Alzheimer's disease (AD) and sleep disorders exhibit a close association, where disruptions in sleep patterns often precede the onset of Mild Cognitive Impairment (MCI) and early-stage AD. This study delves into the potential of utilizing sleep-related electroencephalography (EEG) signals acquired through polysomnography (PSG) for the early detection of AD. Our primary focus is on exploring semi-supervised Deep Learning techniques for the classification of EEG signals due to the clinical scenario characterized by the limited data availability. The methodology entails testing and comparing the performance of semi-supervised models, benchmarked against an unsupervised and a supervised model. The study highlights the significance of spatial and temporal analysis capabilities, conducting independent analyses of each sleep stage. Results demonstrate the effectiveness of one semi-supervised model in leveraging limited labeled data, achieving stable metrics across all sleep stages, and reaching 90% accuracy in its supervised form. Comparative analyses reveal this superior performance over the unsupervised model, while the supervised model ranges between . These findings underscore the potential of semi-supervised models in early AD detection, particularly in overcoming the challenges associated with the scarcity of labeled data. Ablation tests affirm the critical role of spatio-temporal feature extraction in semi-supervised predictive performance, and t-SNE visualizations validate the model's proficiency in distinguishing AD patterns. Overall, this research contributes to the advancement of AD detection through innovative Deep Learning approaches, highlighting the crucial role of semi-supervised learning in addressing data limitations.

Automatic Non-rigid Histological Image Registration (ANHIR) challenge was organized to compare the performance of image registration algorithms on several kinds of microscopy histology images in a fair and independent manner. We have assembled 8 datasets, containing 355 images with 18 different stains, resulting in 481 image pairs to be registered. Registration accuracy was evaluated using manually placed landmarks. In total, 256 teams registered for the challenge, 10 submitted the results, and 6 participated in the workshop. Here, we present the results of 7 well-performing methods from the challenge together with 6 well-known existing methods. The best methods used coarse but robust initial alignment, followed by non-rigid registration, used multiresolution, and were carefully tuned for the data at hand. They outperformed off-the-shelf methods, mostly by being more robust. The best methods could successfully register over 98% of all landmarks and their mean landmark registration accuracy (TRE) was 0.44% of the image diagonal. The challenge remains open to submissions and all images are available for download.

The novel coronavirus 2019 (COVID-19) began infecting humans in late 2019 and then turned into pandemic in the successive months spreading all over the world. At the beginning of July 2020, the global number of confirmed cases reported by the World Health Organization is above 10 million, with more than half million deaths and a rate of new cases of almost 150 000 per day.

We present a dynamic atlas composed of neuromelanin-enhanced magnetic resonance brain images of 40 healthy subjects. The performance of this atlas is evaluated on the fully automated segmentation of two paired neuromelanin-rich brainstem healthy structures: the substantia nigra pars compacta and the locus coeruleus. We show that our dynamic atlas requires in average 60% less images and, therefore, 60% less computation time than a static multi-image atlas while achieving a similar segmentation performance. Then, we show that by applying our dynamic atlas, composed of healthy subjects, to the segmentation and neuromelanin quantification of a set of brain images of 39 Parkinson disease patients, we are able to find significant quantitative differences in the level of neuromelanin between healthy subjects and Parkinson disease patients, thus opening the door to the use of these structures as image biomarkers in future computer aided diagnosis systems for the diagnosis of Parkinson disease.

Image registration is a common task for many biomedical analysis applications. The present work focuses on the benchmarking of registration methods on differently stained histological slides. This is a challenging task due to the differences in the appearance model, the repetitive texture of the details and the large image size, between other issues. Our benchmarking data is composed of 616 image pairs at two different scales - average image diagonal 2.4k and 5k pixels. We compare eleven fully automatic registration methods covering the widely used similarity measures (and optimization strategies with both linear and elastic transformation). For each method, the best parameter configuration is found and subsequently applied to all the image pairs. The performance of the algorithms is evaluated from several perspectives - the registrations (in)accuracy on manually annotated landmarks, the method robustness and its processing computation time.

Traction Force Microscopy (TFM) is a widespread technique to estimate the tractions that cells exert on the surrounding substrate. To recover the tractions, it is necessary to solve an inverse problem, which is ill-posed and needs regularization to make the solution stable. The typical regularization scheme is given by the minimization of a cost functional, which is divided in two terms: the error present in the data or data fidelity term; and the regularization or penalty term. The classical approach is to use zero-order Tikhonov or L 2 -regularization, which uses the L 2 -norm for both terms in the cost function. Recently, some studies have demonstrated an improved performance using L 1 -regularization (L 1 -norm in the penalty term) related to an increase in the spatial resolution and sensitivity of the recovered traction field. In this manuscript, we present a comparison between the previous two regularization schemes (relying in the L 2 -norm for the data fidelity term) and the full L 1 -regularization (using the L 1 -norm for both terms in the cost function) for synthetic and real data. Our results reveal that L 1 -regularizations give an improved spatial resolution (more important for full L 1 -regularization) and a reduction in the background noise with respect to the classical zero-order Tikhonov regularization. In addition, we present an approximation, which makes feasible the recovery of cellular tractions over whole cells on typical full-size microscope images when working in the spatial domain. The proposed full L 1 -regularization improves the sensitivity to recover small stress footprints. Moreover, the proposed method has been validated to work on full-field microscopy images of real cells, what certainly demonstrates it is a promising tool for biological applications.

The geometry of 3D collagen networks is a key factor that influences the behavior of live cells within extracellular matrices. This paper presents a hybrid, two-step method for fully automatic quantification of the 3D collagen network geometry at fiber resolution in confocal reflection microscopy images. First, a coarse binary mask of the entire network is obtained using steerable filtering and local Otsu thresholding. Second, individual collagen fibers are reconstructed by tracing maximum ridges in the Euclidean distance map of the binary mask. The proposed method, validated in a novel framework using 3D collagen gels with various collagen and Matrigel concentrations, reveal that Matrigel affects the collagen network geometry by decreasing the network pore size while preserving the fiber length and fiber persistence length.

MOTIVATION: Automatic tracking of cells in multidimensional time-lapse fluorescence microscopy is an important task in many biomedical applications. A novel framework for objective evaluation of cell tracking algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2013 Cell Tracking Challenge. In this article, we present the logistics, datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. RESULTS: The main contributions of the challenge include the creation of a comprehensive video dataset repository and the definition of objective measures for comparison and ranking of the algorithms. With this benchmark, six algorithms covering a variety of segmentation and tracking paradigms have been compared and ranked based on their performance on both synthetic and real datasets. Given the diversity of the datasets, we do not declare a single winner of the challenge. Instead, we present and discuss the results for each individual dataset separately. AVAILABILITY AND IMPLEMENTATION: The challenge Web site (http://www.codesolorzano.com/celltrackingchallenge) provides access to the training and competition datasets, along with the ground truth of the training videos. It also provides access to Windows and Linux executable files of the evaluation software and most of the algorithms that competed in the challenge.

We present a fast and robust approach to tracking the evolving shape of whole fluorescent cells in time-lapse series. The proposed tracking scheme involves two steps. First, coherence-enhancing diffusion filtering is applied on each frame to reduce the amount of noise and enhance flow-like structures. Second, the cell boundaries are detected by minimizing the Chan-Vese model in the fast level set-like and graph cut frameworks. To allow simultaneous tracking of multiple cells over time, both frameworks have been integrated with a topological prior exploiting the object indication function. The potential of the proposed tracking scheme and the advantages and disadvantages of both frameworks are demonstrated on 2-D and 3-D time-lapse series of rat adipose-derived mesenchymal stem cells and human lung squamous cell carcinoma cells, respectively.

BACKGROUND: High-density oligonucleotide microarray is an appropriate technology for genomic analysis, and is particulary useful in the generation of transcriptional maps, ChIP-on-chip studies and re-sequencing of the genome.Transcriptome analysis of tiling microarray data facilitates the discovery of novel transcripts and the assessment of differential expression in diverse experimental conditions. Although new technologies such as next-generation sequencing have appeared, microarrays might still be useful for the study of small genomes or for the analysis of genomic regions with custom microarrays due to their lower price and good accuracy in expression quantification. RESULTS: Here, we propose a novel wavelet-based method, named ZCL (zero-crossing lines), for the combined denoising and segmentation of tiling signals. The denoising is performed with the classical SUREshrink method and the detection of transcriptionally active regions is based on the computation of the Continuous Wavelet Transform (CWT). In particular, the detection of the transitions is implemented as the thresholding of the zero-crossing lines. The algorithm described has been applied to the public Saccharomyces cerevisiae dataset and it has been compared with two well-known algorithms: pseudo-median sliding window (PMSW) and the structural change model (SCM). As a proof-of-principle, we applied the ZCL algorithm to the analysis of the custom tiling microarray hybridization results of a S. aureus mutant deficient in the sigma B transcription factor. The challenge was to identify those transcripts whose expression decreases in the absence of sigma B. CONCLUSIONS: The proposed method archives the best performance in terms of positive predictive value (PPV) while its sensitivity is similar to the other algorithms used for the comparison. The computation time needed to process the transcriptional signals is low as compared with model-based methods and in the same range to those based on the use of filters. Automatic parameter selection has been incorporated and moreover, it can be easily adapted to a parallel implementation. We can conclude that the proposed method is well suited for the analysis of tiling signals, in which transcriptional activity is often hidden in the noise. Finally, the quantification and differential expression analysis of S. aureus dataset have demonstrated the valuable utility of this novel device to the biological analysis of the S. aureus transcriptome.

The efficient realization of linear space-variant (non-convolution) filters is a challenging computational problem in image processing. In this paper, we demonstrate that it is possible to filter an image with a Gaussian-like elliptic window of varying size, elongation and orientation using a fixed number of computations per pixel. The associated algorithm, which is based upon a family of smooth compactly supported piecewise polynomials, the radially-uniform box splines, is realized using preintegration and local finite-differences. The radially-uniform box splines are constructed through the repeated convolution of a fixed number of box distributions, which have been suitably scaled and distributed radially in an uniform fashion. The attractive features of these box splines are their asymptotic behavior, their simple covariance structure, and their quasi-separability. They converge to Gaussians with the increase of their order, and are used to approximate anisotropic Gaussians of varying covariance simply by controlling the scales of the constituent box distributions. Based upon the second feature, we develop a technique for continuously controlling the size, elongation and orientation of these Gaussian-like functions. Finally, the quasi-separable structure, along with a certain scaling property of box distributions, is used to efficiently realize the associated space-variant elliptical filtering, which requires O(1) computations per pixel irrespective of the shape and size of the filter.

We present an efficient algorithm to compute multidimensional spatially variant convolutions--or inner products--between N-dimensional signals and B-splines--or their derivatives--of any order and arbitrary sizes. The multidimensional B-splines are computed as tensor products of 1-D B-splines, and the input signal is expressed in a B-spline basis. The convolution is then computed by using an adequate combination of integration and scaled finite differences as to have, for moderate and large scale values, a computational complexity that does not depend on the scaling factor. To show in practice the benefit of using our spatially variant convolution approach, we present an adaptive noise filter that adjusts the kernel size to the local image characteristics and a high sensitivity local ridge detector.

It has been shown that employing multiple atlas images improves segmentation accuracy in atlas-based medical image segmentation. Each atlas image is registered to the target image independently and the calculated transformation is applied to the segmentation of the atlas image to obtain a segmented version of the target image. Several independent candidate segmentations result from the process, which must be somehow combined into a single final segmentation. Majority voting is the generally used rule to fuse the segmentations, but more sophisticated methods have also been proposed. In this paper, we show that the use of global weights to ponderate candidate segmentations has a major limitation. As a means to improve segmentation accuracy, we propose the generalized local weighting voting method. Namely, the fusion weights adapt voxel-by-voxel according to a local estimation of segmentation performance. Using digital phantoms and MR images of the human brain, we demonstrate that the performance of each combination technique depends on the gray level contrast characteristics of the segmented region, and that no fusion method yields better results than the others for all the regions. In particular, we show that local combination strategies outperform global methods in segmenting high-contrast structures, while global techniques are less sensitive to noise when contrast between neighboring structures is low. We conclude that, in order to achieve the highest overall segmentation accuracy, the best combination method for each particular structure must be selected.

We demonstrate that it is possible to filter an image with an elliptic window of varying size, elongation and orientation with a fixed computational cost per pixel. Our method involves the application of a suitable global pre-integrator followed by a pointwise-adaptive localization mesh. We present the basic theory for the ID case using a B-spline formalism and then appropriately extend it to 2D using radially-uniform box splines. The size and ellipticity of these radially-uniform box splines is adaptively controlled. Moreover, they converge to Gaussians as the order increases. Finally, we present a fast and practical directional filtering algorithm that has the capability of adapting to the local image features.

In this paper we present an adaptive B-spline smoothing algorithm to reduce noise in biomedical images. The filter consists of a convolution between the input image and an adaptive B-spline kernel that varies its size according to the local image characteristics. We show that this filter can be efficiently implemented by taking advantage of the convolution and factorization properties of B-splines. We tested our filter on phantoms and real images, obtaining very high noise reduction in homogeneous areas with little degradation of the edges.

We propose to design the reduction operator of an image pyramid so as to minimize the approximation error in the l(p)-sense (not restricted to the usual p=2), where p can take noninteger values. The underlying image model is specified using shift-invariant basis functions, such as B-splines. The solution is well-defined and determined by an iterative optimization algorithm based on digital filtering. Its convergence is accelerated by the use of first and second order derivatives. For p close to 1, we show that the ringing is reduced and that the histogram of the detail image is sparse as compared with the standard case, where p=2.

We present an optimal spline-based algorithm for the enlargement or reduction of digital images with arbitrary (noninteger) scaling factors. This projection-based approach can be realized thanks to a new finite difference method that allows the computation of inner products with analysis functions that are B-splines of any degree n. A noteworthy property of the algorithm is that the computational complexity per pixel does not depend on the scaling factor a. For a given choice of basis functions, the results of our method are consistently better than those of the standard interpolation procedure; the present scheme achieves a reduction of artifacts such as aliasing and blocking and a significant improvement of the signal-to-noise ratio. The method can be generalized to include other classes of piecewise polynomial functions, expressed as linear combinations of B-splines and their derivatives.

We present an explicit formula for spline kernels; these are defined as the convolution of several B-splines of variable widths h/sub i/ and degrees n/sub i/. The spline kernels are useful for continuous signal processing algorithms that involve B-spline inner-products or the convolution of several spline basis functions. We apply our results to the derivation of spline-based algorithms for two classes of problems. The first is the resizing of images with arbitrary scaling factors. The second is the computation of the Radon transform and of its inverse. In particular, we present a new spline-based version of the filtered back-projection algorithm for tomographic reconstruction. In both cases, our explicit kernel formula allows for the use of high-degree splines; these offer better approximation performance than the conventional lower-order formulations (e.g., piecewise constant or piece-wise linear models).

We present an optimal spline-based algorithm for the enlargement or reduction of digital images with arbitrary scaling factors. This projection-based approach is realizable thanks to a new finite difference method that allows the computation of inner products with analysis functions that are B-splines of any degree n. For a given choice of basis functions, the results of our method are consistently better that those of the standard interpolation procedure; the present scheme achieves a reduction of artifacts such as aliasing and blocking and a significant improvement of the signal-to-noise ratio.