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The subject of oil price forecasting has obtained an incredible amount of interest from academics and policymakers in recent years due to the widespread impact that it has on various economic fields and markets. Thus, a novel method based on decomposition-reconstruction-ensemble for crude oil price forecasting is proposed. Based on the Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) technique, in this paper we construct a recursive CEEMDAN decomposition-reconstruction-ensemble model considering the complexity traits of crude oil data. In this model, the steps of mode reconstruction, component prediction, and ensemble prediction are driven by complexity traits. For illustration and verification purposes, the West Texas Intermediate (WTI) and Brent crude oil spot prices are used as the sample data. The empirical result demonstrates that the proposed model has better prediction performance than the benchmark models. Thus, the proposed recursive CEEMDAN decomposition-reconstruction-ensemble model can be an effective tool to forecast oil price in the future.
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BACKGROUND: We sought to develop an automatable score to predict hospitalization, critical illness, or death for patients at risk for coronavirus disease 2019 (COVID-19) presenting for urgent care. METHODS: We developed the COVID-19 Acuity Score (CoVA) based on a single-center study of adult outpatients seen in respiratory illness clinics or the emergency department. Data were extracted from the Partners Enterprise Data Warehouse, and split into development (nâ =â 9381, 7 March-2 May) and prospective (nâ =â 2205, 3-14 May) cohorts. Outcomes were hospitalization, critical illness (intensive care unit or ventilation), or death within 7 days. Calibration was assessed using the expected-to-observed event ratio (E/O). Discrimination was assessed by area under the receiver operating curve (AUC). RESULTS: In the prospective cohort, 26.1%, 6.3%, and 0.5% of patients experienced hospitalization, critical illness, or death, respectively. CoVA showed excellent performance in prospective validation for hospitalization (expected-to-observed ratio [E/O]: 1.01; AUC: 0.76), for critical illness (E/O: 1.03; AUC: 0.79), and for death (E/O: 1.63; AUC: 0.93). Among 30 predictors, the top 5 were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS: CoVA is a prospectively validated automatable score for the outpatient setting to predict adverse events related to COVID-19 infection.
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COVID-19/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Estado Terminal , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Pacientes Ambulatoriais , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. Volumetric analysis of cerebellar morphometry in magnetic resonance imaging studies suffers from insufficient resolution, and therefore has had limited impact on disease assessment. Automatic serial polarization-sensitive optical coherence tomography (as-PSOCT) is an emerging technique that offers the advantages of microscopic resolution and volumetric reconstruction of large-scale samples. In this study, we reconstructed multiple cubic centimeters of ex vivo human cerebellum tissue using as-PSOCT. The morphometric and optical properties of the cerebellar cortex across five subjects were quantified. While the molecular and granular layers exhibited similar mean thickness in the five subjects, the thickness varied greatly in the granular layer within subjects. Layer-specific optical property remained homogenous within individual subjects but showed higher cross-subject variability than layer thickness. High-resolution volumetric morphometry and optical property maps of human cerebellar cortex revealed by as-PSOCT have great potential to advance our understanding of cerebellar function and diseases.
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Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colículos Superiores/diagnóstico por imagem , Substância Branca/diagnóstico por imagemRESUMO
Core-shell semiconductor quantum dots (QDs) are one of the biggest nanotechnology successes so far. In particular, type-I QDs with straddling band offset possess the ability to enhance the charge carriers capturing which is useful for memory application. Here, the type-I core-shell QD-based bipolar resistive switching (RS) memory with anomalous multiple SET and RESET processes was demonstrated. The synergy and competition between space charge limited current conduction (arising from charge trapping in potential well of type-I QDs) and electrochemical metallization (ECM, originating from redox reaction of Ag electrode) process were employed for modulating the RS behavior. Through utilizing stochastic RS mechanisms in QD-based devices, four situations of RS behaviors can be classified into three states in Markov chain for implementing the application of a true random number generator. Furthermore, a 6 × 6 cross-bar array was demonstrated to realize the generation of random letters with case distinction.
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Polarization sensitive optical coherence tomography (PSOCT) with serial sectioning has enabled the investigation of 3D structures in mouse and human brain tissue samples. By using intrinsic optical properties of back-scattering and birefringence, PSOCT reliably images cytoarchitecture, myeloarchitecture and fiber orientations. In this study, we developed a fully automatic serial sectioning polarization sensitive optical coherence tomography (as-PSOCT) system to enable volumetric reconstruction of human brain samples with unprecedented sample size and resolution. The 3.5 µm in-plane resolution and 50 µm through-plane voxel size allow inspection of cortical layers that are a single-cell in width, as well as small crossing fibers. We show the abilities of as-PSOCT in quantifying layer thicknesses of the cerebellar cortex and creating microscopic tractography of intricate fiber networks in the subcortical nuclei and internal capsule regions, all based on volumetric reconstructions. as-PSOCT provides a viable tool for studying quantitative cytoarchitecture and myeloarchitecture and mapping connectivity with microscopic resolution in the human brain.
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Encéfalo/ultraestrutura , Imageamento Tridimensional/métodos , Neuroimagem/métodos , Tomografia de Coerência Óptica/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , MasculinoRESUMO
Amyotrophic Lateral Sclerosis (ALS) is a neurological disorder, which impairs tongue function for speech and swallowing. A widely used Diffusion Tensor Imaging (DTI) analysis pipeline is employed for quantifying differences in tongue fiber myoarchitecture between controls and ALS patients. This pipeline uses both high-resolution magnetic resonance imaging (hMRI) and DTI. hMRI is used to delineate tongue muscles, while DTI provides indices to reveal fiber connectivity within and between muscles. The preliminary results using five controls and two patients show quantitative differences between the groups. This work has the potential to provide insights into the detrimental effects of ALS on speech and swallowing.
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Esclerose Lateral Amiotrófica/patologia , Doenças da Língua/patologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/complicações , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Língua/etiologiaRESUMO
Optical coherence tomography (OCT) and optical coherence microscopy (OCM) have demonstrated the ability to investigate cyto- and myelo-architecture in the brain. Polarization-sensitive OCT provides sensitivity to additional contrast mechanisms, specifically the birefringence of myelination and, therefore, is advantageous for investigating white matter fiber tracts. In this Letter, we developed a polarization-sensitive optical coherence microscope (PS-OCM) with a 3.5 µm axial and 1.3 µm transverse resolution to investigate fiber organization and orientation at a finer scale than previously demonstrated with PS-OCT. In a reconstructed mouse brain section, we showed that at the focal depths of 20-70 µm, the PS-OCM reliably identifies the neuronal fibers and quantifies the in-plane orientation.
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Encéfalo/diagnóstico por imagem , Microscopia de Polarização/métodos , Tomografia de Coerência Óptica/métodos , Animais , Birrefringência , Camundongos , NeuroimagemRESUMO
BACKGROUND: The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented. METHODS AND RESULTS: Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells 3 weeks after coronary ligation. In half of the mice the donor and recipient strains were identical, and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to bone marrow mononuclear cell injection was seen in 1 mouse. The response of the majority of mice to bone marrow mononuclear cell injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology. CONCLUSIONS: Diffusion tensor magnetic resonance imaging tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.
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Transplante de Medula Óssea/métodos , Imagem de Tensor de Difusão/métodos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/terapia , Animais , Anisotropia , Modelos Animais de Doenças , Voluntários Saudáveis , Imageamento Tridimensional/métodos , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologiaRESUMO
In current sensorimotor theories pertaining to speech perception, there is a notable emphasis on the involvement of the articulatory-motor system in the processing of speech sounds. Using ultra-high field diffusion-weighted imaging at 7 Tesla, we visualized the white matter tracts connected to areas activated during a simple speech-sound production task in 18 healthy right-handed adults. Regions of interest for white matter tractography were individually determined through 7T functional MRI (fMRI) analyses, based on activations during silent vocalization tasks. These precentral seed regions, activated during the silent production of a lip-vowel sound, demonstrated anatomical connectivity with posterior superior temporal gyrus areas linked to the auditory perception of phonetic sounds. Our study provides a macrostructural foundation for understanding connections in speech production and underscores the central role of the articulatory motor system in speech perception. These findings highlight the value of ultra-high field 7T MR acquisition in unraveling the neural underpinnings of speech.
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Substância Branca , Adulto , Humanos , Substância Branca/diagnóstico por imagem , Percepção Auditiva , Imagem de Difusão por Ressonância Magnética , Mãos , IdiomaRESUMO
Current techniques to image the microstructure of the heart with diffusion tensor MRI (DTI) are highly under-resolved. We present a technique to improve the spatial resolution of cardiac DTI by almost 10-fold and leverage this to measure local gradients in cardiomyocyte alignment or helix angle (HA). We further introduce a phenomapping approach based on voxel-wise hierarchical clustering of these gradients to identify distinct microstructural microenvironments in the heart. Initial development was performed in healthy volunteers (n=8). Thereader, subjects with severe but well-compensated aortic stenosis (AS, n=10) were compared to age-matched controls (CTL, n=10). Radial HA gradient was significantly reduced in AS (8.0±0.8°/mm vs. 10.2±1.8°/mm, p=0.001) but the other HA gradients did not change significantly. Four distinct microstructural clusters could be idenJfied in both the CTL and AS subjects and did not differ significantly in their properties or distribution. Despite marked hypertrophy, our data suggest that the myocardium in well-compensated AS can maintain its microstructural coherence. The described phenomapping approach can be used to characterize microstructural plasticity and perturbation in any organ system and disease.
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Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in gray matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical gray matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1.
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Mapeamento Encefálico/métodos , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Animais , Anisotropia , Difusão , Humanos , MacacaRESUMO
Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.
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Axônios/patologia , Corpo Caloso/patologia , Hipocampo/patologia , Abuso de Maconha/patologia , Fibras Nervosas Mielinizadas/patologia , Neuroimagem/métodos , Adulto , Fatores Etários , Anisotropia , Axônios/ultraestrutura , Estudos de Casos e Controles , Corpo Caloso/ultraestrutura , Imagem de Tensor de Difusão/métodos , Feminino , Hipocampo/ultraestrutura , Humanos , Masculino , Fibras Nervosas Mielinizadas/ultraestrutura , Vias Neurais/patologiaRESUMO
Entorhinal cortex displays a distinctive organization in layer II and forms small elevations on its surface called entorhinal verrucae. In Alzheimer's disease, the verrucae disappear due to neurofibrillary tangle formation and neuronal death. Isosurface models were reconstructed from high-resolution ex vivo MRI volumes scanned at 7.0 T and individual verruca were measured quantitatively for height, width, volume, and surface area on control and mild Alzheimer's cases. Mean verruca height was 0.13 ± 0.04 mm for our cognitively normal (controls) sample set whereas for mild AD samples mean height was 0.11 mm ± 0.05 mm (p < 0.001) in entorhinal cortex (n = 10 cases). These quantitative methods were validated by a significant correlation of verrucae height and volume with qualitative verrucae ratings (n = 36 cases). Entorhinal surfaces were significantly different from other cortical heights such as, cingulate, frontal, occipital, parietal and temporal cortices. Colocalization of verrucae with entorhinal islands was confirmed in ex vivo MRI and, moreover, verrucae ratings were negatively correlated to Braak and Braak pathological stage. This study characterizes novel methods to measure individual entorhinal verruca size, and shows that verrucae size correlates to Alzheimer's pathology. Taken together, these results suggest that verrucae may have the potential to serve as an early and specific morphological marker for mild cognitive impairment and Alzheimer's disease.
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Doença de Alzheimer/patologia , Córtex Entorrinal/patologia , Imageamento por Ressonância Magnética/métodos , Emaranhados Neurofibrilares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Temporal/patologiaRESUMO
The immature cortex (cortical plate [CP]) and underlying subplate (SP), a transient cell layer just below the CP, play critical roles in the formation of intracerebral connections. The purpose of this study was to examine the diffusion characteristics of the developing cortex and subcortical structures and compare to histology. We obtained high-resolution diffusion spectrum images of postnatal day (P) 0 (newborn), P35 (pediatric), and P100 (adult) cat brains, performed tractography analysis, and correlated with histological findings. Tractography revealed radial organization and radial afferent/efferent tracts not only in the CP but also in external SP at P0. Radial organization persisted only in the cortex but decreased at P35 and P100. Radial organization correlated with radial cellular organization, with highest cellular density at P0 (Cresyl Violet staining). At P0, the internal SP contained abundant corticocortical and projection tractography pathways, crossing at wide angles in areas with no myelination by Luxol Fast Blue staining. At P35 and P100, increased directional coherence of white matter was observed, with fewer local tracts, but more long association pathways. These results suggest that diffusion tractography can differentially characterize internal and external SP zones and their transition into mature cortical pathways.
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Axônios/fisiologia , Imagem de Tensor de Difusão/métodos , Neocórtex/anatomia & histologia , Neocórtex/crescimento & desenvolvimento , Vias Neurais/anatomia & histologia , Vias Neurais/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Mapeamento Encefálico/métodos , Gatos , Diferenciação Celular/fisiologia , Processamento de Imagem Assistida por Computador/métodosRESUMO
Metallic silicon could be an inexpensive, alternative reducing agent for CO2 functionalization compared to conventionally used hydrogen or hydrosilanes. Here, metallic silicon recovered from solar panel production is used as a reducing agent for formamide synthesis. Various amines are converted to their corresponding amides with CO2 and H2O via an Si-H intermediate species in the presence of a catalytic amount of tetrabutylammonium fluoride. The reaction system exhibits a wide substrate scope for formamide synthesis. Spectroscopic analysis, including in situ Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), N2 adsorption/desorption analyses, and isotopic experiments reveal that the fluoride catalyst effectively oxidizes Si atoms on both surface and interior of the powdered silicon particles. The solid recovered after catalysis contained mesopores with a high surface area. This unique behavior of the fluoride catalyst in the presence of metallic silicon may be extendable to other reductive reactions, including those with complex substrates. Therefore, this study presents a potential strategy for the efficient utilization of abundant resources.
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The floating body effect in Meta-Stable-Dip RAM (MSDRAM) has been broadly employed in implementing single-transistor capacitor-less (1T0C) dynamic random access memory (DRAM) cells to break through the limitation of finite size reduction of peripheral capacitors. However, the majority of them were broadly demonstrated in conventional CMOS technology, while emerging semiconductor systems are rarely explored. Here, we creatively explore exfoliated multilayer tungsten diselenide (WSe2) for the application of 1T0C DRAM, breaking the limitation of channel thickness in the traditional architecture. Through the comparison of the electrical characteristics among three dual-gate transistors with different lengths of top-gate, we demonstrated the essential role of the floating body effect in achieving the function of 1T0C DRAM displaying two distinct states that are differentiated by hole population within the floating body. Moreover, according to the analysis of in situ electrostatic force microscopy (EFM) measurements and theoretical calculation via density functional theory (DFT), the injection of holes through band-to-band (B2B) tunneling can be ascribed to the effectively electrostatic modulation. These consequences prove our innovative concept to achieve the function of 1T0C DRAM through employing the ML WSe2, which is a vital step toward the breakthrough of the inherent limitations of DRAM cells.
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SemicondutoresRESUMO
BACKGROUND: Neurofibrillary tangle (NFT) accumulation in the entorhinal cortex (EC) precedes the transformation from cognitive controls to mild cognitive impairment and Alzheimer's disease (AD). While tauopathy has been described in the EC before, the order and degree to which the individual subfields within the EC are engulfed by NFTs in aging and the preclinical AD stage is unknown. OBJECTIVE: We aimed to investigate substructures within the EC to map the populations of cortical neurons most vulnerable to tau pathology in aging and the preclinical AD stage. METHODS: We characterized phosphorylated tau (CP13) in 10 cases at eight well-defined anterior-posterior levels and assessed NFT density within the eight entorhinal subfields (described by Insausti and colleagues) at the preclinical stages of AD. We validated with immunohistochemistry and labeled the NFT density ratings on ex vivo MRIs. We measured subfield cortical thickness and reconstructed the labels as three-dimensional isosurfaces, resulting in anatomically comprehensive, histopathologically validated tau "heat maps." RESULTS: We found the lateral EC subfields ELc, ECL, and ECs (lateral portion) to have the highest tau density in semi-quantitative scores and quantitative measurements. We observed significant stepwise higher tau from anterior to posterior levels (pâ<â0.001). We report an age-dependent anatomically-specific vulnerability, with all cases showing posterior tau pathology, yet older individuals displaying an additional anterior tau burden. Finally, cortical thickness of each subfield negatively correlated with respective tau scores (pâ<â0.05). CONCLUSION: Our findings indicate that posterior-lateral subfields within the EC are the most vulnerable to early NFTs and atrophy in aging and preclinical AD.
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Doença de Alzheimer , Tauopatias , Envelhecimento , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Córtex Entorrinal/patologia , Humanos , Emaranhados Neurofibrilares/patologia , Tauopatias/diagnóstico por imagem , Tauopatias/patologia , Proteínas tau/metabolismoRESUMO
The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2'-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements in ex vivo human brain tissue. We show that we can obtain fiber orientation maps of U-fibers that underlie sulci, as well as cortical fibers in the gray matter, including radial fibers in gyri and distinct layers of fibers exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.
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Neuroimaging studies have routinely used hippocampal volume as a measure of Alzheimer's disease severity, but hippocampal changes occur too late in the disease process for potential therapies to be effective. The entorhinal cortex is one of the first cortical areas affected by Alzheimer's disease; its neurons are especially vulnerable to neurofibrillary tangles. Entorhinal atrophy also relates to the conversion from non-clinical to clinical Alzheimer's disease. In neuroimaging, the human entorhinal cortex has so far mostly been considered in its entirety or divided into a medial and a lateral region. Cytoarchitectonic differences provide the opportunity for subfield parcellation. We investigated the entorhinal cortex on a subfield-specific level-at a critical time point of Alzheimer's disease progression. While MRI allows multidimensional quantitative measurements, only histology provides enough accuracy to determine subfield boundaries-the pre-requisite for quantitative measurements within the entorhinal cortex. This study used histological data to validate ultra-high-resolution 7â Tesla ex vivo MRI and create entorhinal subfield parcellations in a total of 10 pre-clinical Alzheimer's disease and normal control cases. Using ex vivo MRI, eight entorhinal subfields (olfactory, rostral, medial intermediate, intermediate, lateral rostral, lateral caudal, caudal, and caudal limiting) were characterized for cortical thickness, volume, and pial surface area. Our data indicated no influence of sex, or Braak and Braak staging on volume, cortical thickness, or pial surface area. The volume and pial surface area for mean whole entorhinal cortex were 1131 ± 55.72â mm3 and 429 ± 22.6â mm2 (mean ± SEM), respectively. The subfield volume percentages relative to the entire entorhinal cortex were olfactory: 18.73 ± 1.82%, rostral: 14.06 ± 0.63%, lateral rostral: 14.81 ± 1.22%, medial intermediate: 6.72 ± 0.72%, intermediate: 23.36 ± 1.85%, lateral caudal: 5.42 ± 0.33%, caudal: 10.99 ± 1.02%, and caudal limiting: 5.91 ± 0.40% (all mean ± SEM). Olfactory and intermediate subfield revealed the most extensive intra-individual variability (cross-subject variance) in volume and pial surface area. This study provides validated measures. It maps individuality and demonstrates human variability in the entorhinal cortex, providing a baseline for approaches in individualized medicine. Taken together, this study serves as a ground-truth validation study for future in vivo comparisons and treatments.
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Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-µm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.