scholarly journals Joint-Label Fusion Brain Atlases for Dementia Research in Down Syndrome

2020 ◽  
Author(s):  
Nazek Queder ◽  
Michael J. Phelan ◽  
Lisa Taylor ◽  
Nicholas Tustison ◽  
Eric Doran ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Ground Truth ◽  
Disease Status ◽  
Brain Regions ◽  
Motion Artifacts ◽  
Brain Atlas ◽  
Positron Emission ◽  
Dementia Research ◽  
Amyloid Load

AbstractResearch suggests a link between Alzheimer’s Disease in Down Syndrome (DS) and the overexpression of amyloid plaques. Using Positron Emission Tomography (PET) we can assess the in-vivo regional amyloid load using several available ligands. To measure amyloid distributions in specific brain regions, a brain atlas is used. A popular method of creating a brain atlas is to segment a participant’s structural Magnetic Resonance Imaging (MRI) scan. Acquiring an MRI is often challenging in intellectually-imparied populations because of contraindications or data exclusion due to significant motion artifacts or incomplete sequences related to general discomfort. When an MRI cannot be acquired, it is typically replaced with a standardized brain atlas derived from neurotypical populations which may be inappropriate for use in DS. In this project, we create a series of disease and diagnosis-specific (cognitively stable, mild cognitive impairment (MCI-DS), and dementia) probabilistic group atlases of participants with DS and evaluate their accuracy of quantifying regional amyloid load compared to our ground truth individual MRI-based segmentations. Further, we compare the diagnostic-specific atlases with a probabilistic atlas constructed from similar-aged cognitively-stable neurotypical participants. We hypothesized that regional PET signals will best match the ground truth by using DS group atlases that aligns with a participant’s disorder and disease status (e.g. DS and MCI-DS). Our results vary by brain region but generally show that using a disorder-specific atlas in DS better matches the ground truth than using an atlas constructed from cognitively-stable neurotypical participants. We found no additional benefit of using a disease-state specific atlas. All atlases are made publicly available for the research community.AbbreviationsAD, DS, Aβ, DSG, CS-DS, CS-NT, LOOCV, ROI, MSE, MRI, PET, JLF, CS, MCI-DS, DEM.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

scholarly journals Cellular sources of TSPO expression in healthy and diseased brain

2021 ◽  
Author(s):  
Erik Nutma ◽  
Kelly Ceyzériat ◽  
Sandra Amor ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
...  
Keyword(s):  
Cell Activity ◽  
Brain Regions ◽  
Cellular Level ◽  
Translocator Protein ◽  
Disease Stage ◽  
Animal Models Of Disease ◽  
Positron Emission ◽  
Neuropsychiatric Diseases ◽  
Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

Changes in synaptic density in the subacute phase after ischemic stroke: A 11C-UCB-J PET/MR study

2021 ◽  
pp. 0271678X2110477
Author(s):  
Laura Michiels ◽  
Nathalie Mertens ◽  
Liselot Thijs ◽  
Ahmed Radwan ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Asymmetry Index ◽  
Cerebellar Hemisphere ◽  
Future Research ◽  
Stroke Patients ◽  
Synaptic Density ◽  
Positron Emission

Functional alterations after ischemic stroke have been described with Magnetic Resonance Imaging (MRI) and perfusion Positron Emission Tomography (PET), but no data on in vivo synaptic changes exist. Recently, imaging of synaptic density became available by targeting synaptic vesicle protein 2 A, a protein ubiquitously expressed in all presynaptic nerve terminals. We hypothesized that in subacute ischemic stroke loss of synaptic density can be evaluated with 11C-UCB-J PET in the ischemic tissue and that alterations in synaptic density can be present in brain regions beyond the ischemic core. We recruited ischemic stroke patients to undergo 11C-UCB-J PET/MR imaging 21 ± 8 days after stroke onset to investigate regional 11C-UCB-J SUVR (standardized uptake value ratio). There was a decrease (but residual signal) of 11C-UCB-J SUVR within the lesion of 16 stroke patients compared to 40 healthy controls (ratiolesion/controls = 0.67 ± 0.28, p = 0.00023). Moreover, 11C-UCB-J SUVR was lower in the non-lesioned tissue of the affected hemisphere compared to the unaffected hemisphere (ΔSUVR = −0.17, p = 0.0035). The contralesional cerebellar hemisphere showed a lower 11C-UCB-J SUVR compared to the ipsilesional cerebellar hemisphere (ΔSUVR = −0.14, p = 0.0048). In 8 out of 16 patients, the asymmetry index suggested crossed cerebellar diaschisis. Future research is required to longitudinally study these changes in synaptic density and their association with outcome.

Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer’s Disease

2019 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Timo Grimmer ◽  
Oliver Goldhardt ◽  
Igor Yakushev ◽  
Marion Ortner ◽  
Christian Sorg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Pittsburgh Compound B ◽  
Positron Emission ◽  
Amyloid Load ◽  
Alzheimer’S Pathology

Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

scholarly journals Accurate localization of linear probe electrodes across multiple brains

2020 ◽  
Author(s):  
Liu D Liu ◽  
Susu Chen ◽  
Michael N Economo ◽  
Nuo Li ◽  
Karel Svoboda
Keyword(s):  
Ground Truth ◽  
Brain Structures ◽  
Brain Regions ◽  
Brain Atlas ◽  
3 Dimensional ◽  
Accurate Localization ◽  
Large Numbers ◽  
Linear Probe ◽  
Electrode Localization ◽  
Recording Electrodes

AbstractRecently developed silicon probes have large numbers of recording electrodes on long linear shanks. Specifically, Neuropixels probes have 960 recording electrodes distributed over 9.6 mm shanks. Because of their length, Neuropixels probe recordings in rodents naturally span multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals have to be aligned to each other and to a standardized brain coordinate system. Here we report a workflow for accurate localization of individual electrodes in standardized coordinates and aligned across individual brains. This workflow relies on imaging brains with fluorescent probe tracks and warping 3-dimensional image stacks to standardized brain atlases. Electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed ground-truth experiments, in which motor cortex outputs are labelled with ChR2 and a fluorescence protein. Recording from brain regions targeted by these outputs reveals better than 100 μm accuracy for electrode localization.

scholarly journals Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

2007 ◽  
Vol 50 (spe) ◽  
pp. 91-96 ◽  
Author(s):  
Camila Godinho Ribeiro ◽  
Regina Moura ◽  
Rosane de Figueiredo Neves ◽  
Jean Pierre Spinosa ◽  
Mario Bernardo-Filho
Keyword(s):  
Nuclear Medicine ◽  
Erectile Dysfunction ◽  
Sexual Arousal ◽  
Single Photon ◽  
Photon Emission ◽  
Brain Regions ◽  
Emission Computed Tomography ◽  
Nuclear Medicine Imaging ◽  
Positron Emission

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction(ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/disfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and spect and ED and pet was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection.

scholarly journals In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation

2019 ◽  
Vol 116 (23) ◽  
pp. 11490-11495 ◽  
Author(s):  
Margaret T. Davis ◽  
Ansel Hillmer ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Potential Role ◽  
Input Function ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Positron Emission

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P’s = 0.001–0.01) and compared with MDD individuals in three regions (P’s = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P’s = 0.001–0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

scholarly journals ADORA2A variation and adenosine A1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christa Hohoff ◽  
Tina Kroll ◽  
Baoyuan Zhao ◽  
Nicole Kerkenberg ◽  
Ilona Lang ◽  
...  
Keyword(s):  
Brain Regions ◽  
Phenotypic Characterization ◽  
Gene Variation ◽  
Quantitative Pet ◽  
Positron Emission ◽  
A1 Receptor ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
The Relationship

AbstractAdenosine, its interacting A1 and A2A receptors, and particularly the variant rs5751876 in the A2A gene ADORA2A have been shown to modulate anxiety, arousal, and sleep. In a pilot positron emission tomography (PET) study in healthy male subjects, we suggested an effect of rs5751876 on in vivo brain A1 receptor (A1AR) availability. As female sex and adenosinergic/dopaminergic interaction partners might have an impact on this rs5751876 effect on A1AR availability, we aimed to (1) further investigate the pilot male-based findings in an independent, newly recruited cohort including women and (2) analyze potential modulation of this rs5751876 effect by additional adenosinergic/dopaminergic gene variation. Healthy volunteers (32/11 males/females) underwent phenotypic characterization including self-reported sleep and A1AR-specific quantitative PET. Rs5751876 and 31 gene variants of adenosine A1, A2A, A2B, and A3 receptors, adenosine deaminase, and dopamine D2 receptor were genotyped. Multivariate analysis revealed an rs5751876 effect on A1AR availability (P = 0.047), post hoc confirmed in 30 of 31 brain regions (false discovery rate (FDR) corrected P values < 0.05), but statistically stronger in anxiety-related regions (e.g., amygdala, hippocampus). Additional effects of ADORA1 rs1874142 were identified; under its influence rs5751876 and rs5751876 × sleep had strengthened effects on A1AR availability (Pboth < 0.02; post hoc FDR-corrected Ps < 0.05 for 29/30 regions, respectively). Our results support the relationship between rs5751876 and A1AR availability. Additional impact of rs1874142, together with rs5751876 and sleep, might be involved in regulating arousal and thus the development of mental disorders like anxiety disorders. The interplay of further detected suggestive ADORA2A × DRD2 interaction, however, necessitates larger future samples more comparable to magnetic resonance imaging (MRI)-based samples.

scholarly journals Measurement of Blood—Brain Barrier Permeability with Positron Emission Tomography and [68Ga]EDTA

1984 ◽  
Vol 4 (3) ◽  
pp. 323-328 ◽  
Author(s):  
R. M. Kessler ◽  
J. C. Goble ◽  
J. H. Bird ◽  
M. E. Girton ◽  
J. L. Doppman ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Quantitative Measure ◽  
Brain Regions ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Blood Brain ◽  
Positron Emission ◽  
Area Product

Positron emission tomography (PET) was employed to examine time-dependent changes in blood–brain barrier (BBB) permeability to [68Ga]ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product ( PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to [68Ga]EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions.

scholarly journals Influence of nicotine upon human brain metabolism, an in vivo noninvasive Near Infrared Spectroscopy (NIRS) study

2021 ◽  
Vol 4 (4) ◽  
pp. 01-07
Author(s):  
Francesco Crespi
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Brain Metabolism ◽  
Near Infrared ◽  
Brain Regions ◽  
Positive Influence ◽  
Total Blood ◽  
Nicotine Administration ◽  
Positron Emission

Nicotine, a natural alkaloid derived from tobacco, is involved in various outcomes ranging from addiction to toxicity and/or neuro-protective actions. Nevertheless, the literature on the effects of nicotine administration upon the activity of brain regions is mixed; either increased, decreased, or no overall effect was reported when being evaluated by various methodologies such as positron emission tomography (PET), functional Magnetic Resonance Imaging (fMRI). In this work, Near Infrared Spectroscopy (NIRS) is applied as it allows monitoring oxygen saturation in the living tissue as well as changes in oxygenation of hemoglobin and when applied on brain studies, it gives indications of cerebral haemo-dynamics as well as brain metabolism. In particular, here NIRS has been applied in human volunteers as this methodology is based upon the use of harmless radiations so that to provide a non-invasive, non-ionizing procedure to monitor 2 main forms of hae­moglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb). The data gathered indicate an overall positive influence of nicotine upon HbO2 levels, as well as total blood volume (V) therefore suggesting an increased brain metabolism. Finally these data further propose NIRS with its characteristics of noninvasiveness, easy to-use, portable, restraint-free therefore relatively psychologically undemanding, as replicable and ideal methodology for clinical applications and translational approaches.

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