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Accumulation of non-heme iron is believed to play a major role in neurodegeneration of the basal ganglia. In healthy aging, however, the temporal relationship between change in brain iron content and age-related volume loss is unclear. Here, we present the first long-term longitudinal multi-occasion investigation of changes in iron content and volume in the neostriatum in a sample of healthy middle-aged and older adults (N=32; ages 49–83years at baseline). Iron content, estimated via R2* relaxometry, increased in the putamen, but not the caudate nucleus. In the former, the rate of accumulation was coupled with change in volume. Moreover, greater baseline iron content predicted faster shrinkage and smaller volumes seven years later. Older age partially accounted for individual differences in neostriatal iron content and volume, but vascular risk did not. Thus, brain iron content may be a promising biomarker of impending decline in normal aging. •Iron-related oxidative stress is a proposed mechanism of brain aging.•Neostriatal iron content and volume were assessed multiple times over seven years.•Middle-aged and older adults showed iron accumulation in putamen but not caudate.•Putamen iron accumulation preceded and predicted shrinkage.•Greater baseline iron predicted faster shrinkage and greater loss after seven years.

The hippocampus (Hc) consists of cytoarchitectonically and functionally distinct subfields: dentate gyrus (DG), cornu ammonis (CA1-3), and subiculum. In adults, a single nucleotide polymorphism (rs17070145, C→ T) in KIBRA , a gene encoding the eponymous (KIdney-BRAin) protein, is associated with variability in Hc subfield volumes and episodic memory. T-allele carriers have larger DG and CA volumes and better episodic memory compared to C-homozygotes. Little is known, however, about KIBRA ’s role in the development of the brain and cognition. In a sample of children, adolescents, and young adults ( N  = 176, ages 5– 25 years) , we replicated the adult association between KIBRA T-allele and larger DG and CA volumes but observed no relationship between KIBRA rs17070145 polymorphism and episodic memory. We noted, however, that a general cognitive performance index (IQ) differed across the allelic groups, with the lowest scores among T-homozygotes and the highest among C-homozygotes. Thus, in this developmental sample, KIBRA appears to have opposing effects on regional brain volume and cognition. These influences of KIBRA SNP may stem from associations between developmental reduction in brain volume and gains in cognitive performance—a hypothesis to be tested in longitudinal studies.

Non-heme iron accumulation contributes to age-related decline in brain structure and cognition via a cascade of oxidative stress and inflammation, although its effect on brain function is largely unexplored. Thus, we examine the impact of striatal iron on dynamic range of BOLD modulation to working memory load. N ​= ​166 healthy adults (age 20–94) underwent cognitive testing and an imaging session including n-back (0-, 2-, 3-, and 4-back fMRI), R2*-weighted imaging, and pcASL to measure cerebral blood flow. A statistical model was constructed to predict voxelwise BOLD modulation by age, striatal iron content and an age ​× ​iron interaction, controlling for cerebral blood flow, sex, and task response time. A significant interaction between age and striatal iron content on BOLD modulation was found selectively in the putamen, caudate, and inferior frontal gyrus. Greater iron was associated with reduced modulation to difficulty, particularly in middle-aged and younger adults with greater iron content. Further, iron-related decreases in modulation were associated with poorer executive function in an age-dependent manner. These results suggest that iron may contribute to differences in functional brain activation prior to older adulthood, highlighting the potential role of iron as an early factor contributing to trajectories of functional brain aging. •Iron accumulation contributes to age-related decline in brain structure and cognition.•Effects of non-heme iron accumulation on brain function are largely unexplored.•Age by striatal iron interaction on BOLD modulation found selectively in striatum.•Greater iron associated with reduced modulation in middle-aged and younger adults.•Iron-related decreases in modulation associated with age-related poorer executive function.

Using Phosphorus Magnetic Resonance Spectroscopy (31P MRS), we examined five metabolites associated with brain energy cycle, and cellular membrane production and degradation in 11 brain regions of 48 children (age 6–15), and 80 middle‐aged and older adults (age 52–87). Levels of phosphomonoesters (PMEs) and phosphodiesters (PDEs), gamma plus alpha adenosine triphosphate (γαATP), phosphocreatine (PCr) and inorganic phosphate (Pi), were residualized on the total amplitude value. PMEs were greater in children compared to adults, whereas PDEs showed the opposite age difference. Higher γαATP and lower Pi were found in children compared to adults. The age group differences were particularly salient in the association cortices and anterior white matter. Among children, age correlated negatively with PMEs and positively with PDEs in association cortices. Compared to children, adults had lower intracellular pH. The results suggest reduction in membrane synthesis and increase in membrane degradation in adolescents and to a greater degree in adults compared to younger children. Concomitant reduction in γαATP and increase in Pi are consistent with reduced energy consumption in adolescents and further drop in middle‐aged and older adults, although it is impossible to distinguish declines in energy supply from reduced demand due to shrinking neuropil, without longitudinal studies. Using 31P MRS, we found age differences in availability of energy substrates and balance between markers of production and degradation of cellular membranes, especially in the association cortices and anterior white matter. Longitudinal studies are needed to clarify the role of these metabolites in lifespan changes in neuropil volume.

PurposeTo evaluate histological changes in stenotic urethral tissue post-radiation therapy. Treatment of prostate cancer by radiation therapy carries a risk of off-target injury to the membranous urethra causing urethral stenosis. Limited characterization of post-radiation urethral stenosis exists in the literature. We hypothesize that specific histopathologic parameters distinguish this stricture etiology.MethodsEighty-two consecutive patients with membranous urethral stenosis underwent urethroplasty between 2013 and 2018. Seventy specimens (86.4%) were available for evaluation: 51 from patients without radiation exposure and 19 from patients with history of radiation therapy for prostate cancer. All specimens were reviewed by a pathologist blinded to patient/stricture information. Histological scoring system was used for the quantification of collagen density, collagen organization, hyalinized fibrosis, vascular density, spindle-cell change, necrosis, hemorrhage, fat entrapment, vacuolation, acute and chronic inflammation, and foreign-body giant cells. Differences in histologic outcomes between groups were statistically analyzed.ResultsPost-radiation specimens had a higher collagen density (p = 0.01), higher collagen organization (p = 0.001), increased hyalinized fibrosis (p = 0.03), fat entrapment (p = 0.005) and spindle cell change (p = 0.005) when compared to membranous specimens without prior exposure to radiation. Post-radiation specimens also had a significantly decreased vascularity compared to specimens of non-radiated etiology (p = 0.0005). Fibrous connective tissue degenerative change with vacuolation was pronounced in post-radiation specimens and seldom seen in those without radiation (p = 0.0001).ConclusionsMembranous urethral stenosis following radiation demonstrates specific histologic characteristics including vascular loss and increased scarring (collagen density, organization). This histologic grading system may be used in grading severity of radiation damage, and conceivably adopted for correlation with clinical outcomes.

Distinguishing differences between authentic artifacts and replicas is a significant challenge in the field of cultural heritage. In this study, we explore the application of neutron grating interferometry and tomography techniques to identify Korean copper coins in the nineteenth century of Joseon period by investigating structural differences between genuine objects and replicas. Neutron grating interferometry provides the microstructural information of coins, including features such as pores and precipitates, through a dark field image derived from small-angle neutron scattering. Additionally, neutron transmission tomography examines the three-dimensional internal structures and potentially hidden features of coins. Both neutron imaging techniques highlight regions that contain lead precipitates in the copper alloy, showing consistent agreement with optical imaging and with the quantitative lead content measured by energy dispersive X-ray spectroscopy. The distinct corrosion patterns observed in the authentic coin and replica provide empirical explanations for the general corrosion mechanism of copper alloy. This interpretation finds support in the moderate contribution of dark field contrast from cuprite, which underlies the signal of lead precipitates.

Neutron interferometry uniquely combines neutron imaging and scattering methods to enable characterization of multiple length scales from 1 nm to 10 µm. However, building, operating, and using such neutron imaging instruments poses constraints on the acquisition time and on the number of measured images per sample. Experiment time-constraints yield small quantities of measured images that are insufficient for automating image analyses using supervised artificial intelligence (AI) models. One approach alleviates this problem by supplementing annotated measured images with synthetic images. To this end, we create a data-driven simulation framework that supplements training data beyond typical data-driven augmentations by leveraging statistical intensity models, such as the Johnson family of probability density functions (PDFs). We follow the simulation framework steps for an image segmentation task including Estimate PDFs → Validate PDFs → Design Image Masks → Generate Intensities → Train AI Model for Segmentation. Our goal is to minimize the manual labor needed to execute the steps and maximize our confidence in simulations and segmentation accuracy. We report results for a set of nine known materials (calibration phantoms) that were imaged using a neutron interferometer acquiring four-dimensional images and segmented by AI models trained with synthetic and measured images and their masks.

We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19–79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development. •Volume change and individual differences in change across brain regions.•Average change: memory & vocabulary; individual differences: fluid intelligence.•Larger baseline brain volumes predicted greater gains in Gf.•Prefrontal gray shrinkage was related to poorer baseline cognitive performance.•Shrinkage of prefrontal white matter correlated with negative change in Gf.

Neuroimaging evidence suggests that the development of the hippocampus, a brain structure critical for memory function, contributes to the improvements of episodic memory between middle childhood to adulthood. However, investigations on age differences in hippocampal activation and functional connectivity and their contributions to the development of memory have yielded mixed results. Given the known structural and functional heterogeneity along the long axis of the hippocampus, we investigated age differences in the activation and functional connectivity in hippocampal subregions with a cross-sectional sample of 96 participants ages 8 to 25 years. We found that anterior and posterior hippocampus supported memory formation, and there was an overall stability in memory-related hippocampal activation with age. Without taking account of memory outcome, direct contrast between subregions showed higher functional connectivity of anterior, compared to posterior hippocampus, with regions in the inferior frontal and lateral temporal lobes, and higher functional connectivity of posterior, compared to anterior hippocampus, with regions in the medial and superior frontal, inferior parietal, and occipital lobes. A direct contrast between the memory-related connectivity patterns of anterior and posterior hippocampus identified a region in the medial frontal cortex, with which anterior and posterior hippocampus were differentially functionally connected. Finally, we identified age differences in memory-related differential hippocampal functional connectivity with several frontal and visual/sensory cortices, underscoring the importance of examining age differences in the patterns of hippocampal connectivity. Moreover, the specific patterns of differential anterior and posterior functional connectivity indicate an increase in the functional specialization along the long axis of the hippocampus and a dynamic shift in hippocampal connectivity patterns that supports memory development.