scholarly journals Whole brain mapping of glutamate in adult and old primates at 11.7T

2021 ◽  
Author(s):  
Clement M Garin ◽  
Nachiket A. Nadkarni ◽  
Jeremy Pepin ◽  
Julien Flament ◽  
Marc Dhenain
Keyword(s):  
Magnetic Field ◽  
Nucleus Accumbens ◽  
High Magnetic Field ◽  
Basal Forebrain ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Whole Brain ◽  
Cortical Areas ◽  
Age Related ◽  
The Brain

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can map glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the glutamate index in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates.

Evaluation of EPI distortion correction methods for quantitative MRI of the brain at high magnetic field

2015 ◽  
Vol 33 (9) ◽  
pp. 1098-1105 ◽  
Author(s):  
Xin Hong ◽  
Xuan Vinh To ◽  
Irvin Teh ◽  
Jian Rui Soh ◽  
Kai-Hsiang Chuang
Keyword(s):  
Magnetic Field ◽  
High Magnetic Field ◽  
Distortion Correction ◽  
Quantitative Mri ◽  
The Brain

scholarly journals NIMG-70. A LABEL-FREE APPROACH TO ASSESS CHEMOTHERAPY DRUG CONCENTRATION USING CHEMICAL EXCHANGE SATURATION TRANSFER MRI – A FEASIBILITY STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi177-vi177
Author(s):  
David Kamson ◽  
Stuart Grossman ◽  
Zheng Han ◽  
Xiang Xu ◽  
Peter van Zijl ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Chemical Exchange ◽  
Detection Threshold ◽  
Chemical Exchange Saturation Transfer ◽  
High Dose ◽  
Label Free ◽  
Saturation Transfer ◽  
Synthetic Urine ◽  
Drug Concentrations ◽  
The Brain

Abstract BACKGROUND Drug delivery is one of the most pressing problems in neuro-oncology as the blood-brain barrier (BBB) uniquely limits penetration of substances into the brain parenchyma. Plasma and CSF drug concentrations are relatively easy to measure, but do not necessarily reflect concentrations in the brain. Furthermore, invasive measurements may be inaccurate in regions of heterogeneous BBB integrity. Advanced non-invasive imaging approaches may help bridge this information gap without the added risk. Chemical exchange saturation transfer (CEST) is an MRI technique that allows in vivo detection of molecules with a suitable hydrogen exchange rate, such as methotrexate (MTX). High-dose MTX is commonly used in oncology and its concentrations in urine (>2000µM), plasma (>1000µM) and enhancing brain tumors (>350µM) are well above the theoretical threshold of CEST. AIM: We aimed to confirm the CEST detectability of MTX in vitro, and to estimate the currently lowest measurable concentrations in solutions mimicking bodily fluids. METHODS We used a 9.4T MRI to assess the spectra of MTX at 37°C at various concentrations (0.1–10.0 mM) in a phosphate-buffered saline (PBS) solution at various pH (6.0–8.0), as well as in synthetic urine at pH 6.2. RESULTS CEST signals attributable to MTX at 1.5 and 2.7ppm were successfully detected in PBS at concentrations as low as 500µM. The optimal field strength was 3.6µT. While increasing pH increased the detection threshold of the 2.7ppm signal, the 1.5ppm signal was minimally affected by pH within physiologic ranges. In synthetic urine, the MTX CEST signal was well-detectable even at concentrations as low as 200µM. CONCLUSIONS These preliminary results suggest that MTX-CEST may be feasible at field strengths achievable in clinical scanners and at MTX concentrations previously measured in enhancing brain tumors treated with high-dose MTX. Further optimization of the technique for in human use is under way.

scholarly journals Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club

2020 ◽  
Author(s):  
Anira Escrichs ◽  
Carles Biarnes ◽  
Josep Garre-Olmo ◽  
José Manuel Fernández-Real ◽  
Rafel Ramos ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Functional Network ◽  
Brain Dynamics ◽  
Whole Brain ◽  
Rich Club ◽  
Brain Functional Network ◽  
Age Related ◽  
Age Range ◽  
The Brain

Abstract Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50–64 years versus older group (n = 310); age range, 65–91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local–global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

scholarly journals Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas

2012 ◽  
Vol 24 (4) ◽  
pp. 1427-1442 ◽  
Author(s):  
Oksana Yu. Naumova ◽  
Dean Palejev ◽  
Natalia V. Vlasova ◽  
Maria Lee ◽  
Sergei Yu. Rychkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
Signaling Systems ◽  
Cortical Areas ◽  
Age Related ◽  
Transcriptional Changes ◽  
Atypical Development ◽  
The Brain ◽  
Age Related Changes

AbstractThe study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.

scholarly journals Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons

2017 ◽  
Vol 115 (2) ◽  
pp. 415-420 ◽  
Author(s):  
Xiangning Li ◽  
Bin Yu ◽  
Qingtao Sun ◽  
Yalun Zhang ◽  
Miao Ren ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Cholinergic Neurons ◽  
Brain Atlas ◽  
Projection Area ◽  
Single Neurons ◽  
Whole Brain ◽  
Cognitive Behaviors ◽  
Optical Images ◽  
The Brain

The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-μm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-μm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.

scholarly journals Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club

2020 ◽  
Author(s):  
Anira Escrichs ◽  
Carles Biarnes ◽  
Josep Garre-Olmo ◽  
José Manuel Fernández-Real ◽  
Rafel Ramos ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Resting State Fmri ◽  
Brain Dynamics ◽  
Whole Brain ◽  
Rich Club ◽  
Brain Functional Network ◽  
Age Related ◽  
Age Range ◽  
The Brain

AbstractNormal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups (‘middle-age group’ (n=310); age range, 50-65 years vs. ‘older group’ (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

scholarly journals Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1983
Author(s):  
Erika Kropf ◽  
Margaret Fahnestock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Basal Forebrain ◽  
Memory Loss ◽  
Reactive Oxygen ◽  
Neurotrophin Receptor ◽  
Nitrogen Species ◽  
Age Related ◽  
The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

scholarly journals BIOFEEDBACK IN THE MAGNETIC FIELD (ON STEREOTOPOGRAPHY OF COGNITIVE FUNCTIONS)

2013 ◽  
Vol 12 (2) ◽  
pp. 7-20 ◽  
Author(s):  
K. G. Mazhirina ◽  
M. A. Pokrovskiy ◽  
M. V. Rezakova ◽  
A. A. Savelov ◽  
A. A. Sokolov ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Self Regulation ◽  
Imitation Game ◽  
Middle Temporal ◽  
The Real ◽  
Cortical Areas ◽  
On Line ◽  
The Brain ◽  
The Magnetic Field ◽  
Qualitative Characteristics

The brain was mapped on-line using fMRI technology in the process of the development of self-regulation skills. We studied the dynamics of new neural networks being created in the real and simulated biofeedback models. It was shown that immersion in a virtual story brings about the large involvement of cortical areas, which are characterized by high values of voxels in the middle-temporal, occipital and frontal regions. We discuss the qualitative characteristics of the real and the imitation game periods.

Cartilage Imaging: Techniques and Developments

2018 ◽  
Vol 22 (02) ◽  
pp. 245-260 ◽  
Author(s):  
Edwin Oei ◽  
Marius Wick ◽  
Anja Müller-Lutz ◽  
Christoph Schleich ◽  
Falk Miese
Keyword(s):  
Cartilage Repair ◽  
Chemical Exchange ◽  
Imaging Techniques ◽  
Cartilage Damage ◽  
Quantitative Computed Tomography ◽  
Joint Space Width ◽  
Chemical Exchange Saturation Transfer ◽  
Imaging Biomarkers ◽  
Cartilage Imaging ◽  
Age Related

AbstractCartilage degeneration is one of the most common chronic age-related joint disorders leading to pain and reduced joint motion. The increasing prevalence of osteoarthritis requires accurate cartilage imaging, both clinically and in research. Detailed cartilage imaging is also necessary for traumatic cartilage lesions and for pre- and postoperative assessment of cartilage repair procedures. Although still widely used, conventional radiography bears significant limitations because it assesses cartilage indirectly by joint space width. Magnetic resonance imaging (MRI) enables direct visualization of cartilage damage along with other concomitantly affected joint tissues. Several semiquantitative grading systems and volumetric analysis methods exist to assess cartilage damage and cartilage repair on MRI. Quantification of hyaline and fibrocartilage biochemical composition is possible with novel MRI methods such as T2- and T1ρ-mapping, delayed gadolinium-enhanced MRI of cartilage, glycosaminoglycan chemical exchange saturation transfer, and sodium imaging, along with quantitative computed tomography arthrography. These techniques provide promising quantitative imaging biomarkers that can detect early cartilage changes before morphological alterations occur.

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