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PloS One 2024White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186...
White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered.
Topics: Humans; White Matter; Adult; Male; Female; Adolescent; Middle Aged; Aged; Young Adult; Child; Aged, 80 and over; Infant; Child, Preschool; Aging; Longevity; Infant, Newborn; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Anisotropy; Brain; Gray Matter
PubMed: 38758830
DOI: 10.1371/journal.pone.0301520 -
Polish Journal of Radiology 2023Diffusion-weighted imaging (DWI) is a valuable diagnostic tool, which provides functional information by exploring the free diffusivity of water molecules into intra-... (Review)
Review
Diffusion-weighted imaging (DWI) is a valuable diagnostic tool, which provides functional information by exploring the free diffusivity of water molecules into intra- and inter-cellular spaces that in tumours mainly depend on cellularity. It provides information regarding the tumour grade and helps with the diagnosis. Often high-grade tumours show restricted diffusion due to a high degree of cellularity, increased nuclear-to-cytoplasmic ratio, and reduced extracellular space. Benign central nervous system (CNS) tumours rarely show restricted diffusion on magnetic resonance imaging (MRI), and most of them have a characteristic imaging appearance. When benign CNS neoplasms reveal restricted diffusion on MRI, the radiologist is compelled to suggest a malignant neoplasm, making their diagnosis challenging. Knowledge of these exceptions helps to avoid possible errors in diagnosis. We present this integrated review with clinical, radiology-pathological correlation.
PubMed: 38020500
DOI: 10.5114/pjr.2023.132536 -
Nature Communications Jan 2024Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of...
Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO. The formation of TiO(e) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.
Topics: Animals; Mice; Action Potentials; Cranial Irradiation; Diffusion; Dopaminergic Neurons
PubMed: 38195782
DOI: 10.1038/s41467-023-44635-8 -
The Journal of Neuroscience : the... Aug 2023Amyloid β protein (Aβ) and tau, the two main proteins implicated in causing Alzheimer's disease (AD), are posited to trigger synaptic dysfunction long before...
Amyloid β protein (Aβ) and tau, the two main proteins implicated in causing Alzheimer's disease (AD), are posited to trigger synaptic dysfunction long before significant synaptic loss occurs in vulnerable circuits. Whereas soluble Aβ aggregates from AD brain are well recognized potent synaptotoxins, less is known about the synaptotoxicity of soluble tau from AD or other tauopathy patient brains. Minimally manipulated patient-derived aqueous brain extracts contain the more diffusible native forms of these proteins. Here, we explore how intracerebral injection of Aβ and tau present in such aqueous extracts of patient brain contribute to disruption of synaptic plasticity in the CA1 area of the male rat hippocampus. Aqueous extracts of certain AD brains acutely inhibited long-term potentiation (LTP) of synaptic transmission in a manner that required both Aβ and tau. Tau-containing aqueous extracts of a brain from a patient with Pick's disease (PiD) also impaired LTP, and diffusible tau from either AD or PiD brain lowered the threshold for AD brain Aβ to inhibit LTP. Remarkably, the disruption of LTP persisted for at least 2 weeks after a single injection. These findings support a critical role for diffusible tau in causing rapid onset, persistent synaptic plasticity deficits, and promoting Aβ-mediated synaptic dysfunction. The microtubule-associated protein tau forms relatively insoluble fibrillar deposits in the brains of people with neurodegenerative diseases including Alzheimer's and Pick's diseases. More soluble aggregates of disease-associated tau may diffuse between cells and could cause damage to synapses in vulnerable circuits. We prepared aqueous extracts of diseased cerebral cortex and tested their ability to interfere with synaptic function in the brains of live rats. Tau in these extracts rapidly and persistently disrupted synaptic plasticity and facilitated impairments caused by amyloid β protein, the other major pathologic protein in Alzheimer's disease. These findings show that certain diffusible forms of tau can mediate synaptic dysfunction and may be a target for therapy.
Topics: Male; Rats; Animals; Amyloid beta-Peptides; Long-Term Potentiation; Alzheimer Disease; tau Proteins; Neuronal Plasticity; Synapses; Hippocampus; Brain
PubMed: 37491315
DOI: 10.1523/JNEUROSCI.0082-23.2023 -
Magnetic Resonance in Medicine Mar 2024Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and...
Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations. Despite its great potential, dMRS remains a challenging technique on all levels: from the data acquisition to the analysis, quantification, modeling, and interpretation of results. These challenges were the motivation behind the organization of the Lorentz Center workshop on "Best Practices & Tools for Diffusion MR Spectroscopy" held in Leiden, the Netherlands, in September 2021. During the workshop, the dMRS community established a set of recommendations to execute robust dMRS studies. This paper provides a description of the steps needed for acquiring, processing, fitting, and modeling dMRS data, and provides links to useful resources.
Topics: Consensus; Brain; Magnetic Resonance Spectroscopy; Diffusion; Diffusion Magnetic Resonance Imaging
PubMed: 37946584
DOI: 10.1002/mrm.29877 -
Frontiers in Oncology 2023To explain adult-type diffuse gliomas heterogeneity through diffusion kurtosis imaging-based habitat characteristics and develop and validate a comprehensive model for...
OBJECTIVE
To explain adult-type diffuse gliomas heterogeneity through diffusion kurtosis imaging-based habitat characteristics and develop and validate a comprehensive model for predicting isocitrate dehydrogenase (IDH) status.
MATERIALS AND METHODS
In this prospective secondary analysis, 103 participants (mean age, 52 years; range, 21-77; 54 [52%] male) pathologically diagnosed with adult-type diffuse gliomas were enrolled between June 2018 and February 2022. The Otsu method was used to generate habitat maps with mean diffusivity (MD) and mean kurtosis (MK) for a total of 4 subhabitats containing 16 habitat features. Habitat heatmaps were created based on the Pearson correlation coefficient. The Habitat imAging aNd clinicraD INtegrated prEdiction SyStem (HANDINESS) was created by combining clinical features, conventional MRI morphological features, and habitat image features. ROC, calibration curve, and decision curve analyses were used to select the optimal model after 32 pipelines for model training and validation.
RESULTS
In the restricted diffusion and high-density subhabitat, MK was highly correlated with MD (R = 0.999), volume (0.608) and percentage of volume (0.663), and this region had the highest MK value (P<.001). The unrestricted diffusion and low-density subhabitat had the highest MD value (P<.001). When MK was less than the Otsu threshold, there was still a difference between restricted diffusion and low-density and unrestricted diffusion and low-density subhabitats (P<.01). The HANDINESS enabled more accurate prediction of the IDH status in the training (AUC=0.951 [0.902-0.987]) and internal validation cohorts (0.938 [0.881-0.949]). AUC values for single-modality models and independent factors ranged from 0.593 to 0.916. Calibration and decision curve analyses showed that the HANDINESS demonstrated a high level of clinical applicability and predictive consistency.
CONCLUSION
Diffusion kurtosis imaging-based habitat analysis provides additional important information on microscopic tumor spatial heterogeneity. The HANDINESS has higher diagnostic performance and robustness than single-modality models.
PubMed: 38090477
DOI: 10.3389/fonc.2023.1202170 -
Scientific Reports Sep 2023Misfolded proteins in Alzheimer's disease and Parkinson's disease follow a well-defined connectomics-based spatial progression. Several anti-tau and anti-alpha synuclein...
Misfolded proteins in Alzheimer's disease and Parkinson's disease follow a well-defined connectomics-based spatial progression. Several anti-tau and anti-alpha synuclein (aSyn) antibodies have failed to provide clinical benefit in clinical trials despite substantial target engagement in the experimentally accessible cerebrospinal fluid (CSF). The proposed mechanism of action is reducing neuronal uptake of oligomeric protein from the synaptic cleft. We built a quantitative systems pharmacology (QSP) model to quantitatively simulate intrasynaptic secretion, diffusion and antibody capture in the synaptic cleft, postsynaptic membrane binding and internalization of monomeric and oligomeric tau and aSyn proteins. Integration with a physiologically based pharmacokinetic (PBPK) model allowed us to simulate clinical trials of anti-tau antibodies gosuranemab, tilavonemab, semorinemab, and anti-aSyn antibodies cinpanemab and prasineuzumab. Maximal target engagement for monomeric tau was simulated as 45% (semorinemab) to 99% (gosuranemab) in CSF, 30% to 99% in ISF but only 1% to 3% in the synaptic cleft, leading to a reduction of less than 1% in uptake of oligomeric tau. Simulations for prasineuzumab and cinpanemab suggest target engagement of free monomeric aSyn of only 6-8% in CSF, 4-6% and 1-2% in the ISF and synaptic cleft, while maximal target engagement of aggregated aSyn was predicted to reach 99% and 80% in the synaptic cleft with similar effects on neuronal uptake. The study generates optimal values of selectivity, sensitivity and PK profiles for antibodies. The study identifies a gradient of decreasing target engagement from CSF to the synaptic cleft as a key driver of efficacy, quantitatively identifies various improvements for drug design and emphasizes the need for QSP modelling to support the development of tau and aSyn antibodies.
Topics: Humans; Network Pharmacology; Antibodies, Monoclonal; Biological Transport; Diffusion; Parkinson Disease
PubMed: 37658103
DOI: 10.1038/s41598-023-41382-0 -
Toxins Sep 2023Blue-green algae, or cyanobacteria, may be prevalent in our rivers and tap water. These minuscule bacteria can grow swiftly and form blooms in warm, nutrient-rich water.... (Review)
Review
Blue-green algae, or cyanobacteria, may be prevalent in our rivers and tap water. These minuscule bacteria can grow swiftly and form blooms in warm, nutrient-rich water. Toxins produced by cyanobacteria can pollute rivers and streams and harm the liver and nervous system in humans. This review highlights the properties of 25 toxin types produced by 12 different cyanobacteria genera. The review also covered strategies for reducing and controlling cyanobacteria issues. These include using physical or chemical treatments, cutting back on fertilizer input, algal lawn scrubbers, and antagonistic microorganisms for biocontrol. Micro-, nano- and ultrafiltration techniques could be used for the removal of internal and extracellular cyanotoxins, in addition to powdered or granular activated carbon, ozonation, sedimentation, ultraviolet radiation, potassium permanganate, free chlorine, and pre-treatment oxidation techniques. The efficiency of treatment techniques for removing intracellular and extracellular cyanotoxins is also demonstrated. These approaches aim to lessen the risks of cyanobacterial blooms and associated toxins. Effective management of cyanobacteria in water systems depends on early detection and quick action. Cyanobacteria cells and their toxins can be detected using microscopy, molecular methods, chromatography, and spectroscopy. Understanding the causes of blooms and the many ways for their detection and elimination will help the management of this crucial environmental issue.
Topics: Humans; Drinking Water; Lakes; Ultraviolet Rays; Diffusion; Cyanobacteria Toxins
PubMed: 37756009
DOI: 10.3390/toxins15090582 -
ACS Photonics Feb 2024Measuring the orientation dynamics of nanoparticles and nonfluorescent molecules in real time with optical methods is still a challenge in nanoscience and biochemistry....
Measuring the orientation dynamics of nanoparticles and nonfluorescent molecules in real time with optical methods is still a challenge in nanoscience and biochemistry. Here, we examine optoplasmonic sensing taking the rotational diffusion of plasmonic nanorods as an experimental model. Our detection method is based on monitoring the dark-field scattering of a relatively large sensor gold nanorod (GNR) (40 nm in diameter and 112 nm in length) as smaller plasmonic nanorods cross its near field. We observe the rotational motion of single small gold nanorods (three samples with about 5 nm in diameter and 15.5, 19.1, and 24.6 nm in length) in real time with a time resolution around 50 ns. Plasmonic coupling enhances the signal of the diffusing gold nanorods, which are 1 order of magnitude smaller in volume (about 300 nm) than those used in our previous rotational diffusion experiments. We find a better angular sensitivity with plasmonic coupling in comparison to the free diffusion in the confocal volume. Yet, the angle sensitivity we find with plasmonic coupling is reduced compared to the sensitivity expected from simulations at fixed positions due to the simultaneous translational and rotational diffusion of the small nanorods. To get a reliable plasmonic sensor with the full angular sensitivity, it will be necessary to construct a plasmonic assembly with positions and orientations nearly fixed around the optimum geometry.
PubMed: 38405388
DOI: 10.1021/acsphotonics.3c01482 -
Human Brain Mapping Nov 2023The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been...
The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current magnetic resonance based neuroimaging techniques. In this work, we used diffusion magnetic resonance imaging (dMRI) and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the neurite orientation dispersion and density imaging (NODDI) model optimized for grey matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the cornu ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibres, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitectonic differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures were separable across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fibre pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo dMRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.
Topics: Humans; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Neuroimaging; Hippocampus; Gray Matter; Neurites; White Matter
PubMed: 37615057
DOI: 10.1002/hbm.26461