Workshop 6: Brain Imaging

(June 9,2008 - June 13,2008 )

Organizers


Sylvain Bouix
Department of Psychiatry, Brigham and Women's Hospital
Allen Tannenbaum
Computer Science and Applied Mathematics, Stony Brook University

Medical imaging has been undergoing a revolution in the past decade with the advent of faster, more accurate, and cheaper imaging modalities. This powerful new hardware has driven the need for corresponding software development, which in turn has provided a major impetus for new algorithms in signal and image processing. Many of these algorithms are based on partial differential equations, curvature driven flows, geometry, and novel statistical techniques. The purpose of this workshop is to bring together researchers from all aspects of medical imaging with the emphasis on brain imaging for a multi-disciplinary workshop in which various views may be shared, and hopefully new research directions may be opened.

A key research area is to formulate biomedical engineering principles based on a rigorous mathematical foundation in order to develop general-purpose software methods that can be integrated into complete therapy delivery systems. Such systems support the more effective delivery of many image-guided procedures--biopsy, minimally invasive surgery, and radiation therapy, among others.

Mathematical models form the basis of biomedical computing in general and medical imaging in particular. Basing those models on data extracted from images continues to be a fundamental technique for achieving scientific progress in experimental, clinical biomedical, and behavioral research. Images, acquired by a range of techniques across all biological scales, are central to understanding biological problems and their impacts on human health purely because images now encompass so many techniques beyond the visible light photographs and microscope images of biology's early years. Today, imaging is better thought of as geometrically arranged arrays of data samples measuring such diverse physical quantities as time-varying hemoglobin deoxygenation during neuronal metabolism or vector-valued measurments of water diffusion through and within tissue. The broadening scope of imaging as a way to organize our observations of the biophysical world has led to a dramatic increase in our ability to apply novel processing techniques and to combine multiple channels of data into sophisticated and complex mathematical models of physiological function and dysfunction.

The workshop will bring together a diverse group of researchers from the medical imaging community with various backgrounds including radiology, psychiatry, signal and image processing, surgery, physics, mathematics, and neurophysiology.

The workshop will focus on the following topics:

  • Medical Imaging Modalities for Brain Imagery: MRI, fMRI, DTI, PET, SPECT, CT;
  • Medical Imaging Processing and Computation: Registration, segmentation, visualization, computer graphics, shape theory;
  • Mathematical Algorithms: Statistical, geometric, partial differential equations;
  • Applications: Image guided surgery (e.g., interventional magnetics), imaging for understanding pathology (Alzheimer's disease, Parkinson's, OCD, clinical depression), image processing and deep brain stimulation.

Accepted Speakers

Sylvain Bouix
Department of Psychiatry, Brigham and Women's Hospital
Allan Dobbins
Dept. of Biomedical Engineering, University of Alabama at Birmingham
James Duncan
Biomedical Engineering, Diagnostic Radiology, and Electrical Engineering, Yale University
James Fallon
Psychiatry and Human Behavior, University of California, Irvine
Polina Golland
Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology
Xiaoping Hu
Biomedical Engineering, Emory University
John Melonakos
School of ECE, Georgia Institute of Technology
Michael Miller
Center for Imaging Science, Johns Hopkins University
Marcel Prastawa
Scientific Computing and Imaging Institute, University of Utah
Yogesh Rathi
Dept. of Psychiatry, Brigham and Women's Hospital, Harvard Medical School
Kaleem Siddiqi
School of Computer Science & Centre for Intelligent Machines, McGill University, Macdonald Campus
Stefano Soatto
Computer Science, University of California, Los Angeles
Ganesh Sundaramoorthi
Department of Computer Science, University of California, Los Angeles
Allen Tannenbaum
Computer Science and Applied Mathematics, Stony Brook University
Zhuowen Tu
Department of Neurology, University of California, Los Angeles
Michael Vannier
Radiology, University of Chicago
William Wells
Department of Radiology, Brigham and Women's Hospital
Keith Worsley
Mathematics and Statistics, McGill University, Macdonald Campus
Steven Zucker
Computer Science, Yale University
Monday, June 9, 2008
Time Session
10:30 AM
11:15 AM
James Fallon - Neuroanatomy and Imaging

Behavior is assumed to emerge from specific circuits in the brain. These circuits are routinely inferred from functional brain imaging patterns. Differences in patterns of functional images between, for example, task conditions, drug conditions, and between control and pathological conditions are routinely used to inform researchers of basic biological mechanisms and pathophysiological processes in normal and abnormal brain function. There are, however, multiple levels and principles of organization of brain circuitry, often beyond the resolution and/or functional capabilities of imaging techniques such as PET, fMRI, and DTI. Furthermore, each neurological/psychiatric disorder differentially affects neuroanatomical modules and types of circuitry, and these must be borne in mind in the analyses and discussion of implied circuitry in imaging experiments.

01:30 PM
02:15 PM
Michael Vannier - Imaging as a Biomarker

Imaging as a biomarker of drug response is becoming an increasingly important field of research. Government, industry and academia have agreed to collaborate on improving the development of therapies and outcomes for common diseases, especially cancer, through biomarker development and evaluation. Biomarkers are biological indicators of disease or therapeutic effects that can be measured by in vivo biomedical imaging and molecular imaging in particular, as well as other in vitro or laboratory methods. Recent work has shown that biomedical imaging can provide an early indication of drug response by use of CT, MRI and PET/SPECT.


Many sources of uncertainty exist in imaging as a biomarker. Biological variability, for example, is a factor both drug- and patient-dependent and thus difficult to characterize or model. However, other uncertainties are associated with the image data collection platform and the robustness of software tools required for reliable, quantitative measurement of change over time, such as tumor volume, radioactive tracer activity, or contrast agent dynamics. All these sources of uncertainty significantly affect the statistical power of clinical drug or therapy trials.


The challenges and opportunities for imaging biomarkers are explored for brain imaging, especially brain traumatic injury and developmental disorders.

Tuesday, June 10, 2008
Time Session
09:00 AM
09:45 AM
Marcel Prastawa - Statistical and Physical Models for Generating a Brain Tumor MR Image Validation Database

Automatic segmentation of pathological brain MR images with tumors is crucial for analyzing tumor characteristics, efficacy of drug treatments, and surgical planning. Many segmentation schemes have been developed, yet validation and performance comparisons are difficult since there are no public brain tumor MRI databases with consistent, reliable ground truth. In this talk, we will present the practical use of statistical and physical modeling for generating synthetic brain tumor MR images with known, objective ground truth. We combine a physical deformation model and a physical infiltration model to generate anatomical data with pathological structures (tumor and edema). We then use a statistical image generation model to obtain synthetic multi-modal brain tumor MR images that correspond to the generated anatomical data. The synthetic brain tumor MRI database has potential uses for validating different segmentation schemes, for surgical simulations, and for clinical training.

10:30 AM
11:15 AM
Michael Miller - Computational Functional Anatomy

Computational Anatomy is the study of the shape and structure of manifolds in human anatomy. This talk reviews results from CA along these lines, including (i) embedding of shapes into a metric structure via flows of diffeomorphisms (ii) conservation laws for geodesics describing metric connection of shapes (iii) statistics on families of shapes encoded via these metrics. The emerging focus in Computational Functional Anatomy is the inclusion of the study of function in the curved coordinates of anatomical manifolds. Methods for performing inference in this setting are examined coupled to morphometric studies.

01:30 PM
02:15 PM
Steven Zucker - N/A

N/A

03:00 PM
03:45 PM
James Duncan - Model-Based Analysis of Brain Structure/Function from MRI

Quantitative analysis of brain structure and function is important in the study of many neurological and neuropsychiatric disorders. This talk will present work grounded in the use of spatial constraints and mathematical optimization to analyze neuroanatomical structure and function of the human brain from Magnetic Resonance Images (MRI). We will first describe our approach to segmenting cortical gray matter using a coupled level set strategy. Next, we will present an approach to subcortical segmentation based on the use of both object self-shape and neighborhood spatial relationship priors, both embedded in a level set- parameterized, maximum a posteriori (MAP) estimation framework. Finally, we will discuss recent work aimed at incorporating prior knowledge of brain activation patterns and segmented anatomical information (gray matter/white matter) to provide improved estimates of activation strength in a functional MRI (fMRI) attention-modulation experiment, again using a MAP estimation approach.

04:15 PM
05:00 PM
Zhuowen Tu - Towards Automated Whole Brain Image Segmentation

Segmenting cortical and sub-cortical structures from 3D brain images is of significant practical importance. In this talk, we will discuss a new statistical modeling/computing framework and show its application for whole brain segmentation. The notion of using context information for solving the medical imaging problem has been increasingly realized in the field. However, how to learn an effective and efficient context model, together with the image appearance, remains mostly unknown. The current literature using Markov Random Fields (MRFs) and Conditional Random Fields (CRFs) often involves specific algorithm design, in which the modeling and computing stages are studied in isolation. Medical images observe complex patterns, contributed by many factors such as textures (homogeneous, inhomogeneous, and structured) and machine parameters. This auto-context model is about a new attempt to push the appearance and context information in a seamless way by automatically incorporating a large number of short-range and long-range features. The resulting algorithm has nearly the identical procedures in computing (testing) as in modeling (training), and thus, achieves rapid performance the holistic medical image segmentation task. We will show a variety of sub-cortical and cortical segmentation results using this model.



 
05:30 PM
06:30 PM
James Fallon - Neuroanatomy and Imaging

Behavior is assumed to emerge from specific circuits in the brain. These circuits are routinely inferred from functional brain imaging patterns. Differences in patterns of functional images between, for example, task conditions, drug conditions, and between control and pathological conditions are routinely used to inform researchers of basic biological mechanisms and pathophysiological processes in normal and abnormal brain function. There are, however, multiple levels and principles of organization of brain circuitry, often beyond the resolution and/or functional capabilities of imaging techniques such as PET, fMRI, and DTI. Furthermore, each neurological/psychiatric disorder differentially affects neuroanatomical modules and types of circuitry, and these must be borne in mind in the analyses and discussion of implied circuitry in imaging experiments.

Wednesday, June 11, 2008
Time Session
09:00 AM
09:45 AM
William Wells - A Marginalized MAP Approach and EM Optimization for Pair-Wise Registration

We formalize the pair-wise registration problem in a maximum a posteriori (MAP) framework that employs a multinomial model of joint intensities with parameters for which we only have a prior distribution. To obtain an MAP estimate of the aligning transformation alone, we treat the multinomial parameters as nuisance parameters, and marginalize them out. If the prior on those is uninformative, the marginalization leads to registration by minimization of joint entropy. With an informative prior, the marginalization leads to minimization of the entropy of the data pooled with pseudo observations from the prior. In addition, we show that the marginalized objective function can be optimized by the Expectation-Maximization (EM) algorithm, which yields a simple and effective iteration for solving entropy-based registration problems. Experimentally, we demonstrate the effectiveness of the resulting EM iteration for rapidly solving a challenging intra-operative registration problem.


This is joint work with Lilla Zollei and Mark Jenkinson

10:30 AM
11:15 AM
Polina Golland - Modeling Anatomical Heterogeneity in Populations

We present iCluster, a fast and efficient algorithm that clusters a set of images while co-registering them using a parameterized, nonlinear transformation model. The output of the algorithm is a small number of template images that represent different modes in a population. This is in contrast with traditional, hypothesis-driven computational anatomy approaches that assume a single template to construct an atlas. We derive the algorithm based on a generative model of an image population as a mixture of deformable template images. The experimental results demonstrate that the algorithm can discover interesting sub-populations, suggesting applications in atlas-based segmentation and statistical analysis of anatomical differences in clinical studies.


This is joint work with Mert Sabuncu and Serdar Balci.

01:30 PM
02:15 PM
Ganesh Sundaramoorthi - Tubular Surface Evolution for Segmentation of Tubular Structures with Applications to the Cingulum Bundle from DW-MRI

In this talk, we provide a framework for extracting tubular structures from medical imagery. The general methodology will be applied to modeling and extracting the cingulum bundle (CB) from diffusion-weighted imagery (DW-MRI) of the brain. The CB is a tube-like structure in the brain that is of major importance to clinicians since it may be helpful in diagnosing schizophrenia. This structure consists of a collection of fibers in the brain that have locally similar diffusion patterns, but vary globally. Standard region-based segmentation techniques adapted to DW-MRI are not suitable for this application because the diffusion pattern of the CB cannot be described by a few simple global statistics. Typical active surface models extended to DW-MRI allow for arbitrary deformations that give rise to unlikely shapes, which do not respect the tubular geometry of the CB. In this work, we explicitly model the CB as a tube-like surface and construct a general class of energies defined on tube-like surfaces. Modeling the CB as a tube-like surface is a natural shape prior. Since a tube is characterized by a center-line and a radius function, the method is reduced to a curve evolution that is computationally much less costly than an arbitrary surface evolution. Our tubular model of the CB also has the advantage that computing shape statistics and functions defined on the CB are simplified.

03:00 PM
03:45 PM
Keith Worsley - Statistical Analysis of Surface Data

This presentation emphasizes the mechanics, rather than the methods, from data to publication. I will present Matlab software (SurfStat) for the statistical analysis of univariate and ultivariate surface data using linear mixed effects models (fitted by ReML) and random field theory (RFT). SurfStat is intended for cortical thickness data on triangular meshes, but it will handle any triangulated surface data; the only requirement is that the triangulation scheme must be the same for all surfaces, i.e. the data must be registered to a common surface. Inference uses RFT for T, F, Hotelling's T2 and Roy's maximum root statistics. An attractive feature is the use of a model formula rather than a design matrix for specifying the linear model. It is fast, because everything is loaded into memory, permitting a truly interactive analysis, with no need for batch. Finally, off-the-shelf Matlab graphics are ready to publish.

04:15 PM
05:15 PM
Daniela Calvetti - N/A

N/A

Thursday, June 12, 2008
Time Session
09:00 AM
09:45 AM
Yogesh Rathi - Directional Functions for Orientation Distribution Function Estimation in the Context of Q-ball Imaging

Orientation distribution functions (ODF) can be used to represent multiple fiber crossings in the brain as recorded by High Angular Resolution Diffusion Imaging (HARDI). Current state-of-the-art methods use spherical radial basis functions or spherical harmonics to represent the ODF. These methods however require many coefficients to represent each ODF and ambiguities can occur when the principal diffusion directions are to be extracted. In this talk, we propose to use "directional functions" for representing the signal and provide closed form expressions to approximate the corresponding ODF. These functions require very few parameters (three) to represent the ODF and the principal diffusion directions are naturally obtained during the estimation process. We will also show how to perform interpolation using these directional functions and propose 2 metrics, a Euclidean and a hybrid-Euclidean-Riemannian, to compute geodesic distances between 2 ODFs.

10:15 AM
11:00 AM
John Melonakos - Tractography Segmentation for DW-MRI Analysis

Many frameworks have been proposed for the analysis of brain DW-MRI imagery. The objective of these frameworks is to yield a greater understanding of structure and connectivity within the brain and the relation of these to function. In this talk, we present a framework for the analysis of DW-MRI datasets that consists of two components: 1) an optimal path connecting two regions of interest and 2) a volumetric fiber bundle segmentation, initialized on the optimal path. This framework has the advantage of providing both connectivity and structural information about fiber bundles. Also, in this talk, we discuss the pros/cons of this framework and challenges in the state-of-the-art of fiber bundle segmentation.

11:15 AM
12:00 PM
Allan Dobbins - Binocular Vision: From Psychophysics to Imaging

Binocular vision is central to both space and form perception and plays a critical role in visuomotor feedback control. In this talk I will describe work that demonstrates a dissociation of perception from feedback control in a way that highlights the different computational requirements of these tasks. Attempts to look at the cortical loci of these processes will be described.

Friday, June 13, 2008
Time Session
Name Affiliation
Abosch , Aviva joh04249@umn.edu Department of Neurosurgery, University of Minnesota
Aguda, Baltazar bdaguda@gmail.com Mathematical Biosciences Institute, The Ohio State University
Baker, Greg baker.27@osu.edu Department of Mathematics, The Ohio State University
Best, Janet jbest@mbi.osu.edu
Borstad, Alexandra borstad.2@osu.edu Allied Medicine, The Ohio State University
Bouix, Sylvain sylvain@bwh.harvard.edu Department of Psychiatry, Brigham and Women's Hospital
Calvetti, Daniela dxc57@case.edu Mathematics and Cognitive Science, Case Western Reserve University
Chaturvedi, Ashu ashu@case.edu Biomedical Engineering, Case Western Reserve University
Chen, Linda chen.151@osu.edu Department of Mathematics, The Ohio State University
Chen, Pengwen pengwen@math.uconn.edu Mathematics, University of Connecticut
Coskun, Huseyin hcusckun@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Day, Judy jday@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Djordjevic, Marko mdjordjevic@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Dobbins, Allan adobbins@uab.edu Dept. of Biomedical Engineering, University of Alabama at Birmingham
Duncan, James james.duncan@yale.edu Biomedical Engineering, Diagnostic Radiology, and Electrical Engineering, Yale University
Enciso, German German_Enciso@hms.harvard.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Fallon, James jfallon@uci.edu Psychiatry and Human Behavior, University of California, Irvine
Fan, Yiying yxf28@case.edu Statistics, Case Western Reserve University
Golland, Polina polina@csail.mit.edu Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology
Gooch, Keith gooch.20@osu.edu Biomedical Engineering, The Ohio State University
Grajdeanu, Paula pgrajdeanu@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Green, Edward egreen@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Grotewold, Erich grotewold.1@osu.edu MBI-Long Term Visitor, The Ohio State University
Hamilton, Ian hamilton.598@osu.edu EEOB, The Ohio State University
Hovmoller, Rasmus rhovmoller@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Hsu, Jason hsu.1@osu.edu Department of Statistics, The Ohio State University
Hu, Xiaoping xhu@bme.gatech.edu Biomedical Engineering, Emory University
Ingram, Ross rni1@pitt.edu Computational Mathematics, University of Pittsburgh
Janoos, Firdaus janoos.1@osu.edu CSE, The Ohio State University
Jia, Guang jia.11@osu.edu Department of Radiology, The Ohio State University
Kanayet, Frank kanayet.1@osu.edu Psychology, The Ohio State University
Kao, Chiu-Yen kao.71@osu.edu MBI - Long Term Visitor, The Ohio State University
Kassen, Rune r.kaasen@mat.dtu.dk MBI-Long Term Visitor, The Ohio State University
Kim, Namhee namhee@stat.ohio-state.edu Department of Statistics, The Ohio State University
Kim, Yangjin ykim@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Laxminarayan, Srinivas slaxmina@gmail.com Electrical and Computer Engineering, Northeastern University
Lin, Shili lin.328@osu.edu Department of Statistics, The Ohio State University
Lin, Xiaodong linxd@math.uc.edu Department of Mathematical Sciences, University of Cincinnati
Liu, Hong liu_hong_hl@lilly.com Lilly Center for Molecular and Anatomical Imaging, Eli Lilly and Company
Lou, Yuan lou@math.ohio-state.edu MBI - Long Term Visitor, The Ohio State University
Machiraju, Raghu machiraju@math.ohio-state.edu Computer Science and Engineering, The Ohio State University
Manukian, Vahagn vemanuki@ncsu.edu Mathematics, North Carolina State University
Martinez, Aliex martinez.158@osu.edu Electrical and Computer Engineering, The Ohio State University
Masoudieh, Amirali masoudieha@mail.nih.gov Biochemistry, The Ohio State University
Matzavinos, Tasos tasos@math.ohio-state.edu MBI - Long term visitor, The Ohio State University
Mays, Nathaniel nhm@pitt.edu Mathematics, University of Pittsburgh
Mazumder, Sarmistha mazumder.3@osu.edu College of Pharmacology, The Ohio State University
Melonakos, John jmelonak@ece.gatech.edu School of ECE, Georgia Institute of Technology
Miller, Michael mim@cis.jhu.edu Center for Imaging Science, Johns Hopkins University
Moss, Jason jmoss@mail.math.fsu.edu Mathematics, Florida State University
Nevai, Andrew anevai@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Occhipinti, Rossana rossana.occhipinti@case.edu Mathematics, Case Western Reserve University
Oster, Andrew aoester@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Passino, Kevin passino.1@osu.edu EEOB, The Ohio State University
Potter, Dustin potter.153@osu.edu Comprehensive Cancer Center, The Ohio State University
Prastawa, Marcel prastawa@sci.utah.edu Scientific Computing and Imaging Institute, University of Utah
Rathi, Yogesh yogesh.rathi@gmail.com Dept. of Psychiatry, Brigham and Women's Hospital, Harvard Medical School
Rayala, Harika rayala.2@osu.edu Department of Neuromechanics, The Ohio State University
Rempe, Michael mrempe@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Santner, Tom santner.1@osu.edu Department of Statistics, The Ohio State University
Schugart, Richard richard.schugart@wku.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Shen, Li shenli@iupui.edu Center for Neuroimaging, Div. of Imaging Sciences, Dept. of Radiology, Indiana University--Purdue University
Shih, Chih-Wen shih@math.ohio-state.edu MBI - Long term visitor, The Ohio State University
Siddiqi , Kaleem siddiqi@cim.mcgill.ca School of Computer Science & Centre for Intelligent Machines, McGill University, Macdonald Campus
Smith, Greg greg@as.wm.edu MBI - Long term visitor, The Ohio State University
Soatto , Stefano soatto@ucla.edu Computer Science, University of California, Los Angeles
Somersalo , Erkki esomersa@math.tkk.fi Mathematics, Helsinki University of Technology
Srinivasan, Partha p.srinivasan35@csuohio.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Stigler, Brandy bstigler@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Sun, Jiayang jsun@case.edu Statistics, Case Western Reserve University
Sun, Shuying ssun@mbi.osu.edu Mathematical Biosciences Institute (MBI), The Ohio State University
Sundaramoorthi, Ganesh ganeshs@ece.gatech.edu Department of Computer Science, University of California, Los Angeles
Szomolay, Barbara b.szomolay@imperial.ac.uk Mathematical Biosciences Institute (MBI), The Ohio State University
Tannenbaum, Allen tannenba@bme.gatech.edu Computer Science and Applied Mathematics, Stony Brook University
Tu, Zhuowen zhuowen.tu@loni.ucla.edu Department of Neurology, University of California, Los Angeles
Vannier, Michael pmartinez@radiology.bsd.uchicago.edu Radiology, University of Chicago
Verducci, Tom verducci.1@osu.edu Department of Statistics, The Ohio State University
Wells, William sw@bwh.harvard.edu Department of Radiology, Brigham and Women's Hospital
Wilson, Leslie les@math.hawaii.edu Mathematics, University of Hawaii at Manoa
Worsley, Keith worsley@math.mcgill.ca; Mathematics and Statistics, McGill University, Macdonald Campus
Xu, Ronald xu.202@osu.edu Biomedical Engineering, The Ohio State University
Yezzi, Tony ayezzi@ece.gatech.edu School of Electrical and Computer Engineering, Georgia Institute of Technology
Zhao, Yi zhao.178@osu.edu Biomedical Engineering, The Ohio State University
Zucker , Steven steven.zucker@yale.edu Computer Science, Yale University
N/A

N/A

Binocular Vision: From Psychophysics to Imaging

Binocular vision is central to both space and form perception and plays a critical role in visuomotor feedback control. In this talk I will describe work that demonstrates a dissociation of perception from feedback control in a way that highlights the different computational requirements of these tasks. Attempts to look at the cortical loci of these processes will be described.

Model-Based Analysis of Brain Structure/Function from MRI

Quantitative analysis of brain structure and function is important in the study of many neurological and neuropsychiatric disorders. This talk will present work grounded in the use of spatial constraints and mathematical optimization to analyze neuroanatomical structure and function of the human brain from Magnetic Resonance Images (MRI). We will first describe our approach to segmenting cortical gray matter using a coupled level set strategy. Next, we will present an approach to subcortical segmentation based on the use of both object self-shape and neighborhood spatial relationship priors, both embedded in a level set- parameterized, maximum a posteriori (MAP) estimation framework. Finally, we will discuss recent work aimed at incorporating prior knowledge of brain activation patterns and segmented anatomical information (gray matter/white matter) to provide improved estimates of activation strength in a functional MRI (fMRI) attention-modulation experiment, again using a MAP estimation approach.

Neuroanatomy and Imaging

Behavior is assumed to emerge from specific circuits in the brain. These circuits are routinely inferred from functional brain imaging patterns. Differences in patterns of functional images between, for example, task conditions, drug conditions, and between control and pathological conditions are routinely used to inform researchers of basic biological mechanisms and pathophysiological processes in normal and abnormal brain function. There are, however, multiple levels and principles of organization of brain circuitry, often beyond the resolution and/or functional capabilities of imaging techniques such as PET, fMRI, and DTI. Furthermore, each neurological/psychiatric disorder differentially affects neuroanatomical modules and types of circuitry, and these must be borne in mind in the analyses and discussion of implied circuitry in imaging experiments.

Imaging Nature and Nurture in the Human Brain: From Psychosis, Aggression and Murder to Politics and Free Will

The conscious volitional self in our brain perceives and interacts with the world through sensory, motor and cognitive systems that involve largely subconscious neural mechanisms. Experimental manipulations of these mechanisms reveal the brain's remarkable ability to adapt to changed conditions. The volitional self can also be extended through artificial devices, such as brain-machine interfaces, which exploit the brain's ability to incorporate prosthetic extensions. Accurate control of brainmachine interfaces depends on a combination of effective decoding algorithms and the brain's ability to adaptively modify its neural activity. Recently developed implantable recurrent brain-computer interfaces provide artificial feedback connections that the brain can learn to incorporate and that can also modify the brain's neural connections. This talk will explore these issues in light of current advances in neuroscience and neuroprosthetics.



 
Modeling Anatomical Heterogeneity in Populations

We present iCluster, a fast and efficient algorithm that clusters a set of images while co-registering them using a parameterized, nonlinear transformation model. The output of the algorithm is a small number of template images that represent different modes in a population. This is in contrast with traditional, hypothesis-driven computational anatomy approaches that assume a single template to construct an atlas. We derive the algorithm based on a generative model of an image population as a mixture of deformable template images. The experimental results demonstrate that the algorithm can discover interesting sub-populations, suggesting applications in atlas-based segmentation and statistical analysis of anatomical differences in clinical studies.


This is joint work with Mert Sabuncu and Serdar Balci.

Tractography Segmentation for DW-MRI Analysis

Many frameworks have been proposed for the analysis of brain DW-MRI imagery. The objective of these frameworks is to yield a greater understanding of structure and connectivity within the brain and the relation of these to function. In this talk, we present a framework for the analysis of DW-MRI datasets that consists of two components: 1) an optimal path connecting two regions of interest and 2) a volumetric fiber bundle segmentation, initialized on the optimal path. This framework has the advantage of providing both connectivity and structural information about fiber bundles. Also, in this talk, we discuss the pros/cons of this framework and challenges in the state-of-the-art of fiber bundle segmentation.

Computational Functional Anatomy

Computational Anatomy is the study of the shape and structure of manifolds in human anatomy. This talk reviews results from CA along these lines, including (i) embedding of shapes into a metric structure via flows of diffeomorphisms (ii) conservation laws for geodesics describing metric connection of shapes (iii) statistics on families of shapes encoded via these metrics. The emerging focus in Computational Functional Anatomy is the inclusion of the study of function in the curved coordinates of anatomical manifolds. Methods for performing inference in this setting are examined coupled to morphometric studies.

Statistical and Physical Models for Generating a Brain Tumor MR Image Validation Database

Automatic segmentation of pathological brain MR images with tumors is crucial for analyzing tumor characteristics, efficacy of drug treatments, and surgical planning. Many segmentation schemes have been developed, yet validation and performance comparisons are difficult since there are no public brain tumor MRI databases with consistent, reliable ground truth. In this talk, we will present the practical use of statistical and physical modeling for generating synthetic brain tumor MR images with known, objective ground truth. We combine a physical deformation model and a physical infiltration model to generate anatomical data with pathological structures (tumor and edema). We then use a statistical image generation model to obtain synthetic multi-modal brain tumor MR images that correspond to the generated anatomical data. The synthetic brain tumor MRI database has potential uses for validating different segmentation schemes, for surgical simulations, and for clinical training.

Directional Functions for Orientation Distribution Function Estimation in the Context of Q-ball Imaging

Orientation distribution functions (ODF) can be used to represent multiple fiber crossings in the brain as recorded by High Angular Resolution Diffusion Imaging (HARDI). Current state-of-the-art methods use spherical radial basis functions or spherical harmonics to represent the ODF. These methods however require many coefficients to represent each ODF and ambiguities can occur when the principal diffusion directions are to be extracted. In this talk, we propose to use "directional functions" for representing the signal and provide closed form expressions to approximate the corresponding ODF. These functions require very few parameters (three) to represent the ODF and the principal diffusion directions are naturally obtained during the estimation process. We will also show how to perform interpolation using these directional functions and propose 2 metrics, a Euclidean and a hybrid-Euclidean-Riemannian, to compute geodesic distances between 2 ODFs.

Tubular Surface Evolution for Segmentation of Tubular Structures with Applications to the Cingulum Bundle from DW-MRI

In this talk, we provide a framework for extracting tubular structures from medical imagery. The general methodology will be applied to modeling and extracting the cingulum bundle (CB) from diffusion-weighted imagery (DW-MRI) of the brain. The CB is a tube-like structure in the brain that is of major importance to clinicians since it may be helpful in diagnosing schizophrenia. This structure consists of a collection of fibers in the brain that have locally similar diffusion patterns, but vary globally. Standard region-based segmentation techniques adapted to DW-MRI are not suitable for this application because the diffusion pattern of the CB cannot be described by a few simple global statistics. Typical active surface models extended to DW-MRI allow for arbitrary deformations that give rise to unlikely shapes, which do not respect the tubular geometry of the CB. In this work, we explicitly model the CB as a tube-like surface and construct a general class of energies defined on tube-like surfaces. Modeling the CB as a tube-like surface is a natural shape prior. Since a tube is characterized by a center-line and a radius function, the method is reduced to a curve evolution that is computationally much less costly than an arbitrary surface evolution. Our tubular model of the CB also has the advantage that computing shape statistics and functions defined on the CB are simplified.

Towards Automated Whole Brain Image Segmentation

Segmenting cortical and sub-cortical structures from 3D brain images is of significant practical importance. In this talk, we will discuss a new statistical modeling/computing framework and show its application for whole brain segmentation. The notion of using context information for solving the medical imaging problem has been increasingly realized in the field. However, how to learn an effective and efficient context model, together with the image appearance, remains mostly unknown. The current literature using Markov Random Fields (MRFs) and Conditional Random Fields (CRFs) often involves specific algorithm design, in which the modeling and computing stages are studied in isolation. Medical images observe complex patterns, contributed by many factors such as textures (homogeneous, inhomogeneous, and structured) and machine parameters. This auto-context model is about a new attempt to push the appearance and context information in a seamless way by automatically incorporating a large number of short-range and long-range features. The resulting algorithm has nearly the identical procedures in computing (testing) as in modeling (training), and thus, achieves rapid performance the holistic medical image segmentation task. We will show a variety of sub-cortical and cortical segmentation results using this model.



 
Imaging as a Biomarker

Imaging as a biomarker of drug response is becoming an increasingly important field of research. Government, industry and academia have agreed to collaborate on improving the development of therapies and outcomes for common diseases, especially cancer, through biomarker development and evaluation. Biomarkers are biological indicators of disease or therapeutic effects that can be measured by in vivo biomedical imaging and molecular imaging in particular, as well as other in vitro or laboratory methods. Recent work has shown that biomedical imaging can provide an early indication of drug response by use of CT, MRI and PET/SPECT.


Many sources of uncertainty exist in imaging as a biomarker. Biological variability, for example, is a factor both drug- and patient-dependent and thus difficult to characterize or model. However, other uncertainties are associated with the image data collection platform and the robustness of software tools required for reliable, quantitative measurement of change over time, such as tumor volume, radioactive tracer activity, or contrast agent dynamics. All these sources of uncertainty significantly affect the statistical power of clinical drug or therapy trials.


The challenges and opportunities for imaging biomarkers are explored for brain imaging, especially brain traumatic injury and developmental disorders.

A Marginalized MAP Approach and EM Optimization for Pair-Wise Registration

We formalize the pair-wise registration problem in a maximum a posteriori (MAP) framework that employs a multinomial model of joint intensities with parameters for which we only have a prior distribution. To obtain an MAP estimate of the aligning transformation alone, we treat the multinomial parameters as nuisance parameters, and marginalize them out. If the prior on those is uninformative, the marginalization leads to registration by minimization of joint entropy. With an informative prior, the marginalization leads to minimization of the entropy of the data pooled with pseudo observations from the prior. In addition, we show that the marginalized objective function can be optimized by the Expectation-Maximization (EM) algorithm, which yields a simple and effective iteration for solving entropy-based registration problems. Experimentally, we demonstrate the effectiveness of the resulting EM iteration for rapidly solving a challenging intra-operative registration problem.


This is joint work with Lilla Zollei and Mark Jenkinson

Statistical Analysis of Surface Data

This presentation emphasizes the mechanics, rather than the methods, from data to publication. I will present Matlab software (SurfStat) for the statistical analysis of univariate and ultivariate surface data using linear mixed effects models (fitted by ReML) and random field theory (RFT). SurfStat is intended for cortical thickness data on triangular meshes, but it will handle any triangulated surface data; the only requirement is that the triangulation scheme must be the same for all surfaces, i.e. the data must be registered to a common surface. Inference uses RFT for T, F, Hotelling's T2 and Roy's maximum root statistics. An attractive feature is the use of a model formula rather than a design matrix for specifying the linear model. It is fast, because everything is loaded into memory, permitting a truly interactive analysis, with no need for batch. Finally, off-the-shelf Matlab graphics are ready to publish.

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