scholarly journals Diffusion MRI of the Unfolded Hippocampus

2020 ◽  
Author(s):  
Uzair Hussain ◽  
Jordan DeKraker ◽  
Nagalingam Rajakumar ◽  
Corey A. Baron ◽  
Ali R. Khan
Keyword(s):  
Neurological Disorders ◽  
Diffusion Mri ◽  
Ex Vivo ◽  
Thin Sheet ◽  
Ultra High Field ◽  
Hippocampal Subfields ◽  
Complicated Geometry ◽  
Mri Image ◽  
Anterior Posterior

AbstractThe hippocampus is implicated in numerous neurological disorders and the ability to detect subtle or focal hippocampal abnormalities earlier in disease progression could significantly improve the treatment of patients. Ex vivo studies with ultra-high field have revealed that diffusion MRI (dMRI) can reveal microstructural variations within the hippocampal subfields and lamina, and may also be sensitive to intra-hippocampal pathways. However, translation to lower resolution in vivo dMRI studies of the hippocampus is challenging due to its complicated geometry. One novel way to overcome some of these obstacles is by transforming the usual Cartesian coordinates in an MRI image to coordinates that are crafted to curve themselves according to the complicated geometry of the hippocampus. This procedure allows us to virtually unfold the hippocampus into a thin sheet. In this work, we introduce an algorithm to map diffusion MRI data to this sheet, allowing us to overcome the difficulties associated with the hippocampus’ complicated geometry. We demonstrate how our method can be readily integrated into existing implementations of traditional tractography methods and how it leads to enhancements in the resulting tracts. Further, our results on high quality in vivo dMRI acquisitions show that unfolding the hippocampus leads to a more anatomically plausible modelling of the connectivity of the hippocampus as probed by probabilistic tractography, revealing key elements of the polysynaptic pathway and anterior-posterior connectivity gradients.

scholarly journals Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Maged Goubran ◽  
Christoph Leuze ◽  
Brian Hsueh ◽  
Markus Aswendt ◽  
Li Ye ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Diffusion Mri ◽  
Multimodal Integration ◽  
Connectivity Analysis ◽  
Histological Changes ◽  
Cellular Effects ◽  
Multimodal Image Registration ◽  
Fiber Tracts ◽  
And Diffusion

Abstract3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.

scholarly journals Anatomical and microstructural determinants of hippocampal subfield functional connectome embedding

2018 ◽  
Vol 115 (40) ◽  
pp. 10154-10159 ◽  
Author(s):  
Reinder Vos de Wael ◽  
Sara Larivière ◽  
Benoît Caldairou ◽  
Seok-Jun Hong ◽  
Daniel S. Margulies ◽  
...  
Keyword(s):  
Resting State ◽  
State Of The Art ◽  
Model System ◽  
Hippocampal Subfields ◽  
Functional Connectome ◽  
Human Hippocampus ◽  
Complex Anatomy ◽  
Robust Evidence ◽  
Anterior Posterior

The hippocampus plays key roles in cognition and affect and serves as a model system for structure/function studies in animals. So far, its complex anatomy has challenged investigations targeting its substructural organization in humans. State-of-the-art MRI offers the resolution and versatility to identify hippocampal subfields, assess its microstructure, and study topographical principles of its connectivity in vivo. We developed an approach to unfold the human hippocampus and examine spatial variations of intrinsic functional connectivity in a large cohort of healthy adults. In addition to mapping common and unique connections across subfields, we identified two main axes of subregional connectivity transitions. An anterior/posterior gradient followed long-axis landmarks and metaanalytical findings from task-based functional MRI, while a medial/lateral gradient followed hippocampal infolding and correlated with proxies of cortical myelin. Findings were consistent in an independent sample and highly stable across resting-state scans. Our results provide robust evidence for long-axis specialization in the resting human hippocampus and suggest an intriguing interplay between connectivity and microstructure.

scholarly journals Quantitative modeling links in vivo microstructural and macrofunctional organization of human and macaque insular cortex, and predicts cognitive control abilities

2019 ◽  
Author(s):  
Vinod Menon ◽  
Gallardo Guillermo ◽  
Mark A. Pinsk ◽  
Van-Dang Nguyen ◽  
Jing-Rebecca Li ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Brain Structure ◽  
Neurological Disorders ◽  
Diffusion Mri ◽  
Large Scale ◽  
Insular Cortex ◽  
Neuronal Morphology ◽  
Anterior Cingulate ◽  
Quantitative Modeling

AbstractThe human insular cortex is a heterogenous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI (dMRI) data from 440 HCP participants revealed that human insula microstructure differs significantly across its functionally defined dorsal anterior, ventral anterior, and posterior insula subdivisions that serve distinct cognitive and affective functions. The microstructural organization of the insula was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchor the salience network, a system important for adaptive switching of cognitive control systems. Novel validation of the human insula findings came from quantitative dMRI modeling in macaques which revealed microstructural features consistent with known primate insula cytoarchitecture. Theoretical analysis and computer simulations, using realistic 3-dimensional models of neuronal morphology from postmortem tissue, demonstrated that dMRI signals reflect the cellular organization of cortical gray matter, and that these signals are sensitive to cell size and the presence of large neurons such as the von Economo neurons. Crucially, insular microstructural features were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.Statement of SignificanceThe human insular cortex is a heterogenous brain structure which plays an integrative role in identifying salient sensory, affective, and cognitive cues for guiding attention and behavior. It is also is one of the most widely activated brain regions in all of human neuroimaging research. Here we use novel quantitative tools with in vivo diffusion MRI in large group (N=440) of individuals to uncover several unique microstructural features of the human insula and its macrofunctional circuits. Crucially, microstructural properties of the insular cortex predicted human cognitive control abilities, in agreement with its crucial role in adaptive human behaviors. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular dysfunction, including autism, schizophrenia, and fronto-temporal dementia.

scholarly journals 3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe

2021 ◽  
Author(s):  
Paul A Yushkevich ◽  
Mónica Muñoz López ◽  
Maria Mercedes Iñiguez de Onzoño Martin ◽  
Ranjit Ittyerah ◽  
Sydney Lim ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Ex Vivo ◽  
Neurofibrillary Tangle ◽  
Imaging Biomarkers ◽  
Synaptic Loss ◽  
The Brain ◽  
Transentorhinal Region ◽  
Anterior Posterior

Abstract Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

scholarly journals Does powder averaging remove dispersion bias in diffusion MRI diameter estimates within real 3D axonal architectures?

2021 ◽  
Author(s):  
Mariam Andersson ◽  
Marco Pizzolato ◽  
Hans Martin Kjer ◽  
Katrine Forum Skodborg ◽  
Henrik Lundell ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Ex Vivo ◽  
Dynamic Properties ◽  
High Signal ◽  
Axon Diameter ◽  
Signal To Noise ◽  
B Values ◽  
Wide Range

Noninvasive estimation of axon diameter with diffusion MRI holds potential to investigate the dynamic properties of the brain network and pathology of neurodegenerative diseases. Recent methods use powder averaging to account for complex white matter architectures, such as fibre crossing regions, but these have not been validated for real axonal geometries. Here, we present 120-313 μm long segmented axons from X-ray nano-holotomography volumes of a splenium and crossing fibre region of a vervet monkey brain. We show that the axons in the complex crossing fibre region, which contains callosal, association, and corticospinal connections, are larger and exhibit a wider distribution than those of the splenium region. To accurately estimate the axon diameter in these regions, therefore, sensitivity to a wide range of diameters is required. We demonstrate how the q-value, b-value, signal-to-noise ratio and the assumed intra-axonal parallel diffusivity influence the range of measurable diameters with powder average approaches. Furthermore, we show how Gaussian distributed noise results in a wider range of measurable diameter at high b-values than with Rician distributed noise, even at high signal-to-noise ratios of 100. The number of gradient directions is also shown to impose a lower bound on measurable diameter. Our results indicate that axon diameter estimation can be performed with only few b-shells, and that additional shells do not improve the accuracy of the estimate. Through Monte Carlo simulations of diffusion, we show that powder averaging techniques succeed in providing accurate estimates of axon diameter across a range of sequence parameters and diffusion times, even in complex white matter architectures. At sufficiently low b-values, the acquisition becomes sensitive to axonal microdispersion and the intra-axonal parallel diffusivity shows time dependency at both in vivo and ex vivo intrinsic diffusivities.

scholarly journals Experimental Fusion of Contrast Enhanced High-Field Magnetic Resonance Imaging and High-Resolution Micro-Computed Tomography in Imaging the Mouse Inner Ear

2015 ◽  
Vol 9 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Allen Counter S ◽  
Peter Damberg ◽  
Sahar Nikkhou Aski ◽  
Kálmán Nagy ◽  
Cecilia Engmér Berglin ◽  
...  
Keyword(s):  
High Resolution ◽  
Inner Ear ◽  
High Field ◽  
Ex Vivo ◽  
Semicircular Canals ◽  
Vestibular Apparatus ◽  
Resonance Imaging ◽  
Micro Computed Tomography ◽  
Ultra High Field

Objective: Imaging cochlear, vestibular, and 8th cranial nerve abnormalities remains a challenge. In this study, the membranous and osseous labyrinths of the wild type mouse inner ear were examined using volumetric data from ultra high-field magnetic resonance imaging (MRI) with gadolinium contrast at 9.4 Tesla and high-resolution micro-computed tomography (µCT) to visualize the scalae and vestibular apparatus, and to establish imaging protocols and parameters for comparative analysis of the normal and mutant mouse inner ear. Methods: For in vivo MRI acquisition, animals were placed in a Milleped coil situated in the isocenter of a horizontal 9.4 T Varian magnet. For µCT examination, cone beam scans were performed ex vivo following MRI using the µCT component of a nanoScan PET/CT in vivo scanner. Results: The fusion of Gd enhanced high field MRI and high-resolution µCT scans revealed the dynamic membranous labyrinth of the perilymphatic fluid filled scala tympani and scala vestibule of the cochlea, and semicircular canals of the vestibular apparatus, within the µCT visualized contours of the contiguous osseous labyrinth. The ex vivo µCT segmentation revealed the surface contours and structural morphology of each cochlea turn and the semicircular canals in 3 planes. Conclusions: The fusion of ultra high-field MRI and high-resolution µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the complex morphological features of the normal mouse inner ear structures, which may offer a valuable approach for the investigation of cochlear and vestibular abnormalities that are associated with birth defects related to genetic inner ear disorders in humans.

scholarly journals Characterization of hippocampal subfields using ex vivo MRI and histology data: Lessons for in vivo segmentation

Hippocampus ◽  
2019 ◽  
Vol 30 (6) ◽  
pp. 545-564 ◽  
Author(s):  
Robin Flores ◽  
David Berron ◽  
Song‐Lin Ding ◽  
Ranjit Ittyerah ◽  
John B. Pluta ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Hippocampal Subfields

Chemical and biological methods for probing the structure and functions of polysialic acids

2018 ◽  
Vol 2 (3) ◽  
pp. 363-376 ◽  
Author(s):  
Surbhi Goswami ◽  
Shubham Parashar ◽  
Vandita Dwivedi ◽  
Asif Shajahan ◽  
Srinivasa-Gopalan Sampathkumar
Keyword(s):  
Brain Development ◽  
Neurological Disorders ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Peripheral Tissues ◽  
Hybrid Strategy ◽  
The Brain ◽  
Structure And Functions

Owing to its poly-anionic charge and large hydrodynamic volume, polysialic acid (polySia) attached to neural cell adhesion molecule regulates axon–axon and axon–substratum interactions and signalling, particularly, in the development of the central nervous system (CNS). Expression of polySia is spatiotemporally regulated by the action of two polysialyl transferases, namely ST8SiaII and ST8SiaIV. PolySia expression peaks during late embryonic and early post-natal period and maintained at a steady state in adulthood in neurogenic niche of the brain. Aberrant polySia expression is associated with neurological disorders and brain tumours. Investigations on the structure and functions, over the past four decades, have shed light on the physiology of polySia. This review focuses on the biological, biochemical, and chemical tools available for polySia engineering. Genetic knockouts, endo-neuraminidases that cleave polySia, antibodies, exogenous expression, and neuroblastoma cells have provided deep insights into the ability of polySia to guide migration of neuronal precursors in neonatal brain development, neuronal clustering, axonal pathway guidance, and axonal targeting. Advent of metabolic sialic acid engineering using ManNAc analogues has enabled reversible and dose-dependent modulation polySia in vitro and ex vivo. In vivo, ManNAc analogues readily engineer the sialoglycans in peripheral tissues, but show no effect in the brain. A recently developed carbohydrate-neuroactive hybrid strategy enables a non-invasive access to the brain in living animals across the blood–brain barrier. A combination of recent advances in CNS drugs and imaging with ManNAc analogues for polySia modulation would pave novel avenues for understanding intricacies of brain development and tackling the challenges of neurological disorders.

scholarly journals Microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Vinod Menon ◽  
Guillermo Gallardo ◽  
Mark A Pinsk ◽  
Van-Dang Nguyen ◽  
Jing-Rebecca Li ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Control Systems ◽  
Neurological Disorders ◽  
Diffusion Mri ◽  
Large Scale ◽  
Insular Cortex ◽  
Anterior Cingulate ◽  
Postmortem Brains ◽  
Functional Circuitry

The human insular cortex is a heterogeneous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI data from 413 participants revealed that human insula microstructure differs significantly across subdivisions that serve distinct cognitive and affective functions. Insular microstructural organization was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchors the salience network, a system important for adaptive switching of cognitive control systems. Furthermore, insular microstructural features, confirmed in Macaca mulatta, were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.

scholarly journals Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification

2018 ◽  
Author(s):  
Kilian Hett ◽  
Vinh-Thong Ta ◽  
Gwenaëlle Catheline ◽  
Thomas Tourdias ◽  
José V. Manjón ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Mri ◽  
Mean Diffusivity ◽  
Disease Classification ◽  
Structural Alterations ◽  
Hippocampal Subfields ◽  
Microstructural Alterations ◽  
Diffusivity Measurements

ABSTRACTNumerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). While anatomical MRI captures structural alterations, studies demonstrated the ability of diffusion MRI to capture microstructural modifications at an earlier stage. Several methods have focused on hippocampus structure to detect AD. To date, the patch-based grading framework provides the best biomarker based on the hippocampus. However, this structure is complex since the hippocampus is divided into several heterogeneous subfields not equally impacted by AD. Former in-vivo imaging studies only investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to study the efficiency of hippocampal subfields compared to the whole hippocampus structure with a multimodal patch-based framework that enables to capture subtler structural and microstructural alterations. To this end, we analyze the significance of the different hippocampal subfields for AD diagnosis and prognosis with volumetric, diffusivity measurements and a novel multimodal patch-based grading framework that combines structural and diffusion MRI. The experiments conducted in this work showed that the whole hippocampus provides the most discriminant biomarkers for advanced AD detection while biomarkers applied into subiculum obtain the best results for AD prediction, improving by 2% the accuracy compared to the whole hippocampus.

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