Real-space processing of helical filaments in SPARX.

We present a major revision of the iterative helical real-space refinement (IHRSR) procedure and its implementation in the SPARX single particle image processing environment. We built on over a decade of experience with IHRSR helical structure determination and we took advantage of the flexible SPARX infrastructure to arrive at an implementation that offers ease of use, flexibility in designing helical structure determination strategy, and high computational efficiency. We introduced the 3D projection matching code which now is able to work with non-cubic volumes, the geometry better suited for long helical filaments, we enhanced procedures for establishing helical symmetry parameters, and we parallelized the code using distributed memory paradigm. Additional features include a graphical user interface that facilitates entering and editing of parameters controlling the structure determination strategy of the program. In addition, we present a novel approach to detect and evaluate structural heterogeneity due to conformer mixtures that takes advantage of helical structure redundancy.

Automated detection of videotaped neonatal seizures based on motion segmentation methods.

OBJECTIVE: This study was aimed at the development of a seizure detection system by training neural networks using quantitative motion information extracted by motion segmentation methods from short video recordings of infants monitored for seizures. METHODS: The motion of the infants' body parts was quantified by temporal motion strength signals extracted from video recordings by motion segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by direct thresholding, by clustering of the pixel velocities, and by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The computational tools and procedures developed for automated seizure detection were tested and evaluated on 240 short video segments selected and labeled by physicians from a set of video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). RESULTS: The experimental study described in this paper provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. Depending on the decision scheme used for interpreting the responses of the trained neural networks, the best neural networks exhibited sensitivity above 90% or specificity above 90%. CONCLUSIONS: The best among the motion segmentation methods developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of this phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion trajectory signals produced by motion tracking methods. SIGNIFICANCE: A video system based upon automated analysis potentially offers a number of advantages. Infants who are at risk for seizures could be monitored continuously using relatively inexpensive and non-invasive video techniques that supplement direct observation by nursery personnel. This would represent a major advance in seizure surveillance and offers the possibility for earlier identification of potential neurological problems and subsequent intervention.

Quantifying motion in video recordings of neonatal seizures by regularized optical flow methods.

This paper presents the development of regularized optical flow computation methods and an evaluation of their performance in the extraction of quantitative motion information from video recordings of neonatal seizures. A general formulation of optical flow computation is presented and a mathematical framework for the development of practical tools for computing optical flow is outlined. In addition, this paper proposes an alternative formulation of the optical flow problem that relies on a discrete approximation of a family of quadratic functionals. These regularized optical flow computation methods are used to extract motion strength signals from video recordings of neonatal seizures.

Dynamic frame pairing in real-time freehand elastography.

Quasi-static ultrasound (US) elastography is now a well-established technique that involves acquiring US (RF/envelope) signals from an imaging plane before and after a small quasi-static compression to form axial strain elastograms (ASE). The image quality of the ASEs is a function of the applied axial strain. This relationship was extensively investigated and formalized in terms of strain filter in the literature. Most of the work in elastography formed elastograms by choosing pre- and post-compression frames separated by a desired compression strain. Although this approach is feasible in simulations and in vitro/in vivo experiments that involve controlled compression, it has been a challenge to do this during freehand compression in real time. In this work, we describe a one-prediction-one- correction method that dynamically selects pre- and post- compression frames to form an elastogram, based on the applied axial strain level. We validate the method using controlled compression experiments on phantoms and compare the performance of the dynamic frame pairing method against successive-frame pairing method in terms of the contrast-to-noise ratio (CNRe). Further, we demonstrate the advantages of the new method with the help of freehand acquired data from phantom experiments and in vivo breast data. The results demonstrate that the frame-pairing identified by the dynamic method matched the frame pairing that was designed to yield an applied axial strain of ~1%. The CNRe obtained by the traditional approach varied from as low as ~5 to as high as ~25, depending on the choice of skip number and compression rate. However, the dynamic frame pairing method provided elastograms with a CNRe that was consistently around ~20, irrespective of the compression rate. The results from analysis of 22 in vivo breast data demonstrated that the dynamic pairing method generated elastograms such that the frame-average axial strain (FAAS) of each frame in the cine-loop is consistently ~1% (0.011 ± 0.001).

Effect of cocaine on structural changes in brain: MRI volumetry using tensor-based morphometry.

Magnetic resonance imaging (MRI) was performed in cocaine-dependent subjects to determine the structural changes in brain compared to non-drug using controls. Cocaine-dependent subjects and controls were carefully screened to rule out brain pathology of undetermined origin. Magnetic resonance images were analyzed using tensor-based morphometry (TBM) and voxel-based morphometry (VBM) without and with modulation to adjust for volume changes during normalization. For TBM analysis, unbiased atlases were generated using two different inverse consistent and diffeomorphic nonlinear registration techniques. Two different control groups were used for generating unbiased atlases. Independent of the nonlinear registration technique and normal cohorts used for creating the unbiased atlases, our analysis failed to detect any statistically significant effect of cocaine on brain volumes. These results show that cocaine-dependent subjects do not show differences in regional brain volumes compared to non-drug using controls.

Symmetric inverse consistent nonlinear registration driven by mutual information.

A nonlinear viscoelastic image registration algorithm based on the demons paradigm and incorporating inverse consistent constraint (ICC) is implemented. An inverse consistent and symmetric cost function using mutual information (MI) as a similarity measure is employed. The cost function also includes regularization of transformation and inverse consistent error (ICE). The uncertainties in balancing various terms in the cost function are avoided by alternatively minimizing the similarity measure, the regularization of the transformation, and the ICE terms. The diffeomorphism of registration for preventing folding and/or tearing in the deformation is achieved by the composition scheme. The quality of image registration is first demonstrated by constructing brain atlas from 20 adult brains (age range 30-60). It is shown that with this registration technique: (1) the Jacobian determinant is positive for all voxels and (2) the average ICE is around 0.004 voxels with a maximum value below 0.1 voxels. Further, the deformation-based segmentation on Internet Brain Segmentation Repository, a publicly available dataset, has yielded high Dice similarity index (DSI) of 94.7% for the cerebellum and 74.7% for the hippocampus, attesting to the quality of our registration method.

Improved cerebellar tissue classification on magnetic resonance images of brain.

PURPOSE: To develop and implement a method for improved cerebellar tissue classification on the MRI of brain by automatically isolating the cerebellum prior to segmentation. MATERIALS AND METHODS: Dual fast spin echo (FSE) and fluid attenuation inversion recovery (FLAIR) images were acquired on 18 normal volunteers on a 3 T Philips scanner. The cerebellum was isolated from the rest of the brain using a symmetric inverse consistent nonlinear registration of individual brain with the parcellated template. The cerebellum was then separated by masking the anatomical image with individual FLAIR images. Tissues in both the cerebellum and rest of the brain were separately classified using hidden Markov random field (HMRF), a parametric method, and then combined to obtain tissue classification of the whole brain. The proposed method for tissue classification on real MR brain images was evaluated subjectively by two experts. The segmentation results on Brainweb images with varying noise and intensity nonuniformity levels were quantitatively compared with the ground truth by computing the Dice similarity indices. RESULTS: The proposed method significantly improved the cerebellar tissue classification on all normal volunteers included in this study without compromising the classification in remaining part of the brain. The average similarity indices for gray matter (GM) and white matter (WM) in the cerebellum are 89.81 (+/-2.34) and 93.04 (+/-2.41), demonstrating excellent performance of the proposed methodology. CONCLUSION: The proposed method significantly improved tissue classification in the cerebellum. The GM was overestimated when segmentation was performed on the whole brain as a single object.

Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.

Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For group analysis of atrophy, an unbiased atlas was constructed from 20 normal brains. The MS brain images were co-registered with the unbiased atlas using a symmetric inverse consistent nonlinear registration. These studies demonstrate significant atrophy of thalamus, caudate nucleus, and putamen even at a modest clinical disability, as assessed by the expanded disability status score (EDSS). A significant correlation between atrophy and EDSS was observed for different DGM structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35 x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x 10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(-7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10); caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)), and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More severe atrophy was observed mainly in thalamus at higher EDSS. These studies appear to suggest a link between the white matter damage and DGM atrophy in MS.

Mutual information driven inverse consistent nonlinear registration.

A fully symmetric nonlinear viscoelastic image registration method, under the demons paradigm is developed. The symmetric cost function includes mutual information (MI) as a similarity measure, regularization of the transformation, and inverse consistent constraint (ICC). Alternative strategy is used to minimize the divergent terms with different properties in the cost function to avoid the difficulties in balancing between the performance of registration and low Inverse Consistency Error (ICE). The diffeomorphism of the registration is achieved by the composition scheme. Validation studies show that the proposed method provides sub-voxel ICE. The improvement of registration performance is also demonstrated.

Information measures-based intensity standardization of MRI.

Scan-to-scan intensity variation, even with the same imaging modality, affects a number of intensity-based image processing methods such as feature map based segmentation and non-rigid registration techniques that minimize sum of squared differences (SSD). Current intensity standardization techniques based on either percentile alignment or polynomial mapping suffer from a number of limitations. We present a novel intensity standardization techniques that exploits information measures obtained from the images. A probability similarity measure obtained by using polynomial mapping with Kullback-Leibler (KL) divergence is used for intensity standardization of pair-wise magnetic resonance (MR) images. For standardization of group-wise MR images, polynomial mapping with minimum entropy as a group probability similarity measure is used for attaining standardization in a group to attain common feature without bias. Our method is more flexible, particularly in mapping high intensity regions, such as lesions, since it does not set any hard limit. The mappings were realized through optimization of cost functions with Powell's search. The performance of the proposed method is demonstrated for non-rigid registration and feature map-based image segmentation of MR brain images.

Automated detection of videotaped neonatal seizures of epileptic origin.

PURPOSE: This study aimed at the development of a seizure-detection system by training neural networks with quantitative motion information extracted from short video segments of neonatal seizures of the myoclonic and focal clonic types and random infant movements. METHODS: The motion of the infants' body parts was quantified by temporal motion-strength signals extracted from video segments by motion-segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The motion of the infants' body parts also was quantified by temporal motion-trajectory signals extracted from video recordings by robust motion trackers based on block-motion models. These motion trackers were developed to adjust autonomously to illumination and contrast changes that may occur during the video-frame sequence. Video segments were represented by quantitative features obtained by analyzing motion-strength and motion-trajectory signals in both the time and frequency domains. Seizure recognition was performed by conventional feed-forward neural networks, quantum neural networks, and cosine radial basis function neural networks, which were trained to detect neonatal seizures of the myoclonic and focal clonic types and to distinguish them from random infant movements. RESULTS: The computational tools and procedures developed for automated seizure detection were evaluated on a set of 240 video segments of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). Regardless of the decision scheme used for interpreting the responses of the trained neural networks, all the neural network models exhibited sensitivity and specificity>90%. For one of the decision schemes proposed for interpreting the responses of the trained neural networks, the majority of the trained neural-network models exhibited sensitivity>90% and specificity>95%. In particular, cosine radial basis function neural networks achieved the performance targets of this phase of the project (i.e., sensitivity>95% and specificity>95%). CONCLUSIONS: The best among the motion segmentation and tracking methods developed in this study produced quantitative features that constitute a reliable basis for detecting neonatal seizures. The performance targets of this phase of the project were achieved by combining the quantitative features obtained by analyzing motion-strength signals with those produced by analyzing motion-trajectory signals. The computational procedures and tools developed in this study to perform off-line analysis of short video segments will be used in the next phase of this project, which involves the integration of these procedures and tools into a system that can process and analyze long video recordings of infants monitored for seizures in real time.

Computerized motion analysis of videotaped neonatal seizures of epileptic origin.

PURPOSE: The main objective of this research is the development of automated video processing and analysis procedures aimed at the recognition and characterization of the types of neonatal seizures. The long-term goal of this research is the integration of these computational procedures into the development of a stand-alone automated system that could be used as a supplement in the neonatal intensive care unit (NICU) to provide 24-h per day noninvasive monitoring of infants at risk for seizures. METHODS: We developed and evaluated a variety of computational tools and procedures that may be used to carry out the three essential tasks involved in the development of a seizure recognition and characterization system: the extraction of quantitative motion information from video recordings of neonatal seizures in the form of motion-strength and motor-activity signals, the selection of quantitative features that convey some unique behavioral characteristics of neonatal seizures, and the training of artificial neural networks to distinguish neonatal seizures from random infant behaviors and to differentiate between myoclonic and focal clonic seizures. RESULTS: The methods were tested on a set of 240 video recordings of 43 patients exhibiting myoclonic seizures (80 cases), focal clonic seizures (80 cases), and random infant movements (80 cases). The outcome of the experiments verified that optical- flow methods are promising computational tools for quantifying neonatal seizures from video recordings in the form of motion-strength signals. The experimental results also verified that the robust motion trackers developed in this study outperformed considerably the motion trackers based on predictive block matching in terms of both reliability and accuracy. The quantitative features selected from motion-strength and motor-activity signals constitute a satisfactory representation of neonatal seizures and random infant movements and seem to be complementary. Such features lead to trained neural networks that exhibit performance levels exceeding the initial goals of this study, the sensitivity goal being >or=80% and the specificity goal being >or=90%. CONCLUSIONS: The outcome of this experimental study provides strong evidence that it is feasible to develop an automated system for the recognition and characterization of the types of neonatal seizures based on video recordings. This will be accomplished by enhancing the accuracy and improving the reliability of the computational tools and methods developed during the course of the study outlined here.