Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

In praise of tedious anatomy

Functional neuroimaging is fundamentally a tool for mapping function to structure, and its success consequently requires neuroanatomical precision and accuracy. Here we review the various means by which functional activation can be localized to neuroanatomy and suggest that the gold standard should be localization to the individual’s or group’s own anatomy through the use of neuroanatomical knowledge and atlases of neuroanatomy. While automated means of localization may be useful, they cannot provide the necessary accuracy, given variability between individuals. We also suggest that the field of functional neuroimaging needs to converge on a common set of methods for reporting functional localization including a common “standard” space and criteria for what constitutes sufficient evidence to report activation in terms of Brodmann’s areas

Imaging Informatics and the Human Brain Project: the Role of Structure, Review

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Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results

Anatomical landmark based registration of contrast enhanced T1-weighted MR images

In many problems involving multiple image analysis, an im- age registration step is required. One such problem appears in brain tumor imaging, where baseline and follow-up image volumes from a tu- mor patient are often to-be compared. Nature of the registration for a change detection problem in brain tumor growth analysis is usually rigid or affine. Contrast enhanced T1-weighted MR images are widely used in clinical practice for monitoring brain tumors. Over this modality, con- tours of the active tumor cells and whole tumor borders and margins are visually enhanced. In this study, a new technique to register serial contrast enhanced T1 weighted MR images is presented. The proposed fully-automated method is based on five anatomical landmarks: eye balls, nose, confluence of sagittal sinus, and apex of superior sagittal sinus. Af- ter extraction of anatomical landmarks from fixed and moving volumes, an affine transformation is estimated by minimizing the sum of squared distances between the landmark coordinates. Final result is refined with a surface registration, which is based on head masks confined to the sur- face of the scalp, as well as to a plane constructed from three of the extracted features. The overall registration is not intensity based, and it depends only on the invariant structures. Validation studies using both synthetically transformed MRI data, and real MRI scans, which included several markers over the head of the patient were performed. In addition, comparison studies against manual landmarks marked by a radiologist, as well as against the results obtained from a typical mutual information based method were carried out to demonstrate the effectiveness of the proposed method

Landmarking the brain for geometric morphometric analysis: An error study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes. © 2014 Chollet et al

Anatomo-functional correspondence in the superior temporal sulcus

The superior temporal sulcus (STS) is an intriguing region both for its complex anatomy and for the multiple functions that it hosts. Unfortunately, most studies explored either the functional organization or the anatomy of the STS only. Here, we link these two aspects by investigating anatomo-functional correspondences between the voice-sensitive cortex (Temporal Voice Areas) and the STS depth. To do so, anatomical and functional scans of 116 subjects were processed such as to generate individual surface maps on which both depth and functional voice activity can be analyzed. Individual depth profiles of manually drawn STS and functional profiles from a voice localizer (voice > non-voice) maps were extracted and compared to assess anatomo-functional correspondences. Three major results were obtained: first, the STS exhibits a highly significant rightward depth asymmetry in its middle part. Second, there is an anatomo-functional correspondence between the location of the voice-sensitive peak and the deepest point inside this asymmetrical region bilaterally. Finally, we showed that this correspondence was independent of the gender and, using a machine learning approach, that it existed at the individual level. These findings offer new perspectives for the understanding of anatomo-functional correspondences in this complex cortical region

Evaluating Spatial Normalization Methods for the Human Brain

Cortical stimulation mapping (CSM) studies have shown cortical locations for language function are highly variable from one subject to the next. Because no two cortical surfaces are alike and language is a higher order cognitive function, observed variability is attributable to a combination of functional and anatomical variation. If individual variation can be normalized, patterns of language organization may emerge that were heretofore hidden. In order to discover whether or not such patterns exist, computer-aided spatial normalization is required. Because CSM data has been collected on the cortical surface, we believe that a surface-based normalization method will provide more accurate results than will a volume-based method. To investigate this hypothesis, we evaluate a surface-based (Caret) and volume-based method (SPM2). For our application, the "ideal" method would i) minimize variation as measured by spread reduction between cortical language sites across subjects while also ii) preserving anatomical localization of sites. Evaluation technique: Eleven MR image volumes and corresponding CSM site coordinates were selected. Images were segmented to create left hemisphere surface reconstruction for each patient. Individual surfaces were registered to the colin27 human brain atlas using each method. Deformation parameters from each method were applied to CSM coordinates to obtain post-normalization coordinates in 2D space and 3D ICBM152 space. Accuracy metrics were calculated i) as mean distance between language sites across subjects in both 2D and 3D space and ii) by visual inspection of post-normalization site locations on a 2D map. Results: Globally, we found no statistically significant difference between CARET (surface-based method) and SPM2 (volume-based method) as measured by both spread reduction and anatomical localization. Local analysis showed that more than twenty percent of total mapping errors were mapped incorrectly by both methods. There was a statistically significant difference between Caret and SPM2 mapping of type 2 errors

Surface fluid registration of conformal representation: Application to detect disease burden and genetic influence on hippocampus

abstract: In this paper, we develop a new automated surface registration system based on surface conformal parameterization by holomorphic 1-forms, inverse consistent surface fluid registration, and multivariate tensor-based morphometty (mTBM). First, we conformally map a surface onto a planar rectangle space with holomorphic 1-forms. Second, we compute surface conformal representation by combining its local conformal factor and mean curvature and linearly scale the dynamic range of the conformal representation to form the feature image of the surface. Third, we align the feature image with a chosen template image via the fluid image registration algorithm, which has been extended into the curvilinear coordinates to adjust for the distortion introduced by surface parameterization. The inverse consistent image registration algorithm is also incorporated in the system to jointly estimate the forward and inverse transformations between the study and template images. This alignment induces a corresponding deformation on the surface. We tested the system on Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset to study AD symptoms on hippocampus. In our system, by modeling a hippocampus as a 3D parametric surface, we nonlinearly registered each surface with a selected template surface. Then we used mTBM to analyze the morphometry difference between diagnostic groups. Experimental results show that the new system has better performance than two publicly available subcortical surface registration tools: FIRST and SPHARM. We also analyzed the genetic influence of the Apolipoprotein E(is an element of)4 allele (ApoE4), which is considered as the most prevalent risk factor for AD. Our work successfully detected statistically significant difference between ApoE4 carriers and non-carriers in both patients of mild cognitive impairment (MCI) and healthy control subjects. The results show evidence that the ApoE genotype may be associated with accelerated brain atrophy so that our work provides a new MRI analysis tool that may help presymptomatic AD research.NOTICE: this is the author’s version of a work that was accepted for publication in NEUROIMAGE. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroimage, 78, 111-134 [2013] http://dx.doi.org/10.1016/j.neuroimage.2013.04.01