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Purpose: Post-reconstruction positron emission tomography (PET) image restoration methods that take advantage of available anatomical information can play an important role in accurate quantification of PET images. However, when using anatomical information, the resulting PET image may lose resolution in certain regions where the anatomy does not agree with the change in functional activity. In this work, this problem is addressed by using both magnetic resonance (MR) and filtered PET images to guide the denoising process., Methods: In this work, two novel post-reconstruction methods for restoring PET images using the subject's registered T1-weighted MR image are proposed. The first method is based on a representation of the image using basis functions extracted from T1-weighted MR and filtered PET image. The coefficients for these basis functions are estimated using a sparsity-penalized least squares objective function. The second method is a noniterative fast method that uses guided kernel filtering in combination with twicing to restore the noisy PET image. When applied after conventional PVE correction, these methods can be considered as voxel-based MR-guided partial volume effect (PVE) correction methods., Results: Using simulation analyses of [ 18 F]FDG PET images of the brain with lesions, the proposed methods are compared to other denoising methods through different figures of merit. The results show promising improvements in image quality as well as reduction in bias and variance of the lesions. We also show the application of the proposed methods on real [ 18 F]FDG data., Conclusion: Two methods for restoring PET images were proposed. The methods were evaluated on simulation and real brain images. Most MR-guided PVE correction methods are only based on segmented T1-weighted images and their accuracy is very sensitive to segmentation errors, especially in regions of abnormalities and lesions. However, both proposed methods can use the T1-weighted image without segmentation. The simplicity and the very low computational cost of the second method make it suitable for clinical applications and large data studies. The proposed methods can be naturally extended to PVE correction and denoising of other functional modalities using corresponding anatomical information., (© 2019 American Association of Physicists in Medicine.)

Purpose: As an inexpensive, noninvasive, and portable clinical imaging modality, ultrasound (US) has been widely employed in many interventional procedures for monitoring potential tissue deformation, surgical tool placement, and locating surgical targets. The application requires the spatial mapping between 2D US images and 3D coordinates of the patient. Although positions of the devices (i.e., ultrasound transducer) and the patient can be easily recorded by a motion tracking system, the spatial relationship between the US image and the tracker attached to the US transducer needs to be estimated through an US calibration procedure. Previously, various calibration techniques have been proposed, where a spatial transformation is computed to match the coordinates of corresponding features in a physical phantom and those seen in the US scans. However, most of these methods are difficult to use for novel users., Methods: We proposed an ultrasound calibration method by constructing a phantom from simple Lego bricks and applying an automated multi-slice 2D-3D registration scheme without volumetric reconstruction. The method was validated for its calibration accuracy and reproducibility., Results: Our method yields a calibration accuracy of [Formula: see text] mm and a calibration reproducibility of 1.29 mm., Conclusion: We have proposed a robust, inexpensive, and easy-to-use ultrasound calibration method.

Background: The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms., Methods: Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction., Results: Hippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = <-0.468, P = <.0005). Cerebrospinal fluid spaces (mm(3)) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy., Conclusions: This work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Mutual information (MI) has been widely used as a similarity measure for rigid registration of multi-modal and uni-modal medical images. However, robust application of MI to deformable registration is challenging mainly because rich structural information, which are critical cues for successful deformable registration, are not incorporated into MI. We propose a self-similarity weighted graph-based implementation of α-mutual information (α-MI) for nonrigid image registration. We use a self-similarity measure that uses local structural information and is invariant to rotation and to local affine intensity distortions, and therefore the new Self Similarity α-MI (SeSaMI) metric inherits these properties and is robust against signal nonstationarity and intensity distortions. We have used SeSaMI as the similarity measure in a regularized cost function with B-spline deformation field to achieve nonrigid registration. Since the gradient of SeSaMI can be derived analytically, the cost function can be efficiently optimized using stochastic gradient descent methods. We show that SeSaMI produces a robust and smooth cost function and outperforms the state of the art statistical based similarity metrics in simulation and using data from image-guided neurosurgery., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Automatic segmentation methods are important tools for quantitative analysis of magnetic resonance images. Recently, patch-based label fusion approaches demonstrated state-of-the-art segmentation accuracy. In this paper, we introduce a new patch-based method using the PatchMatch algorithm to perform segmentation of anatomical structures. Based on an Optimized PAtchMatch Label fusion (OPAL) strategy, the proposed method provides competitive segmentation accuracy in near real time. During our validation on hippocampus segmentation of 80 healthy subjects, OPAL was compared to several state-of-the-art methods. Results show that OPAL obtained the highest median Dice coefficient (89.3%) in less than 1 sec per subject. These results highlight the excellent performance of OPAL in terms of computation time and segmentation accuracy compared to recently published methods.

Cross-sectional analysis of longitudinal anatomical magnetic resonance imaging (MRI) data may be suboptimal as each dataset is analyzed independently. In this study, we evaluate how much variability can be reduced by analyzing structural volume changes in longitudinal data using longitudinal analysis. We propose a two-part pipeline that consists of longitudinal registration and longitudinal classification. The longitudinal registration step includes the creation of subject-specific linear and nonlinear templates that are then registered to a population template. The longitudinal classification step comprises a four-dimensional expectation-maximization algorithm, using a priori classes computed by averaging the tissue classes of all time points obtained cross-sectionally. To study the impact of these two steps, we apply the framework completely ("LL method": Longitudinal registration and Longitudinal classification) and partially ("LC method": Longitudinal registration and Cross-sectional classification) and compare these with a standard cross-sectional framework ("CC method": Cross-sectional registration and Cross-sectional classification). The three methods are applied to (1) a scan-rescan database to analyze reliability and (2) the NIH pediatric population to compare gray matter growth trajectories evaluated with a linear mixed model. The LL method, and the LC method to a lesser extent, significantly reduced the variability in the measurements in the scan-rescan study and gave the best-fitted gray matter growth model with the NIH pediatric MRI database. The results confirm that both steps of the longitudinal framework reduce variability and improve accuracy in comparison with the cross-sectional framework, with longitudinal classification yielding the greatest impact. Using the improved method to analyze longitudinal data, we study the growth trajectories of anatomical brain structures in childhood using the NIH pediatric MRI database. We report age- and gender-related growth trajectories of specific regions of the brain during childhood that could be used as a reference in studying the impact of neurological disorders on brain development., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We present a novel approach for the registration of pre-operative magnetic resonance images to intra-operative ultrasound images for the context of image-guided neurosurgery., Method: Our technique relies on the maximization of gradient orientation alignment in a reduced set of high confidence locations of interest and allows for fast, accurate, and robust registration. Performance is compared with multiple state-of-the-art techniques including conventional intensity-based multi-modal registration strategies, as well as other context-specific approaches. All methods were evaluated on fourteen clinical neurosurgical cases with brain tumors, including low-grade and high-grade gliomas, from the publicly available MNI BITE dataset. Registration accuracy of each method is evaluated as the mean distance between homologous landmarks identified by two or three experts. We provide an analysis of the landmarks used and expose some of the limitations in validation brought forward by expert disagreement and uncertainty in identifying corresponding points., Results: The proposed approach yields a mean error of 2.57 mm across all cases (the smallest among all evaluated techniques). Additionally, it is the only evaluated technique that resolves all cases with a mean distance of less than 1 mm larger than the theoretical minimal mean distance when using a rigid transformation., Conclusion: Finally, our proposed method provides reduced processing times with an average registration time of 0.76 s in a GPU-based implementation, thereby facilitating its integration into the operating room.

In this paper, we propose a new multi-scale technique for multi-modal image registration based on the alignment of selected gradient orientations of reduced uncertainty. We show how the registration robustness and accuracy can be improved by restricting the evaluation of gradient orientation alignment to locations where the uncertainty of fixed image gradient orientations is minimal, which we formally demonstrate correspond to locations of high gradient magnitude. We also embed a computationally efficient technique for estimating the gradient orientations of the transformed moving image (rather than resampling pixel intensities and recomputing image gradients). We have applied our method to different rigid multi-modal registration contexts. Our approach outperforms mutual information and other competing metrics in the context of rigid multi-modal brain registration, where we show sub-millimeter accuracy with cases obtained from the retrospective image registration evaluation project. Furthermore, our approach shows significant improvements over standard methods in the highly challenging clinical context of image guided neurosurgery, where we demonstrate misregistration of less than 2 mm with relation to expert selected landmarks for the registration of pre-operative brain magnetic resonance images to intra-operative ultrasound images.

Purpose: We describe and validate a novel hybrid nonlinear vessel registration algorithm for intra-operative updating of preoperative magnetic resonance (MR) images using Doppler ultrasound (US) images acquired on the dura for the correction of brain-shift and registration inaccuracies. We also introduce an US vessel appearance simulator that generates vessel images similar in appearance to that acquired with US from MR angiography data., Methods: Our registration uses the minimum amount of preprocessing to extract vessels from the raw volumetric images. This prevents the removal of important registration information and minimizes the introduction of artifacts that may affect robustness, while reducing the amount of extraneous information in the image to be processed, thus improving the convergence speed of the algorithm. We then completed 3 rounds of validation for our vessel registration method for robustness and accuracy using (i) a large number of synthetic trials generated with our US vessel simulator, (ii) US images acquired from a real physical phantom made from polyvinyl alcohol cryogel, and (iii) real clinical data gathered intra-operatively from 3 patients., Results: Resulting target registration errors (TRE) of less than 2.5 mm are achieved in more than 90 % of the synthetic trials when the initial TREs are less than 20 mm. TREs of less than 2 mm were achieved when the technique was applied to the physical phantom, and TREs of less than 3 mm were achieved on clinical data., Conclusions: These test trials show that the proposed algorithm is not only accurate but also highly robust to noise and missing vessel segments when working with US images acquired in a wide range of real-world conditions.

The subthalamic nucleus (STN) is one of the most common stimulation targets for treating Parkinson's disease using deep brain stimulation (DBS). This procedure requires precise placement of the stimulating electrode. Common practice of DBS implantation utilizes microelectrode recording to locate the sites with the correct electrical response after an initial location estimate based on a universal human brain atlas that is linearly scaled to the patient's anatomy as seen on the preoperative images. However, this often results in prolonged surgical time and possible surgical complications since the small-sized STN is difficult to visualize on conventional magnetic resonance (MR) images and its intersubject variability is not sufficiently considered in the atlas customization. This paper proposes a multicontrast, multiecho MR imaging (MRI) method that directly delineates the STN and other basal ganglia structures through five co-registered image contrasts (T1-weighted navigation image, R2 map, susceptibility-weighted imaging (phase, magnitude and fusion image)) obtained within a clinically acceptable time. The image protocol was optimized through both simulation and in vivo experiments to obtain the best image quality. Taking advantage of the multiple echoes and high readout bandwidths, no interimage registration is required since all images are produced in one acquisition, and image distortion and chemical shift are reduced. This MRI protocol is expected to mitigate some of the shortcomings of the state-of-the-art DBS implantation methods., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A new Collaborative Approach for eNhanced Denoising under Low-light Excitation (CANDLE) is introduced for the processing of 3D laser scanning multiphoton microscopy images. CANDLE is designed to be robust for low signal-to-noise ratio (SNR) conditions typically encountered when imaging deep in scattering biological specimens. Based on an optimized non-local means filter involving the comparison of filtered patches, CANDLE locally adapts the amount of smoothing in order to deal with the noise inhomogeneity inherent to laser scanning fluorescence microscopy images. An extensive validation on synthetic data, images acquired on microspheres and in vivo images is presented. These experiments show that the CANDLE filter obtained competitive results compared to a state-of-the-art method and a locally adaptive optimized non-local means filter, especially under low SNR conditions (PSNR<8dB). Finally, the deeper imaging capabilities enabled by the proposed filter are demonstrated on deep tissue in vivo images of neurons and fine axonal processes in the Xenopus tadpole brain., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Brain extraction is an important step in the analysis of brain images. The variability in brain morphology and the difference in intensity characteristics due to imaging sequences make the development of a general purpose brain extraction algorithm challenging. To address this issue, we propose a new robust method (BEaST) dedicated to produce consistent and accurate brain extraction. This method is based on nonlocal segmentation embedded in a multi-resolution framework. A library of 80 priors is semi-automatically constructed from the NIH-sponsored MRI study of normal brain development, the International Consortium for Brain Mapping, and the Alzheimer's Disease Neuroimaging Initiative databases. In testing, a mean Dice similarity coefficient of 0.9834±0.0053 was obtained when performing leave-one-out cross validation selecting only 20 priors from the library. Validation using the online Segmentation Validation Engine resulted in a top ranking position with a mean Dice coefficient of 0.9781±0.0047. Robustness of BEaST is demonstrated on all baseline ADNI data, resulting in a very low failure rate. The segmentation accuracy of the method is better than two widely used publicly available methods and recent state-of-the-art hybrid approaches. BEaST provides results comparable to a recent label fusion approach, while being 40 times faster and requiring a much smaller library of priors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Extending mutual information (MI), which has been widely used as a similarity measure for rigid registration of multi-modal images, to deformable registration is an active field of research. We propose a self-similarity weighted graph-based implementation of alpha-mutual information (alpha-MI) for nonrigid image registration. The new Self Similarity alpha-MI (SeSaMI) metric takes local structures into account and is robust against signal non-stationarity and intensity distortions. We have used SeSaMI as the similarity measure in a regularized cost function with B-spline deformation field. Since the gradient of SeSaMI can be derived analytically, the cost function can be efficiently optimized using stochastic gradient descent. We show that SeSaMI produces a robust and smooth cost function and outperforms the state of the art statistical based similarity metrics in simulation and using data from image-guided neurosurgery.

The detection of gad-enhancing lesions in brain MRI of Multiple Sclerosis (MS) patients is of great interest since they are important markers of disease activity. However, many of the enhancing voxels are associated with normal structures (i.e. blood vessels) or noise in the MRI, making the detection of gad-enhancing lesions a challenging task. Furthermore, these lesions are typically small and in close proximity to vessels. In this paper, we present an automatic, probabilistic Hierarchical Conditional Random Field (HCRF) framework for detection of gad-enhancing lesions in brain images of patients with MS. In the first level, a CRF with unary and pairwise potentials is used to identify candidate lesion voxel. In the second level, these lesion candidates are grouped based on anatomical and spatial features, and feature-specific lesion based CRF models are designed for each group. This lesion level CRF incorporates higher order potentials which account for shape, group intensities and symmetries. The proposed algorithm is trained on 92 multimodal clinical datasets acquired from Relapsing-Remitting MS patients during multicenter clinical trials and is evaluated on 30 independent cases. The experimental results show a sensitivity of 98%, a positive predictive value of 66% and an average false positive count of 1.55, outperforming the CRF and MRF frameworks proposed in.

Purpose: We present a new technique for registering magnetic resonance (MR) and ultrasound images in the context of neurosurgery. It involves generating a pseudo-ultrasound (pseudo-US) from a segmented MR image and uses cross-correlation as the cost function to register the pseudo-US to the real ultrasound data. The algorithm's performance is compared with that of a state-of-the-art technique that uses a median-filtered MR image to register to a Gaussian-blurred ultrasound using a normalized mutual information (NMI) objective function., Methods: The two methods were tested on data from 15 patients with brain tumor, including low-and high-grade gliomas, in both first operations and reoperations. Two metrics were used to evaluate registration accuracy: (1) the mean distance between corresponding points, identified on both MR and ultrasound images by two experts, and (2) ratings based on visual comparison by one neurosurgeon., Results: The mean residual distance of the pseudo-US technique, 2.97 mm, is significantly more accurate (p = .0011) than that of the NMI approach, 4.86 mm. The visual assessment shows that only 4 of the 15 cases had a satisfactory initial alignment based on homologous skin-point registration. There is a significant correlation between the quantitative distance measures and the qualitative ratings (rho = 0.785)., Conclusion: The results show that the pseudo-US rigid registration technique robustly improves the MRI-ultrasound alignment when compared with the initial alignment, even when applied to highly distorted brains and a large range of tumor sizes and appearances.

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 present a new automatic method for segmentation of multiple sclerosis (MS) lesions in magnetic resonance images. The method performs tissue classification using a model of intensities of the normal appearing brain tissues. In order to estimate the model, a trimmed likelihood estimator is initialized with a hierarchical random approach in order to be robust to MS lesions and other outliers present in real images. The algorithm is first evaluated with simulated images to assess the importance of the robust estimator in presence of outliers. The method is then validated using clinical data in which MS lesions were delineated manually by several experts. Our method obtains an average Dice similarity coefficient (DSC) of 0.65, which is close to the average DSC obtained by raters (0.66).

Intensity normalization is an important pre-processing step in the study and analysis of Magnetic Resonance Images (MRI) of human brains. As most parametric supervised automatic image segmentation and classification methods base their assumptions regarding the intensity distributions on a standardized intensity range, intensity normalization takes on a very significant role. One of the fast and accurate approaches proposed for intensity normalization is that of Nyul and colleagues. In this work, we present, for the first time, an extensive validation of this approach in real clinical domain where even after intensity inhomogeneity correction that accounts for scanner-specific artifacts, the MRI volumes can be affected from variations such as data heterogeneity resulting from multi-site multi-scanner acquisitions, the presence of multiple sclerosis (MS) lesions and the stage of disease progression in the brain. Using the distributional divergence criteria, we evaluate the effectiveness of the normalization in rendering, under the distributional assumptions of segmentation approaches, intensities that are more homogenous for the same tissue type while simultaneously resulting in better tissue type separation. We also demonstrate the advantage of the decile based piece-wise linear approach on the task of MS lesion segmentation against a linear normalization approach over three image segmentation algorithms: a standard Bayesian classifier, an outlier detection based approach and a Bayesian classifier with Markov Random Field (MRF) based post-processing. Finally, to demonstrate the independence of the effectiveness of normalization from the complexity of segmentation algorithm, we evaluate the Nyul method against the linear normalization on Bayesian algorithms of increasing complexity including a standard Bayesian classifier with Maximum Likelihood parameter estimation and a Bayesian classifier with integrated data priors, in addition to the above Bayesian classifier with MRF based post-processing to smooth the posteriors. In all relevant cases, the observed results are verified for statistical relevance using significance tests., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Several methods exist and are frequently used to quantify grey matter (GM) atrophy in multiple sclerosis (MS). Fundamental to all available techniques is the accurate segmentation of GM in the brain, a difficult task confounded even further by the pathology present in the brains of MS patients. In this paper, we examine the segmentations of six different automated techniques and compare them to a manually defined reference standard. Results demonstrate that, although the algorithms perform similarly to manual segmentations of cortical GM, severe shortcomings are present in the segmentation of deep GM structures. This deficiency is particularly relevant given the current interest in the role of GM in MS and the numerous reports of atrophy in deep GM structures., (Copyright 2010 Elsevier Inc. All rights reserved.)

We describe progress towards fully automatic segmentation of the hippocampus (HC) and amygdala (AG) in human subjects from MRI data. Three methods are described and tested with a set of MRIs from 80 young normal controls, using manual labeling of the HC and AG as a gold standard. The methods include: 1) our ANIMAL atlas-based method that uses non-linear registration to a pre-labeled non-linear average template (ICBM152). HC and AG labels, defined on the template are mapped through the inverse transformation to segment these structures on the subject's MRI. 2) We select the most similar MRI from the set of 80 labeled datasets to use as a template in the standard ANIMAL segmentation scheme. 3) We use label fusion techniques to combine segmentations from the 'n' most similar templates. The label fusion technique yields an optimal median Dice Kappa of 0.886 and similarity of 0.795 for HC, and 0.826 and 0.703 respectively for AG., (Copyright 2010 Elsevier Inc. All rights reserved.)

In this paper, a new object-based method to estimate noise in magnitude MR images is proposed. The main advantage of this object-based method is its robustness to background artefacts such as ghosting. The proposed method is based on the adaptation of the Median Absolute Deviation (MAD) estimator in the wavelet domain for Rician noise. The MAD is a robust and efficient estimator initially proposed to estimate Gaussian noise. In this work, the adaptation of MAD operator for Rician noise is performed by using only the wavelet coefficients corresponding to the object and by correcting the estimation with an iterative scheme based on the SNR of the image. During the evaluation, a comparison of the proposed method with several state-of-the-art methods is performed. A quantitative validation on synthetic phantom with and without artefacts is presented. A new validation framework is proposed to perform quantitative validation on real data. The impact of the accuracy of noise estimation on the performance of a denoising filter is also studied. The results obtained on synthetic images show the accuracy and the robustness of the proposed method. Within the validation on real data, the proposed method obtained very competitive results compared to the methods under study., (Copyright 2010 Elsevier B.V. All rights reserved.)

In ultrasound images, acoustic shadows appear as regions of low signal intensity linked to boundaries with very high acoustic impedance differences. Acoustic shadows can be viewed either as informative features to detect lesions or calcifications, or as damageable artifacts for image processing tasks such as segmentation, registration or 3D reconstruction. In both cases, the detection of these acoustic shadows is useful. This paper proposes a new method to detect these shadows that combines a geometrical approach to estimate the B-scans shape, followed by a statistical test based on a dedicated modeling of ultrasound image statistics. Results demonstrate that the combined geometrical-statistical technique is more robust and yields better results than the previous statistical technique. Integration of regularization over time further improves robustness. Application of the procedure results in (1) improved 3D reconstructions with fewer artifacts, and (2) reduced mean registration error of tracked intraoperative brain ultrasound images., (Copyright 2009 Elsevier B.V. All rights reserved.)

Quantitative magnetic resonance analysis often requires accurate, robust and reliable automatic extraction of anatomical structures. Recently, template-warping methods incorporating a label fusion strategy have demonstrated high accuracy in segmenting cerebral structures. In this study, we propose a novel patch-based method using expert segmentation priors to achieve this task. Inspired by recent work in image denoising, the proposed nonlocal patch-based label fusion produces accurate and robust segmentation. During our experiments, the hippocampi of 80 healthy subjects were segmented. The influence on segmentation accuracy of different parameters such as patch size or number of training subjects was also studied. Moreover, a comparison with an appearance-based method and a template-based method was carried out. The highest median kappa value obtained with the proposed method was 0.884, which is competitive compared with recently published methods.

Cortical multiple sclerosis lesions are difficult to detect in magnetic resonance images due to poor contrast with surrounding grey matter, spatial variation in healthy grey matter and partial volume effects. We propose using an observer-independent laminar profile-based parcellation method to detect cortical lesions. Following cortical surface extraction, profiles are extended from the white matter surface to the grey matter surface. The cortex is parcellated according to profile intensity and shape features using a k-means classifier. The method is applied to a high-resolution quantitative magnetic resonance data set from a fixed post mortem multiple sclerosis brain, and validated using histology.

We propose a new, adaptive local measure based on gradient orientation similarity for the purposes of multimodal image registration. We embed this metric into a hierarchical registration framework, where we show that registration robustness and accuracy can be improved by adapting both the similarity metric and the pixel selection strategy to the Gaussian blurring scale and to the modalities being registered. A computationally efficient estimation of gradient orientations is proposed based on patch-wise rigidity. We have applied our method to both rigid and non-rigid multimodal registration tasks with different modalities. Our approach outperforms mutual information (MI) and previously proposed local approximations of MI for multimodal (e.g. CT/MRI) brain image registration tasks. Furthermore, it shows significant improvements in terms of mTRE over standard methods in the highly challenging clinical context of registering pre-operative brain MRI to intra-operative US images.

Purpose: To adapt the so-called nonlocal means filter to deal with magnetic resonance (MR) images with spatially varying noise levels (for both Gaussian and Rician distributed noise)., Materials and Methods: Most filtering techniques assume an equal noise distribution across the image. When this assumption is not met, the resulting filtering becomes suboptimal. This is the case of MR images with spatially varying noise levels, such as those obtained by parallel imaging (sensitivity-encoded), intensity inhomogeneity-corrected images, or surface coil-based acquisitions. We propose a new method where information regarding the local image noise level is used to adjust the amount of denoising strength of the filter. Such information is automatically obtained from the images using a new local noise estimation method., Results: The proposed method was validated and compared with the standard nonlocal means filter on simulated and real MRI data showing an improved performance in all cases., Conclusion: The new noise-adaptive method was demonstrated to outperform the standard filter when spatially varying noise is present in the images., ((c) 2009 Wiley-Liss, Inc.)

Background: We propose a completely automated methodology to investigate the relationship between magnetic resonance image (MRI) features and changes in cognitive estimates, applied to the study of Mini-Mental State Examination (MMSE) changes in mild cognitive impairment (MCI)., Subjects: A reference group composed of 75 patients with clinically probable Alzheimer's Disease (AD) and 75 age-matched controls; and a study group composed of 49 MCI, 20 having progressed to clinically probable AD and 29 having remained stable after a 48 month follow-up., Methods: We created a pathology-specific reference space using principal component analysis of MRI-based features (intensity, local volume changes) within the medial temporal lobe of T1-weighted baseline images for the reference group. We projected similar data from the study group and identified a restricted set of image features highly correlated with one-year change in MMSE, using a bootstrap sampling estimation. We used robust linear regression models to predict one-year MMSE changes from baseline MRI, baseline MMSE, age, gender, and years of education., Results: All experiments were performed using a leave-one-out paradigm. We found multiple image-based features highly correlated with one-year MMSE changes (/r/>0.425). The model for all N=49 MCI subjects had a correlation of r=0.31 between actual and predicted one-year MMSE change values. A second model only for MCI subjects with MMSE loss larger than 1 U had a pairwise correlation r=0.80 with an adjusted coefficient of determination r(2)=0.61., Findings: Our automated MRI-based technique revealed a strong relationship between baseline MRI features and one-year cognitive changes in a sub-group of MCI subjects. This technique should be generalized to other aspects of cognitive evaluation and to a wider scope of dementias.

Magnetic resonance parameters, such as longitudinal (T1) and transverse (T2) relaxation times and proton density (PD) provide intrinsic information about the human brain. In vivo quantification of these parameters may enable detection of subtle regional grey matter (GM) or white matter (WM) differences and permit neurological disease detection and monitoring. The aims of the study were to quantify T1, T2 and PD values in all cortical gray matter regions for a group of healthy volunteers scanned at 1.5 T and to cluster regions showing statistically distinguishable tissue characteristics. Using a combination of spoiled gradient recalled echo (SPGR) and fast spin echo (FSE) sequences, 3D T1, T2 and PD of the brain were measured at 1.5 T for twenty healthy young volunteers. Cortical GM volumes of interest (VOIs) were identified by transforming 56 labels from an atlas onto each subject volumes: 8 frontal, 5 parietal, 6 occipital and 9 temporal on both the left and right sides. T1, T2 and PD measurements within these anatomical regions were quantified and reported here. Correspondence analysis (CA) and hierarchical clustering (HC) were combined and applied to averaged T1, T2 and PD values within each VOI in order to identify groups of anatomical structures that are related statistically. Interestingly, except for one structure, all VOIs were grouped with left-right symmetry and showed an interesting pattern: the four lobes (frontal, occipital, parietal and temporal) were roughly clustered and the precentral and postcentral gyri were merged together. Our study shows that CA and HC analysis of MRI relaxation parameters and proton density can be used for cortical clustering of atlas-defined cortical regions.

All fields of neuroscience that employ brain imaging need to communicate their results with reference to anatomical regions. In particular, comparative morphometry and group analysis of functional and physiological data require coregistration of brains to establish correspondences across brain structures. It is well established that linear registration of one brain to another is inadequate for aligning brain structures, so numerous algorithms have emerged to nonlinearly register brains to one another. This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted. Fourteen algorithms from laboratories around the world are evaluated using 8 different error measures. More than 45,000 registrations between 80 manually labeled brains were performed by algorithms including: AIR, ANIMAL, ART, Diffeomorphic Demons, FNIRT, IRTK, JRD-fluid, ROMEO, SICLE, SyN, and four different SPM5 algorithms ("SPM2-type" and regular Normalization, Unified Segmentation, and the DARTEL Toolbox). All of these registrations were preceded by linear registration between the same image pairs using FLIRT. One of the most significant findings of this study is that the relative performances of the registration methods under comparison appear to be little affected by the choice of subject population, labeling protocol, and type of overlap measure. This is important because it suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols. Furthermore, we ranked the 14 methods according to three completely independent analyses (permutation tests, one-way ANOVA tests, and indifference-zone ranking) and derived three almost identical top rankings of the methods. ART, SyN, IRTK, and SPM's DARTEL Toolbox gave the best results according to overlap and distance measures, with ART and SyN delivering the most consistently high accuracy across subjects and label sets. Updates will be published on the http://www.mindboggle.info/papers/ website.

Graph Cuts have been shown as a powerful interactive segmentation technique in several medical domains. We propose to automate the Graph Cuts in order to automatically segment Multiple Sclerosis (MS) lesions in MRI. We replace the manual interaction with a robust EM-based approach in order to discriminate between MS lesions and the Normal Appearing Brain Tissues (NABT). Evaluation is performed in synthetic and real images showing good agreement between the automatic segmentation and the target segmentation. We compare our algorithm with the state of the art techniques and with several manual segmentations. An advantage of our algorithm over previously published ones is the possibility to semi-automatically improve the segmentation due to the Graph Cuts interactive feature.

This paper presents feature-based morphometry (FBM), a new, fully data-driven technique for identifying group-related differences in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between all subjects, FBM models images as a collage of distinct, localized image features which may not be present in all subjects. FBM thus explicitly accounts for the case where the same anatomical tissue cannot be reliably identified in all subjects due to disease or anatomical variability. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subgroups of a population, and is automatically learned from a set of subject images and group labels. Features identified indicate group-related anatomical structure that can potentially be used as disease biomarkers or as a basis for computer-aided diagnosis. Scale-invariant image features are used, which reflect generic, salient patterns in the image. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and obtains an equal error classification rate of 0.78 on new subjects.

The estimation of the noise level in MR images is used to assess the consistency of statistical analysis or as an input parameter in some image processing techniques. Most of the existing Rician noise estimation methods are based on background statistics, and as such are sensitive to ghosting artifacts. In this paper, a new object-based method is proposed. This method is based on the adaptation of the Median Absolute Deviation (MAD) estimator in the wavelet domain for Rician noise. The adaptation for Rician noise is performed by using only the wavelet coefficients corresponding to the object and by correcting the estimation with an iterative scheme based on the SNR of the image. A quantitative validation on synthetic phantom with artefacts is presented and a new validation framework is proposed to perform quantitative validation on real data. The results show the accuracy and the robustness of the proposed method.

Pre-operative magnetic resonance (MRI) and computed tomography (CT) image volumes are often used for planning and guidance during functional neurosurgical procedures. These operations can include the creation of lesions in the thalamus (thalamotomy) or the globus pallidus (pallidotomy), or the insertion of deep brain stimulation (DBS) electrodes in the subcortical nuclei. These subcortical targets are often difficult to localize in pre-operative imaging data due to the limited resolution and contrast available in standard MRI or CT techniques. To address this problem, digital atlases of subcortical nuclei are often used to accurately identify surgical targets since they can be warped to fit each patient's unique anatomy. Targeting accuracy thus depends on the quality of the atlas-to-patient warp. In this paper, three atlas-to-patient warping techniques are compared. Two methods rely on an MRI template as an intermediary to estimate a nonlinear atlas-to-patient transformation. The third is novel, and uses a pseudo-MRI derived from an atlas of the basal ganglia and thalamus to estimate the nonlinear atlas-to-patient transformation directly. The methods are compared using (1) manual segmentations of subcortical nuclei and (2) functional data from intra-operative thalamic stimulation. The results demonstrate that the template-based atlas-to-patient warping technique is the best of the three for customizing the atlas onto patient data.

Automated computer classification (ACC) techniques are needed to facilitate physician's diagnosis of complex diseases in individual patients. We provide an example of ACC using computational techniques within the context of cross-sectional analysis of magnetic resonance images (MRI) in neurodegenerative diseases, namely Alzheimer's dementia (AD). In this paper, the accuracy of our ACC methodology is assessed when presented with real life, imperfect data, i.e., cohorts of MRI with varying acquisition parameters and imaging quality. The comparative methodology uses the Jacobian determinants derived from dense deformation fields and scaled grey-level intensity from a selected volume of interest centered on the medial temporal lobe. The ACC performance is assessed in a series of leave-one-out experiments aimed at separating 75 probable AD and 75 age-matched normal controls. The resulting accuracy is 92% using a support vector machine classifier based on least squares optimization. Finally, it is shown in the Appendix that determinants and scaled grey-level intensity are appreciably more robust to varying parameters in validation studies using simulated data, when compared to raw intensities or grey/white matter volumes. The ability of cross-sectional MRI at detecting probable AD with high accuracy could have profound implications in the management of suspected AD candidates.

Ultrasound (US) imaging is often proposed as an interoperative imaging modality. This use nearly always requires that the collected data be registered to preoperative data of another modality. Existing intensity-based registration approaches all begin by reconstructing a 3D US volume from the collected 2D slices. We propose to directly register the set of 2D slices to the preoperative images. We argue this has a number of advantages, including the omission of the potentially complex reconstruction step, greater adaptability of the similarity measures, and easier parallelization. We describe a system for performing this task and present results on phantom data that show that our slice based method consistently outperforms a reconstruction based method in both speed and accuracy.

In model-based segmentation, automated region identification is achieved via registration of novel data to a pre-determined model. The desired structure is typically generated via manual tracing within this model. When model-based segmentation is applied to human cortical data, problems arise if left-right comparisons are desired. The asymmetry of the human cortex requires that both left and right models of a structure be composed in order to effectively segment the desired structures. Paradoxically, defining a model in both hemi-spheres carries a likelihood of introducing bias to one of the structures. This paper describes a novel technique for creating a symmetric average model in which both hemispheres are equally represented and thus left-right comparison is possible. This work is an extension of that proposed by Guimond et al. Hippocampal segmentation is used as a test-case in a cohort of 118 normal eld-erly subjects and results are compared with expert manual tracing.

Three-dimensional (3-D) ultrasound (US) is an emerging new technology with numerous clinical applications. Ultrasound probe calibration is an obligatory step to build 3-D volumes from 2-D images acquired in a freehand US system. The role of calibration is to find the mathematical transformation that converts the 2-D coordinates of pixels in the US image into 3-D coordinates in the frame of reference of a position sensor attached to the US probe. This article is a comprehensive review of what has been published in the field of US probe calibration for 3-D US. The article covers the topics of tracking technologies, US image acquisition, phantom design, speed of sound issues, feature extraction, least-squares minimization, temporal calibration, calibration evaluation techniques and phantom comparisons. The calibration phantoms and methods have also been classified in tables to give a better overview of the existing methods.

Spatial normalization is a key process in cross-sectional studies of brain structure and function using MRI, fMRI, PET and other imaging techniques. A wide range of 2D surface and 3D image deformation algorithms have been developed, all of which involve design choices that are subject to debate. Moreover, most have numerical parameters whose value must be specified by the user. This paper proposes a principled method for evaluating design choices and choosing parameter values. This method can also be used to compare competing spatial normalization algorithms. We demonstrate the method through a performance analysis of a nonaffine registration algorithm for 3D images and a registration algorithm for 2D cortical surfaces.

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain toward a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the International Consortium for Brain Mapping (ICBM) database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which was not detected previously using standard voxel based morphometry.

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain towards a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the ICBM database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which seem to be beyond the scope of the standard voxel based morphometry.