John A. Bogovic

Multi-parametric neuroimaging reproducibility: A 3-T resource study

Modern MRI image processing methods have yielded quantitative, morphometric, functional, and structural assessments of the human brain. These analyses typically exploit carefully optimized protocols for specific imaging targets. Algorithm investigators have several excellent public data resources to use to test, develop, and optimize their methods. Recently, there has been an increasing focus on combining MRI protocols in multi-parametric studies. Notably, these have included innovative approaches for fusing connectivity inferences with functional and/or anatomical characterizations. Yet, validation of the reproducibility of these interesting and novel methods has been severely hampered by the limited availability of appropriate multi-parametric data. We present an imaging protocol optimized to include state-of-the-art assessment of brain function, structure, micro-architecture, and quantitative parameters within a clinically feasible 60-min protocol on a 3-T MRI scanner. We present scan-rescan reproducibility of these imaging contrasts based on 21 healthy volunteers (11 M/10 F, 22-61 years old). The cortical gray matter, cortical white matter, ventricular cerebrospinal fluid, thalamus, putamen, caudate, cerebellar gray matter, cerebellar white matter, and brainstem were identified with mean volume-wise reproducibility of 3.5%. We tabulate the mean intensity, variability, and reproducibility of each contrast in a region of interest approach, which is essential for prospective study planning and retrospective power analysis considerations. Anatomy was highly consistent on structural acquisition (~1-5% variability), while variation on diffusion and several other quantitative scans was higher (~<10%). Some sequences are particularly variable in specific structures (ASL exhibited variation of 28% in the cerebral white matter) or in thin structures (quantitative T2 varied by up to 73% in the caudate) due, in large part, to variability in automated ROI placement. The richness of the joint distribution of intensities across imaging methods can be best assessed within the context of a particular analysis approach as opposed to a summary table. As such, all imaging data and analysis routines have been made publicly and freely available. This effort provides the neuroimaging community with a resource for optimization of algorithms that exploit the diversity of modern MRI modalities. Additionally, it establishes a baseline for continuing development and optimization of multi-parametric imaging protocols.

The Java Image Science Toolkit (JIST) for Rapid Prototyping and Publishing of Neuroimaging Software

Non-invasive neuroimaging techniques enable extraordinarily sensitive and specific in vivo study of the structure, functional response and connectivity of biological mechanisms. With these advanced methods comes a heavy reliance on computer-based processing, analysis and interpretation. While the neuroimaging community has produced many excellent academic and commercial tool packages, new tools are often required to interpret new modalities and paradigms. Developing custom tools and ensuring interoperability with existing tools is a significant hurdle. To address these limitations, we present a new framework for algorithm development that implicitly ensures tool interoperability, generates graphical user interfaces, provides advanced batch processing tools, and, most importantly, requires minimal additional programming or computational overhead. Java-based rapid prototyping with this system is an efficient and practical approach to evaluate new algorithms since the proposed system ensures that rapidly constructed prototypes are actually fully-functional processing modules with support for multiple GUI’s, a broad range of file formats, and distributed computation. Herein, we demonstrate MRI image processing with the proposed system for cortical surface extraction in large cross-sectional cohorts, provide a system for fully automated diffusion tensor image analysis, and illustrate how the system can be used as a simulation framework for the development of a new image analysis method. The system is released as open source under the Lesser GNU Public License (LGPL) through the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC).

Resolution of crossing fibers with constrained compressed sensing using diffusion tensor MRI

Diffusion tensor imaging (DTI) is widely used to characterize tissue micro-architecture and brain connectivity. In regions of crossing fibers, however, the tensor model fails because it cannot represent multiple, independent intra-voxel orientations. Most of the methods that have been proposed to resolve this problem require diffusion magnetic resonance imaging (MRI) data that comprise large numbers of angles and high b-values, making them problematic for routine clinical imaging and many scientific studies. We present a technique based on compressed sensing that can resolve crossing fibers using diffusion MRI data that can be rapidly and routinely acquired in the clinic (30 directions, b-value equal to 700 s/mm2). The method assumes that the observed data can be well fit using a sparse linear combination of tensors taken from a fixed collection of possible tensors each having a different orientation. A fast algorithm for computing the best orientations based on a hierarchical compressed sensing algorithm and a novel metric for comparing estimated orientations are also proposed. The performance of this approach is demonstrated using both simulations and in vivo images. The method is observed to resolve crossing fibers using conventional data as well as a standard q-ball approach using much richer data that requires considerably more image acquisition time.

A multiple object geometric deformable model for image segmentation

Deformable models are widely used for image segmentation, most commonly to find single objects within an image. Although several methods have been proposed to segment multiple objects using deformable models, substantial limitations in their utility remain. This paper presents a multiple object segmentation method using a novel and efficient object representation for both two and three dimensions. The new framework guarantees object relationships and topology, prevents overlaps and gaps, enables boundary-specific speeds, and has a computationally efficient evolution scheme that is largely independent of the number of objects. Maintaining object relationships and straightforward use of object-specific and boundary-specific smoothing and advection forces enables the segmentation of objects with multiple compartments, a critical capability in the parcellation of organs in medical imaging. Comparing the new framework with previous approaches shows its superior performance and scalability.

Robust Statistical Fusion of Image Labels

Image labeling and parcellation (i.e., assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability

Direct segmentation of the major white matter tracts in diffusion tensor images.

Diffusion-weighted images of the human brain are acquired more and more routinely in clinical research settings, yet segmenting and labeling white matter tracts in these images is still challenging. We present in this paper a fully automated method to extract many anatomical tracts at once on diffusion tensor images, based on a Markov random field model and anatomical priors. The approach provides a direct voxel labeling, models explicitly fiber crossings and can handle white matter lesions. Experiments on simulations and repeatability studies show robustness to noise and reproducibility of the algorithm, which has been made publicly available.

Resolution of crossing fibers with constrained compressed sensing using traditional diffusion tensor MRI

Diffusion tensor imaging (DTI) is widely used to characterize tissue micro-architecture and brain connectivity. Yet DTI suffers serious limitations in regions of crossing fibers because traditional tensor techniques cannot represent multiple, independent intra-voxel orientations. Compressed sensing has been proposed to resolve crossing fibers using a tensor mixture model (e.g., Crossing Fiber Angular Resolution of Intra-voxel structure, CFARI). Although similar in spirit to deconvolution approaches, CFARI uses sparsity to stabilize estimation with limited data rather than spatial consistency or limited model order. Here, we extend the CFARI approach to resolve crossing fibers through a strictly positive, parsimonious mixture model. Together with an optimized preconditioned conjugate gradient solver, estimation error and computational burden are greatly reduced over the initial presentation. Reliable estimates of intra-voxel orientations are demonstrated in simulation and in vivo using data representative of typical, low b-value (30 directions, 700 s/mm2) clinical DTI protocols. These sequences are achievable in 5 minutes at 3 T, and the whole brain CFARI analysis is tractable for routine analysis. With these improvements, CFARI provides a robust framework for identifying intra-voxel structure with conventional DTI protocols and shows great promise in helping to resolve the crossing fiber problem in current clinical imaging studies.

Magnetic Resonance Connectome Automated Pipeline: An Overview

This article presents a novel, tightly integrated pipeline for estimating a connectome. The pipeline utilizes magnetic resonance (MR) imaging (MRI) data to produce a high-level estimate of the structural connectivity in the human brain. The MR connectome automated pipeline (MRCAP) is efficient, and its modular construction allows researchers to modify algorithms to meet their specific requirements. The pipeline has been validated, and more than 200 connectomes have been processed and analyzed to date.

A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster

Summary Drosophila melanogaster has a rich repertoire of innate and learned behaviors. Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping. Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM. We developed a custom high-throughput EM platform and imaged the entire brain of an adult female fly at synaptic resolution. To validate the dataset, we traced brain-spanning circuitry involving the mushroom body (MB), which has been extensively studied for its role in learning. All inputs to Kenyon cells (KCs), the intrinsic neurons of the MB, were mapped, revealing a previously unknown cell type, postsynaptic partners of KC dendrites, and unexpected clustering of olfactory projection neurons. These reconstructions show that this freely available EM volume supports mapping of brain-spanning circuits, which will significantly accelerate Drosophila neuroscience. Video Abstract

Automated segmentation of the cerebellar lobules using boundary specific classification and evolution

The cerebellum is instrumental in coordinating many vital functions ranging from speech and balance to eye movement. The effect of cerebellar pathology on these functions is frequently examined using volumetric studies that depend on consistent and accurate delineation, however, no existing automated methods adequately delineate the cerebellar lobules. In this work, we describe a method we call the Automatic Classification of Cerebellar Lobules Algorithm using Implicit Multi-boundary evolution (ACCLAIM). A multiple object geometric deformable model (MGDM) enables each boundary surface of each individual lobule to be evolved under different level set speeds. An important innovation described in this work is that the speed for each lobule boundary is derived from a classifier trained specifically to identify that boundary. We compared our method to segmentations obtained using the atlas-based and multi-atlas fusion techniques, and demonstrate ACCLAIMs superior performance.