Imaging Neurosci (Camb)
May 2024
MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high-resolution dataset of 135 postmortem human brain tissue specimens imaged at 0.
View Article and Find Full Text PDFOur current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield.
View Article and Find Full Text PDFBackground: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, image quality may vary in MRI. Poor quality MR images can lead to unreliable segmentation of MTL subregions.
View Article and Find Full Text PDFMedical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH.
View Article and Find Full Text PDFIntroduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods.
Methods: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere.
Frontotemporal lobar degeneration (FTLD) is a heterogeneous spectrum of age-associated neurodegenerative diseases that include two main pathologic categories of tau (FTLD-Tau) and TDP-43 (FTLD-TDP) proteinopathies. These distinct proteinopathies are often clinically indistinguishable during life, posing a major obstacle for diagnosis and emerging therapeutic trials tailored to disease-specific mechanisms. Moreover, MRI-derived measures have had limited success to date discriminating between FTLD-Tau or FTLD-TDP.
View Article and Find Full Text PDFTau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer's disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease.
View Article and Find Full Text PDFTau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.
View Article and Find Full Text PDFAims: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants.
Methods And Results: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO ), ventilatory threshold (VT), and VO efficiency (ratio of total work performed to O consumed).
Background: Olfactory impairments are prominent in both schizophrenia and the preceding at-risk state. Their presence prior to illness predicts poor functional outcome. In schizophrenia, these impairments reflect peripheral olfactory structural abnormalities, which are hypothesized to arise during early embryonic development.
View Article and Find Full Text PDFPsychiatry Res Neuroimaging
October 2017
Diffusion tensor imaging (DTI) studies in 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with psychosis, report brain white matter (WM) microstructure aberrations. Several studies report that WM disruptions in 22q11DS are similar to deficits in idiopathic schizophrenia.
View Article and Find Full Text PDFBackground: Diffusion tensor imaging (DTI) is applied in investigation of brain biomarkers for neurodevelopmental and neurodegenerative disorders. However, the quality of DTI measurements, like other neuroimaging techniques, is susceptible to several confounding factors (e.g.
View Article and Find Full Text PDFThe Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale study of child development that combines neuroimaging, diverse clinical and cognitive phenotypes, and genomics. Data from this rich resource is now publicly available through the Database of Genotypes and Phenotypes (dbGaP). Here we focus on the data from the PNC that is available through dbGaP and describe how users can access this data, which is evolving to be a significant resource for the broader neuroscience community for studies of normal and abnormal neurodevelopment.
View Article and Find Full Text PDFImportance: The continuum view of the psychosis spectrum (PS) implies that, in population-based samples, PS symptoms should be associated with neural abnormalities similar to those found in help-seeking clinical risk individuals and in schizophrenia. To our knowledge, functional neuroimaging has not previously been applied in large population-based PS samples and can help us understand the neural architecture of psychosis more broadly and identify brain phenotypes beyond symptoms that are associated with the extended psychosis phenotype.
Objective: To examine the categorical and dimensional relationships of PS symptoms to prefrontal hypoactivation during working memory and to amygdala hyperactivation during threat emotion processing.
Background: There is increased risk of developing psychosis in 22q11.2 deletion syndrome (22q11DS). Although this condition is associated with morphologic brain abnormalities, simultaneous examination of multiple high-resolution measures of cortical structure has not been performed.
View Article and Find Full Text PDFPuberty is the defining biological process of adolescent development, yet its effects on fundamental properties of brain physiology such as cerebral blood flow (CBF) have never been investigated. Capitalizing on a sample of 922 youths ages 8-22 y imaged using arterial spin labeled MRI as part of the Philadelphia Neurodevelopmental Cohort, we studied normative developmental differences in cerebral perfusion in males and females, as well as specific associations between puberty and CBF. Males and females had conspicuously divergent nonlinear trajectories in CBF evolution with development as modeled by penalized splines.
View Article and Find Full Text PDFJ Am Acad Child Adolesc Psychiatry
March 2014
Objective: Puberty is the defining process of adolescence, and is accompanied by divergent trajectories of behavior and cognition for males and females. Here we examine whether sex differences exist in the effect of puberty on the morphology of the hippocampus and amygdala.
Method: T1-weighted structural neuroimaging was performed in a sample of 524 pre- or postpubertal individuals ages 10 to 22 years.
Adolescence is characterized by rapid development of executive function. Working memory (WM) is a key element of executive function, but it is not known what brain changes during adolescence allow improved WM performance. Using a fractal n-back fMRI paradigm, we investigated brain responses to WM load in 951 human youths aged 8-22 years.
View Article and Find Full Text PDFThe Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8-21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset.
View Article and Find Full Text PDFSeveral independent studies have demonstrated that small amounts of in-scanner motion systematically bias estimates of resting-state functional connectivity. This confound is of particular importance for studies of neurodevelopment in youth because motion is strongly related to subject age during this period. Critically, the effects of motion on connectivity mimic major findings in neurodevelopmental research, specifically an age-related strengthening of distant connections and weakening of short-range connections.
View Article and Find Full Text PDFPurpose: To evaluate the diagnostic value of susceptibility-weighted imaging (SWI) for studying brain masses.
Materials And Methods: SWI is a high-resolution, three-dimensional, fully velocity-compensated gradient-echo sequence that uses both magnitude and phase data. Custom postprocessing is applied to enhance the contrast in the magnitude images between tissues with different susceptibilities.