The goal of this paper is to increase the statistical power of crossing-fiber statistics in voxelwise analyses of diffusion-weighted magnetic resonance imaging (DW-MRI) data. In the proposed framework, a fiber orientation atlas and a model complexity atlas were used to fit the ball-and-sticks model to diffusion-weighted images of subjects in a prospective population-based cohort study. Reproducibility and sensitivity of the partial volume fractions in the ball-and-sticks model were analyzed using TBSS (tract-based spatial statistics) and compared to a reference framework. The reproducibility was investigated on two scans of 30 subjects acquired with an interval of approximately three weeks by studying the intraclass correlation coefficient (ICC). The sensitivity to true biological effects was evaluated by studying the regression with age on 500 subjects from 65 to 90 years old. Compared to the reference framework, the ICC improved significantly when using the proposed framework. Higher t-statistics indicated that regression coefficients with age could be determined more precisely with the proposed framework and more voxels correlated significantly with age. The application of a fiber orientation atlas and a model complexity atlas can significantly improve the reproducibility and sensitivity of crossing-fiber statistics in TBSS.

Quantitative MRI methods that estimate multiple physical parameters simultaneously often require the fitting of a computational complex signal model defined through the Bloch equations. Repeated Bloch simulations can be avoided by matching the measured signal with a precomputed signal dictionary on a discrete parameter grid (i.e. lookup table) as used in MR Fingerprinting. However, accurate estimation requires discretizing each parameter with a high resolution and consequently high computational and memory costs for dictionary generation, storage, and matching. Here, we reduce the required parameter resolution by approximating the signal between grid points through B-spline interpolation. The interpolant and its gradient are evaluated efficiently which enables a least-squares fitting method for parameter mapping. The resolution of each parameter was minimized while obtaining a user-specified interpolation accuracy. The method was evaluated by phantom and in-vivo experiments using fully-sampled and undersampled unbalanced (FISP) MR fingerprinting acquisitions. Bloch simulations incorporated relaxation effects (T1, T2), proton density (PD), receiver phase (φ0), transmit field inhomogeneity (B1+), and slice profile. Parameter maps were compared with those obtained from dictionary matching, where the parameter resolution was chosen to obtain similar signal (interpolation) accuracy. For both the phantom and the in-vivo acquisition, the proposed method approximated the parameter maps obtained through dictionary matching while reducing the parameter resolution in each dimension (T1, T2, B1+) by - on average - an order of magnitude. In effect, the applied dictionary was reduced from 1.47GB to 464KB. Furthermore, the proposed method was equally robust against undersampling artifacts as dictionary matching. Dictionary fitting with B-spline interpolation reduces the computational and memory costs of dictionary-based methods and is therefore a promising method for multi-parametric mapping.

Registration of images in the presence of intra-image signal fluctuations is a challenging task. The definition of an appropriate objective function measuring the similarity between the images is crucial for accurate registration. This paper introduces an objective function that embeds local phase features derived from the monogenic signal in the modality independent neighborhood descriptor (MIND). The image similarity relies on the autocorrelation of local structure (ALOST) which has two important properties: 1) low sensitivity to space-variant intensity distortions (e.g., differences in contrast enhancement in MRI); 2) high distinctiveness for 'salient' image features such as edges. The ALOST method is quantitatively compared to the MIND approach based on three different datasets: thoracic CT images, synthetic and real abdominal MR images. The proposed method outperformed the NMI and MIND similarity measures on these three datasets. The registration of dynamic contrast enhanced and post-contrast MR images of patients with Crohn's disease led to relative contrast enhancement measures with the highest correlation (r=0.56) to the Crohn's disease endoscopic index of severity.

We propose an information processing pipeline for segmenting parts of the bowel in abdominal magnetic resonance images that are affected with Crohn's disease. Given a magnetic resonance imaging test volume, it is first oversegmented into supervoxels and each supervoxel is analyzed to detect presence of Crohn's disease using random forest (RF) classifiers. The supervoxels identified as containing diseased tissues define the volume of interest (VOI). All voxels within the VOI are further investigated to segment the diseased region. Probability maps are generated for each voxel using a second set of RF classifiers which give the probabilities of each voxel being diseased, normal or background. The negative log-likelihood of these maps are used as penalty costs in a graph cut segmentation framework. Low level features like intensity statistics, texture anisotropy and curvature asymmetry, and high level context features are used at different stages. Smoothness constraints are imposed based on semantic information (importance of each feature to the classification task) derived from the second set of learned RF classifiers. Experimental results show that our method achieves high segmentation accuracy with Dice metric values of 0.90 ± 0.04 and Hausdorff distance of 7.3 ± 0.8 mm. Semantic information and context features are an integral part of our method and are robust to different levels of added noise.

Direct imaging of ligament damage in the wrist remains a challenge. Still, such damage can be assessed indirectly through the analysis of changes in wrist pose and motion pattern. For this purpose we built a statistical reference model that describes healthy motion patterns. We show that such a model can also be used to detect and quantify pathologies. A model that only describes the global translations and rotations of the carpal bones is insufficiently accurate due to size and shape variations of the bones. We present a local statistical motion model that minimizes the influence of size and shape differences by analyzing the coordinate differences of pairs of points on adjacent bone surfaces. These differences are determined in a set of 14 healthy example wrists imaged in a range of poses by means of 4D-RX imaging. The distribution of the differences as a function of the pose form the local statistical motion model (LSMM). Translations of 2 mm and rotations of 20° with respect to the healthy example wrists are detected as outliers in the point pair distributions. An evaluation involving wrists with a damaged ligament between scaphoid and lunate shows that not only joint space widenings can be detected, but also shifts of congruent bone surfaces. The LSMM is also used to perform a virtual reconstruction of the most likely healthy wrist after a simulated perturbation of bones. The reconstruction precision is shown to be about 1 mm. Therefore, the presented 4D statistical model of wrist bone movement may become a valuable clinical tool for diagnosis and surgical planning.

Scientists, engineers and physicians are used to analyze 3D data with slice-based visualizations. Radiologists for example are trained to read slices of medical imaging data. Despite the numerous examples of sophisticated 3D rendering techniques, domain experts, who still prefer slice-based visualization do not consider these to be very useful. Since 3D renderings have the advantage of providing an overview at a glance, while 2D depictions better serve detailed analyses, it is of general interest to better combine these methods. Recently there have been attempts to bridge this gap between 2D and 3D renderings. These attempts include specialized techniques for volume picking in medical imaging data that result in repositioning slices. In this paper, we present a new volume picking technique called WYSIWYP ("what you see is what you pick") that, in contrast to previous work, does not require pre-segmented data or metadata and thus is more generally applicable. The positions picked by our method are solely based on the data itself, the transfer function, and the way the volumetric rendering is perceived by the user. To demonstrate the utility of the proposed method, we apply it to automated positioning of slices in volumetric scalar fields from various application areas. Finally, we present results of a user study in which 3D locations selected by users are compared to those resulting from WYSIWYP. The user study confirms our claim that the resulting positions correlate well with those perceived by the user.

Diffusion Tensor MRI (DTI) is a rather recent image acquisition modality that can help identify disease processes in nerve bundles in the brain. Due to the large and complex nature of such data, its analysis requires new and sophisticated pipelines that are more efficiently executed within a grid environment. We present our progress over the past four years in the development and porting of the DTI analysis pipeline to grids. Starting with simple jobs submitted from the command-line, we moved towards a workflow-based implementation and finally into a web service that can be accessed via web browsers by end-users. The analysis algorithms evolved from basic to state-of-the-art, currently enabling the automatic calculation of a population-specific `atlas' where even complex brain regions are described in an anatomically correct way. Performance statistics show a clear improvement over the years, representing a mutual benefit from both a technology push and application pull.

There is an ongoing debate on how to model diffusivity in fiber crossings. We propose an optimization framework for the selection of a dual tensor model and the set of diffusion weighting parameters b, such that both the diffusion shape and orientation parameters can be precisely as well as accurately estimated. For that, we have adopted the Cramér-Rao lower bound (CRLB) on the variance of the model parameters, and performed Monte Carlo simulations. We have found that the axial diffusion lambda(parallel) needs to be constrained, while an isotropic fraction can be modeled by a single parameter f(iso). Under these circumstances, the Fractional Anisotropy (FA) of both tensors can theoretically be independently estimated with a precision of 9% (at SNR = 25). Levenberg-Marquardt optimization of the Maximum Likelihood function with a Rician noise model approached this precision while the bias was insignificant. A two-element b-vector b = [1.0 3.5] x 10(3) mm(-2)s was found to be sufficient for estimating parameters of heterogeneous tissue with low error. This has allowed us to estimate consistent FA-profiles along crossing tracts. This work defines fundamental limits for comparative studies to correctly analyze crossing white matter structures.

We present a computer-aided detection (CAD) system for computed tomography colonography that orders the polyps according to clinical relevance. The CAD system consists of two steps: candidate detection and supervised classification. The characteristics of the detection step lead to specific choices for the classification system. The candidates are ordered by a linear logistic classifier (logistic regression) based on only three features: the protrusion of the colon wall, the mean internal intensity, and a feature to discard detections on the rectal enema tube. This classifier can cope with a small number of polyps available for training, a large imbalance between polyps and non-polyp candidates, a truncated feature space, unbalanced and unknown misclassification costs, and an exponential distribution with respect to candidate size in feature space. Our CAD system was evaluated with data sets from four different medical centers. For polyps larger than or equal to 6 mm we achieved sensitivities of respectively 95%, 85%, 85%, and 100% with 5, 4, 5, and 6 false positives per scan over 86, 48, 141, and 32 patients. A cross-center evaluation in which the system is trained and tested with data from different sources showed that the trained CAD system generalizes to data from different medical centers and with different patient preparations. This is essential to application in large-scale screening for colorectal polyps.

Today's computer aided detection systems for computed tomography colonography (CTC) enable automated detection and segmentation of colorectal polyps. We present a paradigm shift by proposing a method that measures the amount of protrudedness of a candidate object in a scale adaptive fashion. One of the main results is that the performance of the candidate detection depends only on one parameter, the amount of protrusion. Additionally the method yields correct polyp segmentation without the need of an additional segmentation step. The supervised pattern recognition involves a clear distinction between size related features and features related to shape or intensity. A Mahalanobis transformation of the latter facilitates ranking of the objects using a logistic classifier. We evaluate two implementations of the method on 84 patients with a total of 57 polyps larger than or equal to 6 mm. We obtained a performance of 95% sensitivity at four false positives per scan for polyps larger than or equal to 6 mm.

Comparing wrist shapes of different individuals requires alignment of these wrists into the same pose. Unconstrained registration of the carpal bones results in anatomically nonfeasible wrists. In this paper, we propose to constrain the registration using the shapes of adjacent bones, by keeping the width of the gap between adjacent bones constant. The registration is formulated as an optimization involving two terms. One term aligns the wrist bones by minimizing the distances between corresponding bone surfaces. The second term constrains the registration by minimizing the distances between adjacent sliding surfaces. The registration is based on the Iterative Closest Point algorithm. All bones are registered concurrently so that no bias is introduced towards any of the bones. The proposed registration method delivers anatomically correct configurations of the bones. The registration errors are in the order of the voxel size of the acquired CT data (0.3 x 0.3 x 0.3 mm(3)). The standard deviation in the widths of gaps between adjacent bones is in the order of 10% with an insignificant bias. This is a large improvement over the standard deviations of 30%-80% encountered in unconstrained registration. The value of this method is its capability of accurately registering joints in varying poses resulting in physiological joint configurations.

CT colonography (CTC) is a rapidly evolving technique to screen for colorectal polyps. Fecal residue may occlude or, reversely, mimic polyps. Electronic cleansing aims at removing contrast-enhanced fecal residue from the image. However, thin layers of soft tissue (the colon wall or a fold) or residue are easily misclassified by current electronic cleansing methods, thereby causing holes in the colon wall or other artefacts that hamper visualization and automated detection. We present a thin layer model to detect and characterize such layers to support electronic cleansing. It is demonstrated that the model sustains robust estimation of the location and thickness of such a layer. Such thicknesses of thin layers were measured in real data sets. A lower bound on the thickness of such layers exists and was found to be 1.0 mm for our data.

A fully automated method is presented to classify 3-D CT data into material fractions. An analytical scale-invariant description relating the data value to derivatives around Gaussian blurred step edges--arch model--is applied to uniquely combine robustness to noise, global signal fluctuations, anisotropic scale, noncubic voxels, and ease of use via a straightforward segmentation of 3-D CT images through material fractions. Projection of noisy data value and derivatives onto the arch yields a robust alternative to the standard computed Gaussian derivatives. This results in a superior precision of the method. The arch-model parameters are derived from a small, but over-determined, set of measurements (data values and derivatives) along a path following the gradient uphill and downhill starting at an edge voxel. The model is first used to identify the expected values of the two pure materials (named L and H) and thereby classify the boundary. Second, the model is used to approximate the underlying noise-free material fractions for each noisy measurement. An iso-surface of constant material fraction accurately delineates the material boundary in the presence of noise and global signal fluctuations. This approach enables straightforward segmentation of 3-D CT images into objects of interest for computer-aided diagnosis and offers an easy tool for the design of otherwise complicated transfer functions in high-quality visualizations. The method is applied to segment a tooth volume for visualization and digital cleansing for virtual colonoscopy.

The development of methods to detect slowly progressing diseases is often hampered by the time-consuming acquisition of a sufficiently large data set. In this paper, a method is presented to model the change in images acquired by scanning laser polarimetry, for the detection of glaucomatous progression. The model is based on image series of 23 healthy eyes and incorporates colored noise, incomplete cornea compensation and masking by the retinal blood vessels. Additionally, two methods for detecting progression, taking either one or two follow-up visits into account, are discussed and tested on these simulated images. Both methods are based on Student's t-tests, morphological operations and anisotropic filtering. The images simulated by the model are visually pleasing, show corresponding statistical properties to the real images and are used to optimize the detection methods. The results show that detecting progression based on two follow-up visits greatly improves the sensitivity without adversely affecting the specificity.

Computer-aided diagnosis (CAD) is a helpful addition to laborious visual inspection for preselection of suspected colonic polyps in virtual colonoscopy. Most of the previous work on automatic polyp detection makes use of indicators based on the scalar curvature of the colon wall and can result in many false-positive detections. Our work tries to reduce the number of false-positive detections in the preselection of polyp candidates. Polyp surface shape can be characterized and visualized using lines of curvature. In this paper, we describe techniques for generating and rendering lines of curvature on surfaces and we show that these lines can be used as part of a polyp detection approach. We have adapted existing approaches on explicit triangular surface meshes, and developed a new algorithm on implicit surfaces embedded in 3D volume data. The visualization of shaded colonic surfaces can be enhanced by rendering the derived lines of curvature on these surfaces. Features strongly correlated with true-positive detections were calculated on lines of curvature and used for the polyp candidate selection. We studied the performance of these features on 5 data sets that included 331 pre-detected candidates, of which 50 sites were true polyps. The winding angle had a significant discriminating power for true-positive detections, which was demonstrated by a Wilcoxon rank sum test with p < 0.001. The median winding angle and inter-quartile range (IQR) for true polyps were 7.817 and 6.770 - 9.288 compared to 2.954 and 1.995 - 3.749 for false-positive detections.

Diffusion tensor imaging (DTI) is an MRI-based technique for quantifying water diffusion in living tissue. In the white matter of the brain, water diffuses more rapidly along the neuronal axons than in the perpendicular direction. By exploiting this phenomenon, DTI can be used to determine trajectories of fiber bundles, or neuronal connections between regions, in the brain. The resulting bundles can be visualized. However, the resulting visualizations can be complex and difficult to interpret. An effective approach is to pre-determine trajectories from a large number of positions throughout the white matter (full brain fiber tracking) and to offer facilities to aid the user in selecting fiber bundles of interest. Two factors are crucial for the use and acceptance of this technique in clinical studies: firstly, the selection of the bundles by brain experts should be interactive, supported by real-time visualization of the trajectories registered with anatomical MRI scans. Secondly, the fiber selections should be reproducible, so that different experts will achieve the same results. In this paper we present a practical technique for the interactive selection of fiber-bundles using multiple convex objects that is an order of magnitude faster than similar techniques published earlier. We also present the results of a clinical study with ten subjects that show that our selection approach is highly reproducible for fractional anisotropy (FA) calculated over the selected fiber bundles.

The quality of volume visualization depends strongly on the quality of the underlying data. In virtual colonoscopy, CT data should be acquired at a low radiation dose that results in a low signal-to-noise ratio. Alternatively, MRI data is acquired without ionizing radiation, but suffers from noise and bias (global signal fluctuations). Current volume visualization techniques often do not produce good results with noisy or biased data. This paper describes methods for volume visualization that deal with these imperfections. The techniques are based on specially adapted edge detectors using first and second order derivative filters. The filtering is integrated into the visualization process. The first order derivative method results in good quality images but suffers from localization bias. The second order method has better surface localization, especially in highly curved areas. It guarantees minimal detail smoothing resulting in a better visualization of polyps.

In this paper an existing ridge detector based on the Hessian tensor and a new one based on the structure tensor are evaluated for use in portal/simulator imaging. Tensor smoothing is introduced as a scaling parameter. By changing this scale (as opposed to the image scale) the detectors can be tuned to suppress spurious ridges without moving them. Desirable ridge detector properties for portal/simulator imaging are described and the ridge definitions are tested accordingly. Experiments show that our new ridge detector outperformed the existing one in simulator/portal image matching.

The anterior surface of the eye ('cornea') is extremely important for good sight. Instruments measuring corneal shape conventionally visualize the surface characteristics by mapping the instantaneous radius of curvature onto a rainbow colour scale. This technique is known to have important drawbacks. Firstly, not corneal shape itself is visualized, but rather second order surface properties. Secondly, the type of colouring produces well documented artifacts. We discuss visualization techniques for a more direct representation of the data. In a three part display, shape deviations are presented as a height surface in one window, height lines superimposed over the input image in another, and a colour mapped representation of the mean normal radius of curvature in a third. With the aid of some typical examples, it is shown that these visualizations are easy to interpret by the physician and overcome the limitations of the conventional techniques.

Medical tomographic images are formed by the intersection of the image plane and an object. As the image plane changes, different parts of the object come in view or drop out of view. However, for small changes of the image plane, most parts continue to remain visible and their qualitative embedding in the image remains similar. Therefore, similarity of part embeddings can be used to infer similarity of image planes. Part embeddings are useful features for other vision applications as well. In view of this, a spatial relation called "arrangement" is proposed to describe part embeddings. The relation describes how each part is surrounded by its neighbors. Further, a metric for arrangements is formulated by expressing arrangements in terms of the Voronoi diagram of the parts. Arrangements and their metric are used to retrieve images by image plane similarity in a cardiac magnetic resonance image database. Experiments with the database are reported which (1) validate the observation that similarity of image planes can be inferred from similarity of part embeddings, and (2) compare the performance of arrangement based image retrieval with that of expert radiologists.>