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Chromosome aberration frequencies in human lymphocytes irradiated in a multi-layer array by protons with different LET.

PURPOSE: To provide data on the dose-and linear energy transfer (LET)-dependence of the production of dicentrics in human lymphocytes. MATERIALS AND METHODS: Track segment irradiation with 16.5 MeV protons was performed in a multi-layer array allowing the simultaneous exposure of human peripheral lymphocytes in three successive samples. Within these samples the dose-averaged linear energy transfer (LD) of protons increased with increasing depth, i.e. LD = 3.5, 5.3 and 19.0 keV/microm. Dicentrics were scored in first division solid-stained metaphases. RESULTS: Dicentric yields measured in the first and second samples fit the linear-quadratic model, those of the third sample fit a linear model of the dose response relationship. Relative to 137Cs gamma-rays, limiting RBE values of 2.9, 4.3 and 21.5 were determined from the ratios of the respective linear coefficients of the dose effect curves. The linear dose effect coefficient increases approximately proportionally with increasing LET. The quadratic coefficient is approximately constant for protons with LD of 3.5 and 5.3 keV/microm, and is not significantly different from zero at LD= 19.0 keV/microm. CONCLUSION: This result is well in line with theoretical predictions on the variations of dose-effect coefficients with radiation quality. However, such an evaluation can only be obtained from clearly defined track segment experiments.

Chromosome Aberrations↗

Non-invasive quantitative reconstruction of tissue elasticity using an iterative forward approach.

A novel iterative approach is presented to estimate Young's modulus in homogeneous soft tissues using vibration sonoelastography. A low-frequency (below 100 Hz) external vibration is applied and three or more consecutive frames of B-scan image data are recorded. The internal vibrational motion of the soft tissue structures is calculated from 2D displacements between pairs of consecutive frames, which are estimated using a mesh-based speckle tracking method. An iterative forward finite element approach has been developed to reconstruct Young's modulus from the measured vibrational motion. This is accomplished by subdividing the 2D image domain into sample blocks in which Young's modulus is assumed to be constant. Because the finite element equations are internally consistent, boundary values other than displacement are not required. The sensitivity of the results to Poisson's ratio and the damping coefficient (viscosity) is investigated. The approach is verified using simulated displacement data and using data from tissue-mimicking phantoms.

Algorithms↗

High resolution ultrasound elastomicroscopy imaging of soft tissues: system development and feasibility.

Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimetres, but this is not sufficient for applications to skin, articular cartilage or other fine structures. We developed a prototype high resolution elastomicroscopy system consisting of a 50 MHz ultrasound backscatter microscope system and a calibrated compression device using a load cell to measure the pressure applied to the specimen, which was installed between a rigidly fixed face-plate and a specimen platform. Radiofrequency data were acquired in a B-scan format (10 mm wide x 3 mm deep) in specimens of mouse skin and bovine patellar cartilage. The scanning resolution along the B-scan plane direction was 50 microm, and the ultrasound signals were digitized at 500 MHz to achieve a sensitivity better than 1 microm for the axial displacement measurement. Because of elevated attenuation of ultrasound at high frequencies, special consideration was necessary to design a face-plate permitting efficient ultrasound transmission into the specimen and relative uniformity of the compression. Best results were obtained using a thin plastic film to cover a specially shaped slit in the face-plate. Local tissue strain maps were constructed by applying a cross-correlation tracking method to signals obtained at the same site at different compression levels. The speed of sound in the tissue specimen (1589.8+/-7.8 m s(-1) for cartilage and 1532.4+/-4.4 m s(-1) for skin) was simultaneously measured during the compression test. Preliminary results demonstrated that this ultrasound elastomicroscopy technique was able to map deformations of the skin and articular cartilage specimens to high resolution, in the order of 50 microm. This system can also be potentially used for the assessment of other biological tissues, bioengineered tissues or biomaterials with fine structures.

Animals↗

Long-term survival and outgrowth of mechanically engineered nervous tissue constructs implanted into spinal cord lesions.

While most approaches to repair spinal cord injury (SCI) rely on promoting axon outgrowth, the extensive distance that axons would have to grow to bridge SCI lesions remains an enormous challenge. In this study, we used a new tissue-engineering technique to create long nervous tissue constructs spanned by living axon tracts to repair long SCI lesions. Exploiting the newfound process of extreme axon stretch growth, integrated axon tracts from dorsal root ganglia (DRG) neurons were mechanically elongated in vitro to 10 mm over 7 days and encased in a collagen hydrogel to form a nervous tissue construct. In addition, a modified lateral hemisection SCI model in the rat was developed to create a 1 cm long cavity in the spinal cord. Ten days following SCI, constructs were transplanted into the lesion and the animals were euthanized 4 weeks post-transplantation for histological analyses. Through cell tracking methods and immunohistochemistry, the transplanted elongated cultures were consistently found to survive 4 weeks in the injured spinal cord. In addition, DRG axons were observed extending out of the transplanted construct into the host spinal cord tissue. These results demonstrate the promise of nervous tissue constructs consisting of stretch-grown axons to bridge even extensive spinal cord lesions.

Animals↗

Spatial frequency discrimination in normal vision and in patients with multiple sclerosis.

This article extends our previous reports that multiple sclerosis can cause a visual dysfunction better described as a distortion than as a blurring of vision. An earlier paper reported that multiple sclerosis spares visual acuity in some patients while reducing visual sensitivity for less fine detail. Specifically, these patients experience a loss of contrast sensitivity for low and/or intermediate spatial frequencies, while contrast sensitivity for high spatial frequencies is unimpaired. We report here that some patients also lose spatial frequency discrimination, so that these patients cannot tell which of two clearly visible gratings has the higher spatial frequency even though control subjects accurately report which grating has the higher spatial frequency. One way of regarding this discrimination loss is in terms of a deterioration of the ability to discriminate size. Contrast sensitivity was measured over the spatial frequency range 1 to 20 cycles/deg using the von Békésy tracking method for 10 patients. (20 eyes) and 16 control subjects (32 eyes). The limit of normality was taken as 2.5 standard deviations from the control mean (99 per cent confidence). Spatial frequency discrimination was measured using the criterion-free method of temporal two-alternative forced choice over the spatial frequency range 2 to 16 cycles/deg for 10 patients (20 eyes), and for 14 to 26 control eyes at each spatial frequency. Three control subjects were studied more extensively over the range 1 to 20 cycles/deg. Control subjects could discriminate two spatial frequencies that differed by more than about 5 per cent. This held for all spatial frequencies tested. Grating contrast had little effect on discrimination, provided that all test gratings were clearly visible. The normal limit for discrimination threshold was set at 2.5 standard deviations from the control mean. Seven of 10 patients have abnormal contrast sensitivity at one or more spatial frequencies. Six of 10 patients had abnormal discrimination at one or more spatial frequencies. At any given spatial frequency the correlation between the magnitudes of sensitivity loss and discrimination loss was weak, though an eye that was less sensitive than its fellow also tended to have poorer discrimination. A more subtle relationship between sensitivity loss and discrimination loss was clearly shown by one patient. Sensitivity loss was restricted to spatial frequencies below 8 cycles/deg, while discrimination loss in the same eye was restricted to spatial frequencies above 8 cycles/deg. We propose that this finding can be straightforwardly understood if discrimination is determined by the relative activities of different spatial frequency channels analogously, to the way opponent-colour mechanisms determine colour discrimination.

Adolescent↗

Evaluation of sepsis in a critically ill surgical population.

We report a new clinical rating system which assesses septic patients' ongoing disease course and its severity. Our system incorporates the Therapeutic Intervention Scoring System (TISS) and Acute Physiology and Chronic Health Evaluation to measure discrete organ system abnormalities, plus a multiple system organ failure scale to quantify the number of abnormal organ systems. The resulting score, which reflects the severity of multiple organ dysfunction and grades responsiveness to therapy, was validated against the actual disease course. Retrospective and prospective profiles of individual surgical ICU patients demonstrated that this tracking method was a more effective indicator of severity of sepsis and more sensitive to the day-to-day changes in clinical status than either the TISS or APACHE II components alone. We also demonstrate that a graphic illustration of daily system scores yields clinically useful information relevant to the patients' septic course.

Bacterial Infections↗

A developmental study of smooth pursuit eye movements in normal children from 7 to 15 years of age.

OBJECTIVE: To examine age-related changes in smooth pursuit tracking. METHOD: Using infrared occulography, smooth pursuit eye movements are examined in 53 normal 7- to 15-year-old children during 6 degrees and 12 degrees/second visual pursuit. In addition to smooth pursuit gain and saccadic frequency, measures of mean amplitude per second are introduced to facilitate comparison across age and target speed. RESULTS: The 6 degrees/second task is found to be easier than the 12 degrees/second task. Age is correlated with smooth pursuit system performance but not saccadic system performance during 12 degrees/second pursuit. No measure correlates with age during 6 degrees/second pursuit. CONCLUSIONS: Eye movements improve as children age. The future use of smooth pursuit eye movements to study children and adolescents with and at risk for schizophrenia must control for developmental changes.

Adolescent↗

Clinical relevance of accuracy of pedicle screw placement. A computed tomographic-supported analysis.

STUDY DESIGN: The location of pedicle screws (n = 244) and the increase in the pedicle diameter were determined by computed tomography after screw removal in 50 patients with 360 degrees lumbar fusions. The neurologic findings were examined before and after surgery. OBJECTIVES: To evaluate the correlation between the accuracy of pedicle screw placement and preoperative and postoperative neurologic findings. SUMMARY OF BACKGROUND DATA: Incorrect placement of pedicle screws that was detected by computed tomography has been published in several studies. Simultaneous pathologic neurologic deficits are thought to be created by an eccentric screw track. METHODS: Two observers controlled the screw tracts and pedicle diameters. The results were compared with preoperative and postoperative neurologic findings. RESULTS: Fifty-nine percent (144 of 244) of screws were placed centrally in the pedicle. More than half of the eccentric screws (100, 41%; medial 79, 32.4%; lateral 21, 8.6%) penetrated the pedicle wall less than 2 mm (51; 20.9%). In only one patient (0.5%) a radicular irritation was found without objective electrophysiologic correlation when the screw was more than 6 mm medial to the pedicle wall. After screw removal, an insignificant increase in the size of the pedicle diameter in L1-S1 was noted. CONCLUSIONS: Experienced surgeons implant pedicle screws with an accuracy of approximately 80%. The accuracy could be improved by using image-guided insertion equipment. The neurologic symptoms are rarely influenced by an eccentric pedicle screw tract even if penetration of the pedicle wall is more than 6 mm. The results stress the importance of preoperative planning (pedicle diameter, pedicle angle, screw length) when implanting transpedicular fixators.

Bone Screws↗

Automated tracking of gene expression in individual cells and cell compartments.

Many intracellular signal transduction processes involve the reversible translocation from the cytoplasm to the nucleus of transcription factors. The advent of fluorescently tagged protein derivatives has revolutionized cell biology, such that it is now possible to follow the location of such protein molecules in individual cells in real time. However, the quantitative analysis of the location of such proteins in microscopic images is very time consuming. We describe CellTracker, a software tool designed for the automated measurement of the cellular location and intensity of fluorescently tagged proteins. CellTracker runs in the MS Windows environment, is freely available (at http://www.dbkgroup.org/celltracker/), and combines automated cell tracking methods with powerful image-processing algorithms that are optimized for these applications. When tested in an application involving the nuclear transcription factor NF-kappaB, CellTracker is competitive in accuracy with the manual human analysis of such images but is more than 20 times faster, even on a small task where human fatigue is not an issue. This will lead to substantial benefits for time-lapse-based high-content screening.

Animals↗

Spirochaete-like swimming mode of Campylobacter jejuni in a viscous environment.

The swimming patterns of Campylobacter jejuni in environments of low and high viscosity were examined by a video tracking method. In media of low viscosity, C. jejuni swam with an average velocity of 39.3 microm/s with frequent changes in direction. The velocity of C. jejuni increased in a medium at a little higher viscosity than that of a low viscosity buffer. In addition to this, C. jejuni showed a second increase of velocity in media of a high viscosity of about 40 centipoise. The swimming patterns at these two velocity peaks were compared. In the second peak the wild-type C. jejuni exhibited repeated back and forth swimming patterns which were more like the swimming pattern of spirochaetes than that of monotrichous bacteria. Thus C. jejuni may presumably use a different swimming mode in media of high viscosity than the original swimming mode mediated by the propelling force of the flagella. The spiral shape of this bacterium like that of spirochaetes may strongly influence its swimming ability in media of high viscosity such as the mucous layer of the intestinal tract.

Animals↗

Grain dynamics in a two-dimensional granular flow.

We have used particle tracking methods to study the dynamics of individual balls comprising a granular flow in a small-angle two-dimensional funnel. We statistically analyze many ball trajectories to examine the mechanisms of shock propagation. In particular, we study the creation of, and interactions between, shock waves. We also investigate the role of granular temperature and draw parallels to traffic flow dynamics.

Journal Article↗

Explicit symplectic integrator for s-dependent static magnetic field.

This paper reports our recent work on explicit symplectic integration techniques for the charged particle motion in an s-dependent static magnetic field. Using the extended phase space, symplectic integrators can be developed for Hamiltonians with or without the paraxial approximation using either the space or time as an independent variable. This work extends the successful element-by-element tracking method for studying single-particle nonlinear dynamics to a set of s-dependent magnetic elements. Important applications of this work include the studies of the charged particle dynamics in a storage ring with various insertion devices, superconducting magnets, large aperture magnets with significant fringe fields, and solenoid magnets in the interaction region. Consequently, this work is expected to make an impact on design and optimal operation of existing and future light source rings and high energy physics accelerators.

Journal Article↗

Anomalous diffusion in living yeast cells.

The viscoelastic properties of the cytoplasm of living yeast cells were investigated by studying the motion of lipid granules naturally occurring in the cytoplasm. A large frequency range of observation was obtained by a combination of video-based and laser-based tracking methods. At time scales from 10(-4) to 10(2) s, the granules typically perform subdiffusive motion with characteristics different from previous measurements in living cells. This subdiffusive behavior is thought to be due to the presence of polymer networks and membranous structures in the cytoplasm. Consistent with this hypothesis, we observe that the motion becomes less subdiffusive upon actin disruption.

Actins↗

Quantifying motion in video recordings of neonatal seizures by robust motion trackers based on block motion models.

This paper introduces a methodology for the development of robust motion trackers for video based on block motion models. According to this methodology, the motion of a site between two successive frames is estimated by minimizing an error function defined in terms of the intensities at these frames. The proposed methodology is used to develop robust motion trackers that rely on fractional block motion models. The motion trackers developed in this paper are utilized to extract motor activity signals from video recordings of neonatal seizures. The experimental results reveal that the proposed motion trackers are more accurate and reliable than existing motion tracking methods relying on pure translation and affine block motion models.

Algorithms↗

Tracking tremor frequency in spike trains using the extended Kalman smoother.

Tremor is one of the most disabling symptoms in patients with many movement disorders including Parkinson's disease (PD) and essential tremor (ET). Neural tremor manifests itself as a quasi-periodic fluctuation of the firing rate. We describe a frequency tracking method based on the extended Kalman smoother (EKS) to estimate the instantaneous tremor frequency (ITF) exhibited in binary spike trains detected from neural recordings. Simulation results demonstrate that the EKS frequency tracker can estimate the ITF accurately, even though the signal of interest is not sinusoidal and the noise is not Gaussian. The EKS frequency tracker can obtain a normalized mean squared error (NMSE) as low as 0.1 and performs much better than the conventional approach based on the Hilbert transform.

Action Potentials↗

Motion estimation in ultrasound images using time domain cross correlation with prior estimates.

In this paper we introduce a new speckle tracking method that is based on the standard time-domain cross correlation strain estimation (TDE). We call this method time-domain cross-correlation with prior estimates (TDPE), because it uses prior displacement estimates of neighboring windows to speed up computation. TDPE has all the advantages of TDE, but is much faster. Simulations, as well as experiments with phantoms and tissue, indicate that TDPE is capable of reliably estimating tissue displacement and strain over a large range of displacements in real time. The computational efficiency of TDPE is compared with current time-efficient methods that have been used in real time strain imaging systems. The results show that TDPE is the most time efficient algorithm to date, and is roughly 10 times faster than the TDE. The implementation of TDPE on an Ultrasonix RP500 ultrasound machine runs at 30 fps for strain images of 16000 pixels.

Algorithms↗

Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces.

Cell migrations and deformations play essential roles in biological processes, such as parasite invasion, immune response, embryonic development, and cancer. We describe a fully automatic segmentation and tracking method designed to enable quantitative analyses of cellular shape and motion from dynamic three-dimensional microscopy data. The method uses multiple active surfaces with or without edges, coupled by a penalty for overlaps, and a volume conservation constraint that improves outlining of cell/cell boundaries. Its main advantages are robustness to low signal-to-noise ratios and the ability to handle multiple cells that may touch, divide, enter, or leave the observation volume. We give quantitative validation results based on synthetic images and show two examples of applications to real biological data.

Algorithms↗

A field model for human detection and tracking.

The large shape variability and partial occlusions challenge most object detection and tracking methods for nonrigid targets such as pedestrians. This paper presents a new approach based on a two-layer statistical field model that characterizes the prior of the complex shape variations as a Boltzmann distribution and embeds this prior and the complex image likelihood into a Markov field. A probabilistic variational analysis of this model reveals a set of fixed-point equations characterizing the equilibrium of the field. It leads to computationally efficient methods for calculating the image likelihood and for training the model. Based on that, effective algorithms for detecting nonrigid objects are developed. This new approach has several advantages. First, it is intrinsically suitable for capturing local nonrigidity. In addition, due to the distributed likelihood, this approach is robust to partial occlusions. Moreover, the two-layer structure provides large flexibility of modeling the image observations, which makes the new method robust to clutters. Extensive experiments demonstrate its effectiveness.

Algorithms↗