scholarly journals Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimers Disease

2021 ◽  
Author(s):  
Ashwin V Venkataraman ◽  
Courtney Bishop ◽  
Ayla Mansur ◽  
Gaia Rizzo ◽  
Yvonne Lewis ◽  
...  
Keyword(s):  
Grey Matter ◽  
Diffusion Tensor ◽  
Free Water ◽  
Amyloid Pet ◽  
Alzheimers Disease ◽  
Synaptic Loss ◽  
Brain Volumes ◽  
Total N ◽  
Regional Brain

Background Synaptic loss and neurite dystrophy are early events in Alzheimers Disease (AD). We aimed to characterise early synaptic microstructural changes in vivo. Methods MRI neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI) were used to image cortical microstructure in both sporadic, late onset, amyloid PET positive AD patients and healthy controls (total n = 28). We derived NODDI measures of grey matter extracellular free water (FISO), neurite density (NDI) and orientation dispersion (ODI), which provides an index of neurite branching and orientation, as well as more conventional DTI measures of fractional anisotropy (FA), mean/axial/radial diffusivity (MD, AD, RD, respectively). We also performed [11C]UCB-J PET, which provides a specific measure of the density of pre-synaptic vesicular protein SV2A. Both sets of measures were compared to regional brain volumes. Results The AD patients showed expected relative decreases in regional brain volumes (range, -6 to -23%) and regional [11C]UCB-J densities (range, -2 to -25%). Differences between AD and controls were greatest in the hippocampus. NODDI microstructural measures showed greater FISO (range, +26 to +44%) in AD, with little difference in NDI (range, -1 to +7%) and mild focal changes in ODI (range, -4 to +3%). Regionally greater FISO and lower [11C]UCB-J binding were correlated across grey matter in patients (most strongly in the caudate, r2 = 0.37, p = 0.001). FISO and DTI RD were strongly positively associated, particularly in the hippocampus (r2 = 0.98, p < 7.4 x 10-9). After 12-18 months we found a 5% increase in FISO in the temporal lobe, but little change across all ROIs in NDI and ODI. An exploratory analysis showed higher parietal lobe FISO was associated with lower language scores in people with AD. Conclusions We interpreted the increased extracellular free water as a possible consequence of glial activation. The dynamic range of disease-associated differences and the feasibility of measuring FISO on commercially available imaging systems makes it a potential surrogate for pathology related to synapse loss that could be used to support early-stage evaluations of novel therapeutics for AD.

Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

2020 ◽  
Vol 105 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Alicia J Spittle ◽  
Jian Chen ◽  
Marc L Seal ◽  
...  
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Developmental Outcomes ◽  
Late Preterm ◽  
Brain Volumes ◽  
Regional Brain ◽  
White Matter Microstructure ◽  
Cortical Grey Matter

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

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.

Altered brainstem anatomy in migraine

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 476-486 ◽  
Author(s):  
Kasia K Marciszewski ◽  
Noemi Meylakh ◽  
Flavia Di Pietro ◽  
Vaughan G Macefield ◽  
Paul M Macey ◽  
...  
Keyword(s):  
Grey Matter ◽  
Diffusion Tensor ◽  
Free Water ◽  
Trigeminal System ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Diffusion Weighted Images ◽  
Diffusion Tensor Images ◽  
And Diffusion ◽  
Brainstem Anatomy

Background The exact mechanisms responsible for migraine remain unknown, although it has been proposed that changes in brainstem anatomy and function, even between attacks, may contribute to the initiation and maintenance of headache during migraine attacks. The aim of this investigation is to use brainstem-specific analyses of anatomical and diffusion weighted images to determine if the trigeminal system displays altered structure in individuals with migraine. Methods Voxel-based morphometry of T1-weighted anatomical images (57 controls, 24 migraineurs) and diffusion tensor images (22 controls, 24 migraineurs) were used to assess brainstem anatomy in individuals with migraine compared with controls. Results We found grey matter volume decreases in migraineurs in the spinal trigeminal nucleus and dorsomedial pons. In addition, reduced grey matter volume and increased free water diffusivity occurred in areas of the descending pain modulatory system, including midbrain periaqueductal gray matter, dorsolateral pons, and medullary raphe. These changes were not correlated to migraine frequency, duration, intensity or time to next migraine. Conclusion Brainstem anatomy changes may underlie changes in activity that result in activation of the ascending trigeminal pathway and the perception of head pain during a migraine attack.

scholarly journals Is Diffusion Tensor Imaging-Guided Radiotherapy the New State-of-the-Art? A Review of the Current Literature and Technical Insights

2022 ◽  
Vol 12 (2) ◽  
pp. 816
Author(s):  
Jordan Colman ◽  
Laura Mancini ◽  
Spyros Manolopoulos ◽  
Meetakshi Gupta ◽  
Michael Kosmin ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
State Of The Art ◽  
Imaging Technique ◽  
Neurological Complications ◽  
Current Evidence ◽  
Structural Imaging ◽  
Diffusion Tensor Imaging Dti

Despite the increasing precision of radiotherapy delivery, it is still frequently associated with neurological complications. This is in part due to damage to eloquent white matter (WM) tracts, which is made more likely by the fact they cannot be visualised on standard structural imaging. WM is additionally more vulnerable than grey matter to radiation damage. Primary brain malignancies also are known to spread along the WM. Diffusion tensor imaging (DTI) is the only in vivo method of delineating WM tracts. DTI is an imaging technique that models the direction of diffusion and therefore can infer the orientation of WM fibres. This review article evaluates the current evidence for using DTI to guide intracranial radiotherapy and whether it constitutes a new state-of-the-art technique. We provide a basic overview of DTI and its known applications in radiotherapy, which include using tractography to reduce the radiation dose to eloquent WM tracts and using DTI to detect or predict tumoural spread. We evaluate the evidence for DTI-guided radiotherapy in gliomas, metastatic disease, and benign conditions, finding that the strongest evidence is for its use in arteriovenous malformations. However, the evidence is weak in other conditions due to a lack of case-controlled trials.

scholarly journals Determinants of Disability in Multiple Sclerosis: An Immunological and MRI Study

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Tortorella ◽  
Maria Marcella Laganà ◽  
Marina Saresella ◽  
Eleonora Tavazzi ◽  
Maria Giulia Preti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Mononuclear Cells ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Motor Impairment ◽  
Grey Matter Volume ◽  
Peripheral Blood Mononuclear ◽  
Matter Volume

Multiple sclerosis (MS) is characterized by a wide interpatient clinical variability and available biomarkers of disease severity still have suboptimal reliability. We aimed to assess immunological and MRI-derived measures of brain tissue damage in patients with different motor impairment degrees, forin vivoinvestigating the pathogenesis of MS-related disability. Twenty-two benign (B), 26 secondary progressive (SP), and 11 early, nondisabled relapsing-remitting (RR) MS patients and 37 healthy controls (HC) underwent conventional and diffusion tensor brain MRI and, as regards MS patients, immunophenotypic and functional analysis of stimulated peripheral blood mononuclear cells (PBMC). Corticospinal tract (CST) fractional anisotropy and grey matter volume were lower and CST diffusivity was higher in SPMS compared to RRMS and BMS patients. CD14+IL6+ and CD4+IL25+ cell percentages were higher in BMS than in SPMS patients. A multivariable model having EDSS as the dependent variable retained the following independent predictors: grey matter volume, CD14+IL6+ and CD4+IL25+ cell percentages. In patients without motor impairment after long-lasting MS, the grey matter and CST damage degree seem to remain as low as in the earlier disease stages and an immunological pattern suggestive of balanced pro- and anti-inflammatory activity is observed. MRI-derived and immunological measures might be used as complementary biomarkers of MS severity.

scholarly journals Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS

2018 ◽  
Vol 90 (4) ◽  
pp. 404-411 ◽  
Author(s):  
Rebecca J Broad ◽  
Matt C Gabel ◽  
Nicholas G Dowell ◽  
David J Schwartzman ◽  
Anil K Seth ◽  
...  
Keyword(s):  
Diffusion Mri ◽  
Corticospinal Tract ◽  
Diffusion Tensor ◽  
Free Water ◽  
Cortical Atrophy ◽  
Precentral Gyrus ◽  
Water Fraction ◽  
Sporadic Als ◽  
The Right

BackgroundCorticospinal tract (CST) degeneration and cortical atrophy are consistent features of amyotrophic lateral sclerosis (ALS). We hypothesised that neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, would reveal microstructural changes associated with ALS within the CST and precentral gyrus (PCG) ‘in vivo’.Methods23 participants with sporadic ALS and 23 healthy controls underwent diffusion MRI. Neurite density index (NDI), orientation dispersion index (ODI) and free water fraction (isotropic compartment (ISO)) were derived. Whole brain voxel-wise analysis was performed to assess for group differences. Standard diffusion tensor imaging (DTI) parameters were computed for comparison. Subgroup analysis was performed to investigate for NODDI parameter differences relating to bulbar involvement. Correlation of NODDI parameters with clinical variables were also explored. The results were accepted as significant where p<0.05 after family-wise error correction at the cluster level, clusters formed with p<0.001.ResultsIn the ALS group NDI was reduced in the extensive regions of the CST, the corpus callosum and the right PCG. ODI was reduced in the right anterior internal capsule and the right PCG. Significant differences in NDI were detected between subgroups stratified according to the presence or absence of bulbar involvement. ODI and ISO correlated with disease duration.ConclusionsNODDI demonstrates that axonal loss within the CST is a core feature of degeneration in ALS. This is the main factor contributing to the altered diffusivity profile detected using DTI. NODDI also identified dendritic alterations within the PCG, suggesting microstructural cortical dendritic changes occur together with CST axonal damage.

scholarly journals Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

2021 ◽  
Author(s):  
Robert A. Chesters ◽  
Fiona Pepper ◽  
Celia Morgan ◽  
Jonathan D. Cooper ◽  
Oliver D. Howes ◽  
...  
Keyword(s):  
Grey Matter ◽  
Brain Volume ◽  
Inverse Correlation ◽  
Psychotic Symptoms ◽  
Control Group ◽  
Mri Imaging ◽  
Brain Volumes ◽  
Cohen’S D ◽  
Regional Brain ◽  
Cohen's D

Abstract Rationale Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. Objectives We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. Methods Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. Results Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. Conclusions Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms.

scholarly journals Molecular pathology and synaptic loss in primary tauopathies: [18F]AV-1451 and [11C]UCB-J PET study

2021 ◽  
Author(s):  
Negin Holland ◽  
Maura Malpetti ◽  
Timothy Rittman ◽  
Elijah E Mak ◽  
Luca Passamonti ◽  
...  
Keyword(s):  
Disease Severity ◽  
Pet Imaging ◽  
Molecular Pathology ◽  
Brain Regions ◽  
Synaptic Function ◽  
Amyloid Pet ◽  
Synaptic Loss ◽  
Synaptic Density ◽  
The Relationship

AbstractThe relationship betweenin vivosynaptic density and tau burden in primary tauopathies is key to understanding the impact of tauopathy on functional decline and in informing new early therapeutic strategies. In this cross-sectional observational study, we determine thein vivorelationship between synaptic density and molecular pathology, in the primary tauopathies of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), as a function of disease severity.Twenty three patients with PSP, and twelve patients with Corticobasal Syndrome (CBS) were recruited from a tertiary referral centre. Nineteen education, sex and gender-matched control participants were recruited from the National Institute for Health Research ‘Join Dementia Research’ platform. Cerebral synaptic density and molecular pathology, in all participants, were estimated using PET imaging with the radioligands [11C]UCB-J and [18F]AV-1451, respectively. Patients with CBS also underwent amyloid PET imaging with [11C]PiB to exclude those with likely Alzheimer’s pathology – we refer to the amyloid negative cohort as having CBD although acknowledge other pathologies exist. Disease severity was assessed with the PSP rating scale; regional non-displaceable binding potentials (BPND) of [11C]UCB-J and [18F]AV-1451 were estimated in regions of interest from the Hammersmith Atlas, excluding those with known off-target binding for [18F]AV-1451. As an exploratory analysis, we also investigated the relationship between molecular pathology in cortical brain regions, and synaptic density in connected subcortical areas.Across brain regions, there was apositivecorrelation between [11C]UCB-J and [18F]AV-1451 BPND(β=0.4, t=4.7, p<0.0001). However, the direction of this correlation became less positive as a function of disease severity in patients(β = -0.03, T = -4.0, p = 0.002). Between brain regions, cortical [18F]AV-1451 binding wasnegativelycorrelated with synaptic density in subcortical areas (caudate nucleus, putamen, and substantia nigra).Brain regions with higher synaptic density are associated with a higher [18F]AV-1451 binding in PSP/CBD, but this association diminishes with disease severity. Moreover, higher cortical [18F]AV-1451 binding correlates with lower subcortical synaptic density. Longitudinal imaging is required to confirm the mediation of synaptic loss by molecular pathology. However, the effect of disease severity suggests a biphasic relationship between synaptic density and tauopathy, with synapse rich regions vulnerable to accrual of pathology, followed by a loss of synapses in response to pathology. Given the importance of synaptic function for cognition, our study elucidates the pathophysiology of primary tauopathies and may inform the design of future clinical trials.

Diffusion Tensor Imaging in Preclinical and Human Studies of Huntington’s Disease: What Have we Learned so Far?

2019 ◽  
Vol 15 (6) ◽  
pp. 521-542 ◽  
Author(s):  
Rodolfo Gabriel Gatto ◽  
Carina Weissmann
Keyword(s):  
Diffusion Tensor Imaging ◽  
Animal Models ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Studies ◽  
Animal Studies ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Ultrastructural Changes

Background:Huntington’s Disease is an irreversible neurodegenerative disease characterized by the progressive deterioration of specific brain nerve cells. The current evaluation of cellular and physiological events in patients with HD relies on the development of transgenic animal models. To explore such events in vivo, diffusion tensor imaging has been developed to examine the early macro and microstructural changes in brain tissue. However, the gap in diffusion tensor imaging findings between animal models and clinical studies and the lack of microstructural confirmation by histological methods has questioned the validity of this method.Objective:This review explores white and grey matter ultrastructural changes associated to diffusion tensor imaging, as well as similarities and differences between preclinical and clinical Huntington’s Disease studies.Methods:A comprehensive review of the literature using online-resources was performed (Pub- Med search).Results:Similar changes in fractional anisotropy as well as axial, radial and mean diffusivities were observed in white matter tracts across clinical and animal studies. However, comparative diffusion alterations in different grey matter structures were inconsistent between clinical and animal studies.Conclusion:Diffusion tensor imaging can be related to specific structural anomalies in specific cellular populations. However, some differences between animal and clinical studies could derive from the contrasting neuroanatomy or connectivity across species. Such differences should be considered before generalizing preclinical results into the clinical practice. Moreover, current limitations of this technique to accurately represent complex multicellular events at the single micro scale are real. Future work applying complex diffusion models should be considered.

scholarly journals Age-related grey matter volume correlates of response inhibition and shifting in attention-deficit hyperactivity disorder

2009 ◽  
Vol 194 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Grainne M. McAlonan ◽  
Vinci Cheung ◽  
Siew E. Chua ◽  
Jaap Oosterlaan ◽  
Se-fong Hung ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Grey Matter ◽  
Reaction Times ◽  
Grey Matter Volume ◽  
Brain Volumes ◽  
Hyperactivity Disorder ◽  
Matter Volume ◽  
Regional Brain ◽  
Age Related

BackgroundChildren with attention-deficit hyperactivity disorder (ADHD) have difficulties with executive function and impulse control which may improve with age.AimsTo map the brain correlates of executive function in ADHD and determine age-related changes in reaction times and brain volumes.MethodAttention-deficit hyperactivity disorder and control groups were compared on the change task measures of response inhibition (stop signal reaction time, SSRT) and shifting (change response reaction time, CRRT). Voxel-wise magnetic resonance imaging (MRI) correlations of reaction times and grey matter volume were determined, along with bivariate correlations of reaction times, brain volumes and age.ResultsIndividuals in the ADHD group had longer SSRTs and CRRTs. Anterior cingulate, striatal and medial temporal volumes highly correlated with SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older children had faster reaction times and larger regional brain volumes. In controls, orbitofrontal, medial temporal and cerebellar volumes correlated with CRRT but not SSRT. Neither reaction times nor regional brain volumes were strongly age-dependent.ConclusionsOur evidence supports delayed brain maturation in ADHD and implies that some features of ADHD improve with age.

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