In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces.

BACKGROUND: Hydrocephalus, the pathological expansion of the cerebrospinal fluid (CSF)-filled cerebral ventricles, is a common, deadly disease. In the adult, cardiac and respiratory forces are the main drivers of CSF flow within the brain ventricular system to remove waste and deliver nutrients. In contrast, the mechanics and functions of CSF circulation in the embryonic brain are poorly understood. This is primarily due to the lack of model systems and imaging technology to study these early time points. Here, we studied embryos of the vertebrate Xenopus with optical coherence tomography (OCT) imaging to investigate in vivo ventricular and neural development during the onset of CSF circulation. METHODS: Optical coherence tomography (OCT), a cross-sectional imaging modality, was used to study developing Xenopus tadpole brains and to dynamically detect in vivo ventricular morphology and CSF circulation in real-time, at micrometer resolution. The effects of immobilizing cilia and cardiac ablation were investigated. RESULTS: In Xenopus, using OCT imaging, we demonstrated that ventriculogenesis can be tracked throughout development until the beginning of metamorphosis. We found that during Xenopus embryogenesis, initially, CSF fills the primitive ventricular space and remains static, followed by the initiation of the cilia driven CSF circulation where ependymal cilia create a polarized CSF flow. No pulsatile flow was detected throughout these tailbud and early tadpole stages. As development progressed, despite the emergence of the choroid plexus in Xenopus, cardiac forces did not contribute to the CSF circulation, and ciliary flow remained the driver of the intercompartmental bidirectional flow as well as the near-wall flow. We finally showed that cilia driven flow is crucial for proper rostral development and regulated the spatial neural cell organization. CONCLUSIONS: Our data support a paradigm in which Xenopus embryonic ventriculogenesis and rostral brain development are critically dependent on ependymal cilia-driven CSF flow currents that are generated independently of cardiac pulsatile forces. Our work suggests that the Xenopus ventricular system forms a complex cilia-driven CSF flow network which regulates neural cell organization. This work will redirect efforts to understand the molecular regulators of embryonic CSF flow by focusing attention on motile cilia rather than other forces relevant only to the adult.

Local resolution estimates of cryoEM reconstructions.

The field of cryoEM has quickly advanced in last years with the new biochemical, technological, methodological and computational developments. It has allowed significant progresses in Structural Biology, typically reaching quasi-atomic resolutions in the reconstructed maps. However, this rapid advance has also generated new questions relevant to resolution estimates. The global resolution metrics and their criteria have been deeply discussed in the last decade, but despite that, it remains as an important issue in the field. Recently, the introduction of local resolution measurements has changed how cryoEM reconstructions are interpreted, providing information about the existence of heterogeneity, flexibility, and angular assignment errors, and using it as a tool to aid in modeling. In this review we revisit the concept of local resolution and the different algorithms in the current state of the art. However, the concept of local resolution is not uniquely defined, and each implementation measures different features. This may lead to inappropriate interpretation of local resolution maps. Hence, a set of good practices is provided in this review to avoid misleading and over-interpretation of the reconstructions.

Segmentation of 3D radio frequency echocardiography using a spatio-temporal predictor.

This paper presents an algorithm for segmenting left ventricular endocardial boundaries from RF ultrasound. Our method incorporates a computationally efficient linear predictor that exploits short-term spatio-temporal coherence in the RF data. Segmentation is achieved jointly using an independent identically distributed (i.i.d.) spatial model for RF intensity and a multiframe conditional model that relates neighboring frames in the image sequence. Segmentation using the RF data overcomes challenges due to image inhomogeneities often amplified in B-mode segmentation and provides geometric constraints for RF phase-based speckle tracking. The incorporation of multiple frames in the conditional model significantly increases the robustness and accuracy of the algorithm. Results are generated using between 2 and 5 frames of RF data for each segmentation and are validated by comparison with manual tracings and automated B-mode boundary detection using standard (Chan and Vese-based) level sets on echocardiographic images from 27 3D sequences acquired from six canine studies.

PathMaster: content-based cell image retrieval using automated feature extraction.

OBJECTIVE: Currently, when cytopathology images are archived, they are typically stored with a limited text-based description of their content. Such a description inherently fails to quantify the properties of an image and refers to an extremely small fraction of its information content. This paper describes a method for automatically indexing images of individual cells and their associated diagnoses by computationally derived cell descriptors. This methodology may serve to better index data contained in digital image databases, thereby enabling cytologists and pathologists to cross-reference cells of unknown etiology or nature. DESIGN: The indexing method, implemented in a program called PathMaster, uses a series of computer-based feature extraction routines. Descriptors of individual cell characteristics generated by these routines are employed as indexes of cell morphology, texture, color, and spatial orientation. MEASUREMENTS: The indexing fidelity of the program was tested after populating its database with images of 152 lymphocytes/lymphoma cells captured from lymph node touch preparations stained with hematoxylin and eosin. Images of "unknown" lymphoid cells, previously unprocessed, were then submitted for feature extraction and diagnostic cross-referencing analysis. RESULTS: PathMaster listed the correct diagnosis as its first differential in 94 percent of recognition trials. In the remaining 6 percent of trials, PathMaster listed the correct diagnosis within the first three "differentials." CONCLUSION: PathMaster is a pilot cell image indexing program/search engine that creates an indexed reference of images. Use of such a reference may provide assistance in the diagnostic/prognostic process by furnishing a prioritized list of possible identifications for a cell of uncertain etiology.

Shape-based nonrigid correspondence with application to heart motion analysis.

A common problem in many biomedical imaging studies is that of finding a correspondence between two plane curves which aligns their shapes. A mathematical formulation and solutions to this problem is proposed in this paper. The formulation exhibits desirable properties. It allows for one-to-one as well as non-one-to-one correspondences, it consistently compares shape, even in nonrigid situations, and it is completely symmetric with respect to the two curves. A numerical implementation of the algorithm for finding the optimal correspondence is also reported. The algorithm is used to estimate nonrigid motion of the endocardium in MRI image sequences of normal and post-infarct dog hearts. The return error (the difference between the starting and ending positions of a point) is used as a performance measure to evaluate the technique. Since heart motion is periodic, the return error is a measure of consistency of the algorithm. Preliminary applications to other data sets are reported as well.

Consistency and stability of active contours with Euclidean and non-Euclidean arc lengths.

External energies of active contours are often formulated as Euclidean arc length integrals. In this paper, we show that such formulations are biased. By this we mean that the minimum of the external energy does not occur at an image edge. In addition, we also show that for certain forms of external energy the active contour is unstable--when initialized at the true edge, the contour drifts away and becomes jagged. Both of these phenomena are due to the use of Euclidean arc length integrals. We propose a non-Euclidean arc length which eliminates these problems. This requires a reformulation of active contours where a single external energy function is replaced by a sequence of energy functions and the contour evolves as an integral curve of the gradient of these energies. The resulting active contour not only has unbiased external energy, but is also more controllable. Experimental evidence is provided in support of the theoretical claims.

Medical image databases: a content-based retrieval approach.

Information contained in medical images differs considerably from that residing in alphanumeric format. The difference can be attributed to four characteristics: (1) the semantics of medical knowledge extractable from images is imprecise; (2) image information contains form and spatial data, which are not expressible in conventional language; (3) a large part of image information is geometric; (4) diagnostic inferences derived from images rest on an incomplete, continuously evolving model of normality. This paper explores the differentiating characteristics of text versus images and their impact on design of a medical image database intended to allow content-based indexing and retrieval. One strategy for implementing medical image databases is presented, which employs object-oriented iconic queries, semantics by association with prototypes, and a generic schema.

Deformable 2-D template matching using orthogonal curves.

In this paper a new formulation of the two-dimensional (2-D) deformable template matching problem is proposed. It uses a lower-dimensional search space than conventional methods by precomputing extensions of the deformable template along orthogonal curves. The reduction in search space allows the use of dynamic programming to obtain globally optimal solutions and reduces the sensitivity of the algorithm to initial placement of the template. Further, the technique guarantees that the result is a curve which does not collapse to a point in the absence of strong image gradients and is always nonself intersecting. Examples of the use of the technique on real-world images and in simulations at low signal-to-noise ratios (SNR's) are also provided.

Medical image collection indexing: shape-based retrieval using KD-trees.

The capacity to retrieve images containing objects with shapes similar to a query shape is desirable in medical image databases. We propose a similarity measure and an indexing mechanism for non-rigid comparison of shape which adds this capability to image databases. The (dis-)similarity measure is based on the observations that: (1) the geometry of the same organ in different subjects is not related by a strictly rigid transformation; and (2) the orientation of the organ plays a key role in comparing shape. We propose a similarity measure that computes a non-rigid mapping between curves and uses this mapping to compare oriented shape. We also show how KD-trees can index curves so that retrieval with our similarity measure is efficient. Experiments with real-world data from a database of magnetic resonance images are provided.

Location and geometric description of carpal bones in CT images.

The carpal regions of ten cadaver extremities were imaged by CT. The images were combined into a 3-dimensional model of the carpus using a technique based on a dynamic programming algorithm to find an optimal estimate of the location of the bone boundaries in the CT images. The resulting set of surface points on each bone was used to compute volumes and principal and antipodal axes for the bones. A spatial coordinate system was established based on the positions of the centroids of three bones in the distal carpal row. The angular orientations of all carpal bones were determined with respect to this system. The principal axes for the same bone among ten wrist specimens proved to be more widely dispersed than the antipodal axes for the same bones. The antipodal axes also correspond more closely to an intuitive notion of the "longest axis" of the bones. We conclude that the antipodal axis is a more reliable and useful measure of bone orientation than the principal axis.