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In this study, we construct a spatio-temporal surface atlas of the developing cerebral cortex, which is an important tool for analysing and understanding normal and abnormal cortical development. In utero Magnetic Resonance Imaging (MRI) of 80 healthy fetuses was performed, with a gestational age range of 21.7 to 38.9 weeks. Topologically correct cortical surface models were extracted from reconstructed 3D MRI volumes. Accurate correspondences were obtained by applying a joint spectral analysis to cortices for sets of subjects close to a specific age. Sulcal alignment was found to be accurate in comparison to spherical demons, a state of the art registration technique for aligning 2D cortical representations (average Fréchet distance ≈ 0.4 mm at 30 weeks). We construct consistent, unbiased average cortical surface templates, for each week of gestation, from age-matched groups of surfaces by applying kernel regression in the spectral domain. These were found to accurately capture the average cortical shape of individuals within the cohort, suggesting a good alignment of cortical geometry. Each spectral embedding and its corresponding cortical surface template provide a dual reference space where cortical geometry is aligned and a vertex-wise morphometric analysis can be undertaken.

A cardiac motion atlas provides a space of reference in which the cardiac motion fields of a cohort of subjects can be directly compared. From such atlases, descriptors can be learned for subsequent diagnosis and characterization of disease. Traditionally, such atlases have been formed from imaging data acquired using a single modality. In this work we propose a framework for building a multimodal cardiac motion atlas from MR and ultrasound data and incorporate a multiview classifier to exploit the complementary information provided by the two modalities. We demonstrate that our novel framework is able to detect non ischemic dilated cardiomyopathy patients from ultrasound data alone, whilst still exploiting the MR based information from the multimodal atlas. We evaluate two different approaches based on multiview learning to implement the classifier and achieve an improvement in classification performance from 77.5% to 83.50% compared to the use of US data without the multimodal atlas.

Clinical implementation of super-resolution (SR) ultrasound imaging requires accurate single microbubble detection, and would benefit greatly from automation in order to minimize time requirements and user dependence. We present a machine learning based post-processing tool for the application of SR ultrasound imaging, where we utilize superpixelation and support vector machines (SVMs) for foreground detection and signal differentiation.

This chapter covers the subject of signal and image processing. The basics of storing and reading 1-D signals are introduced, and the signal processing technique of convolution is described in detail. The basics of images in MATLAB are reviewed and extended, including the difference between color and gray scale images, getting information about an image, viewing an image and accessing/saving sub-regions of an image. Simple image processing operations such as binarization and thresholding are covered and it is shown how simple operations can be chained together to produce a more complex pipeline of operations. Finally, image filtering is described and its relationship to convolution is discussed.

The automation of segmentation of medical images is an active research area. However, there has been criticism of the standard of evaluation of methods. We have comprehensively evaluated four novel methods of automatically segmenting subcortical structures using volumetric, spatial overlap and distance-based measures. Two of the methods are atlas-based - classifier fusion and labelling (CFL) and expectation-maximisation segmentation using a dynamic brain atlas (EMS), and two model-based - profile active appearance models (PAM) and Bayesian appearance models (BAM). Each method was applied to the segmentation of 18 subcortical structures in 270 subjects from a diverse pool varying in age, disease, sex and image acquisition parameters. Our results showed that all four methods perform on par with recently published methods. CFL performed significantly better than the other three methods according to all three classes of metrics. © 2008 Springer-Verlag Berlin Heidelberg.

Statistical cardiac motion atlases provide a valuable tool for the quantification and evaluation of heart disease. Typically, such atlases are formed and applied using data from the same modality, e.g. magnetic resonance (MR) or 3D ultrasound (US). This paper presents a feasibility study on building a statistical cardiac motion atlas using one modality (MR), and embedding a new patient into this atlas using another modality (US). We aim to simulate a clinical scenario in which a high quality motion atlas is formed using MR data, and a new patient can be related to this atlas using only low cost ultrasound data, which is widely available in clinics. A leave-one-out technique was used to quantify the similarity between MR and US-derived displacement vectors in a reduced dimensional atlas space. Results show that all subjects' embedding errors were statistically significantly lower than the pairwise distances between each of the MR-derived training embedded points. This feasibility study illustrates the potential of combining two sources of information (i.e. MR-US) for comparing subjects' motions in a common space.

Medical imaging has shown that, during early development, the brain undergoes more changes in size, shape and appearance than at any other time in life. A better understanding of brain development requires a spatio-temporal atlas that characterizes the dynamic changes during this period. In this paper we present an approach for constructing a 4D atlas of the developing brain, between 28 and 44 weeks post-menstrual age at time of scan, using T1 and T2 weighted MR images from 204 premature neonates. The method used for the creation of the average 4D atlas utilizes non-rigid registration between all pairs of images to eliminate bias in the atlas toward any of the original images. In addition, kernel regression is used to produce age-dependent anatomical templates. A novelty in our approach is the use of a time-varying kernel width, to overcome the variations in the distribution of subjects at different ages. This leads to an atlas that retains a consistent level of detail at every time-point. Comparisons between the resulting atlas and atlases constructed using affine and non-rigid registration are presented. The resulting 4D atlas has greater anatomic definition than currently available 4D atlases created using various affine and non-rigid registration approaches, an important factor in improving registrations between the atlas and individual subjects. Also, the resulting 4D atlas can serve as a good representative of the population of interest as it reflects both global and local changes. The atlas is publicly available at www.brain-development.org .

Medical image registration plays an increasingly important role in many clinical applications, including the detection and diagnosis of diseases, planning of therapy, guidance of interventions, and the follow-up and monitoring of patients. The primary goal of image registration is to find corresponding anatomical or functional locations in two or more images. This has many applications: registration can be applied to images from the same subject acquired by different imaging modalities (multimodal image registration) or at different time points (serial image registration). In this article, we will illustrate some of the advances that have been made over recent decades. We will discuss some of the theoretical aspects of nonrigid registration and describe methods for their implementation. Finally, we will illustrate how common problems in medical imaging, such as motion correction and image segmentation, can be solved using image registration.

Automatic anatomical segmentation of magnetic resonance human brain images has been shown to be accurate and robust when based on multiple atlases that encompass the anatomical variability of the cohort of subjects. We observed that the method tends to fail when the segmentation target shows ventricular enlargement that is not captured by the atlas database. By incorporating tissue classification information into the image registration process, we aimed to increase the robustness of the method. For testing, subjects who participated in the Oxford Project to Investigate Memory and Aging (OPTIMA) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) were selected for ventriculomegaly. Segmentation quality was substantially improved in the ventricles and surrounding structures (9/9 successes on visual rating versus 4/9 successes using the baseline method). In addition, the modification resulted in a significant increase of segmentation accuracy in healthy subjects' brain images. Hippocampal segmentation results in a group of patients with temporal lobe epilepsy were near identical with both approaches. The modified approach (MAPER, multi-atlas propagation with enhanced registration) extends the applicability of multi-atlas based automatic whole-brain segmentation to subjects with ventriculomegaly, as seen in normal aging as well as in numerous neurodegenerative diseases.

We propose a novel framework for the automatic propagation of a set of manually labeled brain atlases to a diverse set of images of a population of subjects. A manifold is learned from a coordinate system embedding that allows the identification of neighborhoods which contain images that are similar based on a chosen criterion. Within the new coordinate system, the initial set of atlases is propagated to all images through a succession of multi-atlas segmentation steps. This breaks the problem of registering images that are very "dissimilar" down into a problem of registering a series of images that are "similar". At the same time, it allows the potentially large deformation between the images to be modeled as a sequence of several smaller deformations. We applied the proposed method to an exemplar region centered around the hippocampus from a set of 30 atlases based on images from young healthy subjects and a dataset of 796 images from elderly dementia patients and age-matched controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We demonstrate an increasing gain in accuracy of the new method, compared to standard multi-atlas segmentation, with increasing distance between the target image and the initial set of atlases in the coordinate embedding, i.e., with a greater difference between atlas and image. For the segmentation of the hippocampus on 182 images for which a manual segmentation is available, we achieved an average overlap (Dice coefficient) of 0.85 with the manual reference.

Analysis of structural neuroimaging studies often relies on volume or shape comparisons of labeled neuroanatomical structures in two or more clinical groups. Such studies have common elements involving segmentation, morphological feature extraction for comparison, and subject and group discrimination. We combine two state-of-the-art analysis approaches, namely automated segmentation using label fusion and classification via spectral analysis to explore the relationship between the morphology of neuroanatomical structures and clinical diagnosis in dementia. We apply this framework to a cohort of normal controls and patients with mild dementia where accurate diagnosis is notoriously difficult. We compare and contrast our ability to discriminate normal and abnormal groups on the basis of structural morphology with (supervised) and without (unsupervised) knowledge of each individual's diagnosis. We test the hypothesis that morphological features resulting from Alzheimer disease processes are the strongest discriminator between groups.

Capturing an enclosing volume of moving subjects and organs using fast individual image slice acquisition has shown promise in dealing with motion artefacts. Motion between slice acquisitions results in spatial inconsistencies that can be resolved by slice-to-volume reconstruction (SVR) methods to provide high quality 3D image data. Existing algorithms are, however, typically very slow, specialised to specific applications and rely on approximations, which impedes their potential clinical use. In this paper, we present a fast multi-GPU accelerated framework for slice-to-volume reconstruction. It is based on optimised 2D/3D registration, super-resolution with automatic outlier rejection and an additional (optional) intensity bias correction. We introduce a novel and fully automatic procedure for selecting the image stack with least motion to serve as an initial registration target. We evaluate the proposed method using artificial motion corrupted phantom data as well as clinical data, including tracked freehand ultrasound of the liver and fetal Magnetic Resonance Imaging. We achieve speed-up factors greater than 30 compared to a single CPU system and greater than 10 compared to currently available state-of-the-art multi-core CPU methods. We ensure high reconstruction accuracy by exact computation of the pointspread function for every input data point, which has not previously been possible due to computational limitations. Our framework and its implementation is scalable for available computational infrastructures and tests show a speed-up factor of 1:70 for each additional GPU. This paves the way for the online application of image based reconstruction methods during clinical examinations. The source code for the proposed approach is publicly available.

In this paper, we present a technique that can be used to transform the motion or deformation fields defined in the coordinate system of one subject into the coordinate system of another subject. Such a transformation accounts for the differences in the coordinate systems of the two subjects due to misalignment and size/shape variation, enabling the motion or deformation of each of the subjects to be directly quantitatively and qualitatively compared. The field transformation is performed by using a nonrigid registration algorithm to determine the intersubject coordinate system mapping from the first subject to the second subject. This fixes the relationship between the coordinate systems of the two subjects, and allows us to recover the deformation/motion vectors of the second subject for each corresponding point in the first subject. Since these vectors are still aligned with the coordinate system of the second subject, the inverse of the intersubject coordinate mapping is required to transform these vectors into the coordinate system of the first subject, and we approximate this inverse using a numerical line integral method. The accuracy of our numerical inversion technique is demonstrated using a synthetic example, after which we present applications of our method to sequences of cardiac and brain images.

Free-form deformations are a powerful geometric modeling technique which can be used to represent complex 3D deformations. In recent years, free-form deformations have gained significant popularity in algorithms for the non-rigid registration of medical images. In this chapter we show how free-form deformations can be used in non-rigid registration to model complex local deformations of 3D organs. In particular, we discuss diffeomorphic and non-diffeomorphic representations of 3D deformation fields using free-form deformations as well as different penalty functions that can be used to constrain the deformation fields during the registration. We also show how free-form deformations can be used in combination with mutual information-based similarity metrics for the registration of mono-modal and multi-modal medical images. Finally, we discuss applications of registration techniques based on free-form deformations for the analysis of images of the breast, heart and brain as well as for segmentation and shape modelling.

There is growing interest in exploring fetal functional brain development, particularly with Resting State fMRI. However, during a typical fMRI acquisition, the womb moves due to maternal respiration and the fetus may perform large-scale and unpredictable movements. Conventional fMRI processing pipelines, which assume that brain movements are infrequent or at least small, are not suitable. Previous published studies have tackled this problem by adopting conventional methods and discarding as much as 40% or more of the acquired data.In this work, we developed and tested a processing framework for fetal Resting State fMRI, capable of correcting gross motion. The method comprises bias field and spin history corrections in the scanner frame of reference, combined with slice to volume registration and scattered data interpolation to place all data into a consistent anatomical space. The aim is to recover an ordered set of samples suitable for further analysis using standard tools such as Group Independent Component Analysis (Group ICA).We have tested the approach using simulations and in vivo data acquired at 1.5 T. After full motion correction, Group ICA performed on a population of 8 fetuses extracted 20 networks, 6 of which were identified as matching those previously observed in preterm babies.

Magnetic resonance (MR) imaging is increasingly being used to assess brain growth and development in infants. Such studies are often based on quantitative analysis of anatomical segmentations of brain MR images. However, the large changes in brain shape and appearance associated with development, the lower signal to noise ratio and partial volume effects in the neonatal brain present challenges for automatic segmentation of neonatal MR imaging data. In this study, we propose a framework for accurate intensity-based segmentation of the developing neonatal brain, from the early preterm period to term-equivalent age, into 50 brain regions. We present a novel segmentation algorithm that models the intensities across the whole brain by introducing a structural hierarchy and anatomical constraints. The proposed method is compared to standard atlas-based techniques and improves label overlaps with respect to manual reference segmentations. We demonstrate that the proposed technique achieves highly accurate results and is very robust across a wide range of gestational ages, from 24 weeks gestational age to term-equivalent age.

We automatically quantify patterns of normal cortical folding in the developing fetus from in utero MR images (N=80) over a wide gestational age (GA) range (21.7 to 38.9weeks). This work on data from healthy subjects represents a first step towards characterising abnormal folding that may be related to pathology, facilitating earlier diagnosis and intervention. The cortical boundary was delineated by automatically segmenting the brain MR image into a number of key structures. This utilised a spatio-temporal atlas as tissue priors in an expectation-maximization approach with second order Markov random field (MRF) regularization to improve the accuracy of the cortical boundary estimate. An implicit high resolution surface was then used to compute cortical folding measures. We validated the automated segmentations with manual delineations and the average surface discrepancy was of the order of 1mm. Eight curvature-based folding measures were computed for each fetal cortex and used to give summary shape descriptors. These were strongly correlated with GA (R(2)=0.99) confirming the close link between neurological development and cortical convolution. This allowed an age-dependent non-linear model to be accurately fitted to the folding measures. The model supports visual observations that, after a slow initial start, cortical folding increases rapidly between 25 and 30weeks and subsequently slows near birth. The model allows the accurate prediction of fetal age from an observed folding measure with a smaller error where growth is fastest. We also analysed regional patterns in folding by parcellating each fetal cortex using a nine-region anatomical atlas and found that Gompertz models fitted the change in lobar regions. Regional differences in growth rate were detected, with the parietal and posterior temporal lobes exhibiting the fastest growth, while the cingulate, frontal and medial temporal lobes developed more slowly.

Segmentation of neonatal and fetal brain MR images is a challenging task due to vast differences in shape and appearance across age and across subjects. Expert priors for atlas-based segmentation are often only available for a subset of the population, leading to a reduction in accuracy for images dissimilar from the atlas set. To alleviate the effects of limited prior information on atlas-based segmentation, we present a novel semi-supervised learning framework where labels are propagated among both atlas and test images while modelling the confidence of propagated information. The method relies on a voxel-wise graph interconnecting similar regions in all images based on a patch similarity measure. By iteratively allowing information flow from voxels with high confidence to voxels with lower confidence, segmentations in test images with low similarity to the atlas set can be improved. The method was evaluated on 70 fetal brain MR images of subjects at 22–38 weeks gestational age. Particularly for test populations dissimilar from the atlas population, the proposed method outperformed state-of-the-art patch-based segmentation.

FFD represent a widely used model for the non-rigid registration of medical images. The balance between robustness to noise and accuracy in modelling localised motion is typically controlled by the control point grid spacing and the amount of regularisation. More recently, TFFD have been proposed which extend the FFD approach in order to recover smooth motion from temporal image sequences. In this paper, we revisit the classic FFD approach and propose a sparse representation using the principles of compressed sensing. The sparse representation can model both global and local motion accurately and robustly. We view the registration as a deformation reconstruction problem. The deformation is reconstructed from a pair of images (or image sequences) with a sparsity constraint applied to the parametric space. Specifically, we introduce sparsity into the deformation via L1 regularisation, and apply a bending energy regularisation between neighbouring control points within each level to encourage a grouped sparse solution. We further extend the sparsity constraint to the temporal domain and propose a TSFFD which can capture fine local details such as motion discontinuities in both space and time without sacrificing robustness. We demonstrate the capabilities of the proposed framework to accurately estimate deformations in dynamic 2D and 3D image sequences. Compared to the classic FFD and TFFD approach, a significant increase in registration accuracy can be observed in natural images as well as in cardiac images.

We propose a novel framework for longitudinal registration which can handle large intra-subject anatomical variations. The framework exploits freely available spatio-temporal atlases, which can aid the longitudinal registration process as it provides prior information about the missing anatomical evolution between two scans taken over large time-interval. The spatio-temporal atlas is used to develop an approach to carry out longitudinal registrations via atlas propagation. We carried out evaluation experiments using 50 neonatal subjects with two scans taken at different time-intervals. We used different metrics, including intensity similarity and segmentation overlap, to assess the registration performance. The proposed registration framework outperforms direct registration by providing an accurate and consistent registration, particularly when the time-interval between scans increases. We refer to our approach as a framework for Longitudinal Image registration via Spatio-temporal Atlases (LISA).

In recent years, multi-atlas segmentation has emerged as one of the most accurate techniques for the segmentation of brain magnetic resonance (MR) images, especially when combined with intensity-based refinement techniques such as graph-cut or expectation-maximization (EM) optimization. However, most of the work so far has focused on intensity-based refinement strategies for individual anatomical structures such as the hippocampus. In this work we extend a previously proposed framework for labeling whole brain scans by incorporating a global and stationary Markov random field that ensures the consistency of the neighbourhood relations between structures with an a-priori defined model. In particular we improve the segmentation result of a locally weighted multi-atlas fusion method for 41 different structures simultaneously by applying a subsequent EM optimization step. We evaluate the proposed approach on 30 manually annotated brain MR images and observe an improvement of label overlaps to a manual reference by up to 6%. We also achieved a considerably improved group separation when the proposed segmentation framework is applied to a volumetric analysis of 404 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

The term manifold learning encompasses a class of machine learning techniques that convert data from a high to lower dimensional representation while respecting the intrinsic geometry of the data. The intuition underlying the use of manifold learning in the context of image analysis is that, while each image may be viewed as a single point in a very high-dimensional space, a set of such points for a population of images may be well represented by a sub-manifold of the space that is likely to be non-linear and of a significantly lower dimension. Recently, manifold learning techniques have begun to be applied to the field of medical image analysis. This chapter will review the most popular manifold learning techniques such as Multi-Dimensional Scaling (MDS), Isomap, Local linear embedding, and Laplacian eigenmaps. It will also demonstrate how these techniques can be used for image registration, segmentation, and biomarker discovery from medical images.

Large medical image datasets form a rich source of anatomical descriptions for research into pathology and clinical biomarkers. Many features may be extracted from data such as MR images to provide, through manifold learning methods, new representations of the population's anatomy. However, the ability of any individual feature to fully capture all aspects morphology is limited. We propose a framework for deriving a representation from multiple features or measures which can be chosen to suit the application and are processed using separate manifold-learning steps. The results are then combined to give a single set of embedding coordinates for the data. We illustrate the framework in a population study of neonatal brain MR images and show how consistent representations, correlating well with clinical data, are given by measures of shape and of appearance. These particular measures were chosen as the developing neonatal brain undergoes rapid changes in shape and MR appearance and were derived from extracted cortical surfaces, nonrigid deformations, and image similarities. Combined single embeddings show improved correlations demonstrating their benefit for further studies such as identifying patterns in the trajectories of brain development. The results also suggest a lasting effect of age at birth on brain morphology, coinciding with previous clinical studies.

Motion estimation, also known as optic flow, refers to the process of determining a 2D displacement field that aligns two images. Most methods that estimate motion or deformation fields in biological image sequences rely on sparse, distinct features (landmarks). Going a step forward, we are interested in methods to compute dense deformation fields (for all pixels). In this paper we compare two of such frameworks: the B-splines based free-form deformation (FFD) approach, which is well-known in medical image registration; and the combined local-global (CLG) approach, a popular optic flow method in computer vision. We test both methods on synthetic and real image sequences obtained by confocal light microscopy and by scanning electron microscopy, showing their performance in terms of accuracy and computational cost. As an alternative to traditional sparse techniques, the estimation of dense motion fields would allow tackling other related problems with sub-pixel precision, for example, the segmentation and classification of different biological structures according to their local motion, trajectory, growth and development.

This paper presents a novel, publicly available repository of anatomically segmented brain images of healthy subjects as well as patients with mild cognitive impairment and Alzheimer's disease. The underlying magnetic resonance images have been obtained from the Alzheimer's Disease Neuroimaging Initiative database. T1-weighted images (1.5 T and 3 T) have been processed with the multi-atlas based MAPER procedure, resulting in labels for 83 regions covering the whole brain in 816 subjects. Volumetric outliers were reviewed visually to identify limitations of the procedure and the segmentations. Morphometric comparisons between diagnostic groups showed highly significant group differences for a number of individual regions in the temporal lobe and parietal lobes. The segmentations are self-consistent, as evidenced by strong agreement between segmentations of paired images acquired at different field strengths (Jaccard coefficient: 0.802 ± 0.0146). This repository of segmentations is a potentially valuable resource to researchers working with ADNI data.

Probabilistic atlases have been established in the literature as a standard tool for enhancing the intensity-based classification of brain MRI. The rapidly growing neonatal brain requires an age-specific spatial probabilistic atlas to guide the segmentation process. In this paper we describe a method for dynamically creating a probabilistic atlas for any chosen stage of neonatal brain development. The atlas is created from the segmentations of 153 subjects of different ages using a kernel regression method. For any given age, an intensity template as well as the corresponding tissue probability maps with the correct sizes and shapes of the structures can be dynamically generated. The resulting atlas provides prior tissue probability maps for six structures - cortex, white matter, subcortical gray matter, brainstem and cerebellum, for ages of 29 to 44 weeks of gestation.

We propose a method for simultaneous segmentation of serially acquired magnetic resonance (MR) images. An existing graph-cuts based algorithm is extended and applied to 4-D images. A probabilistic atlas is generated for each baseline scan by intersubject registration of multiple labeled images. The atlases are used for baseline and aligned follow-up images and are combined with an intensity model to define a weighted graph that connects the timepoints. A minimal cut on this graph yields the segmentation for all timepoints. The resulting segmentations are consistent over time in boundary regions with weak gray scale definition, but reflect atrophy well where the structure boundary is well defined by MR intensity. The hippocampus was segmented in 568 baseline and follow-up images provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI). The estimated atrophy rates correctly classified AD patients from controls at a rate of 82% (Atrophy rates: AD 3.85%/y.; MCI 2.31%/y.; controls: 0.85%/y.)

Atlas-based brain image segmentation quality is difficult to assess in the absence of reference target segmentations. We propose a measure of segmentation success based on transforming the atlas label twice: once by registering the atlas to the target and a second time by registering the target to the atlas. Each registration represents transformations by free-form deformations. The overlap between the twice-transformed label and the original (‘mirror overlap’) correlates with the forward overlap (between the once-transformed label and a target reference), especially for subcortical structures. Using mirror overlap as an atlas selection criterion results in improved segmentations versus random selection.

We propose a general framework for segmentation of subcortical structures and the hippocampus in magnetic resonance brain images based on multi-atlas label propagation and graph cuts. The label maps obtained from multi-atlas segmentation are used to build a subject-specific probabilistic atlas of a structure of interest. From this atlas and an intensity model estimated from the unseen image, a Markov random field-based energy function is defined and optimized via graph cuts. Compared to a previously proposed approach, our method does not rely on manual training of the intensity model and is applied to five subcortical structures and the hippocampus. We used this approach to segment the hippocampus on 60 images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and achieved an average overlap (Dice coefficient) of 0.86 with the manually delineated reference segmentations.

The aim of this paper is to investigate techniques that can identify and quantify cross-sectional differences and longitudinal changes in vivo from magnetic resonance images of murine models of brain disease. Two different approaches have been compared. The first approach is a segmentation-based approach: Each subject at each time point is automatically segmented into a number of anatomical structures using atlas-based segmentation. This allows cross-sectional and longitudinal analyses of group differences on a structure-by-structure basis. The second approach is a deformation-based approach: Longitudinal changes are quantified by the registration of each subject's follow-up images to that subject's baseline image. In addition the baseline images can be registered to an atlas allowing voxel-wise analysis of cross-sectional differences between groups. Both approaches have been tested on two groups of mice: A transgenic model of Alzheimer's disease and a wild-type background strain, using serial imaging performed over the age range from 6-14 months. We show that both approaches are able to identify longitudinal and cross-sectional differences. However, atlas-based segmentation suffers from the inability to detect differences across populations and across time in regions which are much smaller than the anatomical regions. In contrast to this, the deformation-based approach can detect statistically significant differences in highly localized areas.

In this work we obtain estimates of tissue growth using longitudinal data comprising MR brain images of 25 preterm children scanned at one and two years. The growth estimates are obtained using segmentation and registration based methods. The segmentation approach used an expectation maximisation (EM) method to classify tissue types and the registration approach used tensor based morphometry (TBM) applied to a free form deformation (FFD) model. The two methods show very good agreement indicating that the registration and segmentation approaches can be used interchangeably. The advantage of the registration based method, however, is that it can provide more local estimates of tissue growth. This is the first longitudinal study of growth in early childhood, previous longitudinal studies have focused on later periods during childhood.

We present methods for the quantitative analysis of brain growth based on the registration of longitudinal MR image data with the use of Jacobian determinant maps to characterise neuroanatomical changes. The individual anatomies, growth maps and tissue classes are also spatially normalised in an ‘average space’ and aggregated to provide atlases for the population at each timepoint. The average space representation is obtained using the average intersubject transformation within each timepoint. In an exemplar study, this approach is used to assess brain development in 25 infants between 1 and 2 years, and we show consistency in growth estimates between registration and segmentation approaches.

This work describes and compares two different methods for identifying growth patterns in preterm infants during the second year of development. One method is based on creating anatomical atlases from the population of subjects within each timepoint and using the transformation between atlases at different timepoints to create average volume change maps. The second method uses multiple longitudinal intra-subject registrations to produce individual volume change maps. These maps are then transformed into a common coordinate system and averaged with the method used for atlas creation. We show that there is a reasonable level of agreement between the two methods and both generate plausible growth patterns implying that either could be used to track development during this period of growth.

In this paper we propose a diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. In contrast to existing non-rigid registration methods based on FFDs the proposed diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. To construct a diffeomorphic transformation we compose a sequence of free-form deformations while ensuring that individual FFDs are one-to-one transformations. We have evaluated the algorithm on 20 normal brain MR images which have been manually segmented into 67 anatomical structures. Using the agreement between manual segmentation and segmentation propagation as a measure of registration quality we have compared the algorithm to an existing FFD registration algorithm and a modified FFD registration algorithm which penalises non-diffeomorphic transformations. The results show that the proposed algorithm generates diffeomorphic transformations while providing similar levels of performance as the existing FFD registration algorithm in terms of registration accuracy.

Segmentations of MR images of the human brain can be generated by propagating an existing atlas label volume to the target image. By fusing multiple propagated label volumes, the segmentation can be improved. We developed a model that predicts the improvement of labelling accuracy and precision based on the number of segmentations used as input. Using a cross-validation study on brain image data as well as numerical simulations, we verified the model. Fit parameters of this model are potential indicators of the quality of a given label propagation method or the consistency of the input segmentations used.

Regions in three-dimensional magnetic resonance (MR) brain images can be classified using protocols for manually segmenting and labeling structures. For large cohorts, time and expertise requirements make this approach impractical. To achieve automation, an individual segmentation can be propagated to another individual using an anatomical correspondence estimate relating the atlas image to the target image. The accuracy of the resulting target labeling has been limited but can potentially be improved by combining multiple segmentations using decision fusion. We studied segmentation propagation and decision fusion on 30 normal brain MR images, which had been manually segmented into 67 structures. Correspondence estimates were established by nonrigid registration using free-form deformations. Both direct label propagation and an indirect approach were tested. Individual propagations showed an average similarity index (SI) of 0.754+/-0.016 against manual segmentations. Decision fusion using 29 input segmentations increased SI to 0.836+/-0.009. For indirect propagation of a single source via 27 intermediate images, SI was 0.779+/-0.013. We also studied the effect of the decision fusion procedure using a numerical simulation with synthetic input data. The results helped to formulate a model that predicts the quality improvement of fused brain segmentations based on the number of individual propagated segmentations combined. We demonstrate a practicable procedure that exceeds the accuracy of previous automatic methods and can compete with manual delineations.

Voxel based non-rigid registration of images involves finding a similarity maximising transformation that deforms a source image to the coordinate system of a target image. In order to do this, interpolation is required to estimate the source intensity values corresponding to transformed target voxels. These interpolated source intensities are used when calculating the similarity measure being optimised. In this work, we compare the extent and nature of artefactual displacements produced by voxel based non-rigid registration techniques for different interpolators and investigate their relationship to image noise and global transformation error. A per-voxel similarity gradient is calculated and the resulting vector field is used to characterise registration artefacts for each interpolator. Finally, we show that the resulting registration artefacts can generate spurious volume changes for image pairs with no expected volume change.