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1.AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that baseline cerebrovascular dysfunction, as measured by an MRI measure of cerebrovascular reactivity (CVR), contributes to the later development of ePVS.MethodsA total of 79 cognitively normal, older adults (46 women, age range 60-84) were recruited to undergo MRI scanning at baseline and 50 participants returned for a follow-up scan approximately 2.5 years later. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. CVR, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon-dioxide inhalation while acquiring blood oxygen-level dependent (BOLD) MR images.ResultsLow baseline CVR values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (coefficient estimate (SE) = -15.87 (3.92), p < 0.001, 95% confidence interval [CI] -23.68 to - 8.05). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (cSVD) (coefficient estimate (SE) = -15.03 (4.00), p < 0.001, CI -23.02 to - 7.05) and neuroimaging markers of cSVD (coefficient estimate (SE) = -13.99 (4.02), p < 0.001, CI -22.03 to -5.95).ConclusionsOur results demonstrate that low baseline CVR is a risk factor for later development of ePVS. MRI-based CVR may represent a promising biomarker of cSVD.

Aging is associated with brain iron accumulation, which has been linked to cognitive decline. However, how brain iron affects the structure and function of cognitive brain networks remains unclear. Here, we explored the possibility that iron load in gray matter is associated with disruption of white matter (WM) microstructure within a network supporting cognitive function, in a cohort of 95 cognitively normal older adults (age range: 60–86). Functional magnetic resonance imaging was used to localize a set of brain regions involved in working memory and diffusion tensor imaging based probabilistic tractography was used to identify a network of WM tracts connecting the functionally defined regions. Brain iron concentration within these regions was evaluated using quantitative susceptibility mapping and microstructural properties were assessed within the identified tracts using neurite orientation dispersion and density imaging. Results indicated that high brain iron concentration was associated with low neurite density (ND) within the task-relevant WM network. Further, regional associations were observed such that brain iron in cortical regions was linked with lower ND in neighboring but not distant WM tracts. Our results provide novel evidence suggesting that age-related increases in brain iron concentration are associated with the disruption of WM tracts supporting cognitive function in normal aging.

IntroductionTo evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.MethodsBaseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).ResultsHigher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values&nbsp

To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).The three biomarkers demonstrated excellent inter-rater reliability (ICC 0.94,The three biomarker kits demonstrated very high inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID).

Educational attainment is widely accepted as a cognitive reserve variable. However, few studies have demonstrated that education statistically moderates the effects of pathology on cognition. Here, we explored this issue in a sample of 441 Alzheimer's disease (AD) and mild cognitive impairment participants from the Alzheimer's Disease Neuroimaging Initiative cohort who had AD markers (Aβ42, tau, structural brain volumes) at baseline and underwent cognitive testing at baseline and at 6-month, 12-month, and 24-month time points. An AD-related biomarker (atrophy/pathology) composite at baseline was developed using stepwise backward linear regression. Potential moderation effects of education on the relationship between AD biomarkers and cognition were explored using linear mixed models. Education was positively correlated with cognition, and biomarkers were negatively correlated with cognition, across domains and diagnostic groups. However, education generally did not moderate the effects of biomarkers on baseline or longitudinal cognition. Our results do not support the hypothesis that education protects cognitive function from brain pathology in the Alzheimer's Disease Neuroimaging Initiative cohort, questioning its accepted status as a reserve variable.

Study Objectives:To assess the sleep detection and staging validity of a non-contact, commercially available bedside bio-motion sensing device (S+, ResMed) and evaluate the impact of algorithm upda...

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of seventy-three healthy older adults (61–86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm to evaluate working memory performance. Nutritional-intake was assessed via a validated questionnaire. Nutrients were grouped into nutrition factors based on previous literature and factor analysis. One factor, comprised of vitamin E, lysine, DHA omega-3 and LA omega-6 PUFA, representing food groups such as nuts, healthy oils and fish, moderated the effects of age on both brain iron concentration and working memory performance, suggesting that these nutrients may slow the rate of brain iron accumulation and working memory declines in aging.

Many individuals with autism spectrum disorder (ASD) have been shown to perceive everyday sensory information differently compared to peers without autism. Research examining these sensory differences has primarily utilized nonnatural stimuli or natural stimuli using static photos with few having utilized dynamic, real-world nonverbal stimuli. Therefore, in this study, we used functional magnetic resonance imaging to characterize brain activation of individuals with high-functioning autism when viewing and listening to a video of a real-world scene (a person bouncing a ball) and anticipating the bounce. We investigated both multisensory and unisensory processing and hypothesized that individuals with ASD would show differential activation in (a) primary auditory and visual sensory cortical and association areas, and in (b) cortical and subcortical regions where auditory and visual information is integrated (e.g. temporal-parietal junction, pulvinar, superior colliculus). Contrary to our hypotheses, the whole-brain analysis revealed similar activation between the groups in these brain regions. However, compared to controls the ASD group showed significant hypoactivation in the left intraparietal sulcus and left putamen/globus pallidus. We theorize that this hypoactivation reflected underconnectivity for mediating spatiotemporal processing of the visual biological motion stimuli with the task demands of anticipating the timing of the bounce event. The paradigm thus may have tapped into a specific left-lateralized aberrant corticobasal circuit or loop involved in initiating or inhibiting motor responses. This was consistent with a dual "when versus where" psychophysical model of corticobasal function, which may reflect core differences in sensory processing of real-world, nonverbal natural stimuli in ASD. Autism Res 2020, 13: 539-549. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: To understand how individuals with autism perceive the real-world, using magnetic resonance imaging we examined brain activation in individuals with autism while watching a video of someone bouncing a basketball. Those with autism had similar activation to controls in auditory and visual sensory brain regions, but less activation in an area that processes information about body movements and in a region involved in modulating movements. These areas are important for understanding the actions of others and developing social skills.

Extended breastfeeding through infancy confers benefits on neurocognitive performance and intelligence tests, though few have examined the biological basis of these effects. To investigate correlations with breastfeeding, we examined the major white matter tracts in 4&ndash, 8 year-old children using diffusion tensor imaging and volumetric measurements of the corpus callosum. We found a significant correlation between the duration of infant breastfeeding and fractional anisotropy scores in left-lateralized white matter tracts, including the left superior longitudinal fasciculus and left angular bundle, which is indicative of greater intrahemispheric connectivity. However, in contrast to expectations from earlier studies, no correlations were observed with corpus callosum size, and thus no correlations were observed when using such measures of global interhemispheric white matter connectivity development. These findings suggest a complex but significant positive association between breastfeeding duration and white matter connectivity, including in pathways known to be functionally relevant for reading and language development.

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults.

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient’s head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk—the Ambulatory Microdose PET (AM-PET)—is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

Background Positron Emission Tomography (PET) is traditionally used to image patients in restrictive positions, with few devices allowing for upright, brain-dedicated imaging. Our team has explored the concept of wearable PET imagers which could provide functional brain imaging of freely moving subjects. To test feasibility and determine future considerations for development, we built a rudimentary proof-of-concept prototype (Helmet_PET) and conducted tests in phantoms and four human volunteers. Methods Twelve Silicon Photomultiplier-based detectors were assembled in a ring with exterior weight support and an interior mechanism that could be adjustably fitted to the head. We conducted brain phantom tests as well as scanned four patients scheduled for diagnostic F18-FDG PET/CT imaging. For human subjects the imager was angled such that field of view included basal ganglia and visual cortex to test for typical resting-state pattern. Imaging in two subjects was performed ~4 hr after PET/CT imaging to simulate lower injected F18-FDG dose by taking advantage of the natural radioactive decay of the tracer (F18 half-life of 110 min), with an estimated imaging dosage of 25% of the standard. Results We found that imaging with a simple lightweight ring of detectors was feasible using a fraction of the standard radioligand dose. Activity levels in the human participants were quantitatively similar to standard PET in a set of anatomical ROIs. Typical resting-state brain pattern activation was demonstrated even in a 1 min scan of active head rotation. Conclusion To our knowledge, this is the first demonstration of imaging a human subject with a novel wearable PET imager that moves with robust head movements. We discuss potential research and clinical applications that will drive the design of a fully functional device. Designs will need to consider trade-offs between a low weight device with high mobility and a heavier device with greater sensitivity and larger field of view.

Our research group constructed a 12-module PET detection ring composed of Hamamatsu multi-pixel photon counter (MMPC) silicon photomultiplier (SiPM) detectors placed in a ring that is fully MRI compatible. This brain imager can be placed around the head of a patient (clinical setting) or subject (research setting) and allow for comfortable upright imaging. However, an alternative way to use this device, as enabled by the technology, is to indeed scan individuals in the supine position in conjuncture with current MRI systems. This PET prototype is able to image simultaneously as the MRI scan is occurring, thus maximizing co-registration and the accuracy of the assignment of metabolically active voxels to their anatomically correct counterparts as identified by the MR image. In this study, we first conducted some basic instrumentation tests to ensure the device was functioning properly outside of the MRI, and additionally scan some phantoms (Derenzo; Hoffman Brain) to assess the quality in which our brain imager is able to produce adequate images. After these initial studies, we conducted multiple different experiments inside a 3 Tesla MRI in order to see how the magnetic field would influence the operation of the PET imager and vice versa. Through simultaneous PET/MRI scanning of a Hoffman brain phantom filled with F18 radioactivity and water, it was shown that the quality of the MR image was largely unaffected by the PET imager. Furthermore, although the quality of PET imaging was affected by the RF pulsing, an acceptable PET image was nevertheless produced. As we discuss following the results, the success of this study shows that our brain imager is indeed MR compatible, and that next generation devices based on its concepts will continue to improve combined PET/MRI functionality. As two of the major advantages of this imager are the potential for low-dose scanning and its adaptability to any MRI scanner, this study suggests that PET/MRI brain imaging with low dose is in principle possible using an insert which could be adapted to any MRI scanner, using standard RF coils for that scanner.