Brain Maturation of Newborns and Infants|
G. Gerig, J.H. Gilmore, W. Lin. Encyclopedia on Early Childhood Development (online): Brain Development in Children - According to Experts, Montreal, Quebec, Centre of Excellence for Early Childhood Development and Strategic Knowledge Cluster on Early Child Development, pp. 1--6. 2011.
Recently, imaging studies of early human development have received more attention, as improved modeling methods might lead to a clearer understanding of the origin, timing, and nature of differences in neurodevelopmental disorders. Non-invasive magnetic resonance imaging (MRI) can provide three-dimensional images of the infant brain in less than 20 minutes, with unprecedented anatomical details and contrast of brain anatomy, cortical and subcortical structures and brain connectivity. Repeating MRI at different stages of development, e.g., in yearly intervals starting after birth, gives scientists the opportunity to study the trajectory of brain growth and compare individual growth trajectories to normative models. These comparisons become highly relevant in personalized medicine, where early diagnosis is a critical juncture for timing and therapy types.
The Viking viewer for connectomics: scalable multi-user annotation and summarization of large volume data sets|
J.R. Anderson, S. Mohammed, B.C. Grimm, B.W. Jones, P. Koshevoy, T. Tasdizen, R.T. Whitaker, R.E. Marc. In Journal of Microscopy, Vol. 241, No. 1, pp. 13--28. 2011.
Modern microscope automation permits the collection of vast amounts of continuous anatomical imagery in both two and three dimensions. These large data sets present significant challenges for data storage, access, viewing, annotation and analysis. The cost and overhead of collecting and storing the data can be extremely high. Large data sets quickly exceed an individual's capability for timely analysis and present challenges in efficiently applying transforms, if needed. Finally annotated anatomical data sets can represent a significant investment of resources and should be easily accessible to the scientific community. The Viking application was our solution created to view and annotate a 16.5 TB ultrastructural retinal connectome volume and we demonstrate its utility in reconstructing neural networks for a distinctive retinal amacrine cell class. Viking has several key features. (1) It works over the internet using HTTP and supports many concurrent users limited only by hardware. (2) It supports a multi-user, collaborative annotation strategy. (3) It cleanly demarcates viewing and analysis from data collection and hosting. (4) It is capable of applying transformations in real-time. (5) It has an easily extensible user interface, allowing addition of specialized modules without rewriting the viewer.
Keywords: Annotation, automated electron microscopy, citizen science, computational methods, connectome, networks, visualization
Semi-automated Neuron Boundary Detection and Slice Traversal Algorithm for Segmentation of Neurons from Electron Microscopy Images|
E. Jurrus, S. Watanabe, R. Guily, A.R.C. Paiva, M.H. Ellisman, E.M. Jorgensen, T. Tasdizen. In Microscopic Image Analysis with Applications in Biology (MIAAB) Workshop, 2011.
Neuroscientists are developing new imaging techniques and generating large volumes of data in an effort to understand the complex structure of the nervous system. To aid in the analysis, new segmentation techniques for identifying neurons in these feature rich datasets are required. However, the extremely anisotropic resolution of the data makes segmentation and tracking across slices difficult. This paper presents a complete method for segmenting neurons in electron microscopy images and visualizing them in three dimensions. First, we present an advanced method for identifying neuron membranes, necessary for whole neuron segmentation, using a machine learning approach. Next, neurons are segmented in each two-dimensional section and connected using correlation of regions between sections. These techniques, combined with a visual user interface, enable users to quickly segment whole neurons in large volumes.
Microfluidic laminate-based phantom for diffusion tensor-magnetic resonance imaging|
R. Samuel, H.J. Sant, F. Jiao, C.R. Johnson, B.K. Gale. In Journal of Micromech. Microeng., Vol. 21, pp. 095027--095038. 2011.
Geometric Correspondence for Ensembles of Nonregular Shapes|
M. Datar, Y. Gur, B. Paniagua, M. Styner, R.T. Whitaker. In Proceedings of Medical Image Computing and Computer-Assisted Intervention (MICCAI 2011), Lecture Notes in Computer Science (LNCS), Vol. 6892, pp. 368--375. 2011.
PubMed ID: 21995050
PubMed Central ID: PMC3346950
An ensemble of biological shapes can be represented and analyzed with a dense set of point correspondences. In previous work, optimal point placement was determined by optimizing an information theoretic criterion that depends on relative spatial locations on different shapes combined with pairwise Euclidean distances between nearby points on the same shape. These choices have prevented such methods from effectively characterizing shapes with complex geometry such as thin or highly curved features. This paper extends previous methods for automatic shape correspondence by taking into account the underlying geometry of individual shapes. This is done by replacing the Euclidean distance for intrashape pairwise particle interactions by the geodesic distance. A novel set of numerical techniques for fast distance computations on curved surfaces is used to extract these distances. In addition, we introduce an intershape penalty term that incorporates surface normal information to achieve better particle correspondences near sharp features. Finally, we demonstrate this new method on synthetic and biological datasets.
Detection of crossing white matter fibers with high-order tensors and rank-k decompositions|
F. Jiao, Y. Gur, C.R. Johnson, S. Joshi. In Proceedings of the International Conference on Information Processing in Medical Imaging (IPMI 2011), Lecture Notes in Computer Science (LNCS), Vol. 6801, pp. 538--549. 2011.
PubMed Central ID: PMC3327305
Fundamental to high angular resolution diffusion imaging (HARDI), is the estimation of a positive-semidefinite orientation distribution function (ODF) and extracting the diffusion properties (e.g., fiber directions). In this work we show that these two goals can be achieved efficiently by using homogeneous polynomials to represent the ODF in the spherical deconvolution approach, as was proposed in the Cartesian Tensor-ODF (CT-ODF) formulation. Based on this formulation we first suggest an estimation method for positive-semidefinite ODF by solving a linear programming problem that does not require special parametrization of the ODF. We also propose a rank-k tensor decomposition, known as CP decomposition, to extract the fibers information from the estimated ODF. We show that this decomposition is superior to the fiber direction estimation via ODF maxima detection as it enables one to reach the full fiber separation resolution of the estimation technique. We assess the accuracy of this new framework by applying it to synthetic and experimentally obtained HARDI data.
Monte Carlo expectation maximization with hidden Markov models to detect functional networks in resting-state fMRI|
W. Liu, S. Awate, J. Anderson, D. Yurgelun-Todd, P.T. Fletcher. In Machine Learning in Medical Imaging, Lecture Notes in Computer Science (LNCS), Vol. 7009/2011, pp. 59--66. 2011.
Functional connectivity magnetic resonance imaging classification of autism|
J.S. Anderson, J.A. Nielsen, A.L. Froehlich, M.B. DuBray, T.J. Druzgal, A.N. Cariello, J.R. Cooperrider, B.A. Zielinski, C. Ravichandran, P.T. Fletcher, A.L. Alexander, E.D. Bigler, N. Lange, J.E. Lainhart. In Brain, pp. (published online). 2011.
PubMed ID: 22006979
Group differences in resting state functional magnetic resonance imaging connectivity between individuals with autism and typically developing controls have been widely replicated for a small number of discrete brain regions, yet the whole-brain distribution of connectivity abnormalities in autism is not well characterized. It is also unclear whether functional connectivity is sufficiently robust to be used as a diagnostic or prognostic metric in individual patients with autism. We obtained pairwise functional connectivity measurements from a lattice of 7266 regions of interest covering the entire grey matter (26.4 million connections) in a well-characterized set of 40 male adolescents and young adults with autism and 40 age-, sex- and IQ-matched typically developing subjects. A single resting state blood oxygen level-dependent scan of 8 min was used for the classification in each subject. A leave-one-out classifier successfully distinguished autism from control subjects with 83% sensitivity and 75\% specificity for a total accuracy of 79\% (P = 1.1 x 10-7). In subjects less than 20 years of age, the classifier performed at 89\% accuracy (P = 5.4 x 10-7). In a replication dataset consisting of 21 individuals from six families with both affected and unaffected siblings, the classifier performed at 71\% accuracy (91\% accuracy for subjects less than 20 years of age). Classification scores in subjects with autism were significantly correlated with the Social Responsiveness Scale (P = 0.05), verbal IQ (P = 0.02) and the Autism Diagnostic Observation Schedule-Generic's combined social and communication subscores (P = 0.05). An analysis of informative connections demonstrated that region of interest pairs with strongest correlation values were most abnormal in autism. Negatively correlated region of interest pairs showed higher correlation in autism (less anticorrelation), possibly representing weaker inhibitory connections, particularly for long connections (Euclidean distance greater than 10 cm). Brain regions showing greatest differences included regions of the default mode network, superior parietal lobule, fusiform gyrus and anterior insula. Overall, classification accuracy was better for younger subjects, with differences between autism and control subjects diminishing after 19 years of age. Classification scores of unaffected siblings of individuals with autism were more similar to those of the control subjects than to those of the subjects with autism. These findings indicate feasibility of a functional connectivity magnetic resonance imaging diagnostic assay for autism.
Geodesic Regression on Riemannian Manifolds|
P.T. Fletcher. In Proceedings of the Third MICCIA International Workshop on Mathematical Foundations of Computational Anatomy (MFCA), Toronto, Canada, pp. 75--86. 2011.
Horoball hulls and extents in positive definite space|
P.T. Fletcher, J. Moeller, J. Phillips, S. Venkatasubramanian. In Algorithms and Data Structures, Lecture Notes in Computer Science (LNCS), Vol. 6844/2011, pp. 386--398. 2011.
WE-E-BRC-06: Comparison of Two Methods of Contouring Internal Target Volume on Multiple 4DCT Data Sets from the Same Subjects: Maximum Intensity Projection and Combination of 10 Phases|
B. Salter, B. Wang, M. Sadinski, S. Ruhnau, V. Sarkar, J. Hinkle, Y. Hitchcock, K. Kokeny, S. Joshi. In Medical Physics, Vol. 38, No. 6, pp. 3820. 2011.
WE-E-BRC-05: Voxel Based Four Dimensional Tissue Deformation Reconstruction (4DTDR) Validation Using a Real Tissue Phantom|
M. Szegedi, J. Hinkle, S. Joshi, V. Sarkar, P. Rassiah-Szegedi, B. Wang, B. Salter. In Medical Physics, Vol. 38, pp. 3819. 2011.
Statistical Growth Modeling of Longitudinal DT-MRI for Regional Characterization of Early Brain Development|
N. Sadeghi, M.W. Prastawa, P.T. Fletcher, J.H. Gilmore, W. Lin, G. Gerig. In Proceedings of the Medical Image Computing and Computer Assisted Intervention (MICCAI) 2011 Workshop on Image Analysis of Human Brain Development, pp. 1507--1510. 2011.
A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.
Sample drift correction in 3D fluorescence photoactivation localization microscopy|
M.J. Mlodzianoski, J.M. Schreiner, S.P. Callahan, K. Smolková, A. Dlasková, J. Šantorová, P. Ježek, J. Bewersdorf. In Optics Express, Vol. 19, No. 16, pp. 15009--15019. 2011.
Comparison of acute and chronic traumatic brain injury using semi-automatic multimodal segmentation of MR volumes|
A. Irimia, M.C. Chambers, J.R. Alger, M. Filippou, M.W. Prastawa, Bo Wang, D. Hovda, G. Gerig, A.W. Toga, R. Kikinis, P.M. Vespa, J.D. Van Horn. In Journal of Neurotrauma, Vol. 28, No. 11, pp. 2287--2306. November, 2011.
PubMed ID: 21787171
Although neuroimaging is essential for prompt and proper management of traumatic brain injury (TBI), there is a regrettable and acute lack of robust methods for the visualization and assessment of TBI pathophysiology, especially for of the purpose of improving clinical outcome metrics. Until now, the application of automatic segmentation algorithms to TBI in a clinical setting has remained an elusive goal because existing methods have, for the most part, been insufficiently robust to faithfully capture TBI-related changes in brain anatomy. This article introduces and illustrates the combined use of multimodal TBI segmentation and time point comparison using 3D Slicer, a widely-used software environment whose TBI data processing solutions are openly available. For three representative TBI cases, semi-automatic tissue classification and 3D model generation are performed to perform intra-patient time point comparison of TBI using multimodal volumetrics and clinical atrophy measures. Identification and quantitative assessment of extra- and intra-cortical bleeding, lesions, edema, and diffuse axonal injury are demonstrated. The proposed tools allow cross-correlation of multimodal metrics from structural imaging (e.g., structural volume, atrophy measurements) with clinical outcome variables and other potential factors predictive of recovery. In addition, the workflows described are suitable for TBI clinical practice and patient monitoring, particularly for assessing damage extent and for the measurement of neuroanatomical change over time. With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options.
Comparison of the endocranial ontogenies between chimpanzees and bonobos via temporal regression and spatiotemporal registration|
S. Durrleman, X. Pennec, A. Trouvé, N. Ayache, J. Braga. In Journal of Human Evolution, pp. 74--88. January, 2011.
PubMed ID: 22137587
This paper aims at quantifying ontogenetic differences between bonobo (Pan paniscus) and chimpanzee (Pan troglodytes) endocrania, using dental development as a timeline. We utilize a methodology based on smooth and invertible deformations combined with a metric of "currents" that defines a distance between endocranial surfaces and does not rely on correspondence between landmarks. This allows us to perform a temporal surface regression that estimates typical endocranial ontogenetic trajectories separately for bonobos and chimpanzees. We highlight non-linear patterns of endocranial ontogenetic change and significant differences between species at local anatomical levels rather than considering the endocranium as a uniform entity. A spatiotemporal registration permits the quantification of inter-species differences decomposed into a morphological deformation (accounting for size and shape differences independently of age) and a time warp (accounting for changes in the dynamics of development). Our statistical simulations suggest that patterns of endocranial volume (EV) increase may differ significantly between bonobos and chimpanzees, with an earlier phase of a relatively rapid increase (preferentially at some endocranial subdivisions) in the former and a much later phase of relatively rapid increase in the latter. As a consequence, the chimpanzee endocranium appears to reach its adult size later. Moreover, the time warp indicates that juvenile bonobos develop much slower than juvenile chimpanzees, suggesting that inter-specific ontogenetic shifts do not only concern EV increase, but also the rate of shape changes over time. Our method provides, for the first time, a quantitative estimation of inter-specific ontogenetic shifts that appear to differentiate non-linearly.
A fast iterative method for solving the Eikonal equation on triangulated surfaces|
Z. Fu, W.-K. Jeong, Y. Pan, R.M. Kirby, R.T. Whitaker. In SIAM Journal of Scientific Computing, Vol. 33, No. 5, pp. 2468--2488. 2011.
PubMed Central ID: PMC3360588
This paper presents an efficient, fine-grained parallel algorithm for solving the Eikonal equation on triangular meshes. The Eikonal equation, and the broader class of Hamilton–Jacobi equations to which it belongs, have a wide range of applications from geometric optics and seismology to biological modeling and analysis of geometry and images. The ability to solve such equations accurately and efficiently provides new capabilities for exploring and visualizing parameter spaces and for solving inverse problems that rely on such equations in the forward model. Efficient solvers on state-of-the-art, parallel architectures require new algorithms that are not, in many cases, optimal, but are better suited to synchronous updates of the solution. In previous work [W. K. Jeong and R. T. Whitaker, SIAM J. Sci. Comput., 30 (2008), pp. 2512–2534], the authors proposed the fast iterative method (FIM) to efficiently solve the Eikonal equation on regular grids. In this paper we extend the fast iterative method to solve Eikonal equations efficiently on triangulated domains on the CPU and on parallel architectures, including graphics processors. We propose a new local update scheme that provides solutions of first-order accuracy for both architectures. We also propose a novel triangle-based update scheme and its corresponding data structure for efficient irregular data mapping to parallel single-instruction multiple-data (SIMD) processors. We provide detailed descriptions of the implementations on a single CPU, a multicore CPU with shared memory, and SIMD architectures with comparative results against state-of-the-art Eikonal solvers.
Synergy of image analysis for animal and human neuroimaging supports translational research on drug abuse|
G. Gerig, I. Oguz, S. Gouttard, J. Lee, H. An, W. Lin, M. McMurray, K. Grewen, J. Johns, M.A. Styner. In Frontiers in Child and Neurodevelopmental Psychiatry, Vol. 2, Edited by Linda Mayes, pp. 9 pages. 2011.
Efficient Probabilistic and Geometric Anatomical Mapping Using Particle Mesh Approximation on GPUs|
L.K. Ha, M.W. Prastawa, G. Gerig, J.H. Gilmore, C.T. Silva. In International Journal of Biomedical Imaging, Special Issue in Parallel Computation in Medical Imaging Applications, Vol. 2011, Note: Article ID 572187, pp. 16 pages. 2011.
Multi-scale Unbiased Diffeomorphic Atlas Construction on Multi-GPUs|
L.K. Ha, J. Krüger, S. Joshi, C.T. Silva. Vol. 1, Ch. 10, Morgan Kaufmann, pp. 42. 2011.
In this chapter, we present a high performance multi-scale 3D image processing framework to exploit the parallel processing power of multiple graphic processing units (Multi-GPUs) for medical image analysis. We developed GPU algorithms and data structures that can be applied to a wide range of 3D image processing applications and efficiently exploit the computational power and massive bandwidth offered by modern GPUs. Our framework helps scientists solve computationally intensive problems which previously required super computing power. To demonstrate the effectiveness of our framework and to compare to existing techniques, we focus our discussions on atlas construction - the application of understanding the development of the brain and the progression of brain diseases.