Comprehensive shape analysis of the cortex in Huntington's disease.

The striatum has traditionally been the focus of Huntington's disease research due to the primary insult to this region and its central role in motor symptoms. Beyond the striatum, evidence of cortical alterations caused by Huntington's disease has surfaced. However, findings are not coherent between studies which have used cortical thickness for Huntington's disease since it is the well-established cortical metric of interest in other diseases. In this study, we propose a more comprehensive approach to cortical morphology in Huntington's disease using cortical thickness, sulcal depth, and local gyrification index. Our results show consistency with prior findings in cortical thickness, including its limitations. Our comparison between cortical thickness and local gyrification index underscores the complementary nature of these two measures-cortical thickness detects changes in the sensorimotor and posterior areas while local gyrification index identifies insular differences. Since local gyrification index and cortical thickness measures detect changes in different regions, the two used in tandem could provide a clinically relevant measure of disease progression. Our findings suggest that differences in insular regions may correspond to earlier neurodegeneration and may provide a complementary cortical measure for detection of subtle early cortical changes due to Huntington's disease.

Automated volumetric determination of high R2 * regions in substantia nigra: A feasibility study of quantifying substantia nigra atrophy in progressive supranuclear palsy.

The establishment of an unbiased protocol for the automated volumetric measurement of iron-rich regions in the substantia nigra (SN) is clinically important for diagnosing neurodegenerative diseases exhibiting midbrain atrophy, such as progressive supranuclear palsy (PSP). This study aimed to automatically quantify the volume and surface properties of the iron-rich 3D regions in the SN using the quantitative MRI-R2 * map. Three hundred and sixty-seven slices of R2 * map and susceptibility-weighted imaging (SWI) at 3-T MRI from healthy control (HC) individuals and Parkinson's disease (PD) patients were used to train customized U-net++ convolutional neural network based on expert-segmented masks. Age- and sex-matched participants were selected from HC, PD, and PSP groups to automate the volumetric determination of iron-rich areas in the SN. Dice similarity coefficient values between expert-segmented and detected masks from the proposed network were 0.91 ± 0.07 for R2 * maps and 0.89 ± 0.08 for SWI. Reductions in iron-rich SN volume from the R2 * map (SWI) were observed in PSP with area under the receiver operating characteristic curve values of 0.96 (0.89) and 0.98 (0.92) compared with HC and PD, respectively. The mean curvature of the PSP showed SN deformation along the side closer to the red nucleus. We demonstrated the automated volumetric measurement of iron-rich regions in the SN using deep learning can quantify the SN atrophy in PSP compared with PD and HC.

Cortical Morphology in Autism: Findings from a Cortical Shape-Adaptive Approach to Local Gyrification Indexing.

It has been challenging to elucidate the differences in brain structure that underlie behavioral features of autism. Prior studies have begun to identify patterns of changes in autism across multiple structural indices, including cortical thickness, local gyrification, and sulcal depth. However, common approaches to local gyrification indexing used in prior studies have been limited by low spatial resolution relative to functional brain topography. In this study, we analyze the aforementioned structural indices, utilizing a new method of local gyrification indexing that quantifies this index adaptively in relation to specific sulci/gyri, improving interpretation with respect to functional organization. Our sample included n = 115 autistic and n = 254 neurotypical participants aged 5-54, and we investigated structural patterns by group, age, and autism-related behaviors. Differing structural patterns by group emerged in many regions, with age moderating group differences particularly in frontal and limbic regions. There were also several regions, particularly in sensory areas, in which one or more of the structural indices of interest either positively or negatively covaried with autism-related behaviors. Given the advantages of this approach, future studies may benefit from its application in hypothesis-driven examinations of specific brain regions and/or longitudinal studies to assess brain development in autism.

Integrating the BIDS Neuroimaging Data Format and Workflow Optimization for Large-Scale Medical Image Analysis.

A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing.

Labeling lateral prefrontal sulci using spherical data augmentation and context-aware training.

The inference of cortical sulcal labels often focuses on deep (primary and secondary) sulcal regions, whereas shallow (tertiary) sulcal regions are largely overlooked in the literature due to the scarcity of manual/well-defined annotations and their large neuroanatomical variability. In this paper, we present an automated framework for regional labeling of both primary/secondary and tertiary sulci of the dorsal portion of lateral prefrontal cortex (LPFC) using spherical convolutional neural networks. We propose two core components that enhance the inference of sulcal labels to overcome such large neuroanatomical variability: (1) surface data augmentation and (2) context-aware training. (1) To take into account neuroanatomical variability, we synthesize training data from the proposed feature space that embeds intermediate deformation trajectories of spherical data in a rigid to non-rigid fashion, which bridges an augmentation gap in conventional rotation data augmentation. (2) Moreover, we design a two-stage training process to improve labeling accuracy of tertiary sulci by informing the biological associations in neuroanatomy: inference of primary/secondary sulci and then their spatial likelihood to guide the definition of tertiary sulci. In the experiments, we evaluate our method on 13 deep and shallow sulci of human LPFC in two independent data sets with different age ranges: pediatric (N=60) and adult (N=36) cohorts. We compare the proposed method with a conventional multi-atlas approach and spherical convolutional neural networks without/with rotation data augmentation. In both cohorts, the proposed data augmentation improves labeling accuracy of deep and shallow sulci over the baselines, and the proposed context-aware training offers further improvement in the labeling of shallow sulci over the proposed data augmentation. We share our tools with the field and discuss applications of our results for understanding neuroanatomical-functional organization of LPFC and the rest of cortex (https://github.com/ilwoolyu/SphericalLabeling).

Anatomical texture patterns identify cerebellar distinctions between essential tremor and Parkinson's disease.

Voxel-based morphometry is an established technique to study focal structural brain differences in neurologic disease. More recently, texture-based analysis methods have enabled a pattern-based assessment of group differences, at the patch level rather than at the voxel level, allowing a more sensitive localization of structural differences between patient populations. In this study, we propose a texture-based approach to identify structural differences between the cerebellum of patients with Parkinson's disease (n = 280) and essential tremor (n = 109). We analyzed anatomical differences of the cerebellum among patients using two features: T1-weighted MRI intensity, and a texture-based similarity feature. Our results show anatomical differences between groups that are localized to the inferior part of the cerebellar cortex. Both the T1-weighted intensity and texture showed differences in lobules VIII and IX, vermis VIII and IX, and middle peduncle, but the texture analysis revealed additional differences in the dentate nucleus, lobules VI and VII, vermis VI and VII. This comparison emphasizes how T1-weighted intensity and texture-based methods can provide a complementary anatomical structure analysis. While texture-based similarity shows high sensitivity for gray matter differences, T1-weighted intensity shows sensitivity for the detection of white matter differences.

Network localization of clinical, cognitive, and neuropsychiatric symptoms in Alzheimer's disease.

There is both clinical and neuroanatomical variability at the single-subject level in Alzheimer's disease, complicating our understanding of brain-behaviour relationships and making it challenging to develop neuroimaging biomarkers to track disease severity, progression, and response to treatment. Prior work has shown that both group-level atrophy in clinical dementia syndromes and complex neurological symptoms in patients with focal brain lesions localize to brain networks. Here, we use a new technique termed 'atrophy network mapping' to test the hypothesis that single-subject atrophy maps in patients with a clinical diagnosis of Alzheimer's disease will also localize to syndrome-specific and symptom-specific brain networks. First, we defined single-subject atrophy maps by comparing cortical thickness in each Alzheimer's disease patient versus a group of age-matched, cognitively normal subjects across two independent datasets (total Alzheimer's disease patients = 330). No more than 42% of Alzheimer's disease patients had atrophy at any given location across these datasets. Next, we determined the network of brain regions functionally connected to each Alzheimer's disease patient's location of atrophy using seed-based functional connectivity in a large (n = 1000) normative connectome. Despite the heterogeneity of atrophied regions at the single-subject level, we found that 100% of patients with a clinical diagnosis of Alzheimer's disease had atrophy functionally connected to the same brain regions in the mesial temporal lobe, precuneus cortex, and angular gyrus. Results were specific versus control subjects and replicated across two independent datasets. Finally, we used atrophy network mapping to define symptom-specific networks for impaired memory and delusions, finding that our results matched symptom networks derived from patients with focal brain lesions. Our study supports atrophy network mapping as a method to localize clinical, cognitive, and neuropsychiatric symptoms to brain networks, providing insight into brain-behaviour relationships in patients with dementia.

Towards Portable Large-Scale Image Processing with High-Performance Computing.

High-throughput, large-scale medical image computing demands tight integration of high-performance computing (HPC) infrastructure for data storage, job distribution, and image processing. The Vanderbilt University Institute for Imaging Science (VUIIS) Center for Computational Imaging (CCI) has constructed a large-scale image storage and processing infrastructure that is composed of (1) a large-scale image database using the eXtensible Neuroimaging Archive Toolkit (XNAT), (2) a content-aware job scheduling platform using the Distributed Automation for XNAT pipeline automation tool (DAX), and (3) a wide variety of encapsulated image processing pipelines called "spiders." The VUIIS CCI medical image data storage and processing infrastructure have housed and processed nearly half-million medical image volumes with Vanderbilt Advanced Computing Center for Research and Education (ACCRE), which is the HPC facility at the Vanderbilt University. The initial deployment was natively deployed (i.e., direct installations on a bare-metal server) within the ACCRE hardware and software environments, which lead to issues of portability and sustainability. First, it could be laborious to deploy the entire VUIIS CCI medical image data storage and processing infrastructure to another HPC center with varying hardware infrastructure, library availability, and software permission policies. Second, the spiders were not developed in an isolated manner, which has led to software dependency issues during system upgrades or remote software installation. To address such issues, herein, we describe recent innovations using containerization techniques with XNAT/DAX which are used to isolate the VUIIS CCI medical image data storage and processing infrastructure from the underlying hardware and software environments. The newly presented XNAT/DAX solution has the following new features: (1) multi-level portability from system level to the application level, (2) flexible and dynamic software development and expansion, and (3) scalable spider deployment compatible with HPC clusters and local workstations.

Development of cortical shape in the human brain from 6 to 24months of age via a novel measure of shape complexity.

The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the 'shape complexity index' (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of secondary and tertiary sulci. Current cortical shape measures, such as the gyrification index (GI) or intrinsic curvature measures, investigate the cortical surface at a different scale and are less well suited to capture these particular cortical surface changes. In our experiments, the proposed SCI demonstrates higher complexity in the gyral/sulcal wall regions, lower complexity in wider gyral ridges and lowest complexity in wider sulcal fundus regions. In early postnatal brain development, our experiments show that SCI reveals a pattern of increased cortical shape complexity with age, as well as sexual dimorphisms in the insula, middle cingulate, parieto-occipital sulcal and Broca's regions. Overall, sex differences were greatest at 6months of age and were reduced at 24months, with the difference pattern switching from higher complexity in males at 6months to higher complexity in females at 24months. This is the first study of longitudinal, cortical complexity maturation and sex differences, in the early postnatal period from 6 to 24months of age with fine scale, cortical shape measures. These results provide information that complement previous studies of gyrification index in early brain development.

Leveraging Input-Level Feature Deformation with Guided-Attention for Sulcal Labeling.

The identification of cortical sulci is key for understanding functional and structural development of the cortex. While large, consistent sulci (or primary/secondary sulci) receive significant attention in most studies, the exploration of smaller and more variable sulci (or putative tertiary sulci) remains relatively under-investigated. Despite its importance, automatic labeling of cortical sulci is challenging due to (1) the presence of substantial anatomical variability, (2) the relatively small size of the regions of interest (ROIs) compared to unlabeled regions, and (3) the scarcity of annotated labels. In this paper, we propose a novel end-to-end learning framework using a spherical convolutional neural network (CNN). Specifically, the proposed method learns to effectively warp geometric features in a direction that facilitates the labeling of sulci while mitigating the impact of anatomical variability. Moreover, we introduce a guided-attention mechanism that takes into account the extent of deformation induced by the learned warping. This extracts discriminative features that emphasize sulcal ROIs, while suppressing irrelevant information of unlabeled regions. In the experiments, we evaluate the proposed method on 8 sulci of the posterior medial cortex. Our method outperforms existing methods particularly in the putative tertiary sulci. The code is publicly available at https://github.com/Shape-Lab/DSPHARM-Net.

Hierarchical particle optimization for cortical shape correspondence in temporal lobe resection.

BACKGROUND: Anterior temporal lobe resection is an effective treatment for temporal lobe epilepsy. The post-surgical structural changes could influence the follow-up treatment. Capturing post-surgical changes necessitates a well-established cortical shape correspondence between pre- and post-surgical surfaces. Yet, most cortical surface registration methods are designed for normal neuroanatomy. Surgical changes can introduce wide ranging artifacts in correspondence, for which conventional surface registration methods may not work as intended. METHODS: In this paper, we propose a novel particle method for one-to-one dense shape correspondence between pre- and post-surgical surfaces with temporal lobe resection. The proposed method can handle partial structural abnormality involving non-rigid changes. Unlike existing particle methods using implicit particle adjacency, we consider explicit particle adjacency to establish a smooth correspondence. Moreover, we propose hierarchical optimization of particles rather than full optimization of all particles at once to avoid trappings of locally optimal particle update. RESULTS: We evaluate the proposed method on 25 pairs of T1-MRI with pre- and post-simulated resection on the anterior temporal lobe and 25 pairs of patients with actual resection. We show improved accuracy over several cortical regions in terms of ROI boundary Hausdorff distance with 4.29 mm and Dice similarity coefficients with average value 0.841, compared to existing surface registration methods on simulated data. In 25 patients with actual resection of the anterior temporal lobe, our method shows an improved shape correspondence in qualitative and quantitative evaluation on parcellation-off ratio with average value 0.061 and cortical thickness changes. We also show better smoothness of the correspondence without self-intersection, compared with point-wise matching methods which show various degrees of self-intersection. CONCLUSION: The proposed method establishes a promising one-to-one dense shape correspondence for temporal lobe resection. The resulting correspondence is smooth without self-intersection. The proposed hierarchical optimization strategy could accelerate optimization and improve the optimization accuracy. According to the results on the paired surfaces with temporal lobe resection, the proposed method outperforms the compared methods and is more reliable to capture cortical thickness changes.

Superficial white matter across development, young adulthood, and aging: volume, thickness, and relationship with cortical features.

Superficial white matter (SWM) represents a significantly understudied part of the human brain, despite comprising a large portion of brain volume and making up a majority of cortico-cortical white matter connections. Using multiple, high-quality datasets with large sample sizes (N = 2421, age range 5-100) in combination with methodological advances in tractography, we quantified features of SWM volume and thickness across the brain and across development, young adulthood, and aging. We had four primary aims: (1) characterize SWM thickness across brain regions (2) describe associations between SWM volume and age (3) describe associations between SWM thickness and age, and (4) quantify relationships between SWM thickness and cortical features. Our main findings are that (1) SWM thickness varies across the brain, with patterns robust across individuals and across the population at the region-level and vertex-level; (2) SWM volume shows unique volumetric trajectories with age that are distinct from gray matter and other white matter trajectories; (3) SWM thickness shows nonlinear cross-sectional changes across the lifespan that vary across regions; and (4) SWM thickness is associated with features of cortical thickness and curvature. For the first time, we show that SWM volume follows a similar trend as overall white matter volume, peaking at a similar time in adolescence, leveling off throughout adulthood, and decreasing with age thereafter. Notably, the relative fraction of total brain volume of SWM continuously increases with age, and consequently takes up a larger proportion of total white matter volume, unlike the other tissue types that decrease with respect to total brain volume. This study represents the first characterization of SWM features across the large portion of the lifespan and provides the background for characterizing normal aging and insight into the mechanisms associated with SWM development and decline.

SPHARM-Net: Spherical Harmonics-Based Convolution for Cortical Parcellation.

We present a spherical harmonics-based convolutional neural network (CNN) for cortical parcellation, which we call SPHARM-Net. Recent advances in CNNs offer cortical parcellation on a fine-grained triangle mesh of the cortex. Yet, most CNNs designed for cortical parcellation employ spatial convolution that depends on extensive data augmentation and allows only predefined neighborhoods of specific spherical tessellation. On the other hand, a rotation-equivariant convolutional filter avoids data augmentation, and rotational equivariance can be achieved in spectral convolution independent of a neighborhood definition. Nevertheless, the limited resources of a modern machine enable only a finite set of spectral components that might lose geometric details. In this paper, we propose (1) a constrained spherical convolutional filter that supports an infinite set of spectral components and (2) an end-to-end framework without data augmentation. The proposed filter encodes all the spectral components without the full expansion of spherical harmonics. We show that rotational equivariance drastically reduces the training time while achieving accurate cortical parcellation. Furthermore, the proposed convolution is fully composed of matrix transformations, which offers efficient and fast spectral processing. In the experiments, we validate SPHARM-Net on two public datasets with manual labels: Mindboggle-101 (N=101) and NAMIC (N=39). The experimental results show that the proposed method outperforms the state-of-the-art methods on both datasets even with fewer learnable parameters without rigid alignment and data augmentation. Our code is publicly available at https://github.com/Shape-Lab/SPHARM-Net.

Generalizing deep learning brain segmentation for skull removal and intracranial measurements.

Total intracranial volume (TICV) and posterior fossa volume (PFV) are essential covariates for brain volumetric analyses with structural magnetic resonance imaging (MRI). Detailed whole brain segmentation provides a non-invasive way to measure brain regions. Furthermore, increasing neuroimaging data are distributed in a skull-stripped manner for privacy protection. Therefore, generalizing deep learning brain segmentation for skull removal and intracranial measurements is an appealing task. However, data availability is challenging due to a limited set of manually traced atlases with whole brain and TICV/PFV labels. In this paper, we employ U-Net tiles to achieve automatic TICV estimation and whole brain segmentation simultaneously on brains w/and w/o the skull. To overcome the scarcity of manually traced whole brain volumes, a transfer learning method is introduced to estimate additional TICV and PFV labels during whole brain segmentation in T1-weighted MRI. Specifically, U-Net tiles are first pre-trained using large-scale BrainCOLOR atlases without TICV and PFV labels, which are created by multi-atlas segmentation. Then the pre-trained models are refined by training the additional TICV and PFV labels using limited BrainCOLOR atlases. We also extend our method to handle skull-stripped brain MR images. From the results, our method provides promising whole brain segmentation and volume estimation results for both brains w/and w/o skull in terms of mean Dice similarity coefficients and mean surface distance and absolute volume similarity. This method has been made available in open source (https://github.com/MASILab/SLANTbrainSeg_skullstripped).

Incomplete Hippocampal Inversion: A Neurodevelopmental Mechanism for Hippocampal Shape Deformation in Schizophrenia.

BACKGROUND: Shape analyses of patients with schizophrenia have revealed bilateral deformations of the anterolateral hippocampus, primarily localized to the CA1 subfield. Incomplete hippocampal inversion (IHI), an anatomical variant of the human hippocampus resulting from an arrest during neurodevelopment, is more prevalent and severe in patients with schizophrenia. We hypothesized that IHI would affect the shape of the hippocampus and contribute to hippocampal shape differences in schizophrenia. METHODS: We studied 199 patients with schizophrenia and 161 healthy control participants with structural magnetic resonance imaging to measure the prevalence and severity of IHI. High-fidelity hippocampal surface reconstructions were generated with the SPHARM-PDM toolkit. We used general linear models in SurfStat to test for group shape differences, the impact of IHI on hippocampal shape variation, and whether IHI contributes to hippocampal shape abnormalities in schizophrenia. RESULTS: Not including IHI as a main effect in our between-group comparison replicated well-established hippocampal shape differences in patients with schizophrenia localized to the CA1 subfield in the anterolateral hippocampus. Shape differences were also observed near the uncus and hippocampal tail. IHI was associated with outward displacements of the dorsal and ventral surfaces of the hippocampus and inward displacements of the medial and lateral surfaces. Including IHI as a main effect in our between-group comparison eliminated the bilateral shape differences in the CA1 subfield. Shape differences in the uncus persisted after including IHI. CONCLUSIONS: IHI impacts hippocampal shape. Our results suggest IHI as a neurodevelopmental mechanism for the well-known shape differences, particularly in the CA1 subfield, in schizophrenia.

Uncovering a tripartite landmark in posterior cingulate cortex.

Understanding brain structure-function relationships, and their development and evolution, is central to neuroscience research. Here, we show that morphological differences in posterior cingulate cortex (PCC), a hub of functional brain networks, predict individual differences in macroanatomical, microstructural, and functional features of PCC. Manually labeling 4511 sulci in 572 hemispheres, we found a shallow cortical indentation (termed the inframarginal sulcus; ifrms) within PCC that is absent from neuroanatomical atlases yet colocalized with a focal, functional region of the lateral frontoparietal network implicated in cognitive control. This structural-functional coupling generalized to meta-analyses consisting of hundreds of studies and thousands of participants. Additional morphological analyses showed that unique properties of the ifrms differ across the life span and between hominoid species. These findings support a classic theory that shallow, tertiary sulci serve as landmarks in association cortices. They also beg the question: How many other cortical indentations have we missed?

Ultra-high-resolution Mapping of Cortical Layers 3T-Guided 7T MRI.

7T MRI provides unprecedented resolution for examining human brain anatomy in vivo. For example, 7T MRI enables deep thickness measurement of laminar subdivisions in the right fusiform area. Existing laminar thickness measurement on 7T is labor intensive, and error prone since the visual inspection of the image is typically along one of the three orthogonal planes (axial, coronal, or sagittal view). To overcome this, we propose a new analytics tool that allows flexible quantification of cortical thickness on a 2D plane that is orthogonal to the cortical surface (beyond axial, coronal, and sagittal views) based on the 3D computational surface reconstruction. The proposed method further distinguishes high quality 2D planes and the low-quality ones by automatically inspecting the angles between the surface normals and slice direction. In our approach, we acquired a pair of 3T and 7T scans (same subject). We extracted the brain surfaces from the 3T scan using MaCRUISE and projected the surface to the 7T scan's space. After computing the angles between the surface normals and axial direction vector, we found that 18.58% of surface points were angled at more than 80° with the axial direction vector and had 2D axial planes with visually distinguishable cortical layers. 15.12% of the surface points with normal vectors angled at 30° or lesser with the axial direction, had poor 2D axial slices for visual inspection of the cortical layers. This effort promises to dramatically extend the area of cortex that can be quantified with ultra-high resolution in-plane imaging methods.

Establishing Surface Correspondence for Post-surgical Cortical Thickness Changes in Temporal Lobe Epilepsy.

In pre- and post-surgical surface shape analysis, establishing shape correspondence is necessary to investigate the postoperative surface changes. However, structural absence after the operation accompanies focal non-rigid changes, which leads to challenges in existing surface registration methods. In this paper, we present a fully automatic particle-based method to establish surface correspondence that can handle partial structural abnormality in the temporal lobe resection. Our method optimizes the coordinates of points which are modeled as particles on surfaces in a hierarchical way to reduce a chance of being trapped in a local minimum during the optimization. In the experiments, we evaluate the effectiveness of our method in comparison with conventional spherical registration (FreeSurfer) on two scenarios: cortical thickness changes in healthy controls within a short scan-rescan time window and patients with temporal lobe resection. The post-surgical scan is acquired at least 1 year after the presurgical scan. In region of interest-wise (ROI-wise) analysis, no changes on cortical thickness are found in both methods on the healthy control group. In patients, since there is no ground truth available, we instead investigated the disagreement between our method and FreeSurfer. We see poorly matched ROIs and large cortical thickness changes using FreeSurfer. On the contrary, our method shows well-matched ROIs and subtle cortical thickness changes. This suggests that the proposed method can establish a stable shape correspondence, which is not fully captured in a conventional spherical registration.

Random Multi-Channel Image Synthesis for Multiplexed Immunofluorescence Imaging.

Multiplex immunofluorescence (MxIF) is an emerging imaging technique that produces the high sensitivity and specificity of single-cell mapping. With a tenet of "seeing is believing", MxIF enables iterative staining and imaging extensive antibodies, which provides comprehensive biomarkers to segment and group different cells on a single tissue section. However, considerable depletion of the scarce tissue is inevitable from extensive rounds of staining and bleaching ("missing tissue"). Moreover, the immunofluorescence (IF) imaging can globally fail for particular rounds ("missing stain"). In this work, we focus on the "missing stain" issue. It would be appealing to develop digital image synthesis approaches to restore missing stain images without losing more tissue physically. Herein, we aim to develop image synthesis approaches for eleven MxIF structural molecular markers (i.e., epithelial and stromal) on real samples. We propose a novel multi-channel high-resolution image synthesis approach, called pixN2N-HD, to tackle possible missing stain scenarios via a high-resolution generative adversarial network (GAN). Our contribution is three-fold: (1) a single deep network framework is proposed to tackle missing stain in MxIF; (2) the proposed "N-to-N" strategy reduces theoretical four years of computational time to 20 hours when covering all possible missing stains scenarios, with up to five missing stains (e.g., "(N-1)-to-1", "(N-2)-to-2"); and (3) this work is the first comprehensive experimental study of investigating cross-stain synthesis in MxIF. Our results elucidate a promising direction of advancing MxIF imaging with deep image synthesis.

Validation of Group-wise Registration for Surface-based Functional MRI Analysis.

Resting-state functional MRI (rsfMRI) provides important information for studying and mapping the activities and functions of the brain. Conventionally, rsfMRIs are often registered to structural images in the Euclidean space without considering cortical surface geometry. Meanwhile, a surface-based representation offers a relaxed coordinate chart, but this still requires surface registration for group-wise data analysis. In this work, we investigate the performance of two existing surface registration methods in a surface-based rsfMRI analysis framework: FreeSurfer and Hierarchical Spherical Deformation (HSD). To minimize registration bias, we establish shape correspondence using both methods in a group-wise manner that estimates the unbiased average of a given cohort. To evaluate their performance, we focus on neuroanatomical alignment as well as the amount of distortion that can potentially bias surface tessellation for secondary level rsfMRI data analyses. In the pilot analysis, we examine a single timepoint of imaging data from 100 subjects out of an aging cohort. Overall, HSD establishes improved shape correspondence with reduced mean curvature deviation (10.94% less on average per subject, paired t-test: p <10-10) and reduced registration distortion (FreeSurfer: average 41.91% distortion per subject, HSD: 18.63%, paired t-test: p <10-10). Furthermore, HSD introduces less distortion than FreeSurfer in the areas identified in the individual components that were extracted by surface-based independent component analysis (ICA) after spatial smoothing and time series normalization. Consequently, we show that FreeSurfer capture individual components with globally similar but locally different patterns in ICA in visual inspection.