Biology subjects

Augustinack, J. C.

Publications and source records attributed to Augustinack, J. C..

9 recordsLinked to original sources

bioRxiv2026

A human subcortical connectome at 400 μm resolution

The fiber pathways of the human subcortex are of particular importance in clinical neuroscience, as they are targeted by neuromodulation therapies, such as deep brain stimulation (DBS) and lesion approaches, in various motor and psychiatric disorders. However, the complexity, size, and position of these pathways make them challenging to image non-invasively with diffusion MRI (dMRI). As a result, recent efforts in atlasing these pathways to guide neuromodulation have resorted to using synthetic data. Here we present the first extensive reconstruction of fiber pathways of the human subcortex with ultra-high-resolution dMRI. We leverage a unique, ex vivo dMRI dataset acquired by the BRAIN CONNECTS center for Large-scale Imaging of Neural Circuits (LINC) on the first-of-its-kind Connectome 2.0 scanner. Our contribution is two-fold. First, by showing the feasibility of reconstructing these pathways with non-invasive neuroimaging at the single subject level, we set the stage for future research into reconstructing them in vivo in individual patients. Second, we provide a high-definition atlas of basal-ganglia-thalamocortical circuits that is readily extensible via our publicly released data and annotations. As a first demonstration of its clinical validity, we align our atlas to "hotspots" from previous DBS studies and identify pathways associated with therapeutic or side effects.

neuroscience↗

bioRxiv2026

Multi-dimensional diffusion MRI at ultra-high gradient strength for mapping axonal architecture and microstructure in the primate brain

We present the most comprehensive sampling of the macaque and human brain with diffusion MRI to date. As part of the BRAIN CONNECTS center for Large-scale Imaging of Neural Circuits, we leverage ultra-high-gradient MRI systems, including the first-of-its-kind Connectome 2.0, for post-mortem acquisitions. Each sample is imaged for [~]250 hours at multiple spatial resolutions down to 0.25 mm isotropic for whole macaque brains and 0.4 mm isotropic for human hemispheres. Our optimized protocols allow us to sample both species across [~]50 diffusion shells varying in b-value, diffusion time, and echo time, reaching ultra-high b-values up to 64000 s/mm2 with high signal-to-noise ratio. We demonstrate that these multi-dimensional data resolve not only white matter connectional architecture but also cortical and subcortical cytoarchitectonic boundaries, at a level of detail previously inaccessible in whole-brain noninvasive imaging. As such, these data are an important resource for both technical development and basic and clinical neuroscience.

neuroscience↗

bioRxiv2025

Tentorium cerebelli notch severity in the human brain: protocol, distribution and histopathology validation

The dura forms an impression, the tentorial notch (TN), on the surface of the entorhinal cortex (EC). To characterize the potential injury to the EC, we evaluated the entorhinal surface in 55 postmortem samples. We developed a semi-quantitative protocol to rate the TN severity and evaluated the impact of the TN on the surrounding tissue. We rated the penumbral injury as: none, moderate or severe. We demonstrate that 96% of the samples showed a TN; specifically mild (33%), moderate (47%) and severe (16%). TN severity correlated positively with penumbra scores (Kendalls coefficient = 0.65, 95% CI [0.535, 0.735]). We found no association between TN severity levels and Braak and Braak stages (Fischers exact P value = .862). We established a robust protocol for assessing the tentorial notch, addressing a gap in understanding anatomical factors that may contribute to EC vulnerability in Alzheimers disease.

neuroscience↗

bioRxiv2024

Automatic Geometry-based Estimation of the Locus Coeruleus Region on T1-Weighted Magnetic Resonance Images

The locus coeruleus (LC) is a key brain structure implicated in cognitive function and neurodegenerative disease. Automatic segmentation of the LC is a crucial step in quantitative non-invasive analysis of the LC in large MRI cohorts. Most publicly available imaging databases for training automatic LC segmentation models take advantage of specialized contrast-enhancing (e.g., neuromelanin-sensitive) MRI. Segmentation models developed with such image contrasts, however, are not readily applicable to existing datasets with conventional MRI sequences. In this work, we evaluate the feasibility of using non-contrast neuroanatomical information to geometrically approximate the LC region from standard 3-Tesla T1-weighted images of 20 subjects from the Human Connectome Project (HCP). We employ this dataset to train and internally/externally evaluate two automatic localization methods, the Expected Label Value and the U-Net. We also test the hypothesis that using the phase image as input can improve the robustness of out-of-sample segmentation. We then apply our trained models to a larger subset of HCP, while exploratorily correlating LC imaging variables and structural connectivity with demographic and clinical data. This report contributes and provides an evaluation of two computational methods estimating neural structure.

neuroscience↗

bioRxiv2023

Quantitative imaging of three-dimensional fiber orientation in the human brain via two illumination angles using polarization-sensitive optical coherence tomography

The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) provide important tools to directly quantify fiber orientation at micrometer resolution. However, brain imaging based on the optic axis by PS-OCT so far has been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work, we present a novel method to obtain the 3D fiber orientation in full angular space with only two illumination angles. We measure the optic axis orientation and the apparent birefringence by PS-OCT from a normal and a 15 deg tilted illumination, and then apply a computational method yielding the 3D optic axis orientation and true birefringence. We verify that our method accurately recovers a large range of through-plane orientations from -85 deg to 85 deg with a high angular precision. We further present 3D fiber orientation maps of entire coronal sections of human cerebrum and brainstem with 10 m in-plane resolution, revealing unprecedented details of fiber configurations. We envision that further development of our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain and other complex fibrous tissues at microscopic level.

neuroscience↗

bioRxiv2023

Multi-Scale Label-free Human Brain Imaging with Integrated Serial Sectioning Polarization Sensitive Optical Coherence Tomography and Two-Photon Microscopy

The study of neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction of the human brain. The development of a multi-scale and volumetric human brain imaging technique that can measure intact brain structure would be a major technical advance. Here, we describe the development of integrated serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging, including scattering, birefringence and autofluorescence of human brain tissue. We demonstrate that high-throughput reconstruction of 4x4x2cm3 sample blocks and simple registration of PSOCT and 2PM images enable comprehensive analysis of myelin content, vascular structure, and cellular information. We show that 2 m in-plane resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical property maps on the same sample, revealing the sophisticated capillary networks and lipofuscin filled cell bodies across the cortical layers. Our method is applicable to the study of a variety of pathological processes, including demyelination, cell loss, and microvascular changes in neurodegenerative diseases such as Alzheimers disease (AD) and Chronic Traumatic Encephalopathy (CTE).

neuroscience↗

bioRxiv2023

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimers disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 {micro}m thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.

neuroscience↗

bioRxiv2021

Scalable mapping of myelin and neuron density in the human brain with micrometer resolution

Optical Coherence Tomography (OCT) is an emerging 3D imaging technique that allows quantification of intrinsic optical properties such as scattering coefficient and back-scattering coefficient, and has proved useful in distinguishing delicate microstructures in the human brain. The origins of scattering in brain tissues are contributed by the myelin content, neuron size and density primarily; however, no quantitative relationships between them have been reported, which hampers the use of OCT in fundamental studies of architectonic areas in the human brain and the pathological evaluations of diseases. To date, histology remains the golden standard, which is prone to errors and can only work on a small number of subjects. Here, we demonstrate a novel method that uses serial sectioning OCT to quantitatively measure myelin content and neuron density in the human brain. We found that the scattering coefficient possesses a strong linear relationship with the myelin content across different regions of the human brain, while the neuron density serves as a secondary contribution that only slightly modulates the overall tissue scattering.

neuroscience↗

bioRxiv2019

Probabilistic atlas of the lateral parabrachial nucleus, medial parabrachial nucleus, vestibular nuclei complex and medullary viscero-sensory-motor nuclei complex in living humans from 7 Tesla MRI

The lateral parabrachial nucleus, medial parabrachial nucleus, vestibular nuclei complex and medullary viscero-sensory-motor nuclei complex (the latter including among others the solitary nucleus, vagus nerve nucleus, and hypoglossal nucleus) are anatomically and functionally connected brainstem gray-matter structures that convey signals across multiple modalities between the brain and the spinal cord to regulate vital bodily functions. It is remarkably difficult to precisely extrapolate the location of these nuclei from ex vivo atlases to conventional 3 Tesla in vivo images; thus, a probabilistic brainstem atlas in stereotaxic neuroimaging space in living humans is needed. We delineated these nuclei using single-subject high contrast 1.1 mm isotropic resolution 7 Tesla MRI images. After precise coregistration of nuclei labels to stereotaxic space, we generated a probabilistic atlas of their anatomical locations. Finally, we validated the nuclei labels in the atlas by assessing their inter-rater agreement, consistency across subjects and volumes. We also performed a preliminary comparison of their location and microstructural properties to histologic sections of a postmortem human brainstem specimen. In future, the resulting probabilistic atlas of these brainstem nuclei in stereotaxic space may assist researchers and clinicians in evaluating autonomic, vestibular and viscero-sensory-motor nuclei structure, function and connectivity in living humans using conventional 3 Tesla MRI scanners.

neuroscience↗