Multi-Atlas Segmentation with Joint Label Fusion.

Multi-atlas segmentation is an effective approach for automatically labeling objects of interest in biomedical images. In this approach, multiple expert-segmented example images, called atlases, are registered to a target image, and deformed atlas segmentations are combined using label fusion. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity have been particularly successful. However, one limitation of these strategies is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this limitation, we propose a new solution for the label fusion problem in which weighted voting is formulated in terms of minimizing the total expectation of labeling error and in which pairwise dependency between atlases is explicitly modeled as the joint probability of two atlases making a segmentation error at a voxel. This probability is approximated using intensity similarity between a pair of atlases and the target image in the neighborhood of each voxel. We validate our method in two medical image segmentation problems: hippocampus segmentation and hippocampus subfield segmentation in magnetic resonance (MR) images. For both problems, we show consistent and significant improvement over label fusion strategies that assign atlas weights independently.

Robust Automated Amygdala Segmentation via Multi-Atlas Diffeomorphic Registration.

Here, we describe a novel method for volumetric segmentation of the amygdala from MRI images collected from 35 human subjects. This approach is adapted from open-source techniques employed previously with the hippocampus (Suh et al., 2011; Wang et al., 2011a,b). Using multi-atlas segmentation and machine learning-based correction, we were able to produce automated amygdala segments with high Dice (Mean = 0.918 for the left amygdala; 0.916 for the right amygdala) and Jaccard coefficients (Mean = 0.850 for the left; 0.846 for the right) compared to rigorously hand-traced volumes. This automated routine also produced amygdala segments with high intra-class correlations (consistency = 0.830, absolute agreement = 0.819 for the left; consistency = 0.786, absolute agreement = 0.783 for the right) and bivariate (r = 0.831 for the left; r = 0.797 for the right) compared to hand-drawn amygdala. Our results are discussed in relation to other cutting-edge segmentation techniques, as well as commonly available approaches to amygdala segmentation (e.g., Freesurfer). We believe this new technique has broad application to research with large sample sizes for which amygdala quantification might be needed.

Measuring longitudinal change in the hippocampal formation from in vivo high-resolution T2-weighted MRI.

The hippocampal formation (HF) is a brain structure of great interest because of its central role in learning and memory, and its associated vulnerability to several neurological disorders. In vivo oblique coronal T2-weighted MRI with high in-plane resolution (~0.5 mm × 0.5 mm), thick slices (~2.0 mm), and a field of view tailored to imaging the hippocampal formation (denoted HF-MRI in this paper) has been advanced as a useful imaging modality for detailed hippocampal morphometry. Cross-sectional analysis of volume measurements derived from HF-MRI has shown the modality's promise to yield sensitive imaging-based biomarker for neurological disorders such as Alzheimer's disease. However, the utility of this modality for making measurements of longitudinal change has not yet been demonstrated. In this paper, using an unbiased deformation-based morphometry (DBM) pipeline, we examine the suitability of HF-MRI for estimating longitudinal change by comparing atrophy rates measured in the whole hippocampus from this modality with those measured from more common isotropic (~1 mm³) T1-weighted MRI in the same set of individuals, in a cohort of healthy controls and patients with cognitive impairment. While measurements obtained from HF-MRI were largely consistent with those obtained from T1-MRI, HF-MRI yielded slightly larger group effect of greater atrophy rates in patients than in controls. The estimated minimum sample size required for detecting a 25% change in patients' atrophy rate in the hippocampus compared to the control group with a statistical power ß=0.8 was N=269. For T1-MRI, the equivalent sample size was N=325. Using a dataset of test-retest scans, we show that the measurements were free of additive bias. We also demonstrate that these results were not a confound of certain methodological choices made in the DBM pipeline to address the challenges of making longitudinal measurements from HF-MRI, using a region of interest (ROI) around the HF to globally align serial images, followed by slice-by-slice deformable registration to measure local volume change. Additionally, we present a preliminary study of atrophy rate measurements within hippocampal subfields using HF-MRI. Cross-sectional differences in atrophy rates were detected in several subfields.

CT-PET weighted image fusion for separately scanned whole body rat.

PURPOSE: The limited resolution and lack of spatial information in positron emission tomography (PET) images require the complementary anatomic information from the computed tomography (CT) and/or magnetic resonance imaging (MRI). Therefore, multimodality image fusion techniques such as PET/CT are critical in mapping the functional images to structural images and thus facilitate the interpretation of PET studies. In our experimental situation, the CT and PET images are acquired in separate scanners at different times and the inherent differences in the imaging protocols produce significant nonrigid changes between the two acquisitions in addition to dissimilar image characteristics. The registration conditions are also poor because CT images have artifacts due to the limitation of current scanning settings, while PET images are very blurry (in transmission-PET) and have vague anatomical structure boundaries (in emission-PET). METHODS: The authors present a new method for whole body small animal multimodal registration. In particular, the authors register whole body rat CT image and PET images using a weighted demons algorithm. The authors use both the transmission-PET and the emission-PET images in the registration process emphasizing particular regions of the moving transmission-PET image using the emission-PET image. After a rigid transformation and a histogram matching between the CT and the transmission-PET images, the authors deformably register the transmission-PET image to the CT image with weights based on the intensity-normalized emission-PET image. For the deformable registration process, the authors develop a weighted demons registration method that can give preferences to particular regions of the input image using a weight image. RESULTS: The authors validate the results with nine rat image sets using the M-Hausdorff distance (M-HD) similarity measure with different outlier-suppression parameters (OSP). In comparison with standard methods such as the regular demons and the normalized mutual information (NMI)-based nonrigid free-form deformation (FFD) registration, the proposed weighted demons registration method shows average M-HD errors: 3.99 ± 1.37 (OSP = 10), 5.04 ± 1.59 (OSP = 20) and 5.92 ± 1.61 (OSP = ∞) with statistical significance (p < 0.0003) respectively, while NMI-based nonrigid FFD has average M-HD errors: 5.74 ± 1.73 (OSP = 10), 7.40 ± 7.84 (OSP = 20) and 9.83 ± 4.13 (OSP = ∞), and the regular demons has average M-HD errors: 6.79 ± 0.83 (OSP = 10), 9.19 ± 2.39 (OSP = 20) and 11.63 ± 3.99 (OSP = ∞), respectively. In addition to M-HD comparisons, the visual comparisons on the faint-edged region between the CT and the aligned PET images also show the encouraging improvements over the other methods. CONCLUSIONS: In the whole body multimodal registration between CT and PET images, the utilization of both the transmission-PET and the emission-PET images in the registration process by emphasizing particular regions of the transmission-PET image using an emission-PET image is effective. This method holds promise for other image fusion applications where multiple (more than two) input images should be registered into a single informative image.

Registration under topological change for CT colonography.

Computed tomography (CT) colonography is a minimally invasive screening technique for colorectal polyps, in which X-ray CT images of the distended colon are acquired, usually in the prone and supine positions of a single patient. Registration of segmented colon images from both positions will be useful for computer-assisted polyp detection. We have previously presented algorithms for registration of the prone and supine colons when both are well distended and there is a single connected lumen. However, due to inadequate bowel preparation or peristalsis, there may be collapsed segments in one or both of the colon images resulting in a topological change in the images. Such changes make deformable registration of the colon images difficult, and at present, there are no registration algorithms that can accommodate them. In this paper, we present an algorithm that can perform volume registration of prone/supine colon images in the presence of a topological change. For this purpose, 3-D volume images are embedded as a manifold in a 4-D space, and the manifold is evolved for nonrigid registration. Experiments using data from 24 patients show that the proposed method achieves good registration results in both the shape alignment of topologically different colon images from a single patient and the polyp location estimation between supine and prone colon images.

A non-rigid registration method for serial lower extremity hybrid SPECT/CT imaging.

Small animal X-ray computed tomographic (microCT) imaging of the lower extremities permits evaluation of arterial growth in models of hindlimb ischemia, and when applied serially can provide quantitative information about disease progression and aid in the evaluation of therapeutic interventions. The quantification of changes in tissue perfusion and concentration of molecular markers concurrently obtained using nuclear imaging requires the ability to non-rigidly register the microCT images over time, a task made more challenging by the potentially large changes in the positions of the legs due to articulation. While non-rigid registration methods have been extensively used in the evaluation of individual organs, application in whole body imaging has been limited, primarily because the scale of possible displacements and deformations is large resulting in poor convergence of most methods. In this paper we present a new method based on the extended demons algorithm that uses a level-set representation of the body contour and skeletal structure as an input. The proposed serial registration method reflects the natural physical moving combination of mouse anatomy in which the movement of bones is the framework for body movements, and the movement of skin constrains the detailed movements of the specific segmented body regions. We applied our method to both the registration of serial microCT mouse images and the quantification of microSPECT component of the serially hybrid microCT-SPECT images demonstrating improved performance as compared to existing registration techniques.

Deformable registration of supine and prone colons for computed tomographic colonography.

Computed tomographic colonography is a minimally invasive technique for detecting colorectal polyps and colon cancer. Most computed tomographic colonography protocols acquire both prone and supine images to improve the visualization of the lumen wall, reduce false-positives, and improve sensitivity. Comparisons between the prone and supine images can be improved by registration between the scans. In this paper, we propose registering colon lumens, segmented from prone and supine images, using feature matching of the colon centerline and nonrigid registration of the lumen shapes represented as distance functions. Experimental registration results (n = 21 subjects) show a correspondence accuracy of 13.77 +/- 6.20 mm for a range of polyp sizes. The overlap in the registered lumen segmentations show an average Jaccard similarity coefficient of 0.915 +/- 0.07.

A non-rigid registration method for serial microCT mouse hindlimb images.

We present a new method for the non-rigid registration of serial mouse microCT images which undergo potentially large changes in the positions of the legs due to articulation. While non-rigid registration methods have been extensively used in the evaluation of individual organs, application in whole body imaging has been limited, primarily because the scale of possible displacements and deformations is large resulting in poor convergence of most methods. Our method is based on the extended demons algorithm that uses a level-set representation of the mouse skin and skeleton as an input, and composed of three steps reflecting the natural physical movements of bony structures. We applied our method to the registration of serial microCT mouse images demonstrating encouraging performances as compared to competitive techniques.

Deformable registration of prone and supine colons for CT colonography.

CT colonography (CTC) is a non-invasive technique for detecting colorectal polyps and colon cancer. Through the addition of the prone scanning with the original supine scanning, the possibility of detecting the polyps is increased. The registration process for this application requires the comparison between the prone and supine colons for diagnosis. A level-set representation of the object boundary using a distance map is presented in this paper as an input to demons registration algorithm for supine and prone CT colonography image data. After first aligning the colon volumes based on the patient's anus position, distances inside and outside the objects' boundary are computed. The level-set from the distance map allows the demons algorithm to decide the moving direction for the initial demons' force between the two colons. We present a result with a 3 dimensional volume of a patient's colon. The results suggest that our method has excellent registration performance with high confidence even with considerable deformation of the colon lumen in 3 dimensional case.