Torsten Rohlfing

Evaluation of Atlas Selection Strategies for Atlas-Based Image Segmentation with Application to Confocal Microscopy Images of Bee Brains

This paper evaluates strategies for atlas selection in atlas-based segmentation of three-dimensional biomedical images. Segmentation by intensity-based nonrigid registration to atlas images is applied to confocal microscopy images acquired from the brains of 20 bees. This paper evaluates and compares four different approaches for atlas image selection: registration to an individual atlas image (IND), registration to an average-shape atlas image (AVG), registration to the most similar image from a database of individual atlas images (SIM), and registration to all images from a database of individual atlas images with subsequent multi-classifier decision fusion (MUL). The MUL strategy is a novel application of multi-classifier techniques, which are common in pattern recognition, to atlas-based segmentation. For each atlas selection strategy, the segmentation performance of the algorithm was quantified by the similarity index (SI) between the automatic segmentation result and a manually generated gold standard. The best segmentation accuracy was achieved using the MUL paradigm, which resulted in a mean similarity index value between manual and automatic segmentation of 0.86 (AVG, 0.84; SIM, 0.82; IND, 0.81). The superiority of the MUL strategy over the other three methods is statistically significant (two-sided paired t test, P < 0.001). Both the MUL and AVG strategies performed better than the best possible SIM and IND strategies with optimal a posteriori atlas selection (mean similarity index for optimal SIM, 0.83; for optimal IND, 0.81). Our findings show that atlas selection is an important issue in atlas-based segmentation and that, in particular, multi-classifier techniques can substantially increase the segmentation accuracy.

Comprehensive maps of Drosophila higher olfactory centers: spatially segregated fruit and pheromone representation.

Summary In Drosophila, ∼50 classes of olfactory receptor neurons (ORNs) send axons to 50 corresponding glomeruli in the antennal lobe. Uniglomerular projection neurons (PNs) relay olfactory information to the mushroom body (MB) and lateral horn (LH). Here, we combine single-cell labeling and image registration to create high-resolution, quantitative maps of the MB and LH for 35 input PN channels and several groups of LH neurons. We find (1) PN inputs to the MB are stereotyped as previously shown for the LH; (2) PN partners of ORNs from different sensillar groups are clustered in the LH; (3) fruit odors are represented mostly in the posterior-dorsal LH, whereas candidate pheromone-responsive PNs project to the anterior-ventral LH; (4) dendrites of single LH neurons each overlap with specific subsets of PN axons. Our results suggest that the LH is organized according to biological values of olfactory input.

Volume-preserving nonrigid registration of MR breast images using free-form deformation with an incompressibility constraint

In this paper, we extend a previously reported intensity-based nonrigid registration algorithm by using a novel regularization term to constrain the deformation. Global motion is modeled by a rigid transformation while local motion is described by a free-form deformation based on B-splines. An information theoretic measure, normalized mutual information, is used as an intensity-based image similarity measure. Registration is performed by searching for the deformation that minimizes a cost function consisting of a weighted combination of the image similarity measure and a regularization term. The novel regularization term is a local volume-preservation (incompressibility) constraint, which is motivated by the assumption that soft tissue is incompressible for small deformations and short time periods. The incompressibility constraint is implemented by penalizing deviations of the Jacobian determinant of the deformation from unity. We apply the nonrigid registration algorithm with and without the incompressibility constraint to precontrast and postcontrast magnetic resonance (MR) breast images from 17 patients. Without using a constraint, the volume of contrast-enhancing lesions decreases by 1%-78% (mean 26%). Image improvement (motion artifact reduction) obtained using the new constraint is compared with that obtained using a smoothness constraint based on the bending energy of the coordinate grid by blinded visual assessment of maximum intensity projections of subtraction images. For both constraints, volume preservation improves, and motion artifact correction worsens, as the weight of the constraint penalty term increases. For a given volume change of the contrast-enhancing lesions (2% of the original volume), the incompressibility constraint reduces motion artifacts better than or equal to the smoothness constraint in 13 out of 17 cases (better in 9, equal in 4, worse in 4). The preliminary results suggest that incorporation of the incompressibility regularization term improves intensity-based free-form nonrigid registration of contrast-enhanced MR breast images by greatly reducing the problem of shrinkage of contrast-enhancing structures while simultaneously allowing motion artifacts to be substantially reduced.

Voxel similarity measures for 3-D serial MR brain image registration

The authors have evaluated eight different similarity measures used for rigid body registration of serial magnetic resonance (MR) brain scans. To assess their accuracy the authors used 33 clinical three-dimensional (3-D) serial MR images, with deformable extradural tissue excluded by manual segmentation and simulated 3-D MR images with added intensity distortion. For each measure the authors determined the consistency of registration transformations for both sets of segmented and unsegmented data. They have shown that of the eight measures tested, the ones based on joint entropy produced the best consistency. In particular, these measures seemed to be least sensitive to the presence of extradural tissue. For these data the difference in accuracy of these joint entropy measures, with or without brain segmentation, was within the threshold of visually detectable change in the difference images.

MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping.

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ1 and ℓ2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ1-regularized QSM versus FDRI and ℓ2-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths.

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: relations to timed performance.

The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (lambdaL), an index of axonal length or number, and transverse diffusivity (lambdaT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of ages effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.

Nonrigid image registration in shared-memory multiprocessor environments with application to brains, breasts, and bees

One major problem with nonrigid image registration techniques is their high computational cost. Because of this, these methods have found limited application to clinical situations where fast execution is required, e.g., intraoperative imaging. This paper presents a parallel implementation of a nonrigid image registration algorithm. It takes advantage of shared-memory multiprocessor computer architectures using multithreaded programming by partitioning of data and partitioning of tasks, depending on the computational subproblem. For three different biomedical applications (intraoperative brain deformation, contrast-enhanced MR mammography, intersubject brain registration), the scaling behavior of the algorithm is quantitatively analyzed. The method is demonstrated to perform the computation of intra-operative brain deformation in less than a minute using 64 CPUs on a 128-CPU shared-memory supercomputer (SGI Origin 3800). It is shown that its serial component is no more than 2% of the total computation time, allowing a speedup of at least a factor of 50. In most cases, the theoretical limit of the speedup is substantially higher (up to 132-fold in the application examples presented in this paper). The parallel implementation of our algorithm is, therefore, capable of solving nonrigid registration problems with short execution time requirements and may be considered an important step in the application of such techniques to clinically important problems such as the computation of brain deformation during cranial image-guided surgery.

Modeling liver motion and deformation during the respiratory cycle using intensity‐based nonrigid registration of gated MR images

We present a technique for modeling liver motion during the respiratory cycle using intensity-based nonrigid registration of gated magnetic resonance (MR) images. Three-dimensional MR images of the abdomens of four volunteers were acquired at end-inspiration, end-expiration, and eight time points in between using respiratory gating. The deformation fields between the images were computed using intensity-based rigid and nonrigid registration algorithms. Global motion is modeled by a rigid transformation while local motion is modeled by a free-form deformation based on B-splines. Much of the liver motion was cranial-caudal translation, which was captured by the rigid transformation. However, there was still substantial residual deformation (approximately 10 mm averaged over the entire liver in four volunteers, and 34 mm at one place in the liver of one volunteer). The computed organ motion model can potentially be used to determine an appropriate respiratory-gated radiotherapy window during which the position of the target is known within a specified excursion.

Performance-based classifier combination in atlas-based image segmentation using expectation-maximization parameter estimation

It is well known in the pattern recognition community that the accuracy of classifications obtained by combining decisions made by independent classifiers can be substantially higher than the accuracy of the individual classifiers. We have previously shown this to be true for atlas-based segmentation of biomedical images. The conventional method for combining individual classifiers weights each classifier equally (vote or sum rule fusion). In this paper, we propose two methods that estimate the performances of the individual classifiers and combine the individual classifiers by weighting them according to their estimated performance. The two methods are multiclass extensions of an expectation-maximization (EM) algorithm for ground truth estimation of binary classification based on decisions of multiple experts (Warfield et al., 2004). The first method performs parameter estimation independently for each class with a subsequent integration step. The second method considers all classes simultaneously. We demonstrate the efficacy of these performance-based fusion methods by applying them to atlas-based segmentations of three-dimensional confocal microscopy images of bee brains. In atlas-based image segmentation, multiple classifiers arise naturally by applying different registration methods to the same atlas, or the same registration method to different atlases, or both. We perform a validation study designed to quantify the success of classifier combination methods in atlas-based segmentation. By applying random deformations, a given ground truth atlas is transformed into multiple segmentations that could result from imperfect registrations of an image to multiple atlas images. In a second evaluation study, multiple actual atlas-based segmentations are combined and their accuracies computed by comparing them to a manual segmentation. We demonstrate in both evaluation studies that segmentations produced by combining multiple individual registration-based segmentations are more accurate for the two classifier fusion methods we propose, which weight the individual classifiers according to their EM-based performance estimates, than for simple sum rule fusion, which weights each classifier equally.

Image Similarity Using Mutual Information of Regions

Mutual information (MI) has emerged in recent years as an effective similarity measure for comparing images. One drawback of MI, however, is that it is calculated on a pixel by pixel basis, meaning that it takes into account only the relationships between corresponding indi- vidual pixels and not those of each pixels respective neighborhood. As a result, much of the spatial information inherent in images is not utilized. In this paper, we propose a novel extension to MI called regional mutual information (RMI). This extension efficiently takes neighborhood regions of corresponding pixels into account. We demonstrate the usefulness of RMI by applying it to a real-world problem in the medical domain— intensity-based 2D-3D registration of X-ray projection images (2D) to a CT image (3D). Using a gold-standard spine image data set, we show that RMI is a more robust similarity meaure for image registration than MI.