Diffusion MRI of the Hippocampus.

The hippocampus is a brain structure that plays key roles in a variety of cognitive processes. Critically, a wide range of neurological disorders are associated with degeneration of the hippocampal microstructure, defined as neurons, dendrites, glial cells, and more. Thus, the hippocampus is a key target for methods that are sensitive to these microscale properties. Diffusion MRI is one such method, which can noninvasively probe neural architecture. Here we review the extensive use of diffusion MRI to capture hippocampal microstructure in both health and disease. The results of these studies indicate that (1) diffusion tensor imaging is sensitive but not specific to the hippocampal microstructure; (2) biophysical modeling of diffusion MRI signals is a promising avenue to capture more specific aspects of the hippocampal microstructure; (3) use of ultra-short diffusion times have shown unique laminar-specific microstructure and response to hippocampal injury; (4) dispersion of microstructure is likely abundant in the hippocampus; and (5) the angular richness of the diffusion MRI signal can be leveraged to improve delineation of the internal hippocampal circuitry. Overall, extant findings suggest that diffusion MRI offers a promising avenue for characterizing hippocampal microstructure.

Mapping the macrostructure and microstructure of the in vivo human hippocampus using diffusion MRI.

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current magnetic resonance based neuroimaging techniques. In this work, we used diffusion magnetic resonance imaging (dMRI) and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the neurite orientation dispersion and density imaging (NODDI) model optimized for grey matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the cornu ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibres, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitectonic differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures were separable across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fibre pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo dMRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Three-dimensional cranial ultrasound and functional near-infrared spectroscopy for bedside monitoring of intraventricular hemorrhage in preterm neonates.

Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopment in preterm infants. Current management relies on 2-dimensional cranial ultrasound (2D cUS) ventricular measurements. Reliable biomarkers are needed to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and subsequent neurodevelopment. In a prospective cohort study, we incorporated 3-dimensional (3D) cUS and functional near-infrared spectroscopy (fNIRS) to monitor neonates with GMH-IVH. Preterm neonates (≤ 32 weeks' gestation) were enrolled following a GMH-IVH diagnosis. Neonates underwent sequential measurements: 3D cUS images were manually segmented using in-house software, and the ventricle volumes (VV) were extracted. Multichannel fNIRS data were acquired using a high-density system, and spontaneous functional connectivity (sFC) was calculated. Of the 30 neonates enrolled in the study, 19 (63.3%) had grade I-II and 11 (36.7%) grade III-IV GMH-IVH; of these, 7 neonates (23%) underwent surgical interventions to divert cerebrospinal fluid (CSF). In infants with severe GMH-IVH, larger VV were significantly associated with decreased |sFC|. Our findings of increased VV and reduced sFC suggest that regional disruptions of ventricular size may impact the development of the underlying white matter. Hence, 3D cUS and fNIRS are promising bedside tools for monitoring the progression of GMH-IVH in preterm neonates.

Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold.

Like neocortical structures, the archicortical hippocampus differs in its folding patterns across individuals. Here, we present an automated and robust BIDS-App, HippUnfold, for defining and indexing individual-specific hippocampal folding in MRI, analogous to popular tools used in neocortical reconstruction. Such tailoring is critical for inter-individual alignment, with topology serving as the basis for homology. This topological framework enables qualitatively new analyses of morphological and laminar structure in the hippocampus or its subfields. It is critical for refining current neuroimaging analyses at a meso- as well as micro-scale. HippUnfold uses state-of-the-art deep learning combined with previously developed topological constraints to generate uniquely folded surfaces to fit a given subject's hippocampal conformation. It is designed to work with commonly employed sub-millimetric MRI acquisitions, with possible extension to microscopic resolution. In this paper, we describe the power of HippUnfold in feature extraction, and highlight its unique value compared to several extant hippocampal subfield analysis methods.