Robust joint registration of multiple stains and MRI for multimodal 3D histology reconstruction: Application to the Allen human brain atlas

Joint registration of a stack of 2D histological sections to recover 3D structure ("3D histology reconstruction") finds application in areas such as atlas building and validation of in vivo imaging. Straightforward pairwise registration of neighbouring sections yields smooth reconstructions but has well-known problems such as "banana effect" (straightening of curved structures) and "z-shift" (drift). While these problems can be alleviated with an external, linearly aligned reference (e.g., Magnetic Resonance (MR) images), registration is often inaccurate due to contrast differences and the strong nonlinear distortion of the tissue, including artefacts such as folds and tears. In this paper, we present a probabilistic model of spatial deformation that yields reconstructions for multiple histological stains that that are jointly smooth, robust to outliers, and follow the reference shape. The model relies on a spanning tree of latent transforms connecting all the sections and slices of the reference volume, and assumes that the registration between any pair of images can be see as a noisy version of the composition of (possibly inverted) latent transforms connecting the two images. Bayesian inference is used to compute the most likely latent transforms given a set of pairwise registrations between image pairs within and across modalities. We consider two likelihood models: Gaussian (ℓ2 norm, which can be minimised in closed form) and Laplacian (ℓ1 norm, minimised with linear programming). Results on synthetic deformations on multiple MR modalities, show that our method can accurately and robustly register multiple contrasts even in the presence of outliers. The framework is used for accurate 3D reconstruction of two stains (Nissl and parvalbumin) from the Allen human brain atlas, showing its benefits on real data with severe distortions. Moreover, we also provide the registration of the reconstructed volume to MNI space, bridging the gaps between two of the most widely used atlases in histology and MRI. The 3D reconstructed volumes and atlas registration can be downloaded from https://openneuro.org/datasets/ds003590. The code is freely available at https://github.com/acasamitjana/3dhirest

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Automated hippocampal segmentation in 3D MRI using random undersampling with boosting algorithm

The automated identification of brain structure in Magnetic Resonance Imaging is very important both in neuroscience research and as a possible clinical diagnostic tool. In this study, a novel strategy for fully automated hippocampal segmentation in MRI is presented. It is based on a supervised algorithm, called RUSBoost, which combines data random undersampling with a boosting algorithm. RUSBoost is an algorithm specifically designed for imbalanced classification, suitable for large data sets because it uses random undersampling of the majority class. The RUSBoost performances were compared with those of ADABoost, Random Forest and the publicly available brain segmentation package, FreeSurfer. This study was conducted on a data set of 50 T1-weighted structural brain images. The RUSBoost-based segmentation tool achieved the best results with a Dice’s index of (Formula presented.) (Formula presented.) for the left (right) brain hemisphere. An independent data set of 50 T1-weighted structural brain scans was used for an independent validation of the fully trained strategies. Again the RUSBoost segmentations compared favorably with manual segmentations with the highest performances among the four tools. Moreover, the Pearson correlation coefficient between hippocampal volumes computed by manual and RUSBoost segmentations was 0.83 (0.82) for left (right) side, statistically significant, and higher than those computed by Adaboost, Random Forest and FreeSurfer. The proposed method may be suitable for accurate, robust and statistically significant segmentations of hippocampi

Interactive computation and visualization of structural connectomes in real-time

Structural networks contain high dimensional data that raise huge computational and visualization problems, especially when attempting to characterise them using graph theory. As a result, it can be non-intuitive to grasp the contribution of each edge within a graph, both at a local and global scale. Here, we introduce a new platform that enables tractography-based networks to be explored in a highly interactive real-time fashion. The framework allows one to interactively tune graph-related parameters on the fly, as opposed to conventional visualization softwares that rely on pre-computed connectivity matrices. From a neurosurgical perspective, the method also provides enhanced understanding regarding the potential removal of a specific node or transection of an edge from the network, allowing surgeons and clinicians to discern the value of each node

Image Registration and Predictive Modeling: Learning the Metric on the Space of Diffeomorphisms

We present a method for metric optimization in the Large Deformation Diffeomorphic Metric Mapping (LDDMM) framework, by treating the induced Riemannian metric on the space of diffeomorphisms as a kernel in a machine learning context. For simplicity, we choose the kernel Fischer Linear Discriminant Analysis (KLDA) as the framework. Optimizing the kernel parameters in an Expectation-Maximization framework, we define model fidelity via the hinge loss of the decision function. The resulting algorithm optimizes the parameters of the LDDMM norm-inducing differential operator as a solution to a group-wise registration and classification problem. In practice, this may lead to a biology-aware registration, focusing its attention on the predictive task at hand such as identifying the effects of disease. We first tested our algorithm on a synthetic dataset, showing that our parameter selection improves registration quality and classification accuracy. We then tested the algorithm on 3D subcortical shapes from the Schizophrenia cohort Schizconnect. Our Schizophrenia-Control predictive model showed significant improvement in ROC AUC compared to baseline parameters

Joint registration and synthesis using a probabilistic model for alignment of MRI and histological sections

Nonlinear registration of 2D histological sections with corresponding slices of MRI data is a critical step of 3D histology reconstruction. This task is difficult due to the large differences in image contrast and resolution, as well as the complex nonrigid distortions produced when sectioning the sample and mounting it on the glass slide. It has been shown in brain MRI registration that better spatial alignment across modalities can be obtained by synthesizing one modality from the other and then using intra-modality registration metrics, rather than by using mutual information (MI) as metric. However, such an approach typically requires a database of aligned images from the two modalities, which is very difficult to obtain for histology/MRI. Here, we overcome this limitation with a probabilistic method that simultaneously solves for registration and synthesis directly on the target images, without any training data. In our model, the MRI slice is assumed to be a contrast-warped, spatially deformed version of the histological section. We use approximate Bayesian inference to iteratively refine the probabilistic estimate of the synthesis and the registration, while accounting for each other's uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in the framework for increased performance. Experiments on a synthetic dataset show that, compared with MI, the proposed method makes it possible to use a much more flexible deformation model in the registration to improve its accuracy, without compromising robustness. Moreover, our framework also exploits information in manually placed landmarks more efficiently than MI, since landmarks inform both synthesis and registration - as opposed to registration alone. Finally, we show qualitative results on the public Allen atlas, in which the proposed method provides a clear improvement over MI based registration

Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples

Previous research has shown associations between brain structure and resting state high-frequency heart rate variability (HF-HRV). Age affects both brain structure and HF-HRV. Therefore we sought to examine the relationship between brain structure and HF-HRV as a function of age. Data from two independent studies were used for the present analysis. Study 1 included 19 older adults (10 male, age range 62-78 years) and 19 younger adults (12 male, age range 19-37). Study 2 included 23 older adults (13 males; age range 55-75) and 27 younger adults (19 males; age range 18-34). The rootmean- square of successive R-R-interval differences (RMSSD) from ECG recordings was used as timedomain measure of HF-HRV. MRI scans were performed on a 3.0-T Siemens Magnetom Trio scanner. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis suite, including 12 regions as regions-of-interests (ROI). Zero-order and partial correlations were used to assess the correlation of RMSSD with cortical thickness in selected ROIs. Lateral orbitofrontal cortex (OFC) cortical thickness was significantly associated with RMSSD. Further, both studies, in line with previous research, showed correlations between RMSSD and anterior cingulate cortex (ACC) cortical thickness. Meta-analysis on adjusted correlation coefficients from individual studies confirmed an association of RMSSD with the left rostral ACC and the left lateral OFC. Future longitudinal studies are necessary to trace individual trajectories in the association of HRV and brain structure across aging

Prevalence and 1-year incidence of frailty among women with and without HIV in the Women's Interagency HIV Study

A previous cross-sectional analysis of 2028 women in the Women’s Interagency HIV Study (WIHS), who were on average 39 years old, found a frailty prevalence of 17% and 10% in women with or at risk for HIV, respectively [1]. To our knowledge, the only two longitudinal studies of frailty among people with HIV were conducted in the Multicenter AIDS Cohort Study (MACS), which includes only men [2,3]. Data on the distribution of frailty components are limited, and have not been reported for HIV-seropositive people in the United State

A geometric network model of intrinsic grey-matter connectivity of the human brain

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuro- science is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections