Atlas construction generally includes first an image registration step to normalize all images into a common space and then an atlas building step to fuse the information from all the aligned images. Although numerous atlas construction studies have been performed to improve the accuracy of the image registration step, unweighted or simply weighted average is often used in the atlas building step. In this article, we propose a novel patch-based sparse representation method for atlas construction after all images have been registered into the common space. By taking advantage of local sparse representation, more anatomical details can be recovered in the built atlas. To make the anatomical structures spatially smooth in the atlas, the anatomical feature constraints on group structure of representations and also the overlapping of neighboring patches are imposed to ensure the anatomical consistency between neighboring patches. The proposed method has been applied to 73 neonatal MR images with poor spatial resolution and low tissue contrast, for constructing a neonatal brain atlas with sharp anatomical details. Experimental results demonstrate that the proposed method can significantly enhance the quality of the constructed atlas by discovering more anatomical details especially in the highly convoluted cortical regions. The resulting atlas demonstrates superior performance of our atlas when applied to spatially normalizing three different neonatal datasets, compared with other start-of-the-art neonatal brain atlases.

Hippocampal atrophy rate-measured using automated techniques applied to structural MRI scans-is considered a sensitive marker of disease progression in Alzheimer's disease, frequently used as an outcome measure in clinical trials. Using publicly accessible data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined 1-year hippocampal atrophy rates generated by each of five automated or semiautomated hippocampal segmentation algorithms in patients with Alzheimer's disease, subjects with mild cognitive impairment, or elderly controls. We analyzed MRI data from 398 and 62 subjects available at baseline and at 1 year at MRI field strengths of 1.5 T and 3 T, respectively. We observed a high rate of hippocampal segmentation failures across all algorithms and diagnostic categories, with only 50.8% of subjects at 1.5 T and 58.1% of subjects at 3 T passing stringent segmentation quality control. We also found that all algorithms identified several subjects (between 2.94% and 48.68%) across all diagnostic categories showing increases in hippocampal volume over 1 year. For any given algorithm, hippocampal "growth" could not entirely be explained by excluding patients with flawed hippocampal segmentations, scan-rescan variability, or MRI field strength. Furthermore, different algorithms did not uniformly identify the same subjects as hippocampal "growers," and showed very poor concordance in estimates of magnitude of hippocampal volume change over time (intraclass correlation coefficient 0.319 at 1.5 T and 0.149 at 3 T). This precluded a meaningful analysis of whether hippocampal "growth" represents a true biological phenomenon. Taken together, our findings suggest that longitudinal hippocampal volume change should be interpreted with considerable caution as a biomarker. Hum Brain Mapp 38:2875-2896, 2017. © 2017 Wiley Periodicals, Inc.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1-weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.

Progressive brain atrophy is a key neuropathological hallmark of Alzheimer's disease (AD) dementia. However, atrophy patterns along the progression of AD dementia are diffuse and variable and are often missed by univariate methods. Consequently, identifying the major regional atrophy patterns underlying AD dementia progression is challenging. In the current study, we propose a method that evaluates the degree to which specific regional atrophy patterns are predictive of AD dementia progression, while holding all other atrophy changes constant using a total sample of 334 subjects. We first trained a dense convolutional neural network model to differentiate individuals with mild cognitive impairment (MCI) who progress to AD dementia versus those with a stable MCI diagnosis. Then, we retested the model multiple times, each time occluding different regions of interest (ROIs) from the model's testing set's input. We also validated this approach by occluding ROIs based on Braak's staging scheme. We found that the hippocampus, fusiform, and inferior temporal gyri were the strongest predictors of AD dementia progression, in agreement with established staging models. We also found that occlusion of limbic ROIs defined according to Braak stage III had the largest impact on the performance of the model. Our predictive model reveals the major regional patterns of atrophy predictive of AD dementia progression. These results highlight the potential for early diagnosis and stratification of individuals with prodromal AD dementia based on patterns of cortical atrophy, prior to interventional clinical trials.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia among older adults. Mild cognitive impairment (MCI) is considered a transitional phase between healthy cognitive aging and dementia. Progressive brain volume reduction/atrophy, particularly of the hippocampus, is associated with the transition from normal to MCI, and then to AD. We aimed to develop methods to characterize the shape of hippocampus and explore its potential as an imaging marker to monitor clinical AD progression. We implemented a 3D Zernike transformation to characterize the shape changes of hippocampus in 428 older subjects with high-quality T1 -weighted volumetric brain scans from the Alzheimer's Disease Neuroimaging Initiative data set (151 normal, 258 MCI, and 19 AD). Over 2 years, 15 cognitively normal subjects converted to MCI, and 42 subjects with MCI converted to AD. We found a significant correlation between hippocampal volume changes and Zernike shape metrics. Before a clinical diagnosis of AD, the shapes of the left and right hippocampi changed slowly. After AD diagnosis, both volume and shape changed rapidly but were uncorrelated to each other. During the transition from a clinical diagnosis of MCI to AD, the shape of the left and right hippocampi changed in a correlated manner but became uncorrelated after AD diagnosis. Finally, the pace of hippocampus shape change was associated with its shape and the subject's age and disease condition. In conclusion, the hippocampus shape features characterized with 3D Zernike transformation, in complement to volume measures, may serve as a novel imaging marker to monitor clinical AD progression.

Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2  ∈ [.924, .940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.

Multimodality based methods have shown great advantages in classification of Alzheimer's disease (AD) and its prodromal stage, that is, mild cognitive impairment (MCI). Recently, multitask feature selection methods are typically used for joint selection of common features across multiple modalities. However, one disadvantage of existing multimodality based methods is that they ignore the useful data distribution information in each modality, which is essential for subsequent classification. Accordingly, in this paper we propose a manifold regularized multitask feature learning method to preserve both the intrinsic relatedness among multiple modalities of data and the data distribution information in each modality. Specifically, we denote the feature learning on each modality as a single task, and use group-sparsity regularizer to capture the intrinsic relatedness among multiple tasks (i.e., modalities) and jointly select the common features from multiple tasks. Furthermore, we introduce a new manifold-based Laplacian regularizer to preserve the data distribution information from each task. Finally, we use the multikernel support vector machine method to fuse multimodality data for eventual classification. Conversely, we also extend our method to the semisupervised setting, where only partial data are labeled. We evaluate our method using the baseline magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) data of subjects from AD neuroimaging initiative database. The experimental results demonstrate that our proposed method can not only achieve improved classification performance, but also help to discover the disease-related brain regions useful for disease diagnosis.

The ε4 allele of the gene Apolipoprotein E is the major genetic risk factor for Alzheimer's Disease. APOE ε4 has been associated with changes in brain structure in cognitively impaired and unimpaired subjects, including atrophy of the hippocampus, which is one of the brain structures that is early affected by AD. In this work we analyzed the impact of APOE ε4 gene dose and its association with age, on hippocampal shape assessed with multivariate surface analysis, in a ε4-enriched cohort of n = 479 cognitively healthy individuals. Furthermore, we sought to replicate our findings on an independent dataset of n = 969 individuals covering the entire AD spectrum. We segmented the hippocampus of the subjects with a multi-atlas-based approach, obtaining high-dimensional meshes that can be analyzed in a multivariate way. We analyzed the effects of different factors including APOE, sex, and age (in both cohorts) as well as clinical diagnosis on the local 3D hippocampal surface changes. We found specific regions on the hippocampal surface where the effect is modulated by significant APOE ε4 linear and quadratic interactions with age. We compared between APOE and diagnosis effects from both cohorts, finding similarities between APOE ε4 and AD effects on specific regions, and suggesting that age may modulate the effect of APOE ε4 and AD in a similar way.

Recent work within neuroimaging consortia have aimed to identify reproducible, and often subtle, brain signatures of psychiatric or neurological conditions. To allow for high-powered brain imaging analyses, it is often necessary to pool MR images that were acquired with different protocols across multiple scanners. Current retrospective harmonization techniques have shown promise in removing site-related image variation. However, most statistical approaches may over-correct for technical, scanning-related, variation as they cannot distinguish between confounded image-acquisition based variability and site-related population variability. Such statistical methods often require that datasets contain subjects or patient groups with similar clinical or demographic information to isolate the acquisition-based variability. To overcome this limitation, we consider site-related magnetic resonance (MR) imaging harmonization as a style transfer problem rather than a domain transfer problem. Using a fully unsupervised deep-learning framework based on a generative adversarial network (GAN), we show that MR images can be harmonized by inserting the style information encoded from a single reference image, without knowing their site/scanner labels a priori. We trained our model using data from five large-scale multisite datasets with varied demographics. Results demonstrated that our style-encoding model can harmonize MR images, and match intensity profiles, without relying on traveling subjects. This model also avoids the need to control for clinical, diagnostic, or demographic information. We highlight the effectiveness of our method for clinical research by comparing extracted cortical and subcortical features, brain-age estimates, and case-control effect sizes before and after the harmonization. We showed that our harmonization removed the site-related variances, while preserving the anatomical information and clinical meaningful patterns. We further demonstrated that with a diverse training set, our method successfully harmonized MR images collected from unseen scanners and protocols, suggesting a promising tool for ongoing collaborative studies. Source code is released in USC-IGC/style_transfer_harmonization (github.com).

Mild cognitive impairment (MCI) has received increasing attention not only because of its potential as a precursor for Alzheimer's disease but also as a predictor of conversion to other neurodegenerative diseases. Although MCI has been defined clinically, accurate and efficient diagnosis is still challenging. Although neuroimaging techniques hold promise, compared to commonly used biomarkers including amyloid plaques, tau protein levels and brain tissue atrophy, neuroimaging biomarkers are less well validated. In this article, we propose a connectomes-scale assessment of structural and functional connectivity in MCI via two independent multimodal DTI/fMRI datasets. We first used DTI-derived structural profiles to explore and tailor the most common and consistent landmarks, then applied them in a whole-brain functional connectivity analysis. The next step fused the results from two independent datasets together and resulted in a set of functional connectomes with the most differentiation power, hence named as "connectome signatures." Our results indicate that these "connectome signatures" have significantly high MCI-vs-controls classification accuracy, at more than 95%. Interestingly, through functional meta-analysis, we found that the majority of "connectome signatures" are mainly derived from the interactions among different functional networks, for example, cognition-perception and cognition-action domains, rather than from within a single network. Our work provides support for using functional "connectome signatures" as neuroimaging biomarkers of MCI.

Multiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Measures included: demographics, APOE4 genotype, CSF (amyloid-β42, total tau, phosphorylated tau), [18F ]florbetapir, hippocampal volume and brain-age. We examined: (a) the independent value of each biomarker; and (b) whether modelling nonlinear interactions between biomarkers improved predictions. Each measured added complementary information when predicting conversion to Alzheimer's. A linear model classifying stable from progressive MCI explained over half the variance (R2 = 0.51, p < .001); the strongest independently contributing biomarker was hippocampal volume (R2 = 0.13). When comparing sensitivity of different models to progressive MCI (independent biomarker models, additive models, nonlinear interaction models), we observed a significant improvement (p < .001) for various two-way interaction models. The best performing model included an interaction between amyloid-β-PET and P-tau, while accounting for hippocampal volume (sensitivity = 0.77, AUC = 0.826). Closely related biomarkers contributed uniquely to predict conversion to Alzheimer's. Nonlinear biomarker interactions were also implicated, and results showed that although for some patients adding additional biomarkers may add little value (i.e., when hippocampal volume is high), for others (i.e., with low hippocampal volume) further invasive and expensive examination may be warranted. Our framework enables visualisation of these interactions, in individual patient biomarker 'space', providing information for personalised or stratified healthcare or clinical trial design.

Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state-of-the-art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I-II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.

Alzheimer's disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with a rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HCs). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the Apolipoprotein E4 allele, from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Gray-matter volume was measured using voxel-wise morphometry and group differences in terms of SDB, cognitive status, and their interaction were assessed. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants' age from their structural images. Cognitive decline and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. Brains age was well predicted from the morphological data in HCs and, as expected, elevated in MCI and particularly in AD subjects. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status, nor in SDB-by-cognitive status interaction. Moreover, we found no difference in estimated chronological age gap related to SDB, or by-cognitive status interaction. Contrary to our hypothesis, we were not able to find a general or a diagnostic-dependent association of SDB with either gray-matter volumetric or brain aging.

This study is an observational study that takes the existing longitudinal data from Alzheimer's disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s-MCI), 304 Alzheimer's Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c-MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s-MCI, and AD groups and corresponded to a greater decline of memory and attention in the s-MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s-MCI group. Interestingly, patients with c-MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c-MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.

Volumetric estimates of subcortical and cortical structures, extracted from T1-weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer gray matter (GM) structure volumes and its possible bias on functional relationships. T1-weighted images from 1,077 participants (4,321 timepoints) from the Alzheimer's Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2-weighted or Fluid-attenuated inversion recovery images. Mixed-effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overall WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. Participants with higher WMH volumes had higher overlaps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (p < .0001). When not corrected for WMHs, caudate volumes increased with age (p < .0001) and were not different between cognitively healthy individuals and age-matched probable Alzheimer's disease patients. After correcting for WMHs, caudate volumes decreased with age (p < .0001), and Alzheimer's disease patients had lower caudate volumes than cognitively healthy individuals (p < .01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (p < .0001). Presence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

This article assesses the feasibility of using shape information to detect and quantify the subcortical and ventricular structural changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate structural shape abnormalities in MCI and AD as compared with healthy controls (HC). Exploring the development to AD, we then divide the MCI participants into two subgroups based on longitudinal clinical information: (1) MCI patients who remained stable; (2) MCI patients who converted to AD over time. We focus on seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151 converted to AD over time, and 175 AD). The hippocampus and amygdala were further subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer exploration. For MCI and AD, prominent ventricular expansions were detected and we found that these patients had strongest hippocampal atrophy occurring at CA1 and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal ganglia structures was also detected in MCI and AD. Stronger atrophy in the amygdala and hippocampus, and greater expansion in ventricles was observed in MCI converters, relative to those MCI who remained stable. Furthermore, we performed principal component analysis on a linear shape space of each structure. A subsequent linear discriminant analysis on the principal component values of hippocampus, amygdala, and ventricle leads to correct classification of 88% HC subjects and 86% AD subjects.

18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) enables in-vivo capture of the topographic metabolism patterns in the brain. These images have shown great promise in revealing the altered metabolism patterns in Alzheimer's disease (AD). The AD pathology is progressive, and leads to structural and functional alterations that lie on a continuum. There is a need to quantify the altered metabolism patterns that exist on a continuum into a simple measure. This work proposes a 3D convolutional neural network with residual connections that generates a probability score useful for interpreting the FDG-PET images along the continuum of AD. This network is trained and tested on images of stable normal control and stable Dementia of the Alzheimer's type (sDAT) subjects, achieving an AUC of 0.976 via repeated fivefold cross-validation. An independent test set consisting of images in between the two extreme ends of the DAT spectrum is used to further test the generalization performance of the network. Classification performance of 0.811 AUC is achieved in the task of predicting conversion of mild cognitive impairment to DAT for conversion time of 0-3 years. The saliency and class activation maps, which highlight the regions of the brain that are most important to the classification task, implicate many known regions affected by DAT including the posterior cingulate cortex, precuneus, and hippocampus.

Cortical thickness mapping is a widely used method for the analysis of neuroanatomical differences between subject groups. We applied power analysis methods over a range of image processing parameters to derive a model that allows researchers to calculate the number of subjects required to ensure a well-powered cross-sectional cortical thickness study.

This article describes a novel approach to extract cortical morphological abnormality patterns from structural magnetic resonance imaging (MRI) data to improve the prediction accuracy of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). Conventional approaches extract cortical morphological information, such as regional mean cortical thickness and regional cortical volumes, independently at different regions of interest (ROIs) without considering the relationship between these regions. Our approach involves constructing a similarity map where every element in the map represents the correlation of regional mean cortical thickness between a pair of ROIs. We will demonstrate in this article that this correlative morphological information gives significant improvement in classification performance when compared with ROI-based morphological information. Classification performance is further improved by integrating the correlative information with ROI-based information via multi-kernel support vector machines. This integrated framework achieves an accuracy of 92.35% for AD classification with an area of 0.9744 under the receiver operating characteristic (ROC) curve, and an accuracy of 83.75% for MCI classification with an area of 0.9233. In differentiating MCI subjects who converted to AD within 36 months from non-converters, an accuracy of 75.05% with an area of 0.8426 under ROC curve was achieved, indicating excellent diagnostic power and generalizability. The current work provides an alternative approach to extraction of high-order cortical information from structural MRI data for prediction of neurodegenerative diseases such as AD.

Tissue segmentation of infant brain MRIs with risk of autism is critically important for characterizing early brain development and identifying biomarkers. However, it is challenging due to low tissue contrast caused by inherent ongoing myelination and maturation. In particular, at around 6 months of age, the voxel intensities in both gray matter and white matter are within similar ranges, thus leading to the lowest image contrast in the first postnatal year. Previous studies typically employed intensity images and tentatively estimated tissue probabilities to train a sequence of classifiers for tissue segmentation. However, the important prior knowledge of brain anatomy is largely ignored during the segmentation. Consequently, the segmentation accuracy is still limited and topological errors frequently exist, which will significantly degrade the performance of subsequent analyses. Although topological errors could be partially handled by retrospective topological correction methods, their results may still be anatomically incorrect. To address these challenges, in this article, we propose an anatomy-guided joint tissue segmentation and topological correction framework for isointense infant MRI. Particularly, we adopt a signed distance map with respect to the outer cortical surface as anatomical prior knowledge, and incorporate such prior information into the proposed framework to guide segmentation in ambiguous regions. Experimental results on the subjects acquired from National Database for Autism Research demonstrate the effectiveness to topological errors and also some levels of robustness to motion. Comparisons with the state-of-the-art methods further demonstrate the advantages of the proposed method in terms of both segmentation accuracy and topological correctness.