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Despite the cerebellum's crucial role in brain functions, its early development, particularly in relation to the cerebrum, remains poorly understood. Here, we examine cerebellocortical connectivity using over 1,000 high-quality resting-state functional MRI scans of children from birth to 60 months. By mapping cerebellar topography with fine temporal detail for the first time, we show the hierarchical and contralateral organization of cerebellocortical connectivity from birth. We observe dynamic shifts in cerebellar network gradients, which become more focal with age while maintaining stable anchor points similar to adults, highlighting the cerebellum's evolving yet stable role in functional integration during early development. Our findings provide the first evidence of cerebellar connections to higher-order networks at birth, which generally strengthen with age, emphasizing the cerebellum's early role in cognitive processing beyond sensory and motor functions. Our study provides insights into early cerebellocortical interactions, reveals functional asymmetry and sexual dimorphism in cerebellar development, and lays the groundwork for future research on cerebellum-related disorders in children., Competing Interests: Competing Interests The authors declare that they have no competing financial interests.

Delineating the normative developmental profile of functional connectome is important for both standardized assessment of individual growth and early detection of diseases. However, functional connectome has been mostly studied using functional connectivity (FC), where undirected connectivity strengths are estimated from statistical correlation of resting-state functional MRI (rs-fMRI) signals. To address this limitation, we applied regression dynamic causal modeling (rDCM) to delineate the developmental trajectories of effective connectivity (EC), the directed causal influence among neuronal populations, in whole-brain networks from infancy to adolescence (0-22 years old) based on high-quality rs-fMRI data from Baby Connectome Project (BCP) and Human Connectome Project Development (HCP-D). Analysis with linear mixed model demonstrates significant age effect on the mean nodal EC which is best fit by a "U" shaped quadratic curve with minimal EC at around 2 years old. Further analysis indicates that five brain regions including the left and right cuneus, left precuneus, left supramarginal gyrus and right inferior temporal gyrus have the most significant age effect on nodal EC ( p < 0.05, FDR corrected). Moreover, the frontoparietal control (FPC) network shows the fastest increase from early childhood to adolescence followed by the visual and salience networks. Our findings suggest complex nonlinear developmental profile of EC from infancy to adolescence, which may reflect dynamic structural and functional maturation during this critical growth period.

Recent evidence indicates that the organization of the human neocortex is underpinned by smooth spatial gradients of functional connectivity (FC). These gradients provide crucial insight into the relationship between the brain's topographic organization and the texture of human cognition. However, no studies to date have charted how intrinsic FC gradient architecture develops across the entire human lifespan. In this work, we model developmental trajectories of the three primary gradients of FC using a large, high-quality, and temporally-dense functional MRI dataset spanning from birth to 100 years of age. The gradient axes, denoted as sensorimotor-association (SA), visual-somatosensory (VS), and modulation-representation (MR), encode crucial hierarchical organizing principles of the brain in development and aging. By tracking their evolution throughout the human lifespan, we provide the first ever comprehensive low-dimensional normative reference of global FC hierarchical architecture. We observe significant age-related changes in global network features, with global markers of hierarchical organization increasing from birth to early adulthood and decreasing thereafter. During infancy and early childhood, FC organization is shaped by primary sensory processing, dense short-range connectivity, and immature association and control hierarchies. Functional differentiation of transmodal systems supported by long-range coupling drives a convergence toward adult-like FC organization during late childhood, while adolescence and early adulthood are marked by the expansion and refinement of SA and MR hierarchies. While gradient topographies remain stable during late adulthood and aging, we observe decreases in global gradient measures of FC differentiation and complexity from 30 to 100 years. Examining cortical microstructure gradients alongside our functional gradients, we observed that structure-function gradient coupling undergoes differential lifespan trajectories across multiple gradient axes., Competing Interests: Competing Interests The authors declare that they have no competing financial interests.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduced pleural adhesion in animal studies, but its effect on human had not been studied. A retrospective study was carried out for patients with solitary pulmonary nodules without a pre-operative tissue diagnosis positive for malignancy. The impact of the use of NSAIDs after stage one wedge resection was assessed by the degree of pleural adhesions encountered during second-stage, redo completion lobectomy. From April 2016 to March 2022, 50 consecutive patients meeting the inclusion criteria were included, and 44 patients were selected for analysis after exclusion (Treatment group with NSAID: N = 27; Control group without NSAID: N = 17). The preoperative characteristics and the final tumor pathologies were similar between the groups. The use of NSAID was significantly associated with lower risk of severe pleural adhesions and complete pleural symphysis (risk difference = -29%, p = 0.03). After controlling the effect of tumor size and chest drain duration, only the use of NSAID was statistically associated with the lowered risk of severe pleural adhesions and complete pleural symphysis. No statistically significant effects of NSAID on operative time (p = 0.86), blood loss (p = 0.72), and post-operative length of stay (p = 0.72) were demonstrated. In human, NSAIDs attenuated the formation of pleural adhesions after pleural disruptions. Physicians and surgeons should avoid the use of NSAIDs when pleural adhesion formation is the intended treatment outcome., (© 2023. Springer Nature Limited.)

Brain atlases are spatial references for integrating, processing, and analyzing brain features gathered from different individuals, sources, and scales. Here we introduce a collection of joint surface-volume atlases that chart postnatal development of the human brain in a spatiotemporally dense manner from two weeks to two years of age. Our month-specific atlases chart normative patterns and capture key traits of early brain development and are therefore conducive to identifying aberrations from normal developmental trajectories. These atlases will enhance our understanding of early structural and functional development by facilitating the mapping of diverse features of the infant brain to a common reference frame for precise multifaceted quantification of cortical and subcortical changes., (© 2022. The Author(s).)

Cephalometric analysis relies on accurate detection of craniomaxillofacial (CMF) landmarks from cone-beam computed tomography (CBCT) images. However, due to the complexity of CMF bony structures, it is difficult to localize landmarks efficiently and accurately. In this paper, we propose a deep learning framework to tackle this challenge by jointly digitalizing 105 CMF landmarks on CBCT images. By explicitly learning the local geometrical relationships between the landmarks, our approach extends Mask R-CNN for end-to-end prediction of landmark locations. Specifically, we first apply a detection network on a down-sampled 3D image to leverage global contextual information to predict the approximate locations of the landmarks. We subsequently leverage local information provided by higher-resolution image patches to refine the landmark locations. On patients with varying non-syndromic jaw deformities, our method achieves an average detection accuracy of 1.38± 0.95mm, outperforming a related state-of-the-art method.

Brain functional connectivity network (FCN) based on resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to identify neuropsychiatric disorders such as autism spectrum disorder (ASD). Most existing FCN-based methods only estimate the correlation between brain regions of interest (ROIs), without exploring more informative higher-level interactions among multiple ROIs which could be beneficial to disease diagnosis. To fully explore the discriminative information provided by different brain networks, a cluster-based multi-view high-order FCN (Ho-FCN) framework is proposed in this paper. Specifically, we first group the functional connectivity (FC) time series into different clusters and compute the multi-order central moment series for the FC time series in each cluster. Then we utilize the correlation of central moment series between different clusters to reveal the high-order FC relationships among multiple ROIs. In addition, to address the phase mismatch issue in conventional FCNs, we also adopt the central moments of the correlation time series as the temporal-invariance features to capture the dynamic characteristics of low-order dynamic FCN (Lo-D-FCN). Experimentalresults on the ABIDE dataset validate that: 1) the proposed multi-view Ho-FCNs is able to explore rich discriminative information for ASD diagnosis; 2) the phase mismatch issue can be well circumvented by using central moments; and 3) the combination of different types of FCNs can significantly improve the diagnostic accuracy of ASD (86.2%).

In this article, we study a novel problem: "automatic prescription recommendation for PD patients." To realize this goal, we first build a dataset by collecting 1) symptoms of PD patients, and 2) their prescription drug provided by neurologists. Then, we build a novel computer-aided prescription model by learning the relation between observed symptoms and prescription drug. Finally, for the new coming patients, we could recommend (predict) suitable prescription drug on their observed symptoms by our prescription model. From the methodology part, our proposed model, namely Prescription viA Learning lAtent Symptoms (PALAS), could recommend prescription using the multi-modality representation of the data. In PALAS, a latent symptom space is learned to better model the relationship between symptoms and prescription drug, as there is a large semantic gap between them. Moreover, we present an efficient alternating optimization method for PALAS. We evaluated our method using the data collected from 136 PD patients at Nanjing Brain Hospital, which can be regarded as a large dataset in PD research community. The experimental results demonstrate the effectiveness and clinical potential of our method in this recommendation task, if compared with other competing methods.

Objective: To estimate a patient-specific reference bone shape model for a patient with craniomaxillofacial (CMF) defects due to facial trauma., Methods: We proposed an automatic facial bone shape estimation framework using pre-traumatic conventional portrait photos and post-traumatic head computed tomography (CT) scans via a 3D face reconstruction and a deformable shape model. Specifically, a three-dimensional (3D) face was first reconstructed from the patient's pre-traumatic portrait photos. Second, a correlation model between the skin and bone surfaces was constructed using a sparse representation based on the CT images of training normal subjects. Third, by feeding the reconstructed 3D face into the correlation model, an initial reference shape model was generated. In addition, we refined the initial estimation by applying non-rigid surface matching between the initially estimated shape and the patient's post-traumatic bone based on the adaptive-focus deformable shape model (AFDSM). Furthermore, a statistical shape model, built from the training normal subjects, was utilized to constrain the deformation process to avoid overfitting., Results and Conclusion: The proposed method was evaluated using both synthetic and real patient data. Experimental results show that the patient's abnormal facial bony structure can be recovered using our method, and the estimated reference shape model is considered clinically acceptable by an experienced CMF surgeon., Significance: The proposed method is more suitable to the complex CMF defects for CMF reconstructive surgical planning.

Antisocial behavior (ASB) is believed to have neural substrates; however, the association between ASB and functional brain networks remains unclear. The temporal variability of the functional connectivity (or dynamic FC) derived from resting-state functional MRI has been suggested as a useful metric for studying abnormal behaviors including ASB. This is the first study using low-frequency fluctuations of the dynamic FC to unravel potential system-level neural correlates with ASB. Specifically, we individually associated the dynamic FC patterns with the ASB scores (measured by Antisocial Process Screening Device) of the male offenders (age: 23.29 ± 3.36 years) based on machine learning. Results showed that the dynamic FCs were associated with individual ASB scores. Moreover, we found that it was mainly the inter-network dynamic FCs that were negatively associated with the ASB severity. Three major high-order cognitive functional networks and the sensorimotor network were found to be more associated with ASB. We further found that impaired behavior in the ASB subjects was mainly associated with decreased FC dynamics in these networks, which may explain why ASB subjects usually have impaired executive control and emotional processing functions. Our study shows that temporal variation of the FC could be a promising tool for ASB assessment, treatment, and prevention., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Fast and automated image quality assessment (IQA) of diffusion MR images is crucial for making timely decisions for rescans. However, learning a model for this task is challenging as the number of annotated data is limited and the annotation labels might not always be correct. As a remedy, we will introduce in this paper an automatic image quality assessment (IQA) method based on hierarchical non-local residual networks for pediatric diffusion MR images. Our IQA is performed in three sequential stages, i.e., 1) slice-wise IQA, where a nonlocal residual network is first pre-trained to annotate each slice with an initial quality rating (i.e., pass/questionable/fail), which is subsequently refined via iterative semi-supervised learning and slice self-training; 2) volume-wise IQA, which agglomerates the features extracted from the slices of a volume, and uses a nonlocal network to annotate the quality rating for each volume via iterative volume self-training; and 3) subject-wise IQA, which ensembles the volumetric IQA results to determine the overall image quality pertaining to a subject. Experimental results demonstrate that our method, trained using only samples of modest size, exhibits great generalizability, and is capable of conducting rapid hierarchical IQA with near-perfect accuracy.

During the first years of life, the human brain undergoes dynamic spatially-heterogeneous changes, invo- lving differentiation of neuronal types, dendritic arbori- zation, axonal ingrowth, outgrowth and retraction, synaptogenesis, and myelination. To better quantify these changes, this article presents a method for probing tissue microarchitecture by characterizing water diffusion in a spectrum of length scales, factoring out the effects of intra-voxel orientation heterogeneity. Our method is based on the spherical means of the diffusion signal, computed over gradient directions for a set of diffusion weightings (i.e., b -values). We decompose the spherical mean profile at each voxel into a spherical mean spectrum (SMS), which essentially encodes the fractions of spin packets undergoing fine- to coarse-scale diffusion proce- sses, characterizing restricted and hindered diffusion stemming respectively from intra- and extra-cellular water compartments. From the SMS, multiple orientation distribution invariant indices can be computed, allowing for example the quantification of neurite density, microscopic fractional anisotropy ( μ FA), per-axon axial/radial diffusivity, and free/restricted isotropic diffusivity. We show that these indices can be computed for the developing brain for greater sensitivity and specificity to development related changes in tissue microstructure. Also, we demonstrate that our method, called spherical mean spectrum imaging (SMSI), is fast, accurate, and can overcome the biases associated with other state-of-the-art microstructure models.

Most brain microstructure models are dedicated to the quantification of white matter microstructure, using for example sticks, cylinders, and zeppelins to model intra- and extra-axonal environments. Gray matter presents unique micro-architecture with cell bodies (somas) exhibiting diffusion characteristics that differ from axons in white matter. In this paper, we introduce a method to quantify soma microstructure, giving measures such as volume fraction, diffusivity, and kurtosis. Our method captures a spectrum of diffusion patterns and scales and does not rely on restrictive model assumptions. We show that our method yields unique and meaningful contrasts that are in agreement with histological data. We demonstrate its application in the mapping of the distinct spatial patterns of soma density in the cortex.

Accurate segmentation of organs at risk (OARs) from head and neck (H&N) CT images is crucial for effective H&N cancer radiotherapy. However, the existing deep learning methods are often not trained in an end-to-end fashion, i.e., they independently predetermine the regions of target organs before organ segmentation, causing limited information sharing between related tasks and thus leading to suboptimal segmentation results. Furthermore, when conventional segmentation network is used to segment all the OARs simultaneously, the results often favor big OARs over small OARs. Thus, the existing methods often train a specific model for each OAR, ignoring the correlation between different segmentation tasks. To address these issues, we propose a new multi-view spatial aggregation framework for joint localization and segmentation of multiple OARs using H&N CT images. The core of our framework is a proposed region-of-interest (ROI)-based fine-grained representation convolutional neural network (CNN), which is used to generate multi-OAR probability maps from each 2D view (i.e., axial, coronal, and sagittal view) of CT images. Specifically, our ROI-based fine-grained representation CNN (1) unifies the OARs localization and segmentation tasks and trains them in an end-to-end fashion, and (2) improves the segmentation results of various-sized OARs via a novel ROI-based fine-grained representation. Our multi-view spatial aggregation framework then spatially aggregates and assembles the generated multi-view multi-OAR probability maps to segment all the OARs simultaneously. We evaluate our framework using two sets of H&N CT images and achieve competitive and highly robust segmentation performance for OARs of various sizes.

In this paper, we introduce an image quality assessment (IQA) method for pediatric T1- and T2-weighted MR images. IQA is first performed slice-wise using a nonlocal residual neural network (NR-Net) and then volume-wise by agglomerating the slice QA results using random forest. Our method requires only a small amount of quality-annotated images for training and is designed to be robust to annotation noise that might occur due to rater errors and the inevitable mix of good and bad slices in an image volume. Using a small set of quality-assessed images, we pre-train NR-Net to annotate each image slice with an initial quality rating (i.e., pass, questionable, fail), which we then refine by semi-supervised learning and iterative self-training. Experimental results demonstrate that our method, trained using only samples of modest size, exhibit great generalizability, capable of real-time (milliseconds per volume) large-scale IQA with nearperfect accuracy.

Compared to computed tomography (CT), magnetic resonance imaging (MRI) delineation of craniomaxillofacial (CMF) bony structures can avoid harmful radiation exposure. However, bony boundaries are blurry in MRI, and structural information needs to be borrowed from CT during the training. This is challenging since paired MRI-CT data are typically scarce. In this paper, we propose to make full use of unpaired data, which are typically abundant, along with a single paired MRI-CT data to construct a one-shot generative adversarial model for automated MRI segmentation of CMF bony structures. Our model consists of a cross-modality image synthesis sub-network, which learns the mapping between CT and MRI, and an MRI segmentation sub-network. These two sub-networks are trained jointly in an end-to-end manner. Moreover, in the training phase, a neighbor-based anchoring method is proposed to reduce the ambiguity problem inherent in cross-modality synthesis, and a feature-matching-based semantic consistency constraint is proposed to encourage segmentation-oriented MRI synthesis. Experimental results demonstrate the superiority of our method both qualitatively and quantitatively in comparison with the state-of-the-art MRI segmentation methods.

Fusing multi-modality data is crucial for accurate identification of brain disorder as different modalities can provide complementary perspectives of complex neurodegenerative disease. However, there are at least four common issues associated with the existing fusion methods. First, many existing fusion methods simply concatenate features from each modality without considering the correlations among different modalities. Second, most existing methods often make prediction based on a single classifier, which might not be able to address the heterogeneity of the Alzheimer's disease (AD) progression. Third, many existing methods often employ feature selection (or reduction) and classifier training in two independent steps, without considering the fact that the two pipelined steps are highly related to each other. Forth, there are missing neuroimaging data for some of the participants (e.g., missing PET data), due to the participants' "no-show" or dropout. In this paper, to address the above issues, we propose an early AD diagnosis framework via novel multi-modality latent space inducing ensemble SVM classifier. Specifically, we first project the neuroimaging data from different modalities into a latent space, and then map the learned latent representations into the label space to learn multiple diversified classifiers. Finally, we obtain the more reliable classification results by using an ensemble strategy. More importantly, we present a Complete Multi-modality Latent Space (CMLS) learning model for complete multi-modality data and also an Incomplete Multi-modality Latent Space (IMLS) learning model for incomplete multi-modality data. Extensive experiments using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset have demonstrated that our proposed models outperform other state-of-the-art methods., (Copyright © 2019. Published by Elsevier B.V.)

Diffusion MRI (dMRI) is typically time consuming as it involves acquiring a series of 3D volumes, each associated with a wave-vector in q-space that determines the diffusion direction and strength. The acquisition time is further increased when "blip-up blip-down" scans are acquired with opposite phase encoding directions (PEDs) to facilitate distortion correction. In this work, we show that geometric distortions can be corrected without acquiring with opposite PEDs for each wave-vector, and hence the acquisition time can be halved. Our method uses complimentary rotation-invariant contrasts across shells of different diffusion weightings. Distortion-free structural T1-/T2-weighted MRI is used as reference for nonlinear registration in correcting the distortions. Signal dropout and pileup are corrected with the help of spherical harmonics. To demonstrate that our method is robust to changes in image appearance, we show that distortion correction with good structural alignment can be achieved within minutes for dMRI data of infants between 1 to 24 months of age.

In this paper, we introduce a method for estimating patient-specific reference bony shape models for planning of reconstructive surgery for patients with acquired craniomaxillofacial (CMF) trauma. We propose an automatic bony shape estimation framework using pre-traumatic portrait photographs and post-traumatic head computed tomography (CT) scans. A 3D facial surface is first reconstructed from the patient's pre-traumatic photographs. An initial estimation of the patient's normal bony shape is then obtained with the reconstructed facial surface via sparse representation using a dictionary of paired facial and bony surfaces of normal subjects. We further refine the bony shape model by deforming the initial bony shape model to the post-traumatic 3D CT bony model, regularized by a statistical shape model built from a database of normal subjects. Experimental results show that our method is capable of effectively recovering the patient's normal facial bony shape in regions with defects, allowing CMF surgical planning to be performed precisely for a wider range of defects caused by trauma.

The fusion of complementary information contained in multi-modality data [e.g., magnetic resonance imaging (MRI), positron emission tomography (PET), and genetic data] has advanced the progress of automated Alzheimer's disease (AD) diagnosis. However, multi-modality based AD diagnostic models are often hindered by the missing data, i.e., not all the subjects have complete multi-modality data. One simple solution used by many previous studies is to discard samples with missing modalities. However, this significantly reduces the number of training samples, thus leading to a sub-optimal classification model. Furthermore, when building the classification model, most existing methods simply concatenate features from different modalities into a single feature vector without considering their underlying associations. As features from different modalities are often closely related (e.g., MRI and PET features are extracted from the same brain region), utilizing their inter-modality associations may improve the robustness of the diagnostic model. To this end, we propose a novel latent representation learning method for multi-modality based AD diagnosis. Specifically, we use all the available samples (including samples with incomplete modality data) to learn a latent representation space. Within this space, we not only use samples with complete multi-modality data to learn a common latent representation, but also use samples with incomplete multi-modality data to learn independent modality-specific latent representations. We then project the latent representations to the label space for AD diagnosis. We perform experiments using 737 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and the experimental results verify the effectiveness of our proposed method.

Accurate segmentation of infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is an indispensable foundation for early studying of brain growth patterns and morphological changes in neurodevelopmental disorders. Nevertheless, in the isointense phase (approximately 6-9 months of age), due to inherent myelination and maturation process, WM and GM exhibit similar levels of intensity in both T1-weighted (T1w) and T2-weighted (T2w) MR images, making tissue segmentation very challenging. Despite many efforts were devoted to brain segmentation, only few studies have focused on the segmentation of 6-month infant brain images. With the idea of boosting methodological development in the community, iSeg-2017 challenge (http://iseg2017.web.unc.edu) provides a set of 6-month infant subjects with manual labels for training and testing the participating methods. Among the 21 automatic segmentation methods participating in iSeg-2017, we review the 8 top-ranked teams, in terms of Dice ratio, modified Hausdorff distance and average surface distance, and introduce their pipelines, implementations, as well as source codes. We further discuss limitations and possible future directions. We hope the dataset in iSeg-2017 and this review article could provide insights into methodological development for the community.

In this article, the authors aim to maximally utilize multimodality neuroimaging and genetic data for identifying Alzheimer's disease (AD) and its prodromal status, Mild Cognitive Impairment (MCI), from normal aging subjects. Multimodality neuroimaging data such as MRI and PET provide valuable insights into brain abnormalities, while genetic data such as single nucleotide polymorphism (SNP) provide information about a patient's AD risk factors. When these data are used together, the accuracy of AD diagnosis may be improved. However, these data are heterogeneous (e.g., with different data distributions), and have different number of samples (e.g., with far less number of PET samples than the number of MRI or SNPs). Thus, learning an effective model using these data is challenging. To this end, we present a novel three-stage deep feature learning and fusion framework, where deep neural network is trained stage-wise. Each stage of the network learns feature representations for different combinations of modalities, via effective training using the maximum number of available samples. Specifically, in the first stage, we learn latent representations (i.e., high-level features) for each modality independently, so that the heterogeneity among modalities can be partially addressed, and high-level features from different modalities can be combined in the next stage. In the second stage, we learn joint latent features for each pair of modality combination by using the high-level features learned from the first stage. In the third stage, we learn the diagnostic labels by fusing the learned joint latent features from the second stage. To further increase the number of samples during training, we also use data at multiple scanning time points for each training subject in the dataset. We evaluate the proposed framework using Alzheimer's disease neuroimaging initiative (ADNI) dataset for AD diagnosis, and the experimental results show that the proposed framework outperforms other state-of-the-art methods., (© 2018 Wiley Periodicals, Inc.)

Discriminative methods commonly produce models with relatively good generalization abilities. However, this advantage is challenged in real-world applications (e.g., medical image analysis problems), in which there often exist outlier data points (sample-outliers) and noises in the predictor values (feature-noises). Methods robust to both types of these deviations are somewhat overlooked in the literature. We further argue that denoising can be more effective, if we learn the model using all the available labeled and unlabeled samples, as the intrinsic geometry of the sample manifold can be better constructed using more data points. In this paper, we propose a semi-supervised robust discriminative classification method based on the least-squares formulation of linear discriminant analysis to detect sample-outliers and feature-noises simultaneously, using both labeled training and unlabeled testing data. We conduct several experiments on a synthetic, some benchmark semi-supervised learning, and two brain neurodegenerative disease diagnosis datasets (for Parkinson's and Alzheimer's diseases). Specifically for the application of neurodegenerative diseases diagnosis, incorporating robust machine learning methods can be of great benefit, due to the noisy nature of neuroimaging data. Our results show that our method outperforms the baseline and several state-of-the-art methods, in terms of both accuracy and the area under the ROC curve.

Brain-wide and genome-wide association (BW-GWA) study is presented in this paper to identify the associations between the brain imaging phenotypes (i.e., regional volumetric measures) and the genetic variants [i.e., single nucleotide polymorphism (SNP)] in Alzheimer's disease (AD). The main challenges of this study include the data heterogeneity, complex phenotype-genotype associations, high-dimensional data (e.g., thousands of SNPs), and the existence of phenotype outliers. Previous BW-GWA studies, while addressing some of these challenges, did not consider the diagnostic label information in their formulations, thus limiting their clinical applicability. To address these issues, we present a novel joint projection and sparse regression model to discover the associations between the phenotypes and genotypes. Specifically, to alleviate the negative influence of data heterogeneity, we first map the genotypes into an intermediate imaging-phenotype-like space. Then, to better reveal the complex phenotype-genotype associations, we project both the mapped genotypes and the original imaging phenotypes into a diagnostic-label-guided joint feature space, where the intraclass projected points are constrained to be close to each other. In addition, we use l 2,1 -norm minimization on both the regression loss function and the transformation coefficient matrices, to reduce the effect of phenotype outliers and also to encourage sparse feature selections of both the genotypes and phenotypes. We evaluate our method using AD neuroimaging initiative dataset, and the results show that our proposed method outperforms several state-of-the-art methods in term of the average root-mean-square error of genome-to-phenotype predictions. Besides, the associated SNPs and brain regions identified in this study have also been shown in the previous AD-related studies, thus verifying the effectiveness and potential of our proposed method in AD pathogenesis study.

Precise quantification of brain tissue micro-architecture using diffusion MRI is hampered by the conflation of diffusion-attenuated signals from micro-environments that can be orientationally heterogeneous due to complex fiber configurations, such as crossing, fanning, and bending, and compartmentally heterogeneous due to variability in tissue organization. In this paper, we introduce a method, called Spherical Mean Spectrum Imaging (SMSI), for quantification of tissue microstructure. SMSI does not assume a fixed number of compartments, but characterizes the signal as a spectrum of fine- to coarse-scale diffusion processes. Using SMSI, multiple orientation distribution invariant indices can be computed, allowing for example the quantification of neurite density, microscopic fractional anisotropy ( μ FA), per-axon axial/radial diffusivity, and free/restricted isotropic diffusivity. We show that SMSI is fast, accurate, and can overcome biases in state-of-the-art microstructure models. We demonstrate its application in probing microstructural changes in the baby brain during the first two years of life.

Fast and automated image quality assessment (IQA) for diffusion MR images is crucial so that a rescan decision can be made swiftly during or after the scanning session. However, learning this task is challenging as the number of annotated data is limited and the annotated label is not always perfect. To this end, we introduce an automatic multistage IQA method for pediatric diffusion MR images. Our IQA is performed in three sequential stages, i.e., slice-wise quality assessment (QA) using a nonlocal residual network, volume-wise QA by agglomerating the extracted features of slices belonging to one volume using a nonlocal network, and subject-wise QA by ensembling the QA results of volumes belonging to one subject. In addition, we employ semi-supervised learning to make full use of a small amount of annotated data and a large amount of unlabeled data to train our network. Specifically, we first pretrain our network using labeled data, which are iteratively expanded by labeling the unlabeled data with the trained network. Furthermore, we devise a self-training strategy which iteratively relabels and prunes the labeled dataset when training the network to deal with noisy labels. Experimental results demonstrate that our network, trained using only samples of modest size, exhibits great generalizability and is capable of conducting large-scale rapid IQA with near-perfect accuracy.

Complex tissue microstructure involving various types of cells and their membranes can deviate the movement of water molecules from the typical Gaussian diffusion. This deviation can be quantified using excess kurtosis to characterize tissue structural complexity. However, true kurtosis measurements can be obscured by complex white matter configurations such as fiber crossing, bending, and branching, which are ubiquitous in the brain. In this paper, we extend diffusion kurtosis imaging (DKI) to allow characterization of diffusional kurtosis in microstructural environments that are oriented heterogeneously. Our method, called microscopic DKI ( μ DKI), fits a cylindrically symmetric kurtosis model to the spherical mean of the diffusion signal as a function of diffusion weighting. The spherical mean, computed for each b -shell, is invariant to the fiber orientation distribution and is a function of per-axon microstructural properties. Experimental results indicate that μ DKI yields significantly higher consistency in quantifying microstructure than the conventional DKI in the presence of orientation heterogeneity.

Recent studies have shown that fusing multi-modal neuroimaging data can improve the performance of Alzheimer's Disease (AD) diagnosis. However, most existing methods simply concatenate features from each modality without appropriate consideration of the correlations among multi-modalities. Besides, existing methods often employ feature selection (or fusion) and classifier training in two independent steps without consideration of the fact that the two pipelined steps are highly related to each other. Furthermore, existing methods that make prediction based on a single classifier may not be able to address the heterogeneity of the AD progression. To address these issues, we propose a novel AD diagnosis framework based on latent space learning with ensemble classifiers, by integrating the latent representation learning and ensemble of multiple diversified classifiers learning into a unified framework. To this end, we first project the neuroimaging data from different modalities into a common latent space, and impose a joint sparsity constraint on the concatenated projection matrices. Then, we map the learned latent representations into the label space to learn multiple diversified classifiers and aggregate their predictions to obtain the final classification result. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that our method outperforms other state-of-the-art methods.

In this paper, we aim to predict conversion and time-to-conversion of mild cognitive impairment (MCI) patients using multi-modal neuroimaging data and clinical data, via cross-sectional and longitudinal studies. However, such data are often heterogeneous, high-dimensional, noisy, and incomplete. We thus propose a framework that includes sparse feature selection, low-rank affinity pursuit denoising (LRAD), and low-rank matrix completion (LRMC) in this study. Specifically, we first use sparse linear regressions to remove unrelated features. Then, considering the heterogeneity of the MCI data, which can be assumed as a union of multiple subspaces, we propose to use a low rank subspace method (i.e., LRAD) to denoise the data. Finally, we employ LRMC algorithm with three data fitting terms and one inequality constraint for joint conversion and time-to-conversion predictions. Our framework aims to answer a very important but yet rarely explored question in AD study, i.e., when will the MCI convert to AD? This is different from survival analysis, which provides the probabilities of conversion at different time points that are mainly used for global analysis, while our time-to-conversion prediction is for each individual subject. Evaluations using the ADNI dataset indicate that our method outperforms conventional LRMC and other state-of-the-art methods. Our method achieves a maximal pMCI classification accuracy of 84% and time prediction correlation of 0.665., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It is vital to identify Mild Cognitive Impairment (MCI) subjects who will progress to Alzheimer's Disease (AD), so that early treatment can be administered. Recent studies show that using complementary information from multi-modality data may improve the model performance of the above prediction problem. However, multi-modality data is often incomplete, causing the prediction models that rely on complete data unusable. One way to deal with this issue is by first imputing the missing values, and then building a classifier based on the completed data. This two-step approach, however, may generate non-optimal classifier output, as the errors of the imputation may propagate to the classifier during training. To address this issue, we propose a unified framework that jointly performs feature selection, data denoising, missing values imputation, and classifier learning. To this end, we use a low-rank constraint to impute the missing values and denoise the data simultaneously, while using a regression model for feature selection and classification. The feature weights learned by the regression model are integrated into the low rank formulation to focus on discriminative features when denoising and imputing data, while the resulting low-rank matrix is used for classifier learning. These two components interact and correct each other iteratively using Alternating Direction Method of Multiplier (ADMM). The experimental results using incomplete multi-modality ADNI dataset shows that our proposed method outperforms other comparison methods.

In this paper, we aim to maximally utilize multimodality neuroimaging and genetic data to predict Alzheimer's disease (AD) and its prodromal status, i.e., a multi-status dementia diagnosis problem. Multimodality neuroimaging data such as MRI and PET provide valuable insights to abnormalities, and genetic data such as Single Nucleotide Polymorphism (SNP) provide information about a patient's AD risk factors. When used in conjunction, AD diagnosis may be improved. However, these data are heterogeneous (e.g., having different data distributions), and have different number of samples (e.g., PET data is having far less number of samples than the numbers of MRI or SNPs). Thus, learning an effective model using these data is challenging. To this end, we present a novel three-stage deep feature learning and fusion framework , where the deep neural network is trained stage-wise. Each stage of the network learns feature representations for different combination of modalities, via effective training using maximum number of available samples . Specifically, in the first stage, we learn latent representations (i.e., high-level features) for each modality independently, so that the heterogeneity between modalities can be better addressed and then combined in the next stage. In the second stage, we learn the joint latent features for each pair of modality combination by using the high-level features learned from the first stage. In the third stage, we learn the diagnostic labels by fusing the learned joint latent features from the second stage. We have tested our framework on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for multi-status AD diagnosis, and the experimental results show that the proposed framework outperforms other methods.

MGMT promoter methylation and IDH1 mutation in high-grade gliomas (HGG) have proven to be the two important molecular indicators associated with better prognosis. Traditionally, the statuses of MGMT and IDH1 are obtained via surgical biopsy, which is laborious, invasive and time-consuming. Accurate presurgical prediction of their statuses based on preoperative imaging data is of great clinical value towards better treatment plan. In this paper, we propose a novel Multi-label Inductive Matrix Completion (MIMC) model, highlighted by the online inductive learning strategy, to jointly predict both MGMT and IDH1 statuses. Our MIMC model not only uses the training subjects with possibly missing MGMT/IDH1 labels, but also leverages the unlabeled testing subjects as a supplement to the limited training dataset. More importantly, we learn inductive labels, instead of directly using transductive labels, as the prediction results for the testing subjects, to alleviate the overfitting issue in small-sample-size studies. Furthermore, we design an optimization algorithm with guaranteed convergence based on the block coordinate descent method to solve the multivariate non-smooth MIMC model. Finally, by using a precious single-center multi-modality presurgical brain imaging and genetic dataset of primary HGG, we demonstrate that our method can produce accurate prediction results, outperforming the previous widely-used single- or multi-task machine learning methods. This study shows the promise of utilizing imaging-derived brain connectome phenotypes for prognosis of HGG in a non-invasive manner.

It is challenging to use incomplete multimodality data for Alzheimer's Disease (AD) diagnosis. The current methods to address this challenge, such as low-rank matrix completion ( i.e ., imputing the missing values and unknown labels simultaneously) and multi-task learning ( i.e ., defining one regression task for each combination of modalities and then learning them jointly), are unable to model the complex data-to-label relationship in AD diagnosis and also ignore the heterogeneity among the modalities. In light of this, we propose a new Maximum Mean Discrepancy (MMD) based Multiple Kernel Learning (MKL) method for AD diagnosis using incomplete multimodality data. Specifically, we map all the samples from different modalities into a Reproducing Kernel Hilbert Space (RKHS), by devising a new MMD algorithm. The proposed MMD method incorporates data distribution matching, pair-wise sample matching and feature selection in an unified formulation, thus alleviating the modality heterogeneity issue and making all the samples comparable to share a common classifier in the RKHS. The resulting classifier obviously captures the nonlinear data-to-label relationship. We have tested our method using MRI and PET data from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for AD diagnosis. The experimental results show that our method outperforms other methods.

Utilization of biomedical data from multiple modalities improves the diagnostic accuracy of neurodegenerative diseases. However, multi-modality data are often incomplete because not all data can be collected for every individual. When using such incomplete data for diagnosis, current approaches for addressing the problem of missing data, such as imputation, matrix completion and multi-task learning, implicitly assume linear data-to-label relationship, therefore limiting their performances. We thus propose multi-task deep learning for incomplete data, where prediction tasks that are associated with different modality combinations are learnt jointly to improve the performance of each task. Specifically, we devise a multi-input multi-output deep learning framework, and train our deep network subnet-wise, partially updating its weights based on the availability of modality data. The experimental results using the ADNI dataset show that our method outperforms the state-of-the-art methods.

Distinguishing progressive mild cognitive impairment (pMCI) from stable mild cognitive impairment (sMCI) is critical for identification of patients who are at risk for Alzheimer's disease (AD), so that early treatment can be administered. In this paper, we propose a pMCI/sMCI classification framework that harnesses information available in longitudinal magnetic resonance imaging (MRI) data, which could be incomplete, to improve diagnostic accuracy. Volumetric features were first extracted from the baseline MRI scan and subsequent scans acquired after 6, 12, and 18 months. Dynamic features were then obtained using the 18th month scan as the reference and computing the ratios of feature differences for the earlier scans. Features that are linearly or non-linearly correlated with diagnostic labels are then selected using two elastic net sparse learning algorithms. Missing feature values due to the incomplete longitudinal data are imputed using a low-rank matrix completion method. Finally, based on the completed feature matrix, we build a multi-kernel support vector machine (mkSVM) to predict the diagnostic label of samples with unknown diagnostic statuses. Our evaluation indicates that a diagnosis accuracy as high as 78.2 % can be achieved when information from the longitudinal scans is used-6.6 % higher than the case using only the reference time point image. In other words, information provided by the longitudinal history of the disease improves diagnosis accuracy.

Effective utilization of heterogeneous multi-modal data for Alzheimer's Disease (AD) diagnosis and prognosis has always been hampered by incomplete data. One method to deal with this is low-rank matrix completion (LRMC), which simultaneous imputes missing data features and target values of interest. Although LRMC yields reasonable results, it implicitly weights features from all the modalities equally, ignoring the differences in discriminative power of features from different modalities. In this paper, we propose stability-weighted LRMC (swLRMC), an LRMC improvement that weights features and modalities according to their importance and reliability . We introduce a method, called stability weighting , to utilize subsampling techniques and outcomes from a range of hyper-parameters of sparse feature learning to obtain a stable set of weights. Incorporating these weights into LRMC, swLRMC can better account for differences in features and modalities for improving diagnosis. Experimental results confirm that the proposed method outperforms the conventional LRMC, feature-selection based LRMC, and other state-of-the-art methods.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease and affects a large population in the world. Cognitive scores at multiple time points can be reliably used to evaluate the progression of the disease clinically. In recent studies, machine learning techniques have shown promising results on the prediction of AD clinical scores. However, there are multiple limitations in the current models such as linearity assumption and missing data exclusion. Here, we present a nonlinear supervised sparse regression-based random forest (RF) framework to predict a variety of longitudinal AD clinical scores. Furthermore, we propose a soft-split technique to assign probabilistic paths to a test sample in RF for more accurate predictions. In order to benefit from the longitudinal scores in the study, unlike the previous studies that often removed the subjects with missing scores, we first estimate those missing scores with our proposed soft-split sparse regression-based RF and then utilize those estimated longitudinal scores at all the previous time points to predict the scores at the next time point. The experiment results demonstrate that our proposed method is superior to the traditional RF and outperforms other state-of-art regression models. Our method can also be extended to be a general regression framework to predict other disease scores., Competing Interests: statement The authors have no conflicts of interest to disclose., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This paper proposes a framework of fast neuroimaging-based retrieval and AD analysis, by three key steps: (1) landmark detection , which efficiently extracts landmark-based neuroimaging features without the need of nonlinear registration in testing stage; (2) landmark selection , which removes redundant/noisy landmarks via proposing a feature selection method that considers structural information among landmarks; and (3) hashing , which converts high-dimensional features of subjects into binary codes, for efficiently conducting approximate nearest neighbor search and diagnosis of AD. We have conducted experiments on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and demonstrated that our framework could achieve higher performance than the comparison methods, in terms of accuracy and speed (at least 100 times faster).

Neuroimaging data have been widely used to derive possible biomarkers for Alzheimer's Disease (AD) diagnosis. As only certain brain regions are related to AD progression, many feature selection methods have been proposed to identify informative features ( i.e. , brain regions) to build an accurate prediction model. These methods mostly only focus on the feature-target relationship to select features which are discriminative to the targets ( e.g. , diagnosis labels). However, since the brain regions are anatomically and functionally connected, there could be useful intrinsic relationships among features. In this paper, by utilizing both the feature-target and feature-feature relationships, we propose a novel sparse regression model to select informative features which are discriminative to the targets and also representative to the features. We argue that the features which are representative ( i.e. , can be used to represent many other features) are important, as they signify strong "connection" with other ROIs, and could be related to the disease progression. We use our model to select features for both binary and multi-class classification tasks, and the experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that the proposed method outperforms other comparison methods considered in this work.

Autism spectrum disorder (ASD) is a wide range of disabilities that cause life-long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for identifying high-risk ASD infants at as early as six months after birth. This is based on the observation that ASD-induced abnormalities in white matter (WM) tracts and whole-brain connectivity have already started to appear within 24 months after birth. In particular, we propose a novel multikernel support vector machine classification framework by using the connectivity features gathered from WM connectivity networks, which are generated via multiscale regions of interest (ROIs) and multiple diffusion statistics such as fractional anisotropy, mean diffusivity, and average fiber length. Our proposed framework achieves an accuracy of 76% and an area of 0.80 under the receiver operating characteristic curve (AUC), in comparison to the accuracy of 70% and the AUC of 70% provided by the best single-parameter single-scale network. The improvement in accuracy is mainly due to the complementary information provided by multiparameter multiscale networks. In addition, our framework also provides the potential imaging connectomic markers and an objective means for early ASD diagnosis., (© 2015 Wiley Periodicals, Inc.)

Identifying progressive mild cognitive impairment (pMCI) patients and predicting when they will convert to Alzheimer's disease (AD) are important for early medical intervention. Multi-modality and longitudinal data provide a great amount of information for improving diagnosis and prognosis. But these data are often incomplete and noisy. To improve the utility of these data for prediction purposes, we propose an approach to denoise the data, impute missing values, and cluster the data into low-dimensional subspaces for pMCI prediction. We assume that the data reside in a space formed by a union of several low-dimensional subspaces and that similar MCI conditions reside in similar subspaces. Therefore, we first use incomplete low-rank representation (ILRR) and spectral clustering to cluster the data according to their representative low-rank subspaces. At the same time, we denoise the data and impute missing values. Then we utilize a low-rank matrix completion (LRMC) framework to identify pMCI patients and their time of conversion. Evaluations using the ADNI dataset indicate that our method outperforms conventional LRMC method.

Accurate classification of Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI), plays a critical role in possibly preventing progression of memory impairment and improving quality of life for AD patients. Among many research tasks, it is of a particular interest to identify noninvasive imaging biomarkers for AD diagnosis. In this paper, we present a robust deep learning system to identify different progression stages of AD patients based on MRI and PET scans. We utilized the dropout technique to improve classical deep learning by preventing its weight coadaptation, which is a typical cause of overfitting in deep learning. In addition, we incorporated stability selection, an adaptive learning factor, and a multitask learning strategy into the deep learning framework. We applied the proposed method to the ADNI dataset, and conducted experiments for AD and MCI conversion diagnosis. Experimental results showed that the dropout technique is very effective in AD diagnosis, improving the classification accuracies by 5.9% on average as compared to the classical deep learning methods.

Recently, multi-atlas patch-based label fusion has received an increasing interest in the medical image segmentation field. After warping the anatomical labels from the atlas images to the target image by registration, label fusion is the key step to determine the latent label for each target image point. Two popular types of patch-based label fusion approaches are (1) reconstruction-based approaches that compute the target labels as a weighted average of atlas labels, where the weights are derived by reconstructing the target image patch using the atlas image patches; and (2) classification-based approaches that determine the target label as a mapping of the target image patch, where the mapping function is often learned using the atlas image patches and their corresponding labels. Both approaches have their advantages and limitations. In this paper, we propose a novel patch-based label fusion method to combine the above two types of approaches via matrix completion (and hence, we call it transversal). As we will show, our method overcomes the individual limitations of both reconstruction-based and classification-based approaches. Since the labeling confidences may vary across the target image points, we further propose a sequential labeling framework that first labels the highly confident points and then gradually labels more challenging points in an iterative manner, guided by the label information determined in the previous iterations. We demonstrate the performance of our novel label fusion method in segmenting the hippocampus in the ADNI dataset, subcortical and limbic structures in the LONI dataset, and mid-brain structures in the SATA dataset. We achieve more accurate segmentation results than both reconstruction-based and classification-based approaches. Our label fusion method is also ranked 1st in the online SATA Multi-Atlas Segmentation Challenge., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a variety of developmental disorders that cause life-long communication and social deficits. However, ASD could only be diagnosed at children as early as 2 years of age, while early signs may emerge within the first year. White matter (WM) connectivity abnormalities have been documented in the first year of lives of ASD subjects. We introduce a novel multi-kernel support vector machine (SVM) framework to identify infants at high-risk for ASD at 6 months old, by utilizing the diffusion parameters derived from a hierarchical set of WM connectomes. Experiments show that the proposed method achieves an accuracy of 76%, in comparison to 70% with the best single connectome. The complementary information extracted from hierarchical networks enhances the classification performance, with the top discriminative connections consistent with other studies. Our framework provides essential imaging connectomic markers and contributes to the evaluation of ASD risks as early as 6 months.

In this paper, we propose a multi-view learning method using Magnetic Resonance Imaging (MRI) data for Alzheimer's Disease (AD) diagnosis. Specifically, we extract both Region-Of-Interest (ROI) features and Histograms of Oriented Gradient (HOG) features from each MRI image, and then propose mapping HOG features onto the space of ROI features to make them comparable and to impose high intra-class similarity with low inter-class similarity. Finally, both mapped HOG features and original ROI features are input to the support vector machine for AD diagnosis. The purpose of mapping HOG features onto the space of ROI features is to provide complementary information so that features from different views can not only be comparable ( i.e., homogeneous) but also be interpretable. For example, ROI features are robust to noise, but lack of reflecting small or subtle changes, while HOG features are diverse but less robust to noise. The proposed multi-view learning method is designed to learn the transformation between two spaces and to separate the classes under the supervision of class labels. The experimental results on the MRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that the proposed multi-view method helps enhance disease status identification performance, outperforming both baseline methods and state-of-the-art methods.

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method.

In this work, we are interested in predicting the diagnostic statuses of potentially neurodegenerated patients using feature values derived from multi-modality neuroimaging data and biological data, which might be incomplete. Collecting the feature values into a matrix, with each row containing a feature vector of a sample, we propose a framework to predict the corresponding associated multiple target outputs (e.g., diagnosis label and clinical scores) from this feature matrix by performing matrix shrinkage following matrix completion. Specifically, we first combine the feature and target output matrices into a large matrix and then partition this large incomplete matrix into smaller submatrices, each consisting of samples with complete feature values (corresponding to a certain combination of modalities) and target outputs. Treating each target output as the outcome of a prediction task, we apply a 2-step multi-task learning algorithm to select the most discriminative features and samples in each submatrix. Features and samples that are not selected in any of the submatrices are discarded, resulting in a shrunk version of the original large matrix. The missing feature values and unknown target outputs of the shrunk matrix is then completed simultaneously. Experimental results using the ADNI dataset indicate that our proposed framework achieves higher classification accuracy at a greater speed when compared with conventional imputation-based classification methods and also yields competitive performance when compared with the state-of-the-art methods., (Copyright © 2014 Elsevier Inc. All rights reserved.)