Fully supervised polyp segmentation relies on costly pixel-level annotations. Although semi- and weakly supervised methods reduce annotation requirements, they still depend on partial mask supervision. Text-supervised segmentation is a promising alternative; however, for polyps, the key challenge is to ground instance-specific phrases to the correct lesion region under cluttered backgrounds and large appearance variations. Existing approaches often rely on coarse text-image alignment, limiting precise region-level semantic correspondence. In this paper, we propose Text-Image Co-Alignment (TICoA), a text-supervised framework for polyp segmentation. TICoA leverages large language models (LLMs)-generated structured clinical descriptions as weak supervision and formulates segmentation as a fine-grained phrase-region co-alignment problem. Through contrastive learning, TICoA explicitly associates query phrases with corresponding image regions to achieve robust semantic grounding under weak supervision. Architecturally, we adopt a State-Space Model (Mamba) to efficiently model long-range dependencies with linear computational complexity. To support effective cross-modal interaction, we further design a dedicated Mamba Fusion module with a Bi-Dimension Fusion (BiDF) strategy, which progressively propagates information along spatial and channel dimensions. Experiments on polyp datasets, with additional validation on skin lesion segmentation, demonstrate that TICoA is competitive with state-of-the-art weakly supervised methods. Our code and data are available at https://github.com/silentyuchen/TICoA.

The goal of offline model-based optimization (MBO) is to propose new designs that maximize a reward function given only an offline dataset. However, an important desiderata is to also propose a *diverse* set of final candidates that capture many optimal and near-optimal design configurations. We propose **D**iversit**y** I**n** **A**dversarial **M**odel-based **O**ptimization (**DynAMO**) as a novel method to introduce design diversity as an explicit objective into any MBO problem. Our key insight is to formulate diversity as a *distribution matching problem* where the distribution of generated designs captures the inherent diversity contained within the offline dataset. Extensive experiments spanning multiple scientific domains show that DynAMO can be used with common optimization methods to significantly improve the diversity of proposed designs while still discovering high-quality candidates.

Deep Learning in Image Registration (DLIR) methods have been tremendously successful in image registration due to their speed and ability to incorporate weak label supervision at training time. However, existing DLIR methods forego many of the benefits and invariances of optimization methods. The lack of a task-specific inductive bias in DLIR methods leads to suboptimal performance, especially in the presence of domain shift. Our method aims to bridge this gap between statistical learning and optimization by explicitly incorporating optimization as a layer in a deep network. A deep network is trained to predict multi-scale dense feature images that are registered using a black box iterative optimization solver. This optimal warp is then used to minimize image and label alignment errors. By implicitly differentiating end-to-end through an iterative optimization solver, we explicitly exploit invariances of the correspondence matching problem induced by the optimization, while learning registration and label-aware features, and guaranteeing the warp functions to be a local minima of the registration objective in the feature space. Our framework shows excellent performance on in-domain datasets, and is agnostic to domain shift such as anisotropy and varying intensity profiles. For the first time, our method allows switching between arbitrary transformation representations (free-form to diffeomorphic) at test time with zero retraining. End-to-end feature learning also facilitates interpretability of features and arbitrary test-time regularization, which is not possible with existing DLIR methods.

While deep networks have achieved broad success in analyzing natural images, when applied to medical scans, they often fail in unexcepted situations. We investigate this challenge and focus on model sensitivity to domain shifts, such as data sampled from different hospitals or data confounded by demographic variables such as sex, race, etc, in the context of chest X-rays and skin lesion images. A key finding we show empirically is that existing visual backbones lack an appropriate prior from the architecture for reliable generalization in these settings. Taking inspiration from medical training, we propose giving deep networks a prior grounded in explicit medical knowledge communicated in natural language. To this end, we introduce Knowledge-enhanced Bottlenecks (KnoBo), a class of concept bottleneck models that incorporates knowledge priors that constrain it to reason with clinically relevant factors found in medical textbooks or PubMed. KnoBo uses retrieval-augmented language models to design an appropriate concept space paired with an automatic training procedure for recognizing the concept. We evaluate different resources of knowledge and recognition architectures on a broad range of domain shifts across 20 datasets. In our comprehensive evaluation with two imaging modalities, KnoBo outperforms fine-tuned models on confounded datasets by 32.4% on average. Finally, evaluations reveal that PubMed is a promising resource for making medical models less sensitive to domain shift, outperforming other resources on both diversity of information and final prediction performance.

Classical optimization and learning-based methods are the two reigning paradigms in deformable image registration. While optimization-based methods boast generalizability across modalities and robust performance, learning-based methods promise peak performance, incorporating weak supervision and amortized optimization. However, the exact conditions for either paradigm to perform well over the other are shrouded and not explicitly outlined in the existing literature. In this paper, we make an explicit correspondence between the mutual information of the distribution of per-pixel intensity and labels, and the performance of classical registration methods. This strong correlation hints to the fact that architectural designs in learning-based methods is unlikely to affect this correlation, and therefore, the performance of learning-based methods. This hypothesis is thoroughly validated with state-of-the-art classical and learning-based methods. However, learning-based methods with weak supervision can perform high-fidelity intensity and label registration, which is not possible with classical methods. Next, we show that this high-fidelity feature learning does not translate to invariance to domain shift, and learning-based methods are sensitive to such changes in the data distribution. We reassess and recalibrate performance expectations from classical and DLIR methods under access to label supervision, training time, and its generalization capabilities under minor domain shifts.

Offline model-based optimization seeks to optimize against a learned surrogate model without querying the true oracle objective function during optimization. Such tasks are commonly encountered in protein design, robotics, and clinical medicine where evaluating the oracle function is prohibitively expensive. However, inaccurate surrogate model predictions are frequently encountered along offline optimization trajectories. To address this limitation, we propose *generative adversarial model-based optimization* using **adaptive source critic regularization (aSCR)**—a task- and optimizer- agnostic framework for constraining the optimization trajectory to regions of the design space where the surrogate function is reliable. We propose a computationally tractable algorithm to dynamically adjust the strength of this constraint, and show how leveraging aSCR with standard Bayesian optimization outperforms existing methods on a suite of offline generative design tasks. Our code is available at https://github.com/michael-s-yao/gabo.

Feature matching, which refers to establishing the correspondence of regions between two images (usually voxel features), is a crucial prerequisite of feature-based registration. For deformable image registration tasks, traditional feature-based registration methods typically use an iterative matching strategy for interest region matching, where feature selection and matching are explicit, but specific feature selection schemes are often useful in solving application-specific problems and require several minutes for each registration. In the past few years, the feasibility of learning-based methods, such as VoxelMorph and TransMorph, has been proven, and their performance has been shown to be competitive compared to traditional methods. However, these methods are usually single-stream, where the two images to be registered are concatenated into a 2-channel whole, and then the deformation field is output directly. The transformation of image features into interimage matching relationships is implicit. In this paper, we propose a novel end-to-end dual-stream unsupervised framework, named TransMatch, where each image is fed into a separate stream branch, and each branch performs feature extraction independently. Then, we implement explicit multilevel feature matching between image pairs via the query-key matching idea of the self-attention mechanism in the Transformer model. Comprehensive experiments are conducted on three 3D brain MR datasets, LPBA40, IXI, and OASIS, and the results show that the proposed method achieves state-of-the-art performance in several evaluation metrics compared to the commonly utilized registration methods, including SyN, NiftyReg, VoxelMorph, CycleMorph, ViT-V-Net, and TransMorph, demonstrating the effectiveness of our model in deformable medical image registration.

Correctness of instance segmentation constitutes counting the number of objects, correctly localizing all predictions and classifying each localized prediction. Average Precision is the de-facto metric used to measure all these constituents of segmentation. However, this metric does not penalize duplicate predictions in the high-recall range, and cannot distinguish instances that are localized correctly but categorized incorrectly. This weakness has inadvertently led to network designs that achieve significant gains in AP but also introduce a large number of false positives. We therefore cannot rely on AP to choose a model that provides an optimal tradeoff between false positives and high recall. To resolve this dilemma, we review alternative metrics in the literature and propose two new measures to explicitly measure the amount of both spatial and categorical duplicate predictions. We also propose a Semantic Sorting and NMS module to remove these duplicates based on a pixel occupancy matching scheme. Experiments show that modern segmentation networks have significant gains in AP, but also contain a considerable amount of duplicates. Our Semantic Sorting and NMS can be added as a plug-and-play module to mitigate hedged predictions and preserve AP.

Deformable image registration (DIR), aiming to find spatial correspondence between images, is one of the most critical problems in the domain of medical image analysis. In this paper, we present a novel, generic, and accurate diffeomorphic image registration framework that utilizes neural ordinary differential equations (NODEs). We model each voxel as a moving particle and consider the set of all voxels in a 3D image as a high-dimensional dynamical system whose trajectory determines the targeted deformation field. Our method leverages deep neural networks for their expressive power in modeling dynamical systems, and simultaneously optimizes for a dynamical system between the image pairs and the corresponding transformation. Our formulation allows various constraints to be imposed along the transformation to maintain desired regularities. Our experiment results show that our method outperforms the benchmarks under various metrics. Additionally, we demonstrate the feasibility to expand our framework to register multiple image sets using a unified form of transformation, which could possibly serve a wider range of applications.

We propose an image synthesis approach that provides stratified navigation in the latent code space. With a tiny amount of partial or very low-resolution image, our approach can consistently out-perform state-of-the-art counterparts in terms of generating the closest sampled image to the ground truth. We achieve this through scale-independent editing while expanding scale-specific diversity. Scale-independence is achieved with a nested scale disentanglement loss. Scale-specific diversity is created by incorporating a progressive diversification constraint. We introduce semantic persistency across the scales by sharing common latent codes. Together they provide better control of the image synthesis process. We evaluate the effectiveness of our proposed approach through various tasks, including image outpainting, image superresolution, and cross-domain image translation.

Single image super-resolution (SISR) reconstruction for magnetic resonance imaging (MRI) has generated significant interest because of its potential to not only speed up imaging but to improve quantitative processing and analysis of available image data. Generative Adversarial Networks (GAN) have proven to perform well in image recovery tasks. In this work, we followed the GAN framework and developed a generator coupled with discriminator to tackle the task of 3D SISR on T1 brain MRI images. We developed a novel 3D memory-efficient residual-dense block generator (MRDG) that achieves state-of-the-art performance in terms of SSIM (Structural Similarity), PSNR (Peak Signal to Noise Ratio) and NRMSE (Normalized Root Mean Squared Error) metrics. We also designed a pyramid pooling discriminator (PPD) to recover details on different size scales simultaneously. Finally, we introduced model blending, a simple and computational efficient method to balance between image and texture quality in the final output, to the task of SISR on 3D images.

As an important machine learning task, multi-label learning deals with the problem where each sample instance (feature vector) is associated with multiple labels simultaneously. Most existing approaches focus on manipulating the label space, such as exploiting correlations between labels and reducing label space dimension, with identical feature space in the process of classification. One potential drawback of this traditional strategy is that each label might have its own specific characteristics and using identical features for all label cannot lead to optimized performance. In this article, we propose an effective algorithm named LSDM, i.e., leveraging label-specific discriminant mapping features for multi-label learning , to overcome the drawback. LSDM sets diverse ratio parameter values to conduct cluster analysis on the positive and negative instances of identical label. It reconstructs label-specific feature space which includes distance information and spatial topology information. Our experimental results show that combining these two parts of information in the new feature representation can better exploit the clustering results in the learning process. Due to the problem of diverse combinations for identical label, we employ simplified linear discriminant analysis to efficiently excavate optimal one for each label and perform classification by querying the corresponding results. Comparison with the state-of-the-art algorithms on a total of 20 benchmark datasets clearly manifests the competitiveness of LSDM.

Health information exchanges have been popular for some time with their advantages known and widely researched. In spite of their utility in increasing provider efficiency and decreasing administrative costs, one challenge that has persisted is the data owners inability to control data after transmission. The lack of technical mechanisms to effectively control patients' health data in the network significantly affects participation of health and medical institutions while perpetrating the silo-based data management that locks value and potential inherent in the data. This not only affects researchers due to the lack of data for research and analysis but the quality of life of patients.We present a blockchain-supported architectural framework for secure control of personal data in a health information exchange by pairing user-generated acceptable use policies with smart contracts. We highlight the merits of our system, its user-centric focus and also show experimental results along with directions for extending our work. The framework introduces minimal risk to data by architecting a mechanism for controlling data after sharing. In adopting our framework, health service providers can deliver a stronger assurance for data management than is possible with current systems.

We present novel techniques for single-image vignetting correction based on symmetries of two forms of image gradients: semicircular tangential gradients (SCTG) and radial gradients (RG). For a given image pixel, an SCTG is an image gradient along the tangential direction of a circle centered at the presumed optical center and passing through the pixel. An RG is an image gradient along the radial direction with respect to the optical center. We observe that the symmetry properties of SCTG and RG distributions are closely related to the vignetting in the image. Based on these symmetry properties, we develop an automatic optical center estimation algorithm by minimizing the asymmetry of SCTG distributions, and also present two methods for vignetting estimation based on minimizing the asymmetry of RG distributions. In comparison to prior approaches to single-image vignetting correction, our methods do not rely on image segmentation and they produce more accurate results. Experiments show our techniques to work well for a wide range of images while achieving a speed-up of 3-5 times compared to a state-of-the-art method.

We propose a new approach to front propagation algorithms based on a topological variant of well-composedness which contrasts with previous methods based on simple point detection. This provides for a theoretical justification, based on the digital Jordan separation theorem, for digitally "gluing" evolved well-composed objects separated by well-composed curves or surfaces. Additionally, our framework can be extended to more relaxed topologically constrained algorithms based on multisimple points. For both methods this framework has the additional benefit of obviating the requirement for both a user-specified connectivity and a topologically-consistent marching cubes/squares algorithm in meshing the resulting segmentation.

In this paper, we used a nonconservative Lagrangian mechanics approach to formulate a new statistical algorithm for fluid registration of 3-D brain images. This algorithm is named SAFIRA, acronym for statistically-assisted fluid image registration algorithm. A nonstatistical version of this algorithm was implemented , where the deformation was regularized by penalizing deviations from a zero rate of strain. In , the terms regularizing the deformation included the covariance of the deformation matrices (Σ) and the vector fields (q) . Here, we used a Lagrangian framework to reformulate this algorithm, showing that the regularizing terms essentially allow nonconservative work to occur during the flow. Given 3-D brain images from a group of subjects, vector fields and their corresponding deformation matrices are computed in a first round of registrations using the nonstatistical implementation. Covariance matrices for both the deformation matrices and the vector fields are then obtained and incorporated (separately or jointly) in the nonconservative terms, creating four versions of SAFIRA. We evaluated and compared our algorithms' performance on 92 3-D brain scans from healthy monozygotic and dizygotic twins; 2-D validations are also shown for corpus callosum shapes delineated at midline in the same subjects. After preliminary tests to demonstrate each method, we compared their detection power using tensor-based morphometry (TBM), a technique to analyze local volumetric differences in brain structure. We compared the accuracy of each algorithm variant using various statistical metrics derived from the images and deformation fields. All these tests were also run with a traditional fluid method, which has been quite widely used in TBM studies. The versions incorporating vector-based empirical statistics on brain variation were consistently more accurate than their counterparts, when used for automated volumetric quantification in new brain images. This suggests the advantages of this approach for large-scale neuroimaging studies.

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.

We introduce a labeled point set registration algorithm based on a family of novel information-theoretic measures derived as a generalization of the well-known Shannon entropy. This generalization, known as the Havrda-Charvat-Tsallis entropy, permits a fine-tuning between solution types of varying degrees of robustness of the divergence measure between multiple point sets. A variant of the traditional free-form deformation approach, known as directly manipulated free-form deformation, is used to model the transformation of the registration solution. We provide an overview of its open source implementation based on the Insight Toolkit of the National Institutes of Health. Characterization of the proposed framework includes comparison with other state of the art kernel-based methods and demonstration of its utility for lung registration via labeled point set representation of lung anatomy.

We propose a new scheme to estimate image bias field through introducing two sparsity constraints. One is that the bias-free image has concise representation with image gradients or coefficients of other image transformations. The other constraint is that model fit on the bias field should be as concise as possible. The new scheme enables adaptive specifications of the estimated bias field's smoothness, and results in extremely accurate solutions with more efficient optimization techniques, e.g. linear programming. These distinguish our approaches from many previous methods. Our techniques can be applied to intensity inhomogeneity correction of medical images, illumination and vignetting estimation of images captured by digital cameras.

This paper presents a novel method for assisting surgeons in automatically computing an optimal surgical plan by directly specifying the desired correction to a facial outline. First, the desired facial appearance is designed using a 3D sculpturing tool, while the cut regions of the skull are defined based on facial anatomy. Then, the deformation of the face meshes is performed using an improved biomechanical model in which virtual external forces are driven by the displacements corresponding to the differences of node coordinates between the original and specified face meshes, and free nodes and fixed nodes are defined in terms of the contact surfaces between the soft tissues and the bones within the cut regions. Finally, the shape of the contact surfaces is updated following the deformation of the soft tissues. After registering the deformable contact surfaces and the cut surfaces, the final positions of the cut bones are estimated. Evaluation of preliminary experimental results quantitatively shows the effectiveness of the proposed approach.

A variant of the popular nonparametric nonuniform intensity normalization (N3) algorithm is proposed for bias field correction. Given the superb performance of N3 and its public availability, it has been the subject of several evaluation studies. These studies have demonstrated the importance of certain parameters associated with the B-spline least-squares fitting. We propose the substitution of a recently developed fast and robust B-spline approximation routine and a modified hierarchical optimization scheme for improved bias field correction over the original N3 algorithm. Similar to the N3 algorithm, we also make the source code, testing, and technical documentation of our contribution, which we denote as "N4ITK," available to the public through the Insight Toolkit of the National Institutes of Health. Performance assessment is demonstrated using simulated data from the publicly available Brainweb database, hyperpolarized (3)He lung image data, and 9.4T postmortem hippocampus data.

Previous contributions to both the research and open source software communities detailed a generalization of a fast scalar field fitting technique for cubic B-splines based on the work originally proposed by Lee . One advantage of our proposed generalized B-spline fitting approach is its immediate application to a class of nonrigid registration techniques frequently employed in medical image analysis. Specifically, these registration techniques fall under the rubric of free-form deformation (FFD) approaches in which the object to be registered is embedded within a B-spline object. The deformation of the B-spline object describes the transformation of the image registration solution. Representative of this class of techniques, and often cited within the relevant community, is the formulation of Rueckert who employed cubic splines with normalized mutual information to study breast deformation. Similar techniques from various groups provided incremental novelty in the form of disparate explicit regularization terms, as well as the employment of various image metrics and tailored optimization methods. For several algorithms, the underlying gradient-based optimization retained the essential characteristics of Rueckert's original contribution. The contribution which we provide in this paper is two-fold: 1) the observation that the generic FFD framework is intrinsically susceptible to problematic energy topographies and 2) that the standard gradient used in FFD image registration can be modified to a well-understood preconditioned form which substantially improves performance. This is demonstrated with theoretical discussion and comparative evaluation experimentation.

We present a measure of gray matter (GM) thickness based on local surface models in the image domain. Thickness is measured by integrating GM probability maps along the white matter (WM) surface normal direction. The method is simple to implement and allows statistical tests to be performed in the gray matter volume. A novel topology preserving segmentation method is introduced that is able to accurately recover GM in deep sulci. We apply this methodology to a longitudinal study of gray matter atrophy in a patient cohort diagnosed with frontotemporal dementia (FTD) spectrum disorders. Following image-based normalization of GM thickness maps, results show significant reduction in cortical thickness in several Brodmann areas spanning temporal, parietal and frontal lobes across subjects.

We propose an efficient image registration strategy that is based on learned prior distributions of transformation parameters. These priors are used to constrain a finite- time multi-start optimization method. Motivation for this approach comes from the fact that standard affine brain image registration methods, especially those based on gradient descent optimization alone, are affected by the initial search position. While global optimization methods can resolve this problem, they are are often very time consuming. Our goal is to build an explicit prior model of the gap between a typical registration solution and the solution gained by a global optimization method. We use this learned prior model to restrict randomized search in the relevant parameter space surrounding the initial solution. Global optimization in this restricted parameter space provides, in finite time, results that are superior to both gradient descent and the general multi-start strategy. The performance of our method is illustrated on a data set of 67 elderly and neurodegenerative brains. Our novel learning strategy and the associated registration method are shown to outperform other approaches. Theoretical, synthetic and real-world examples illustrate this improvement.

Due to their computational efficiency and other salient properties, B-splines form the basis not only in comprising the de facto standard for curve and surface representation but also for various nonrigid registration techniques frequently employed in medical image analysis. These registration techniques fall under the rubric of Free-Form Deformation (FFD) approaches in which the object to be registered is embedded within a B-spline object. The deformation of the B-spline object represents the transformation of the registration. Representative, and often cited within the relevant community, of this class of techniques is the formulation of Rueckert et. al [7] who employed cubic splines with normalized mutual information to study breast deformation. Similar techniques from various groups provided incremental novelty in the form of disparate explicit regularization terms as well as the employment of various image metrics and tailored optimization methods. For several algorithms, the underlying gradient-based optimization retained its essential characteristics since Rueckert's incarnation. We assert that such a straightforward gradient-learning is suboptimal in certain cases and to remedy this sub-optimality, we propose a fitting-based strategy for registration in the spirit of Thirion 's Demons [14] and directly manipulated free-form deformations [2], which takes advantage of our previously developed generalized B-spline fitting algorithm [17].

This paper describes a new statistical analysis framework for diffusion-based white matter studies. The framework is based on a recent unbiased normalization algorithm for diffusion tensor images. Taking advantage of the fact that most human white matter tracts are thin sheet-like structures, this framework uses deformable medial models to represent six of the major tracts in a white matter atlas derived for a given set of images. The medial representation allows one to average tensor-based features along directions perpendicular to the tracts, thus reducing data dimensionality and accounting for errors in normalization. Unlike earlier work in the area of tract-based spatial statistics (Smith et al, 2006), this framework enables the analysis of individual white matter structures, and provides a range of possibilities for computing statistics and visualizing differences between cohorts. The framework is demonstrated in a study of white matter differences in pediatric chromosome 22q deletion syndrome.

Large scale gene expression studies in the mammalian brain offer the promise of understanding the topology, networks and ultimately the function of its complex anatomy, opening previously unexplored avenues in neuroscience. High-throughput methods permit genome-wide searches to discover genes that are uniquely expressed in brain circuits and regions that control behavior. Previous gene expression mapping studies in model organisms have employed situ hybridization (ISH), a technique that uses labeled nucleic acid probes to bind to specific mRNA transcripts in tissue sections. A key requirement for this effort is the development of fast and robust algorithms for anatomically mapping and quantifying gene expression for ISH. We describe a neuroinformatics pipeline for automatically mapping expression profiles of ISH data and its use to produce the first genomic scale 3-D mapping of gene expression in a mammalian brain. The pipeline is fully automated and adaptable to other organisms and tissues. Our automated study of over 20,000 genes indicates that at least 78.8 percent are expressed at some level in the adult C56BL/6J mouse brain. In addition to providing a platform for genomic scale search, high-resolution images and visualization tools for expression analysis are available at the Allen Brain Atlas web site (http://www.brain-map.org).

This paper presents a novel fuzzy-segmentation method for diffusion tensor (DT) and magnetic resonance (MR) images. Typical fuzzy-segmentation schemes, e.g., those based on fuzzy C means (FCM), incorporate Gaussian class models that are inherently biased towards ellipsoidal clusters characterized by a mean element and a covariance matrix. Tensors in fiber bundles, however, inherently lie on specific manifolds in Riemannian spaces. Unlike FCM-based schemes, the proposed method represents these manifolds using nonparametric data-driven statistical models. The paper describes a statistically-sound (consistent) technique for nonparametric modeling in Riemannian DT spaces. The proposed method produces an optimal fuzzy segmentation by maximizing a novel information-theoretic energy in a Markov-random-field framework. Results on synthetic and real, DT and MR images, show that the proposed method provides information about the uncertainties in the segmentation decisions, which stem from imaging artifacts including noise, partial voluming, and inhomogeneity. By enhancing the nonparametric model to capture the spatial continuity and structure of the fiber bundle, we exploit the framework to extract the cingulum fiber bundle. Typical tractography methods for tract delineation, incorporating thresholds on fractional anisotropy and fiber curvature to terminate tracking, can face serious problems arising from partial voluming and noise. For these reasons, tractography often fails to extract thin tracts with sharp changes in orientation, such as the cingulum. The results demonstrate that the proposed method extracts this structure significantly more accurately as compared to tractography.

The 16 papers in this special issue focus on the growing field of computational neuroanatomy. Some of the topics covered include: new work on deformable geometry and surface-based anatomical modeling; analysis of anatomical shape, with applications to disease classification and computer-aided diagnosis; new types of statistical analyses of structural brain images; and image registration.

The continuous medial representation (cm-rep) is an approach that makes it possible to model, normalize, and analyze anatomical structures on the basis of medial geometry. Having recently presented a partial differential equation (PDE)-based approach for 3-D cm-rep modeling [1], here we present an equivalent 2-D approach that involves solving an ordinary differential equation. This paper derives a closed form solution of this equation and shows how Pythagorean hodograph curves can be used to express the solution as a piecewise polynomial function, allowing efficient and robust medial modeling. The utility of the approach in medical image analysis is demonstrated by applying it to the problem of shape-based normalization of the midsagittal section of the corpus callosum. Using diffusion tensor tractography, we show that shape-based normalization aligns subregions of the corpus callosum, defined by connectivity, more accurately than normalization based on volumetric registration. Furthermore, shape-based normalization helps increase the statistical power of group analysis in an experiment where features derived from diffusion tensor tractography are compared between two cohorts. These results suggest that cm-rep is an appropriate tool for normalizing the corpus callosum in white matter studies.

Spatial normalization of diffusion tensor images plays a key role in voxel-based analysis of white matter (WM) group differences. Currently, it has been achieved using low-dimensional registration methods in the large majority of clinical studies. This paper aims to motivate the use of high-dimensional normalization approaches by generating evidence of their impact on the findings of such studies. Using an ongoing amyotrophic lateral sclerosis (ALS) study, we evaluated three normalization methods representing the current range of available approaches: low-dimensional normalization using the fractional anisotropy (FA), high-dimensional normalization using the FA, and high-dimensional normalization using full tensor information. Each method was assessed in terms of its ability to detect significant differences between ALS patients and controls. Our findings suggest that inadequate normalization with low-dimensional approaches can result in insufficient removal of shape differences which in turn can confound FA differences in a complex manner, and that utilizing high-dimensional normalization can both significantly minimize the confounding effect of shape differences to FA differences and provide a more complete description of WM differences in terms of both size and tissue architecture differences. We also found that high-dimensional approaches, by leveraging full tensor features instead of tensor-derived indices, can further improve the alignment of WM tracts.

The m-rep approach pioneered by Pizer et al. (2003) is a powerful morphological tool that makes it possible to employ features derived from medial loci (skeletons) in shape analysis. This paper extends the medial representation paradigm into the continuous realm, modeling skeletons and boundaries of three-dimensional objects as continuous parametric manifolds, while also maintaining the proper geometric relationship between these manifolds. The parametric representation of the boundary-medial relationship makes it possible to fit shape-based coordinate systems to the interiors of objects, providing a framework for combined statistical analysis of shape and appearance. Our approach leverages the idea of inverse skeletonization, where the skeleton of an object is defined first and the object's boundary is derived analytically from the skeleton. This paper derives a set of sufficient conditions ensuring that inverse skeletonization is well-posed for single-manifold skeletons and formulates a partial differential equation whose solutions satisfy the sufficient conditions. An efficient variational algorithm for deformable template modeling using the continuous medial representation is described and used to fit a template to the hippocampus in 87 subjects from a schizophrenia study with sub-voxel accuracy and 95% mean overlap.

We illustrate the application of intelligent medical image analysis techniques in order to reduce the computational cost of statistical voxel-wise analysis for detecting discriminative regions of morphological variability among different populations. We demonstrate that novel statistical image processing techniques that operate selectively on groups of pixels are suitable for morphological analysis of anatomical structures visualized by modern medical imaging modalities. We also show that the proposed methodology effectively decreases the number of statistical tests performed, alleviating the effect of the multiple comparison problem. We show that our approach detects regions of statistically significant morphological variability. Our results validate previous findings, while being robust across a wide range of experimental settings.

We present a new general Bayesian formulation for simultaneously restoring and segmenting piecewise smooth images. This implies estimation of the associated parameters of the classes within an image, the class label for each image pixel and the number of classes. The intensity image is modelled by parametric models based on regularized networks. The method fits the regions (or classes) with complex spatial intensity distributions with an identifiable group of simple models. Prior information is introduced in form of a two-level Markov random field (MRF). The low--level MRF models the information required to recover piecewise restorations, while the high-level MRF constraints the segmentation. The high--level MRF supports a merging process of simple intensity models into classes.

We address the problem of applying spatial transformations (or "image warps") to diffusion tensor magnetic resonance images. The orientational information that these images contain must be handled appropriately when they are transformed spatially during image registration. We present solutions for global transformations of three-dimensional images up to 12-parameter affine complexity and indicate how our methods can be extended for higher order transformations. Several approaches are presented and tested using synthetic data. One method, the preservation of principal direction algorithm, which takes into account shearing, stretching and rigid rotation, is shown to be the most effective. Additional registration experiments are performed on human brain data obtained from a single subject, whose head was imaged in three different orientations within the scanner. All of our methods improve the consistency between registered and target images over naïve warping algorithms.

In this paper, we discuss matching of magnetic resonance, diffusion tensor (DT) images of the human brain. Issues concerned with matching and transforming these complex images are discussed. In particular, we outline a method for preserving the intrinsic orientation of the data during nonrigid warps of the image and a number of similarity measures are proposed, based on the DT itself, on the DT deviatoric, and on indices derived from the DT. Each measure is used to drive an elastic matching algorithm applied to the task of registration of 3D images of the human brain. The performance of the various similarity measures is compared empirically by the use of several quality of match measures computed over a pair of matched images. Results indicate that the best matches are obtained from a Euclidean difference measure using the full DT.

In this paper, we discuss matching of diffusion tensor (DT) MRIs of the human brain. Issues concerned with matching and transforming these complex images are discussed. A number of similarity measures are proposed, based on indices derived from the DT, the DT itself and the DT deviatoric. Each measure is used to drive an elastic matching algorithm applied to the task of registration of 3D images of the human brain. The performance of the various similarity measures is compared empirically by use of several quality of match measures computed over a pair of matched images. Results indicate that the best matches are obtained from a Euclidean difference measure using the full DT. 1 Introduction Diffusion tensor (DT) imaging is a recent innovation in magnetic resonance imaging (MRI), [1]. In DT imaging, the measurement acquired at each voxel in an image volume is a symmetric second order tensor, which describes the local water diffusion properties of the material being imaged. Th...

In this paper we discuss work on the use of diffusion tensor MRIs for inter-subject brain matching. A multiresolution elastic matching algorithm for spatial normalisation of 3D image data, has been adapted for use with diffusion tensor data. The hope is that by exploitation of the added information contained in the diffusion tensor image, improved anatomical matches can be found, particularly in white matter regions of the brain. Results show that by matching on the diffusion tensor alone, anisotropic regions of the brain (white matter) are aligned better than if the match is computed on standard structural data. However, there is a cost of some accuracy in the alignment of prominent features in more conventional, structural MRI data, such as PD-, TI- and T2-weighted imagery. If both types of data to drive the matching process, prominent features in both images can be aligned simultaneously. The motivation for this work lies in the characterisation of the distribution of brain images taken from population groups.

Conventional diagnostic protocols in radiological viewing require the availability of a large display space, as exemplified by the film alternator (or lightbox). However, the recent trend in medical imaging workstation design is the use of relatively small display screens to present radiological images. In the study, the efficacy of an alternatorfilmstrip metaphor for navigating through and displaying the images of a patient study is evaluated. The metaphor relies on the availability of a ‘pictorial directory’ and accommodates the concurrent display of a variable number of images on the screen. In addition the study also evaluated the utility of two commonly available operations for manipulating the appearance of an image: contrast enhancement and image magnification. The study consisted of two experimental variables: availability of a pictorial directory (yes, no) and number of concurrently displayed images (1, 2, or 4). Twelve radiologists viewed two sets of X-ray computed tomography (CT) studies for each of the six treatment conditions and were asked to record an interpretation for each study. Results indicate that interpretations using the two-image display formats took the least amount of time per study, whereas the single-image format with access to the pictorial directory required the longest mean interpretation time. The image magnification capability was generally not found to be useful for image interpretation, whereas the contrast manipulation operations were judged extremely helpful. Implications of the results for medical imaging workstation design are discussed.