine-induced signaling serves as a basis for leukocyte arrest on inflamed endothelium. Current models of integrin activation include increased affinity for ligand, molecular extension, and others. In this study, using real-time fluorescence resonance energy transfer to assess alpha(4)beta(1) integrin conformational unbending and fluorescent ligand binding to assess affinity, we report at least four receptor states with independent regulation of affinity and unbending. Moreover, kinetic analysis of chemokine-induced integrin conformational unbending and ligand-binding affinity revealed conditions under which the affinity change was transient whereas the unbending was sustained. In a VLA-4/VCAM-1-specific myeloid cell adhesion model system, changes in the affinity of the VLA-4-binding pocket were reflected in rapid cell aggregation and disaggregation. However, the initial rate of cell aggregation increased 9-fold upon activation, of which only 2.5-fold was attributable to the increased affinity of the binding pocket. These data show that independent regulation of affinity and conformational unbending represents a novel and fundamental mechanism for regulation of integrin-dependent adhesion in which the increased affinity appears to account primarily for the increasing lifetime of the alpha(4)beta(1) integrin/VCAM-1 bond, whereas the unbending accounts for the increased capture efficiency.     

Effects of water stress on leaf growth in tall fescue, Italian ryegrass and their hybrid: rheological properties of expansion zones of leaves, measured on growing and killed tissue

In Expt 1, plants of tall fescue (Festuca arundinacea Schreb.), Italian ryegrass (Lolium multiflorum Lam.) and their F1 hybrid were grown in soil-based compost in a controlled environment, and subjected to full or partial irrigation for 20 d. In Expt 2, plants of the parent species were grown in nutrient solution in the same environment and subjected to osmotic stress (0.76 MPa) for 2 d. In both experiments, distribution of growth in the leaf growing zone (at the base of the growing leaf) was determined, and elastic and plastic compliances were measured on methanol-killed samples of growing zone and of mature lamina using an extensiometer. In Expt 2 plastic compliance coefficient of extension, extensibility, and hydraulic conductance were calculated from changes in leaf extension rate occasioned by imposing linear stress. 'Plastic and elastic compliances of growing zones were 10-20 times greater than those of mature laminae. In both species, drought reduced (a) leaf extension rate, (b) the length of the growing zone, the height of maximum growth, (d) the plastic compliance of whole bases (Expt 1), and (e) hydraulic conductance. The elastic compliance of whole leaf bases was unaffected by drought, but when expressed per unit length of growing zone was increased by drought. Killing with methanol reduced the plastic compliance of leaf bases in control plants, but not in droughted plants.F. arundinacea differed from L. multiflorum in having (a) a lower leaf extension rate (although drought reduced extension by the same proportion in both species), (b) a longer growing zone in droughted plants in Expt 2, a lower elastic and plastic compliance of whole killed leaf bases and laminae, (d) slightly higher plastic compliance in attached growing leaves, and (e) lower plastic compliance per unit length of growing zone in attached leaves. The hybrid was generally intermediate between the parents. the results are discussed in relation to methodology and to crop improvement.Key words: Extensibility, extension coefficient, hydraulic conductance, elastic compliance, plastic compliance, leaf growth, leaf extension rate.      

Free Form Deformation–Based Image Registration Improves Accuracy of Traction Force Microscopy

Traction Force Microscopy (TFM) is a widespread method used to recover cellular tractions from the deformation that they cause in their surrounding substrate. Particle Image Velocimetry (PIV) is commonly used to quantify the substrate’s deformations, due to its simplicity and efficiency. However, PIV relies on a block-matching scheme that easily underestimates the deformations. This is especially relevant in the case of large, locally non-uniform deformations as those usually found in the vicinity of a cell’s adhesions to the substrate. To overcome these limitations, we formulate the calculation of the deformation of the substrate in TFM as a non-rigid image registration process that warps the image of the unstressed material to match the image of the stressed one. In particular, we propose to use a B-spline -based Free Form Deformation (FFD) algorithm that uses a connected deformable mesh to model a wide range of flexible deformations caused by cellular tractions. Our FFD approach is validated in 3D fields using synthetic (simulated) data as well as with experimental data obtained using isolated endothelial cells lying on a deformable, polyacrylamide substrate. Our results show that FFD outperforms PIV providing a deformation field that allows a better recovery of the magnitude and orientation of tractions. Together, these results demonstrate the added value of the FFD algorithm for improving the accuracy of traction recovery.     

Large deformation of elastic tubes

In this paper a study is made of the large deformation of elastic tubes. Analysis is confined to the case of statical deformation. The energy of deformation is considered to be a function of the three strain invariants only. In order to determine its form for actual materials it is expanded in its Taylor's series. From the theoretical analysis of the inflation and extension of tubes, linear algebraic equations in the elastic constants are developed. Using these and appropriate measurements of diametral change and longitudinal stretch, obtained from experiments, elastic constants for the non-linear theory of elasticity are explicity determined with the aid of a computer program. The highly non-linear forms of deformation of tubes computed on the basis of the theory are compared with our experimental findings for a latex rubber tubing and for some bio-physical data taken from the literature.     

Analysis of deformation and contraction in cylindrical crystals due to dispirations or dislocations.

Cylindrical crystal structures are common in biology. The shape changes and movements of cylindrical crystals are basic to the understanding of the contractile mechanisms in biological systems such as tobacco mosaic viruses and the tail sheath of T-even bacteriophages. It has been suggested that the concept of defects in crystal physics can be applied to study these contractile mechanisms. The defect believed to be responsible for the shape changes of cylindrical crystals is known as a dispiration. Dispirations are characterized by the shear displacement on the slip plane through a screw symmetry operation. The elastic field of a dispiration can be decomposed into its translational (dislocation) and rotational (disclination) components. The magnitude of the translational and rotational displacements in a cylindrical crystal has been related to the crystal structural parameters. The passage of a dispiration along a helical plane in a cylindrical crystal can induce one of two types of shape changes. In one type, only the disclination component of the dispiration contributes to contraction, whereas in the other type, both the disclination and dislocation components are responsible for the shape change. Estimates of the magnitude of contraction are made in terms of the dimensional and structural parameters of the cylindrical crystal. The reversal of the direction of helical slip results in extension instead of contraction of the cylindrical crystal. The local elastic deformation of a dispiration dipole situated on the helical plane of a cylindrical crystal is examined. It has been shown that, for the first type of deformation mentioned above, closed form solutions of the stress field can be obtained by superposing the stress fields of two dispiration dipoles with slip planes parallel and normal to the cylinder axis, respectively. The approximations of shallow shell theory are adopted in the analysis. Future problems of biological interests are identified.     

Physical Constraint Finite Element Model for Medical Image Registration

Due to being derived from linear assumption, most elastic body based non-rigid image registration algorithms are facing challenges for soft tissues with complex nonlinear behavior and with large deformations. To take into account the geometric nonlinearity of soft tissues, we propose a registration algorithm on the basis of Newtonian differential equation. The material behavior of soft tissues is modeled as St. Venant-Kirchhoff elasticity, and the nonlinearity of the continuum represents the quadratic term of the deformation gradient under the Green- St.Venant strain. In our algorithm, the elastic force is formulated as the derivative of the deformation energy with respect to the nodal displacement vectors of the finite element; the external force is determined by the registration similarity gradient flow which drives the floating image deforming to the equilibrium condition. We compared our approach to three other models: 1) the conventional linear elastic finite element model (FEM); 2) the dynamic elastic FEM; 3) the robust block matching (RBM) method. The registration accuracy was measured using three similarities: MSD (Mean Square Difference), NC (Normalized Correlation) and NMI (Normalized Mutual Information), and was also measured using the mean and max distance between the ground seeds and corresponding ones after registration. We validated our method on 60 image pairs including 30 medical image pairs with artificial deformation and 30 clinical image pairs for both the chest chemotherapy treatment in different periods and brain MRI normalization. Our method achieved a distance error of 0.320±0.138 mm in x direction and 0.326±0.111 mm in y direction, MSD of 41.96±13.74, NC of 0.9958±0.0019, NMI of 1.2962±0.0114 for images with large artificial deformations; and average NC of 0.9622±0.008 and NMI of 1.2764±0.0089 for the real clinical cases. Student’s t-test demonstrated that our model statistically outperformed the other methods in comparison (p-values <0.05).     

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation.A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code.The similarity analysis demonstrated the superiority of the deformable registrations (p < .001).Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL.Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.     

Smart process development: Application of machine-learning and integrated process modeling for inclusion body purification processes

The development of a biopharmaceutical production process usually occurs sequentially, and tedious optimization of each individual unit operation is very time-consuming. Here, the conditions established as optimal for one-step serve as input for the following step. Yet, this strategy does not consider potential interactions between a priori distant process steps and therefore cannot guarantee for optimal overall process performance. To overcome these limitations, we established a smart approach to develop and utilize integrated process models using machine learning techniques and genetic algorithms. We evaluated the application of the data-driven models to explore potential efficiency increases and compared them to a conventional development approach for one of our development products. First, we developed a data-driven integrated process model using gradient boosting machines and Gaussian processes as machine learning techniques and a genetic algorithm as recommendation engine for two downstream unit operations, namely solubilization and refolding. Through projection of the results into our large-scale facility, we predicted a twofold increase in productivity. Second, we extended the model to a three-step model by including the capture chromatography. Here, depending on the selected baseline-process chosen for comparison, we obtained between 50% and 100% increase in productivity. These data show the successful application of machine learning techniques and optimization algorithms for downstream process development. Finally, our results highlight the importance of considering integrated process models for the whole process chain, including all unit operations.     

Determination of the parameters of the hot plasma formed during the implosion of wire arrays from time-resolved X-ray spectra of H- and He-like ions

A system for recording X-ray ion spectra by means of a spherical crystal with the subsequent transformation of the X-ray spectrum into an optical image recorded with the help of an optical streak camera is described. A computer code intended to recover the plasma parameters from the intensities of spectral lines of H- and He-like ions of some chemical elements (z = 6–29) is developed. Results of experiments on the determination of the parameters of hot plasma formed during the implosion of nested aluminum wire arrays at the S-300 high-current generator are presented.     

Stretching and Relaxation of Malaria-Infected Red Blood Cells

The invasion of red blood cells (RBCs) by malaria parasites is a complex dynamic process, in which the infected RBCs gradually lose their deformability and their ability to recover their original shape is greatly reduced with the maturation of the parasites. In this work, we developed two types of cell model, one with an included parasite, and the other without an included parasite. The former is a representation of real malaria-infected RBCs, in which the parasite is treated as a rigid body. In the latter, where the parasite is absent, the membrane modulus and viscosity are elevated so as to produce the same features present in the parasite model. In both cases, the cell membrane is modeled as a viscoelastic triangular network connected by wormlike chains. We studied the transient behaviors of stretching deformation and shape relaxation of malaria-infected RBCs based on these two models and found that both models can generate results in agreement with those of previously published studies. With the parasite maturation, the shape deformation becomes smaller and smaller due to increasing cell rigidity, whereas the shape relaxation time becomes longer and longer due to the cell’s reduced ability to recover its original shape.     

Stretching and Relaxation of Malaria-Infected Red Blood Cells

The invasion of red blood cells (RBCs) by malaria parasites is a complex dynamic process, in which the infected RBCs gradually lose their deformability and their ability to recover their original shape is greatly reduced with the maturation of the parasites. In this work, we developed two types of cell model, one with an included parasite, and the other without an included parasite. The former is a representation of real malaria-infected RBCs, in which the parasite is treated as a rigid body. In the latter, where the parasite is absent, the membrane modulus and viscosity are elevated so as to produce the same features present in the parasite model. In both cases, the cell membrane is modeled as a viscoelastic triangular network connected by wormlike chains. We studied the transient behaviors of stretching deformation and shape relaxation of malaria-infected RBCs based on these two models and found that both models can generate results in agreement with those of previously published studies. With the parasite maturation, the shape deformation becomes smaller and smaller due to increasing cell rigidity, whereas the shape relaxation time becomes longer and longer due to the cell’s reduced ability to recover its original shape.