Patch-Based Nonlinear Image Registration for Gigapixel Whole Slide Images.

OBJECTIVE: Image registration of whole slide histology images allows the fusion of fine-grained information-like different immunohistochemical stains-from neighboring tissue slides. Traditionally, pathologists fuse this information by looking subsequently at one slide at a time. If the slides are digitized and accurately aligned at cell level, automatic analysis can be used to ease the pathologist's work. However, the size of those images exceeds the memory capacity of regular computers. METHODS: We address the challenge to combine a global motion model that takes the physical cutting process of the tissue into account with image data that is not simultaneously globally available. Typical approaches either reduce the amount of data to be processed or partition the data into smaller chunks to be processed separately. Our novel method first registers the complete images on a low resolution with a nonlinear deformation model and later refines this result on patches by using a second nonlinear registration on each patch. Finally, the deformations computed on all patches are combined by interpolation to form one globally smooth nonlinear deformation. The NGF distance measure is used to handle multistain images. RESULTS: The method is applied to ten whole slide image pairs of human lung cancer data. The alignment of 85 corresponding structures is measured by comparing manual segmentations from neighboring slides. Their offset improves significantly, by at least 15%, compared to the low-resolution nonlinear registration. CONCLUSION/SIGNIFICANCE: The proposed method significantly improves the accuracy of multistain registration which allows us to compare different antibodies at cell level.

[An Experimental Set-Up for Navigated-Contrast-Agent and Radiation Sparing Endovascular Aortic Repair (Nav-CARS EVAR)]. / Ein Prototyp für die navigierte Implantation von Aortenstentprothesen zur Reduzierung der Kontrastmittel- und Strahlenbelastung: Das Nav-CARS-EVAR-Konzept (Navigated-Contrast-Agent and Radiation Sparing Endovascular Aortic Repair).

INTRODUCTION: Over the last decade endovascular stenting of aortic aneurysm (EVAR) has been developed from single centre experiences to a standard procedure. With increasing clinical expertise and medical technology advances treatment of even complex aneurysms are feasible by endovascular methods. One integral part for the success of this minimally invasive procedure is innovative and improved vascular imaging to generate exact measurements and correct placement of stent prosthesis. One of the greatest difficulty in learning and performing this endovascular therapy is the fact that the three-dimensional vascular tree has to be overlaid with the two-dimensional angiographic scene by the vascular surgeon. MATERIAL AND METHODS: We report the development of real-time navigation software, which allows a three-dimensional endoluminal view of the vascular system during an EVAR procedure in patients with infrarenal aortic aneurysm. We used the preoperative planning CT angiography for three-dimensional reconstruction of aortic anatomy by volume-rendered segmentation. At the beginning of the intervention the relevant landmarks are matched in real-time with the two-dimensional angiographic scene. During the intervention the software continously registers the position of the guide-wire or the stent. An additional 3D-screen shows the generated endoluminal view during the whole intervention in real-time. RESULTS: We examined the combination of hardware and software components including complex image registration and fibre optic sensor technology (fibre-bragg navigation) with integration in stent graft introducer sheaths using patient-specific vascular phantoms in an experimental setting. From a technical point of view the feasibility of fibre-Bragg navigation has been proven in our experimental setting with patient-based vascular models. Three-dimensional preoperative planning including registration and simulation of virtual angioscopy in real time are realised. CONCLUSION: The aim of the Nav-CARS-EVAR concept is reduction of contrast medium and radiation dose by a three-dimensional navigation during the EVAR procedure. To implement fibre-Bragg navigation further experimental studies are necessary to verify accuracy before clinical application.

Lung registration using automatically detected landmarks.

OBJECTIVES: Accurate registration of lung CT images is inevitable for numerous clinical applications. Usually, nonlinear intensity-based methods are used. Their accuracy is typically evaluated using corresponding anatomical points (landmarks; e.g. bifurcations of bronchial and vessel trees) annotated by medical experts in the images to register. As image registration can be interpreted as correspondence finding problem, these corresponding landmarks can also be used in feature-based registration techniques. Recently, approaches for automated identification of such landmark correspondences in lung CT images have been presented. In this work, a novel combination of variational nonlinear intensity-based registration with an approach for automated landmark correspondence detection in lung CT pairs is presented and evaluated. METHODS: The main blocks of the proposed hybrid intensity- and feature-based registration scheme are a two-step landmark correspondence detection and the so-called CoLD (Combining Landmarks and Distance Measures) framework. The landmark correspondence identification starts with feature detection in one image followed by a blockmatching-based transfer of the features to the other image. The established correspondences are used to compute a thin-plate spline (TPS) transformation. Within CoLD, the TPS transformation is improved by minimization of an objective function consisting of a Normalized Gradient Field distance measure and a curvature regularizer; the landmark correspondences are guaranteed to be preserved by optimization on the kernel of the discretized landmark constraints. RESULTS: Based on ten publicly available end-inspiration/expiration CT scan pairs with anatomical landmark sets annotated by medical experts from the DIR-Lab database, it is shown that the hybrid registration approach is superior in terms of accuracy: The mean distance of expert landmarks is decreased from 8.46 mm before to 1.15 mm after registration, outperforming both the TPS transformation (1.68 mm) and a nonlinear registration without usage of automatically detected landmarks (2.44 mm). The improvement is statistically significant in eight of ten datasets in comparison to TPS and in nine of ten datasets in comparison to the intensity-based registration. Furthermore, CoLD globally estimates the breathing-induced lung volume change well and results in smooth and physiologically plausible motion fields of the lungs. CONCLUSIONS: We demonstrated that our novel landmark-based registration pipeline outperforms both TPS and the underlying nonlinear intensity-based registration without landmark usage. This highlights the potential of automatic landmark correspondence detection for improvement of lung CT registration accuracy.

Diffeomorphic susceptibility artifact correction of diffusion-weighted magnetic resonance images.

Diffusion-weighted magnetic resonance imaging is a key investigation technique in modern neuroscience. In clinical settings, diffusion-weighted imaging and its extension to diffusion tensor imaging (DTI) are usually performed applying the technique of echo-planar imaging (EPI). EPI is the commonly available ultrafast acquisition technique for single-shot acquisition with spatial encoding in a Cartesian system. A drawback of these sequences is their high sensitivity against small perturbations of the magnetic field, caused, e.g., by differences in magnetic susceptibility of soft tissue, bone and air. The resulting magnetic field inhomogeneities thus cause geometrical distortions and intensity modulations in diffusion-weighted images. This complicates the fusion with anatomical T1- or T2-weighted MR images obtained with conventional spin- or gradient-echo images and negligible distortion. In order to limit the degradation of diffusion-weighted MR data, we present here a variational approach based on a reference scan pair with reversed polarity of the phase- and frequency-encoding gradients and hence reversed distortion. The key novelty is a tailored nonlinear regularization functional to obtain smooth and diffeomorphic transformations. We incorporate the physical distortion model into a variational image registration framework and derive an accurate and fast correction algorithm. We evaluate the applicability of our approach to distorted DTI brain scans of six healthy volunteers. For all datasets, the automatic correction algorithm considerably reduced the image degradation. We show that, after correction, fusion with T1- or T2-weighted images can be obtained by a simple rigid registration. Furthermore, we demonstrate the improvement due to the novel regularization scheme. Most importantly, we show that it provides meaningful, i.e. diffeomorphic, geometric transformations, independent of the actual choice of the regularization parameters.

Three-dimensional cytoarchitectonic analysis of the posterior bank of the human precentral sulcus.

Studies employing functional magnetic resonance imaging have identified the human frontal eye field as being in the anterior and partly in the posterior wall, as well as at the base of the precentral sulcus. Moreover, it is known that the frontal eye field extends rostrally to the superior frontal sulcus. According to Brodmann's cytoarchitectonic map, this region belongs to the dysgranular Brodmann area 6 of the premotor cortex. However, the frontal eye field in non-human primates has been located within the arcuate sulcus in Brodmann area 8, generating considerable debate about where to locate exactly the frontal eye field in humans. Functional studies of the primate frontal eye field have revealed a principal homology of voluntary saccadic control systems in human and old-world monkeys, especially the macaque. But these homologies seem to be contradicted by the reported topographic localization at the cytoarchitectonic level. Therefore, we studied the cytoarchitectonic structure of the posterior bank of the precentral sulcus of a human brain, employing newly developed spatial mapping techniques to provide data about whether or not this region should be considered cytoarchitecturally homogeneous or heterogeneous. We used functional magnetic resonance imaging results, as an initial guide in localizing a region which is activated by saccadic tasks. A maximum of activation was detected around the junction of the superior frontal sulcus and the precentral sulcus extending 1.5 cm along the precentral sulcus in direction of the lateral sulcus. Here, one human brain has been analyzed to obtain preliminary data about the cytoarchitectonical changes of a part of area 6. Statistical analysis of the three-dimensional architectonic data from this region allowed us to identify a zone at the posterior bank, which in other studies has been associated with a functional region that controls pursuit eye movements and performs sensory-to-motor transformations. We found two significant sectors along the ventral part of the posterior bank of the precentral sulcus. The caudal transition region coincides partly with a region that integrates retinal and eye position signals for target location, arm, and axial movements. The second more ventrally located region is attributed to process oral-facial movements. The caudal transition region coincides with our functional magnetic resonance imaging investigation. It was revealed that this region lies at the inferior frontal eye field, where a pronounced activation over a larger region can be stimulated. Currently, more studies are needed to combine functional magnetic resonance imaging data of maximal activation with data from whole histologic brain sections of more individuals and to quantify the variability of this region and its sub-regions by means of a standardized brain atlas.

Intensity-based image registration with a guaranteed one-to-one point match.

OBJECTIVES: In this paper, we propose a novel registration technique, which combines the concepts of landmark and automatic, non-rigid intensity-based approaches. A general framework, which might be used for many different registration problems is presented. The novel approach enables the incorporation of different distance measures as well as different smoothers. METHODS: The proposed scheme minimizes a regularized distance measure subject to some interpolation constraints. The desired deformation is computed iteratively using an Euler-scheme for the first variation of the chosen objective functional. RESULTS: A fast and robust numerical scheme for the computation of the wanted minimizer is developed, implemented, and applied to various registration tasks. This includes the registration of pre- and post-intervention images of the human eye. CONCLUSIONS: A novel framework for a parameter-free, non-rigid registration scheme which allows for the additional incorporation of user-defined landmarks is proposed. It enhances the reliability of conventional approaches considerably and thereby their acceptability by practitioners in a clinical environment.