Designing volume visualizations showing various structures of interest is critical to the exploratory analysis of volumetric data. The last few years have witnessed dramatic advances in the use of convolutional neural networks for identification of objects in large image collections. Whereas such machine learning methods have shown superior performance in a number of applications, their direct use in volume visualization has not yet been explored. In this paper, we present a deep-learning-assisted volume visualization to depict complex structures, which are otherwise challenging for conventional approaches. A significant challenge in designing volume visualizations based on the high-dimensional deep features lies in efficiently handling the immense amount of information that deep-learning methods provide. In this paper, we present a new technique that uses spectral methods to facilitate user interactions with high-dimensional features. We also present a new deep-learning-assisted technique for hierarchically exploring a volumetric dataset. We have validated our approach on two electron microscopy volumes and one magnetic resonance imaging dataset.

We introduce a tomographic reconstruction method implemented using a shape-based regularization technique. Spatial models of known features in the structure being reconstructed are integrated into the reconstruction process as regularizers. Our regularization scheme is driven locally through shape information obtained from segmentation and compared with a known spatial model. We demonstrated our method on tomography data from digital phantoms, simulated data, and experimental electron tomography (ET) data of virus complexes. Our reconstruction showed reduced blurring and an improvement in the resolution of the reconstructed volume was also measured. This method also produced improved demarcation of spike boundaries in viral membranes when compared with popular techniques like weighted back projection and the algebraic reconstruction technique. Improved ET reconstructions will provide better structure elucidation and improved feature visualization, which can aid in solving key biological issues. Our method can also be generalized to other tomographic modalities.

Advances in automated data acquisition in electron tomography have led to an explosion in the amount of data that can be obtained about the spatial architecture of a variety of biologically and medically relevant objects with sizes in the "nano" range of 10-1000 nm. The development of methods to analyze the vast amounts of information contained in these tomograms is a major challenge since the electron tomograms are intrinsically noisy. A fundamental step in the automatic analysis of large amounts of data for statistical inference is to segment 3D features in cellular tomograms that can work robustly and rapidly despite of low signal to noise ratios inherent to biological electron microscopy. This work evaluates various denoising techniques on tomograms obtained using dual-axis simultaneous iterative reconstruction (SIRT) technique. Using three-dimensional images of HIV in infected human macrophages as an example, we demonstrate that transform domain-denoising techniques significantly improve the fidelity of automated feature extraction. Importantly, our approaches represent an vital step in automating the efficient extraction of useful information from large datasets in biological tomography, and facilitate the overall goal of speeding up the process of reducing gigabyte-sized tomograms to byte-sized data.

Electron tomography allows for the determination of the three-dimensional structures of cells and tissues at resolutions significantly higher than that which is possible with optical microscopy. Electron tomograms contain, in principle, vast amounts of information on the locations and architectures of large numbers of subcellular assemblies and organelles. The development of reliable quantitative approaches for the analysis of features in tomograms is an important problem, and a challenging prospect due to the low signal-to-noise ratios that are inherent to biological electron microscopic images. This is, in part, a consequence of the tremendous complexity of biological specimens. We report on a new method for the automated segmentation of HIV particles and selected cellular compartments in electron tomograms recorded from fixed, plastic-embedded sections derived from HIV-infected human macrophages. Individual features in the tomogram are segmented using a novel robust algorithm that finds their boundaries as global minimal surfaces in a metric space defined by image features. The optimization is carried out in a transformed spherical domain with the center an interior point of the particle of interest, providing a proper setting for the fast and accurate minimization of the segmentation energy. This method provides tools for the semi-automated detection and statistical evaluation of HIV particles at different stages of assembly in the cells and presents opportunities for correlation with biochemical markers of HIV infection. The segmentation algorithm developed here forms the basis of the automated analysis of electron tomograms and will be especially useful given the rapid increases in the rate of data acquisition. It could also enable studies of much larger data sets, such as those which might be obtained from the tomographic analysis of HIV-infected cells from studies of large populations.