scholarly journals Superficial white matter imaging: Contrast mechanisms and whole-brain in vivo mapping

2020 ◽  
Vol 6 (41) ◽  
pp. eaaz9281 ◽  
Author(s):  
Evgeniya Kirilina ◽  
Saskia Helbling ◽  
Markus Morawski ◽  
Kerrin Pine ◽  
Katja Reimann ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Connectivity ◽  
Ion Beam ◽  
Postmortem Brain ◽  
Biophysical Modeling ◽  
Fiber Density ◽  
High Fiber ◽  
Postmortem Brain Tissue ◽  
Association Fibers

Superficial white matter (SWM) contains the most cortico-cortical white matter connections in the human brain encompassing the short U-shaped association fibers. Despite its importance for brain connectivity, very little is known about SWM in humans, mainly due to the lack of noninvasive imaging methods. Here, we lay the groundwork for systematic in vivo SWM mapping using ultrahigh resolution 7 T magnetic resonance imaging. Using biophysical modeling informed by quantitative ion beam microscopy on postmortem brain tissue, we demonstrate that MR contrast in SWM is driven by iron and can be linked to the microscopic iron distribution. Higher SWM iron concentrations were observed in U-fiber–rich frontal, temporal, and parietal areas, potentially reflecting high fiber density or late myelination in these areas. Our SWM mapping approach provides the foundation for systematic studies of interindividual differences, plasticity, and pathologies of this crucial structure for cortico-cortical connectivity in humans.

scholarly journals Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia

2021 ◽  
Vol 11 (1) ◽  
pp. 53
Author(s):  
Sara Kierońska ◽  
Milena Świtońska ◽  
Grzegorz Meder ◽  
Magdalena Piotrowska ◽  
Paweł Sokal
Keyword(s):  
White Matter ◽  
Brain Connectivity ◽  
Three Dimensional ◽  
Cerebral White Matter ◽  
Neural Pathways ◽  
Uncinate Fasciculus ◽  
Arcuate Fasciculus ◽  
Fiber Tractography ◽  
Post Stroke

Fiber tractography based on diffuse tensor imaging (DTI) can reveal three-dimensional white matter connectivity of the human brain. Tractography is a non-invasive method of visualizing cerebral white matter structures in vivo, including neural pathways surrounding the ischemic area. DTI may be useful for elucidating alterations in brain connectivity resulting from neuroplasticity after stroke. We present a case of a male patient who developed significant mixed aphasia following ischemic stroke. The patient had been treated by mechanical thrombectomy followed by an early rehabilitation, in conjunction with transcranial direct current stimulation (tDCS). DTI was used to examine the arcuate fasciculus and uncinate fasciculus upon admission and again at three months post-stroke. Results showed an improvement in the patient’s symptoms of aphasia, which was associated with changes in the volume and numbers of tracts in the uncinate fasciculus and the arcuate fasciculus.

scholarly journals Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Yu ◽  
Xinzhen Yin ◽  
Hui Hong ◽  
Shuyue Wang ◽  
Yeerfan Jiaerken ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Extracellular Fluid ◽  
Free Water ◽  
Inverse Correlation ◽  
Brain Regions ◽  
Fiber Density ◽  
Four Levels

Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.

scholarly journals Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1216
Author(s):  
Nityanand Jain ◽  
Marks Smirnovs ◽  
Samanta Strojeva ◽  
Modra Murovska ◽  
Sandra Skuja
Keyword(s):  
White Matter ◽  
Substantia Nigra ◽  
Human Herpesvirus ◽  
Chronic Alcoholism ◽  
Postmortem Brain ◽  
Rich Region ◽  
Cd11b Expression ◽  
Dominant Type ◽  
Postmortem Brain Tissue

Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, we hypothesize the presence of possible synergism between alcoholism and HHV-6 infection in the SN region and report a comprehensive quantification and characterization of microglial functions and morphology in postmortem brain tissue from 44 healthy, age-matched alcoholics and chronic alcoholics. A decrease in the perivascular CD68+ microglia in alcoholics was noted in both the gray and white matter. Additionally, the CD68+/Iba1− microglial subpopulation was found to be the dominant type in the controls. Conversely, in alcoholics, dystrophic changes in microglia were seen with a significant increase in Iba1 expression and perivascular to diffuse migration. An increase in CD11b expression was noted in alcoholics, with the Iba1+/CD11b− subtype promoting inflammation. All the controls were found to be negative for HHV-6 whilst the alcoholics demonstrated HHV-6 positivity in both gray and white matter. Amongst HHV-6 positive alcoholics, all the above-mentioned changes were found to be heightened when compared with HHV-6 negative alcoholics, thereby highlighting the compounding relationship between alcoholism and HHV-6 infection that promotes microglia-mediated neuroinflammation.

scholarly journals Alpha-Synuclein PET Tracer Development—An Overview about Current Efforts

2021 ◽  
Vol 14 (9) ◽  
pp. 847 ◽  
Author(s):  
Špela Korat ◽  
Natasha Shalina Rajani Bidesi ◽  
Federica Bonanno ◽  
Adriana Di Nanni ◽  
Anh Nguyên Nhât Hoàng ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Postmortem Brain ◽  
Comprehensive Overview ◽  
Pet Tracers ◽  
Ligand Selectivity ◽  
Affinity Ligand ◽  
Pet Tracer ◽  
Positron Emission ◽  
Postmortem Brain Tissue

Neurodegenerative diseases such as Parkinson’s disease (PD) are manifested by inclusion bodies of alpha-synuclein (α-syn) also called α-synucleinopathies. Detection of these inclusions is thus far only possible by histological examination of postmortem brain tissue. The possibility of non-invasively detecting α-syn will therefore provide valuable insights into the disease progression of α-synucleinopathies. In particular, α-syn imaging can quantify changes in monomeric, oligomeric, and fibrillic α-syn over time and improve early diagnosis of various α-synucleinopathies or monitor treatment progress. Positron emission tomography (PET) is a non-invasive in vivo imaging technique that can quantify target expression and drug occupancies when a suitable tracer exists. As such, novel α-syn PET tracers are highly sought after. The development of an α-syn PET tracer faces several challenges. For example, the low abundance of α-syn within the brain necessitates the development of a high-affinity ligand. Moreover, α-syn depositions are, in contrast to amyloid proteins, predominantly localized intracellularly, limiting their accessibility. Furthermore, another challenge is the ligand selectivity over structurally similar amyloids such as amyloid-beta or tau, which are often co-localized with α-syn pathology. The lack of a defined crystal structure of α-syn has also hindered rational drug and tracer design efforts. Our objective for this review is to provide a comprehensive overview of current efforts in the development of selective α-syn PET tracers.

Beyond the Dopamine Hypothesis

1989 ◽  
Vol 155 (3) ◽  
pp. 305-316 ◽  
Author(s):  
G. P. Reynolds
Keyword(s):  
Amino Acid ◽  
Drug Treatment ◽  
Dopamine Neurons ◽  
Postmortem Brain ◽  
Neuroleptic Drug ◽  
Neuroleptic Drugs ◽  
Imaging Studies ◽  
Postmortem Brain Tissue ◽  
Dopamine Hypothesis

The dopamine hypothesis still provides a valuable approach to the study of schizophrenia and its treatment by drugs. Although the neuroleptic drugs appear to act via an inhibition of dopamine receptors, measurements of dopamine metabolites in vivo, or of the transmitter and its receptors in postmortem brain tissue, do not provide unequivocal evidence of a hyperactivity of dopaminergic neurotransmission in the disease. Nevertheless, increased dopamine function might be a consequence of a primary neuronal abnormality in another system. Recent imaging studies and neuropathological reports suggest that, in some patients, there may be a deficit and/or disturbance of neurons in certain temporal limbic regions, and this is supported by some neurochemical investigations, particularly of neuropeptide and amino-acid transmitter systems. A loss of such neurons could conceivably lead to a disinhibition of limbic dopamine neurons, providing the means whereby neuroleptic drug treatment might ameliorate the effects of a neuronal deficit in schizophrenia.

scholarly journals Cellular abnormalities in depression: evidence from postmortem brain tissue

2004 ◽  
Vol 6 (2) ◽  
pp. 185-197
Keyword(s):  
Brain Tissue ◽  
Basic Research ◽  
Brain Regions ◽  
Microscopic Level ◽  
Anterior Cingulate ◽  
Postmortem Brain ◽  
Cell Counting ◽  
The Past ◽  
Postmortem Brain Tissue

During the past two decades, in vivo neuroimaging studies have permitted significant insights into the general location of dysfunctional brain regions in depression. In parallel and often intersecting ways, neuroanatomical, pharmacological, and biochemical studies of postmortem brain tissue are permitting new insights into the pathophysiology of depression. In addition to long-recognized neurochemical abnormalities in depression, novel studies at the microscopic level support the contention that mood disorders are associated with abnormalities in cell morphology and distribution. In the past 6 years, cell-counting studies have identified changes in the density and size of both neurons and glia in a number of frontolimbic brain regions, including dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortex, and the amygdala and hippocampus. Convergence of cellular changes at the microscopic level with neuroimaging changes detected in vivo provides a compelling integration of clinical and basic research for disentangling the pathophysiology of depression. The ultimate integration of these two research approaches will occur with premortem longitudinal clinical studies on well-characterized patients linked to postmortem studies of the same subjects.

scholarly journals The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

2019 ◽  
Author(s):  
Maritza Oñate ◽  
Alejandra Catenaccio ◽  
Natalia Salvadores ◽  
Cristian Saquel ◽  
Alexis Martinez ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Axonal Degeneration ◽  
Neuronal Loss ◽  
Postmortem Brain ◽  
Death Process ◽  
Early Event ◽  
Genetic Ablation ◽  
Postmortem Brain Tissue

AbstractParkinson’s disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in vivo, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.

scholarly journals In Vivo Detection of Cerebral Cortical Microinfarcts with High-Resolution 7T MRI

2012 ◽  
Vol 33 (3) ◽  
pp. 322-329 ◽  
Author(s):  
Susanne J van Veluw ◽  
Jaco JM Zwanenburg ◽  
JooYeon Engelen-Lee ◽  
Wim GM Spliet ◽  
Jeroen Hendrikse ◽  
...  
Keyword(s):  
High Resolution ◽  
Cognitive Decline ◽  
Ex Vivo ◽  
Brain Slices ◽  
Postmortem Brain ◽  
Vascular Pathology ◽  
Elderly Subjects ◽  
Postmortem Brain Tissue ◽  
Fluid Attenuated Inversion Recovery

Cerebrovascular disease has an important role in cognitive decline and dementia. In this context, cerebral microinfarcts are attracting increasing attention, but these lesions could thus far not be detected in vivo. The aim of this study was to try to identify possible cortical microinfarcts on high-resolution 7T in vivo magnetic resonance imaging (MRI) and to perform a histopathologic validation study on similar appearing lesions on 7T ex vivo MRI of postmortem brain tissue. The study population consisted of 22 elderly subjects, who underwent 7T MRI. The fluid attenuated inversion recovery, T2, and T1 weighted scans of these subjects were examined for possible cortical microinfarcts. In the ex vivo MRI study, 15 formalin-fixed coronal brain slices of 6 subjects with Alzheimer and vascular pathology were examined and subjected to histopathologic verification. On the in vivo scans, 15 cortical lesions could be identified that were likely to be microinfarcts in 6 subjects. In the postmortem tissue, 6 similar appearing lesions were identified of which 5 were verified as cortical microinfarcts on histopathology. This study provides strong evidence that cortical microinfarcts can be detected in vivo, which will be of great value in further studies into the role of vascular disease in cognitive decline and dementia.

scholarly journals Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging

2019 ◽  
Author(s):  
Miruna C. Barbu ◽  
Athina Spiliopoulou ◽  
Marco Colombo ◽  
Paul McKeigue ◽  
Toni-Kim Clarke ◽  
...  
Keyword(s):  
Gene Expression ◽  
White Matter ◽  
Quantitative Trait ◽  
Brain Connectivity ◽  
Structural Connectivity ◽  
Genotype Data ◽  
Eqtl Mapping ◽  
Uk Biobank ◽  
Genome Wide

AbstractBackgroundExpression quantitative trait loci (eQTL) are genetic variants associated with gene expression. Using genome-wide genotype data, it is now possible to impute gene expression using eQTL mapping efforts. This approach can be used to analyse previously unexplored relationships between gene expression and heritable in vivo measures of human brain structural connectivity.MethodsUsing large-scale eQTL mapping studies, we computed 6,457 gene expression scores (eQTL scores) using genome-wide genotype data in UK Biobank, where each score represents a genetic proxy measure of gene expression. These scores were then tested for associations with two diffusion tensor imaging measures, fractional anisotropy (NFA=14,518) and mean diffusivity (NMD=14,485), representing white matter structural integrity.ResultsWe found FDR-corrected significant associations between 8 eQTL scores and structural connectivity phenotypes, including global and regional measures (βabsolute FA=0.0339-0.0453; MD=0.0308-0.0381) and individual tracts (βabsolute FA=0.0320-0.0561; MD=0.0295-0.0480). The loci within these eQTL scores have been reported to regulate expression of genes involved in various brain-related processes and disorders, such as neurite outgrowth and Parkinson’s disease (DCAKD, SLC35A4, SEC14L4, SRA1, NMT1, CPNE1, PLEKHM1, UBE3C).DiscussionOur findings indicate that eQTL scores are associated with measures of in vivo brain connectivity and provide novel information not previously found by conventional genome-wide association studies. Although the role of expression of these genes regarding white matter microstructural integrity is not yet clear, these findings suggest it may be possible, in future, to map potential trait- and disease-associated eQTL to in vivo brain connectivity and better understand the mechanisms of psychiatric disorders and brain traits, and their associated imaging findings.

scholarly journals The visual white matter: The application of diffusion MRI and fiber tractography to vision science

2016 ◽  
Author(s):  
Ariel Rokem ◽  
Hiromasa Takemura ◽  
Andrew Bock ◽  
K. Suzanne Scherf ◽  
Marlene Behrmann ◽  
...  
Keyword(s):  
White Matter ◽  
Visual Information ◽  
Diffusion Mri ◽  
Brain Connectivity ◽  
Open Data ◽  
Data Sets ◽  
Fiber Tractography ◽  
Vision Science ◽  
Visual Neuroscience

AbstractVisual neuroscience has traditionally focused much of its attention on understanding the response properties of neurons along the visual pathways. This review focuses instead on the properties of the white matter connections between these neurons. Specifically, we provide an introduction to methods to study the human visual white matter using diffusion MRI (dMRI). This method allows us to measure the white matter connections in individual visual systems in vivo, allows us to trace long-range connections between different parts of the visual system, and to measure the biophysical properties of these connections. We explain the principles underlying dMRI measurements and the basics of modeling these data. We review a range of findings from recent studies on connections between different visual field maps, on the effects of visual impairment on the white matter, and on the properties underlying networks that process visual information that supports visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open data-sets that are becoming available to study brain connectivity and white matter properties, and open-source software for the analysis of these data.

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