Wachinger C, Golland P, Kremen W, Fischl B, Reuter M, Reuter M. BrainPrint: A Discriminative Characterization of Brain Morphology. Neuroimage. 2015;109 :232-48.Abstract
We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace-Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets.
Mandl RCW, Pasternak O, Cahn W, Kubicki M, Kahn RS, Shenton ME, Hulshoff Pol HE. Comparing Free Water Imaging and Magnetization Transfer Measurements in Schizophrenia. Schizophr Res. 2015;161 (1) :126-32.Abstract
Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) - a putative measure of white matter myelination - can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalyzed data from a previous study by using a fiber-based analysis of free-water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free-water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and free-water imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia.
Radmanesh A, Zamani AA, Whalen S, Tie Y, Suarez RO, Golby AJ. Comparison of seeding methods for visualization of the corticospinal tracts using single tensor tractography. Clin Neurol Neurosurg. 2015;129 :44-9.Abstract
OBJECTIVES: To compare five different seeding methods to delineate hand, foot, and lip components of the corticospinal tract (CST) using single tensor tractography. METHODS: We studied five healthy subjects and 10 brain tumor patients. For each subject, we used five different seeding methods, from (1) cerebral peduncle (CP), (2) posterior limb of the internal capsule (PLIC), (3) white matter subjacent to functional MRI activations (fMRI), (4) whole brain and then selecting the fibers that pass through both fMRI and CP (WBF-CP), and (5) whole brain and then selecting the fibers that pass through both fMRI and PLIC (WBF-PLIC). Two blinded neuroradiologists rated delineations as anatomically successful or unsuccessful tractography. The proportions of successful trials from different methods were compared by Fisher's exact test. RESULTS: To delineate hand motor tract, seeding through fMRI activation areas was more effective than through CP (p<0.01), but not significantly different from PLIC (p>0.1). WBF-CP delineated hand motor tracts in a larger proportion of trials than CP alone (p<0.05). Similarly, WBF-PLIC depicted hand motor tracts in a larger proportion of trials than PLIC alone (p<0.01). Foot motor tracts were delineated in all trials by either PLIC or whole brain seeding (WBF-CP and WBF-PLIC). Seeding from CP or fMRI activation resulted in foot motor tract visualization in 87% of the trials (95% confidence interval: 60-98%). The lip motor tracts were delineated only by WBF-PLIC and in 36% of trials (95% confidence interval: 11-69%). CONCLUSIONS: Whole brain seeding and then selecting the tracts that pass through two anatomically relevant ROIs can delineate more plausible hand and lip motor tracts than seeding from a single ROI. Foot motor tracts can be successfully delineated regardless of the seeding method used.
Ning L, Georgiou TT, Tannenbaum A, Boyd SP. Linear Models Based on Noisy Data and the Frisch Scheme. SIAM Rev Soc Ind Appl Math. 2015;57 (2) :167-97.Abstract

We address the problem of identifying linear relations among variables based on noisy measurements. This is a central question in the search for structure in large data sets. Often a key assumption is that measurement errors in each variable are independent. This basic formulation has its roots in the work of Charles Spearman in 1904 and of Ragnar Frisch in the 1930s. Various topics such as errors-in-variables, factor analysis, and instrumental variables all refer to alternative viewpoints on this problem and on ways to account for the anticipated way that noise enters the data. In the present paper we begin by describing certain fundamental contributions by the founders of the field and provide alternative modern proofs to certain key results. We then go on to consider a modern viewpoint and novel numerical techniques to the problem. The central theme is expressed by the Frisch-Kalman dictum, which calls for identifying a noise contribution that allows a maximal number of simultaneous linear relations among the noise-free variables-a rank minimization problem. In the years since Frisch's original formulation, there have been several insights, including trace minimization as a convenient heuristic to replace rank minimization. We discuss convex relaxations and theoretical bounds on the rank that, when met, provide guarantees for global optimality. A complementary point of view to this minimum-rank dictum is presented in which models are sought leading to a uniformly optimal quadratic estimation error for the error-free variables. Points of contact between these formalisms are discussed, and alternative regularization schemes are presented.

Wachinger C, Golland P, Magnain C, Fischl B, Reuter M. Multi-modal Robust Inverse-consistent Linear Registration. Hum Brain Mapp. 2015;36 (4) :1365-80.Abstract
Registration performance can significantly deteriorate when image regions do not comply with model assumptions. Robust estimation improves registration accuracy by reducing or ignoring the contribution of voxels with large intensity differences, but existing approaches are limited to monomodal registration. In this work, we propose a robust and inverse-consistent technique for cross-modal, affine image registration. The algorithm is derived from a contextual framework of image registration. The key idea is to use a modality invariant representation of images based on local entropy estimation, and to incorporate a heteroskedastic noise model. This noise model allows us to draw the analogy to iteratively reweighted least squares estimation and to leverage existing weighting functions to account for differences in local information content in multimodal registration. Furthermore, we use the nonparametric windows density estimator to reliably calculate entropy of small image patches. Finally, we derive the Gauss-Newton update and show that it is equivalent to the efficient second-order minimization for the fully symmetric registration approach. We illustrate excellent performance of the proposed methods on datasets containing outliers for alignment of brain tumor, full head, and histology images.
Stamm JM, Koerte IK, Muehlmann M, Pasternak O, Bourlas AP, Baugh CM, Giwerc MY, Zhu A, Coleman MJ, Bouix S, et al. Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players. J Neurotrauma. 2015;32 (22) :1768-76.Abstract
Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure.
Wachinger C, Fritscher K, Sharp G, Golland P. Contour-Driven Atlas-Based Segmentation. IEEE Trans Med Imaging. 2015;34 (12) :2492-505.Abstract
We propose new methods for automatic segmentation of images based on an atlas of manually labeled scans and contours in the image. First, we introduce a Bayesian framework for creating initial label maps from manually annotated training images. Within this framework, we model various registration- and patch-based segmentation techniques by changing the deformation field prior. Second, we perform contour-driven regression on the created label maps to refine the segmentation. Image contours and image parcellations give rise to non-stationary kernel functions that model the relationship between image locations. Setting the kernel to the covariance function in a Gaussian process establishes a distribution over label maps supported by image structures. Maximum a posteriori estimation of the distribution over label maps conditioned on the outcome of the atlas-based segmentation yields the refined segmentation. We evaluate the segmentation in two clinical applications: the segmentation of parotid glands in head and neck CT scans and the segmentation of the left atrium in cardiac MR angiography images.
Ning L, Westin C-F, Rathi Y. Estimating diffusion propagator and its moments using directional radial basis functions. IEEE Trans Med Imaging. 2015;34 (10) :2058-78.Abstract
The ensemble average diffusion propagator (EAP) obtained from diffusion MRI (dMRI) data captures important structural properties of the underlying tissue. As such, it is imperative to derive an accurate estimate of the EAP from the acquired diffusion data. In this work, we propose a novel method for estimating the EAP by representing the diffusion signal as a linear combination of directional radial basis functions scattered in q-space. In particular, we focus on a special case of anisotropic Gaussian basis functions and derive analytical expressions for the diffusion orientation distribution function (ODF), the return-to-origin probability (RTOP), and mean-squared-displacement (MSD). A significant advantage of the proposed method is that the second and the fourth order moment tensors of the EAP can be computed explicitly. This allows for computing several novel scalar indices (from the moment tensors) such as mean-fourth-order-displacement (MFD) and generalized kurtosis (GK)-which is a generalization of the mean kurtosis measure used in diffusion kurtosis imaging. Additionally, we also propose novel scalar indices computed from the signal in q-space, called the q-space mean-squared-displacement (QMSD) and the q-space mean-fourth-order-displacement (QMFD), which are sensitive to short diffusion time scales. We validate our method extensively on data obtained from a physical phantom with known crossing angle as well as on in-vivo human brain data. Our experiments demonstrate the robustness of our method for different combinations of b-values and number of gradient directions.
Batmanghelich NK, Saeedi A, Cho M, Estepar RSJ, Golland P. Generative Method to Discover Genetically Driven Image Biomarkers. Inf Process Med Imaging. 2015;24 :30-42.Abstract
We present a generative probabilistic approach to discovery of disease subtypes determined by the genetic variants. In many diseases, multiple types of pathology may present simultaneously in a patient, making quantification of the disease challenging. Our method seeks common co-occurring image and genetic patterns in a population as a way to model these two different data types jointly. We assume that each patient is a mixture of multiple disease subtypes and use the joint generative model of image and genetic markers to identify disease subtypes guided by known genetic influences. Our model is based on a variant of the so-called topic models that uncover the latent structure in a collection of data. We derive an efficient variational inference algorithm to extract patterns of co-occurrence and to quantify the presence of heterogeneous disease processes in each patient. We evaluate the method on simulated data and illustrate its use in the context of Chronic Obstructive Pulmonary Disease (COPD) to characterize the relationship between image and genetic signatures of COPD subtypes in a large patient cohort.
Sandhu R, Georgiou T, Reznik E, Zhu L, Kolesov I, Senbabaoglu Y, Tannenbaum A. Graph Curvature for Differentiating Cancer Networks. Sci Rep. 2015;5 :12323.Abstract
Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures of robustness, reliability, performance, and efficiency, are intrinsically tied to the topology and geometry of the underlying graph. Utilizing recently proposed geometric notions of curvature on weighted graphs, we investigate the features of gene co-expression networks derived from large-scale genomic studies of cancer. We find that the curvature of these networks reliably distinguishes between cancer and normal samples, with cancer networks exhibiting higher curvature than their normal counterparts. We establish a quantitative relationship between our findings and prior investigations of network entropy. Furthermore, we demonstrate how our approach yields additional, non-trivial pair-wise (i.e. gene-gene) interactions which may be disrupted in cancer samples. The mathematical formulation of our approach yields an exact solution to calculating pair-wise changes in curvature which was computationally infeasible using prior methods. As such, our findings lay the foundation for an analytical approach to studying complex biological networks.
Eriksson S, Lasič S, Nilsson M, Westin C-F, Topgaard D. NMR Diffusion-Encoding with Axial Symmetry and Variable Anisotropy: Distinguishing Between Prolate and Oblate Microscopic Diffusion Tensors with Unknown Orientation Distribution. J Chem Phys. 2015;142 (10) :104201.Abstract
We introduce a nuclear magnetic resonance method for quantifying the shape of axially symmetric microscopic diffusion tensors in terms of a new diffusion anisotropy metric, DΔ, which has unique values for oblate, spherical, and prolate tensor shapes. The pulse sequence includes a series of equal-amplitude magnetic field gradient pulse pairs, the directions of which are tailored to give an axially symmetric diffusion-encoding tensor b with variable anisotropy bΔ. Averaging of data acquired for a range of orientations of the symmetry axis of the tensor b renders the method insensitive to the orientation distribution function of the microscopic diffusion tensors. Proof-of-principle experiments are performed on water in polydomain lyotropic liquid crystals with geometries that give rise to microscopic diffusion tensors with oblate, spherical, and prolate shapes. The method could be useful for characterizing the geometry of fluid-filled compartments in porous solids, soft matter, and biological tissues.
Li M, Miller K, Joldes GR, Doyle B, Garlapati RR, Kikinis R, Wittek A. Patient-specific biomechanical model as whole-body CT image registration tool. Med Image Anal. 2015;22 (1) :22-34.Abstract
Whole-body computed tomography (CT) image registration is important for cancer diagnosis, therapy planning and treatment. Such registration requires accounting for large differences between source and target images caused by deformations of soft organs/tissues and articulated motion of skeletal structures. The registration algorithms relying solely on image processing methods exhibit deficiencies in accounting for such deformations and motion. We propose to predict the deformations and movements of body organs/tissues and skeletal structures for whole-body CT image registration using patient-specific non-linear biomechanical modelling. Unlike the conventional biomechanical modelling, our approach for building the biomechanical models does not require time-consuming segmentation of CT scans to divide the whole body into non-overlapping constituents with different material properties. Instead, a Fuzzy C-Means (FCM) algorithm is used for tissue classification to assign the constitutive properties automatically at integration points of the computation grid. We use only very simple segmentation of the spine when determining vertebrae displacements to define loading for biomechanical models. We demonstrate the feasibility and accuracy of our approach on CT images of seven patients suffering from cancer and aortic disease. The results confirm that accurate whole-body CT image registration can be achieved using a patient-specific non-linear biomechanical model constructed without time-consuming segmentation of the whole-body images.
Chen Z, Tie Y, Olubiyi O, Rigolo L, Mehrtash A, Norton I, Pasternak O, Rathi Y, Golby AJ, O'Donnell LJ. Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography. Neuroimage Clin. 2015;7 :815-22.Abstract
BACKGROUND: Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. METHODS: Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. RESULTS: Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). CONCLUSIONS: Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.
Garlapati RR, Mostayed A, Joldes GR, Wittek A, Doyle B, Miller K. Towards measuring neuroimage misalignment. Comput Biol Med. 2015;64 :12-23.Abstract
To enhance neuro-navigation, high quality pre-operative images must be registered onto intra-operative configuration of the brain. Therefore evaluation of the degree to which structures may remain misaligned after registration is critically important. We consider two Hausdorff Distance (HD)-based evaluation approaches: the edge-based HD (EBHD) metric and the Robust HD (RHD) metric as well as various commonly used intensity-based similarity metrics such as Mutual Information (MI), Normalised Mutual Information (NMI), Entropy Correlation Coefficient (ECC), Kullback-Leibler Distance (KLD) and Correlation Ratio (CR). We conducted the evaluation by applying known deformations to simple sample images and real cases of brain shift. We conclude that the intensity-based similarity metrics such as MI, NMI, ECC, KLD and CR do not correlate well with actual alignment errors, and hence are not useful for assessing misalignment. On the contrary, the EBHD and the RHD metrics correlated well with actual alignment errors; however, they have been found to underestimate the actual misalignment. We also note that it is beneficial to present HD results as a percentile-HD curve rather than a single number such as the 95-percentile HD. Percentile-HD curves present the full range of alignment errors and also facilitate the comparison of results obtained using different approaches. Furthermore, the qualities that should be possessed by an ideal evaluation metric were highlighted. Future studies could focus on developing such an evaluation metric.
Ohtani T, Bouix S, Lyall AE, Hosokawa T, Saito Y, Melonakos E, Westin C-F, Seidman LJ, Goldstein J, Mesholam-Gately R, et al. Abnormal White Matter Connections between Medial Frontal Regions Predict Symptoms in Patients with First Episode Schizophrenia. Cortex. 2015;71 :264-76.Abstract
INTRODUCTION: The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ). METHODS: After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions. RESULTS: Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ. CONCLUSIONS: The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia.
Ning L, Setsompop K, Michailovich O, Makris N, Westin C-F, Rathi Y. A Compressed-Sensing Approach for Super-Resolution Reconstruction of Diffusion MRI. Inf Process Med Imaging. 2015;24 :57-68.Abstract

We present an innovative framework for reconstructing high-spatial-resolution diffusion magnetic resonance imaging (dMRI) from multiple low-resolution (LR) images. Our approach combines the twin concepts of compressed sensing (CS) and classical super-resolution to reduce acquisition time while increasing spatial resolution. We use subpixel-shifted LR images with down-sampled and non-overlapping diffusion directions to reduce acquisition time. The diffusion signal in the high resolution (HR) image is represented in a sparsifying basis of spherical ridgelets to model complex fiber orientations with reduced number of measurements. The HR image is obtained as the solution of a convex optimization problem which can be solved using the proposed algorithm based on the alternating direction method of multipliers (ADMM). We qualitatively and quantitatively evaluate the performance of our method on two sets of in-vivo human brain data and show its effectiveness in accurately recovering very high resolution diffusion images.

Pujol S, Wells III WM, Pierpaoli C, Brun C, Gee J, Cheng G, Vemuri B, Commowick O, Prima S, Stamm A, et al. The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery. J Neuroimaging. 2015;25 (6) :875-82.Abstract
BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop. METHODS: Eight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods. RESULTS: The evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues. CONCLUSIONS: The DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making.
Toews M, Wachinger C, Estepar RSJ, Wells III WM. A Feature-Based Approach to Big Data Analysis of Medical Images. Inf Process Med Imaging. 2015;24 :339-50.Abstract

This paper proposes an inference method well-suited to large sets of medical images. The method is based upon a framework where distinctive 3D scale-invariant features are indexed efficiently to identify approximate nearest-neighbor (NN) feature matches-in O (log N) computational complexity in the number of images N. It thus scales well to large data sets, in contrast to methods based on pair-wise image registration or feature matching requiring O(N) complexity. Our theoretical contribution is a density estimator based on a generative model that generalizes kernel density estimation and K-nearest neighbor (KNN) methods.. The estimator can be used for on-the-fly queries, without requiring explicit parametric models or an off-line training phase. The method is validated on a large multi-site data set of 95,000,000 features extracted from 19,000 lung CT scans. Subject-level classification identifies all images of the same subjects across the entire data set despite deformation due to breathing state, including unintentional duplicate scans. State-of-the-art performance is achieved in predicting chronic pulmonary obstructive disorder (COPD) severity across the 5-category GOLD clinical rating, with an accuracy of 89% if both exact and one-off predictions are considered correct.

Wachinger C, Golland P. Sampling from Determinantal Point Processes for Scalable Manifold Learning. Inf Process Med Imaging. 2015;24 :687-98.Abstract
High computational costs of manifold learning prohibit its application for large datasets. A common strategy to overcome this problem is to perform dimensionality reduction on selected landmarks and to successively embed the entire dataset with the Nyström method. The two main challenges that arise are: (i) the landmarks selected in non-Euclidean geometries must result in a low reconstruction error, (ii) the graph constructed from sparsely sampled landmarks must approximate the manifold well. We propose to sample the landmarks from determinantal distributions on non-Euclidean spaces. Since current determinantal sampling algorithms have the same complexity as those for manifold learning, we present an efficient approximation with linear complexity. Further, we recover the local geometry after the sparsification by assigning each landmark a local covariance matrix, estimated from the original point set. The resulting neighborhood selection .based on the Bhattacharyya distance improves the embedding of sparsely sampled manifolds. Our experiments show a significant performance improvement compared to state-of-the-art landmark selection techniques on synthetic and medical data.
Parisot S, Arslan S, Passerat-Palmbach J, Wells III WM, Rueckert D. Tractography-Driven Groupwise Multi-scale Parcellation of the Cortex. Inf Process Med Imaging. 2015;24 :600-12.Abstract

The analysis of the connectome of the human brain provides key insight into the brain's organisation and function, and its evolution in disease or ageing. Parcellation of the cortical surface into distinct regions in terms of structural connectivity is an essential step that can enable such analysis. The estimation of a stable connectome across a population of healthy subjects requires the estimation of a groupwise parcellation that can capture the variability of the connectome across the population. This problem has solely been addressed in the literature via averaging of connectivity profiles or finding correspondences between individual parcellations a posteriori. In this paper, we propose a groupwise parcellation method of the cortex based on diffusion MR images (dMRI). We borrow ideas from the area of cosegmentation in computer vision and directly estimate a consistent parcellation across different subjects and scales through a spectral clustering approach. The parcellation is driven by the tractography connectivity profiles, and information between subjects and across scales. Promising qualitative and quantitative results on a sizeable data-set demonstrate the strong potential of the method.