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Biomedical subjects

Michael Unser

Publications and source records attributed to Michael Unser.

At least 19 recordsLinked to original sources

User-friendly semiautomated assembly of accurate image mosaics in microscopy.

We present a semiautomated software solution to the problem of extending the lateral field of view of a classical microscope. The initial requirements are a set of overlapping images, along with their user-provided coarse mosaic. Our solution then refines this initial mosaic in a fully automatic fashion. We rely on a highly accurate registration engine to perform the pairwise registration of the individual images, and on an efficient strategy to minimize the amount of computations while maintaining the highest possible global quality. We describe these ingredients, which we make available as a free multiplatform user-friendly software package. We also highlight why and how the specific aspects of the present microscopy application differ from those encountered while creating more common mosaics such as panoramas. Finally, we present experimental results that illustrate and validate our method on a real biological sample. We conclude by showing that we are able to reach subpixel accuracy.

Algorithms↗

Wavelet-based multi-resolution statistics for optical imaging signals: Application to automated detection of odour activated glomeruli in the mouse olfactory bulb.

Optical imaging techniques offer powerful solutions to capture brain networks processing in animals, especially when activity is distributed in functionally distinct spatial domains. Despite the progress in imaging techniques, the standard analysis procedures and statistical assessments for this type of data are still limited. In this paper, we perform two in vivo non-invasive optical recording techniques in the mouse olfactory bulb, using a genetically expressed activity reporter fluorescent protein (synaptopHfluorin) and intrinsic signals of the brain. For both imaging techniques, we show that the odour-triggered signals can be accurately parameterized using linear models. Fitting the models allows us to extract odour specific signals with a reduced level of noise compared to standard methods. In addition, the models serve to evaluate statistical significance, using a wavelet-based framework that exploits spatial correlation at different scales. We propose an extension of this framework to extract activation patterns at specific wavelet scales. This method is especially interesting to detect the odour inputs that segregate on the olfactory bulb in small spherical structures called glomeruli. Interestingly, with proper selection of wavelet scales, we can isolate significantly activated glomeruli and thus determine the odour map in an automated manner. Comparison against manual detection of glomeruli shows the high accuracy of the proposed method. Therefore, beyond the advantageous alternative to the existing treatments of optical imaging signals in general, our framework propose an interesting procedure to dissect brain activation patterns on multiple scales with statistical control.

Algorithms↗

3D reconstruction and comparison of shapes of DNA minicircles observed by cryo-electron microscopy.

We use cryo-electron microscopy to compare 3D shapes of 158 bp long DNA minicircles that differ only in the sequence within an 18 bp block containing either a TATA box or a catabolite activator protein binding site. We present a sorting algorithm that correlates the reconstructed shapes and groups them into distinct categories. We conclude that the presence of the TATA box sequence, which is believed to be easily bent, does not significantly affect the observed shapes.

Algorithms↗

Unsupervised image classification of medical ultrasound data by multiresolution elastic registration.

Thousands of medical images are saved in databases every day and the need for algorithms able to handle such data in an unsupervised manner is steadily increasing. The classification of ultrasound images is an outstandingly difficult task, due to the high noise level of these images. We present a detailed description of an algorithm based on multiscale elastic registration capable of unsupervised, landmark-free classification of cardiac ultrasound images into their respective views (apical four chamber, two chamber, parasternal long axis and short axis views). We validated the algorithm with 90 unselected, consecutive echocardiographic images recorded during daily clinical work. When the two visually very similar apical views (four chamber and two chamber) are combined into one class, we obtained a 93.0% correct classification (chi2 = 123.8, p < 0.0001, cross-validation 93.0%; chi2 = 131.1, p < 0.0001). Classification into the 4 classes reached a 90.0% correct classification (chi2 = 205.4, p < 0.0001, cross-validation 82.2%; chi2 = 165.9, p < 0.0001).

Algorithms↗

3-D shape estimation of DNA molecules from stereo cryo-electron micro-graphs using a projection-steerable snake.

We introduce a three-dimensional (3-D) parametric active contour algorithm for the shape estimation of DNA molecules from stereo cryo-electron micrographs. We estimate the shape by matching the projections of a 3-D global shape model with the micrographs; we choose the global model as a 3-D filament with a B-spline skeleton and a specified radial profile. The active contour algorithm iteratively updates the B-spline coefficients, which requires us to evaluate the projections and match them with the micrographs at every iteration. Since the evaluation of the projections of the global model is computationally expensive, we propose a fast algorithm based on locally approximating it by elongated blob-like templates. We introduce the concept of projection-steerability and derive a projection-steerable elongated template. Since the two-dimensional projections of such a blob at any 3-D orientation can be expressed as a linear combination of a few basis functions, matching the projections of such a 3-D template involves evaluating a weighted sum of inner products between the basis functions and the micrographs. The weights are simple functions of the 3-D orientation and the inner-products are evaluated efficiently by separable filtering. We choose an internal energy term that penalizes the average curvature magnitude. Since the exact length of the DNA molecule is known a priori, we introduce a constraint energy term that forces the curve to have this specified length. The sum of these energies along with the image energy derived from the matching process is minimized using the conjugate gradients algorithm. We validate the algorithm using real, as well as simulated, data and show that it performs well.

Algorithms↗

Polyharmonic smoothing splines and the multidimensional Wiener filtering of fractal-like signals.

Motivated by the fractal-like behavior of natural images, we develop a smoothing technique that uses a regularization functional which is a fractional iterate of the Laplacian. This type of functional was initially introduced by Duchon for the approximation of nonuniformily sampled, multidimensional data. He proved that the general solution is a smoothing spline that is represented by a linear combination of radial basis functions (RBFs). Unfortunately, this is tedious to implement for images because of the poor conditioning of RBFs and their lack of decay. Here, we present a much more efficient method for the special case of a uniform grid. The key idea is to express Duchon's solution in a fractional polyharmonic B-spline basis that spans the same space as the RBFs. This allows us to derive an algorithm where the smoothing is performed by filtering in the Fourier domain. Next, we prove that the above smoothing spline can be optimally tuned to provide the MMSE estimation of a fractional Brownian field corrupted by white noise. This is a strong result that not only yields the best linear filter (Wiener solution), but also the optimal interpolation space, which is not bandlimited. It also suggests a way of using the noisy data to identify the optimal parameters (order of the spline and smoothing strength), which yields a fully automatic smoothing procedure. We evaluate the performance of our algorithm by comparing it against an oracle Wiener filter, which requires the knowledge of the true noiseless power spectrum of the signal. We find that our approach performs almost as well as the oracle solution over a wide range of conditions.

Algorithms↗

Elastic registration of biological images using vector-spline regularization.

We present an elastic registration algorithm for the alignment of biological images. Our method combines and extends some of the best techniques available in the context of medical imaging. We express the deformation field as a B-spline model, which allows us to deal with a rich variety of deformations. We solve the registration problem by minimizing a pixelwise mean-square distance measure between the target image and the warped source. The problem is further constrained by way of a vector-spline regularization which provides some control over two independent quantities that are intrinsic to the deformation: its divergence, and its curl. Our algorithm is also able to handle soft landmark constraints, which is particularly useful when parts of the images contain very little information or when its repartition is uneven. We provide an optimal analytical solution in the case when only landmarks and smoothness considerations are taken into account. We have applied our approach to perform the elastic registration of images such as electrophoretic gels and fly embryos. The validation of the results by experts has been favorable in all cases.

Algorithms↗

Myocardial motion analysis from B-mode echocardiograms.

The quantitative assessment of cardiac motion is a fundamental concept to evaluate ventricular malfunction. We present a new optical-flow-based method for estimating heart motion from two-dimensional echocardiographic sequences. To account for typical heart motions, such as contraction/expansion and shear, we analyze the images locally by using a local-affine model for the velocity in space and a linear model in time. The regional motion parameters are estimated in the least-squares sense inside a sliding spatiotemporal B-spline window. Robustness and spatial adaptability is achieved by estimating the model parameters at multiple scales within a coarse-to-fine multiresoluion framework. We use a wavelet-like algorithm for computing B-spline-weighted inner products and moments at dyadic scales to increase computational efficiency. In order to characterize myocardial contractility and to simplify the detection of myocardial dysfunction, the radial component of the velocity with respect to a reference point is color coded and visualized inside a time-varying region of interest. The algorithm was first validated on synthetic data sets that simulate a beating heart with a speckle-like appearance of echocardiograms. The ability to estimate motion from real ultrasound sequences was demonstrated by a rotating phantom experiment. The method was also applied to a set of in vivo echocardiograms from an animal study. Motion estimation results were in good agreement with the expert echocardiographic reading.

Algorithms↗

Variational image reconstruction from arbitrarily spaced samples: a fast multiresolution spline solution.

We propose a novel method for image reconstruction from nonuniform samples with no constraints on their locations. We adopt a variational approach where the reconstruction is formulated as the minimizer of a cost that is a weighted sum of two terms: (1) the sum of squared errors at the specified points and (2) a quadratic functional that penalizes the lack of smoothness. We search for a solution that is a uniform spline and show how it can be determined by solving a large, sparse system of linear equations. We interpret the solution of our approach as an approximation of the analytical solution that involves radial basis functions and demonstrate the computational advantages of our approach. Using the two-scale relation for B-splines, we derive an algebraic relation that links together the linear systems of equations specifying reconstructions at different levels of resolution. We use this relation to develop a fast multigrid algorithm. We demonstrate the effectiveness of our approach on some image reconstruction examples.

Algorithms↗

Robust real-time segmentation of images and videos using a smooth-spline snake-based algorithm.

This paper deals with fast image and video segmentation using active contours. Region-based active contours using level sets are powerful techniques for video segmentation, but they suffer from large computational cost. A parametric active contour method based on B-Spline interpolation has been proposed in to highly reduce the computational cost, but this method is sensitive to noise. Here, we choose to relax the rigid interpolation constraint in order to robustify our method in the presence of noise: by using smoothing splines, we trade a tunable amount of interpolation error for a smoother spline curve. We show by experiments on natural sequences that this new flexibility yields segmentation results of higher quality at no additional computational cost. Hence, real-time processing for moving objects segmentation is preserved.

Algorithms↗

Automatic tracking of individual fluorescence particles: application to the study of chromosome dynamics.

We present a new, robust, computational procedure for tracking fluorescent markers in time-lapse microscopy. The algorithm is optimized for finding the time-trajectory of single particles in very noisy dynamic (two- or three-dimensional) image sequences. It proceeds in three steps. First, the images are aligned to compensate for the movement of the biological structure under investigation. Second, the particle's signature is enhanced by applying a Mexican hat filter, which we show to be the optimal detector of a Gaussian-like spot in 1/omega2 noise. Finally, the optimal trajectory of the particle is extracted by applying a dynamic programming optimization procedure. We have used this software, which is implemented as a Java plug-in for the public-domain ImageJ software, to track the movement of chromosomal loci within nuclei of budding yeast cells. Besides reducing trajectory analysis time by several 100-fold, we achieve high reproducibility and accuracy of tracking. The application of the method to yeast chromatin dynamics reveals different classes of constraints on mobility of telomeres, reflecting differences in nuclear envelope association. The generic nature of the software allows application to a variety of similar biological imaging tasks that require the extraction and quantitation of a moving particle's trajectory.

Algorithms↗

Isotropic polyharmonic B-splines: scaling functions and wavelets.

In this paper, we use polyharmonic B-splines to build multidimensional wavelet bases. These functions are nonseparable, multidimensional basis functions that are localized versions of radial basis functions. We show that Rabut's elementary polyharmonic B-splines do not converge to a Gaussian as the order parameter increases, as opposed to their separable B-spline counterparts. Therefore, we introduce a more isotropic localization operator that guarantees this convergence, resulting into the isotropic polyharmonic B-splines. Next, we focus on the two-dimensional quincunx subsampling scheme. This configuration is of particular interest for image processing because it yields a finer scale progression than the standard dyadic approach. However, up until now, the design of appropriate filters for the quincunx scheme has mainly been done using the McClellan transform. In our approach, we start from the scaling functions, which are the polyharmonic B-splines and, as such, explicitly known, and we derive a family of polyharmonic spline wavelets corresponding to different flavors of the semi-orthogonal wavelet transform; e.g., orthonormal, B-spline, and dual. The filters are automatically specified by the scaling relations satisfied by these functions. We prove that the isotropic polyharmonic B-spline wavelet converges to a combination of four Gabor atoms, which are well separated in the frequency domain. We also show that these wavelets are nearly isotropic and that they behave as an iterated Laplacian operator at low frequencies. We describe an efficient fast Fourier transform-based implementation of the discrete wavelet transform based on polyharmonic B-splines.

Algorithms↗

Spatio-temporal nonrigid registration for ultrasound cardiac motion estimation.

We propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method.

Artificial Intelligence↗

Multiscale motion mapping: a novel computer vision technique for quantitative, objective echocardiographic motion measurement independent of Doppler: first clinical description and validation.

BACKGROUND: Objective, quantitative, segmental noninvasive/bedside measurement of cardiac motion is highly desirable in cardiovascular medicine, but current technology suffers from significant drawbacks, such as subjectivity of conventional echocardiographic reading, angle dependence of tissue Doppler measurements, radiation exposure by computer tomography, and infrastructure requirements in MRI. We hypothesized that computer vision technology could represent a powerful new paradigm for quantification in echocardiography. METHODS AND RESULTS: We present multiscale motion mapping, a novel computer vision technology that is based on mathematical image processing and that exploits echocardiographic information in a fashion similar to the human visual system. It allows Doppler- and border-independent determination of motion and deformation in echocardiograms at arbitrary locations. Correctness of the measurements was documented in synthetic echocardiograms and phantom experiments. Exploratory case studies demonstrated its usefulness in a series of complex motion analyses that included abnormal septal motion and analysis of myocardial twisting. Clinical applicability was shown in a consecutive series of echocardiograms, in which good feasibility, good correlation with expert rating, and good intraobserver and interobserver concordance were documented. Separate assessment of 2D displacement and deformation at the same location was successfully applied to elucidate paradoxical septal motion, a common clinical problem. CONCLUSIONS: This is the first clinical report of multiscale motion mapping, a novel approach to echocardiographic motion quantification. For the first time, full 2D echocardiographic assessment of both motion and deformation is shown to be feasible. Overcoming current limitations, this computer vision-based technique opens a new door to objective analysis of complex heart motion.

Algorithms↗

Complex wavelets for extended depth-of-field: a new method for the fusion of multichannel microscopy images.

Microscopy imaging often suffers from limited depth-of-field. However, the specimen can be "optically sectioned" by moving the object along the optical axis. Then different areas appear in focus in different images. Extended depth-of-field is a fusion algorithm that combines those images into one single sharp composite. One promising method is based on the wavelet transform. Here, we show how the wavelet-based image fusion technique can be improved and easily extended to multichannel data. First, we propose the use of complex-valued wavelet bases, which seem to outperform traditional real-valued wavelet transforms. Second, we introduce a way to apply this technique for multichannel images that suppresses artifacts and does not introduce false colors, an important requirement for multichannel optical microscopy imaging. We evaluate our method on simulated image stacks and give results relevant to biological imaging.

Animals↗

Integrated wavelet processing and spatial statistical testing of fMRI data.

We introduce an integrated framework for detecting brain activity from fMRI data, which is based on a spatial discrete wavelet transform. Unlike the standard wavelet-based approach for fMRI analysis, we apply the suitable statistical test procedure in the spatial domain. For a desired significance level, this scheme has one remaining degree of freedom, characterizing the wavelet processing, which is optimized according to the principle of minimal approximation error. This allows us to determine the threshold values in a way that does not depend on data. While developing our framework, we make only conservative assumptions. Consequently, the detection of activation is based on strong evidence. We have implemented this framework as a toolbox (WSPM) for the SPM2 software, taking advantage of multiple options and functions of SPM such as the setup of the linear model and the use of the hemodynamic response function. We show by experimental results that our method is able to detect activation patterns; the results are comparable to those obtained by SPM even though statistical assumptions are more conservative.

Attention↗

Multiresolution moment filters: theory and applications.

We introduce local weighted geometric moments that are computed from an image within a sliding window at multiple scales. When the window function satisfies a two-scale relation, we prove that lower order moments can be computed efficiently at dyadic scales by using a multiresolution wavelet-like algorithm. We show that B-splines are well-suited window functions because, in addition to being refinable, they are positive, symmetric, separable, and very nearly isotropic (Gaussian shape). We present three applications of these multiscale local moments. The first is a feature-extraction method for detecting and characterizing elongated structures in images. The second is a noise-reduction method which can be viewed as a multiscale extension of Savitzky-Golay filtering. The third is a multiscale optical-flow algorithm that uses a local affine model for the motion field, extending the Lucas-Kanade optical-flow method. The results obtained in all cases are promising.

Algorithms↗

Linear interpolation revitalized.

We present a simple, original method to improve piecewise-linear interpolation with uniform knots: we shift the sampling knots by a fixed amount, while enforcing the interpolation property. We determine the theoretical optimal shift that maximizes the quality of our shifted linear interpolation. Surprisingly enough, this optimal value is nonzero and close to 1/5. We confirm our theoretical findings by performing several experiments: a cumulative rotation experiment and a zoom experiment. Both show a significant increase of the quality of the shifted method with respect to the standard one. We also observe that, in these results, we get a quality that is similar to that of the computationally more costly "high-quality" cubic convolution.

Algorithms↗