Eric Earl

High-Resolution Steady-State Cerebral Blood Volume Maps in Patients with Central Nervous System Neoplasms Using Ferumoxytol, a Superparamagnetic Iron Oxide Nanoparticle

Cerebral blood volume (CBV) measurement complements conventional magnetic resonance imaging (MRI) to indicate pathologies in the central nervous system (CNS). Dynamic susceptibility contrast (DSC) perfusion imaging is limited by low resolution and distortion. Steady-state (SS) imaging may provide higher resolution CBV maps but was not previously possible in patients. We tested the feasibility of clinical SS-CBV measurement using ferumoxytol, a nanoparticle blood pool contrast agent. SS-CBV measurement was analyzed at various ferumoxytol doses and compared with DSC-CBV using gadoteridol. Ninety nine two-day MRI studies were acquired in 65 patients with CNS pathologies. The SS-CBV maps showed improved contrast to noise ratios, decreased motion artifacts at increasing ferumoxytol doses. Relative CBV (rCBV) values obtained in the thalamus and tumor regions indicated good consistency between the DSC and SS techniques when the higher dose (510 mg) ferumoxytol was used. The SS-CBV maps are feasible using ferumoxytol in a clinical dose of 510 mg, providing higher resolution images with comparable rCBV values to the DSC technique. Physiologic imaging using nanoparticles will be beneficial in visualizing CNS pathologies with high vascularity that may or may not correspond with blood–brain barrier abnormalities.

2015 Brainhack Proceedings

Table of contentsI1 Introduction to the 2015 Brainhack ProceedingsR. Cameron Craddock, Pierre Bellec, Daniel S. Margules, B. Nolan Nichols, Jörg P. PfannmöllerA1 Distributed collaboration: the case for the enhancement of Brainspell’s interfaceAmanPreet Badhwar, David Kennedy, Jean-Baptiste Poline, Roberto ToroA2 Advancing open science through NiDataBen Cipollini, Ariel RokemA3 Integrating the Brain Imaging Data Structure (BIDS) standard into C-PACDaniel Clark, Krzysztof J. Gorgolewski, R. Cameron CraddockA4 Optimized implementations of voxel-wise degree centrality and local functional connectivity density mapping in AFNIR. Cameron Craddock, Daniel J. ClarkA5 LORIS: DICOM anonymizerSamir Das, Cécile Madjar, Ayan Sengupta, Zia MohadesA6 Automatic extraction of academic collaborations in neuroimagingSebastien DeryA7 NiftyView: a zero-footprint web application for viewing DICOM and NIfTI filesWeiran DengA8 Human Connectome Project Minimal Preprocessing Pipelines to NipypeEric Earl, Damion V. Demeter, Kate Mills, Glad Mihai, Luka Ruzic, Nick Ketz, Andrew Reineberg, Marianne C. Reddan, Anne-Lise Goddings, Javier Gonzalez-Castillo, Krzysztof J. GorgolewskiA9 Generating music with resting-state fMRI dataCaroline Froehlich, Gil Dekel, Daniel S. Margulies, R. Cameron CraddockA10 Highly comparable time-series analysis in NitimeBen D. FulcherA11 Nipype interfaces in CBRAINTristan Glatard, Samir Das, Reza Adalat, Natacha Beck, Rémi Bernard, Najmeh Khalili-Mahani, Pierre Rioux, Marc-Étienne Rousseau, Alan C. EvansA12 DueCredit: automated collection of citations for software, methods, and dataYaroslav O. Halchenko, Matteo Visconti di Oleggio CastelloA13 Open source low-cost device to register dog’s heart rate and tail movementRaúl Hernández-Pérez, Edgar A. Morales, Laura V. CuayaA14 Calculating the Laterality Index Using FSL for Stroke Neuroimaging DataKaori L. Ito, Sook-Lei LiewA15 Wrapping FreeSurfer 6 for use in high-performance computing environmentsHans J. JohnsonA16 Facilitating big data meta-analyses for clinical neuroimaging through ENIGMA wrapper scriptsErik Kan, Julia Anglin, Michael Borich, Neda Jahanshad, Paul Thompson, Sook-Lei LiewA17 A cortical surface-based geodesic distance package for PythonDaniel S Margulies, Marcel Falkiewicz, Julia M HuntenburgA18 Sharing data in the cloudDavid O’Connor, Daniel J. Clark, Michael P. Milham, R. Cameron CraddockA19 Detecting task-based fMRI compliance using plan abandonment techniquesRamon Fraga Pereira, Anibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe MeneguzziA20 Self-organization and brain functionJörg P. Pfannmöller, Rickson Mesquita, Luis C.T. Herrera, Daniela DenticoA21 The Neuroimaging Data Model (NIDM) APIVanessa Sochat, B Nolan NicholsA22 NeuroView: a customizable browser-base utilityAnibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe MeneguzziA23 DIPY: Brain tissue classificationJulio E. Villalon-Reina, Eleftherios Garyfallidis

Real-time motion analytics during brain MRI improve data quality and reduce costs

Abstract Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post‐hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional ‘buffer data’, an expensive practice that, by itself, does not guarantee sufficient high‐quality MRI data for a given participant. Therefore, we developed an easy‐to‐setup, easy‐to‐use Framewise Integrated Real‐time MRI Monitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real‐time, allowing them to scan each subject until the desired amount of low‐movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more. Graphical abstract Figure. No Caption available.

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

Zika virus infection early after birth has deleterious effects on the developing brain and long-term behavioral changes in rhesus macaques. Postnatal perturbation by Zika virus Much of the concern surrounding Zika virus infections focuses on fetuses infected in utero. Mavigner et al. reasoned that this neurotropic virus may have deleterious effects even after birth, so they set up a postnatal infection model to investigate. They found that infant rhesus macaques infected with Zika virus also had peripheral and central nervous system pathology. Longitudinal magnetic resonance imaging studies revealed that macaques that had been infected with Zika virus had structural and functional abnormalities and also altered emotional responses. These differences persisted months after the virus had been cleared. Although the work involved a small number of animals, their results suggest that infants and young children exposed to Zika virus should undergo more than just routine monitoring. The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites

The ABCD study is recruiting and following the brain development and health of over 10,000 9–10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature.

Changes in spontaneous activity assessed by accelerometry correlate with extent of cerebral ischemia-reperfusion injury in the nonhuman primate.

The use of accelerometry to monitor activity in human stroke patients has revealed strong correlations between objective activity measurements and subjective neurological findings. The goal of our study was to assess the applicability of accelerometry-based measurements in experimental animals undergoing surgically induced cerebral ischemia. Using a nonhuman primate cortical stroke model, we demonstrate for the first time that monitoring locomotor activity prior to and following cerebrovascular ischemic injury using an accelerometer is feasible in adult male rhesus macaques and that the measured activity outcomes significantly correlate with severity of brain injury. The use of accelerometry as an unobtrusive, objective preclinical efficacy determinant could complement standard practices involving subjective neurological scoring and magnetic resonance imaging in nonhuman primates. Similar activity monitoring devices to those employed in this study are currently in use in human clinical studies, underscoring the feasibility of this approach for assessing the clinical potential of novel treatments for cerebral ischemia.

Behavioral interventions for reducing head motion during MRI scans in children

&NA; A major limitation to structural and functional MRI (fMRI) scans is their susceptibility to head motion artifacts. Even submillimeter movements can systematically distort functional connectivity, morphometric, and diffusion imaging results. In patient care, sedation is often used to minimize head motion, but it incurs increased costs and risks. In research settings, sedation is typically not an ethical option. Therefore, safe methods that reduce head motion are critical for improving MRI quality, especially in high movement individuals such as children and neuropsychiatric patients. We investigated the effects of (1) viewing movies and (2) receiving real‐time visual feedback about head movement in 24 children (5–15 years old). Children completed fMRI scans during which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and during some of the scans they also received real‐time visual feedback about head motion. Head motion was significantly reduced during movie watching compared to rest and when receiving feedback compared to receiving no feedback. However, these results depended on age, such that the effects were largely driven by the younger children. Children older than 10 years showed no significant benefit. We also found that viewing movies significantly altered the functional connectivity of fMRI data, suggesting that fMRI scans during movies cannot be equated to standard resting‐state fMRI scans. The implications of these results are twofold: (1) given the reduction in head motion with behavioral interventions, these methods should be tried first for all clinical and structural MRIs in lieu of sedation; and (2) for fMRI research scans, these methods can reduce head motion in certain groups, but investigators must keep in mind the effects on functional MRI data. HighlightsIn young children, movie watching during MRI scans reduces head motion.Real‐time head motion feedback also reduces motion during MRI scans in young children.Motion effects were specific to younger (5‐10 years) not older children (11‐15 years).Movies, but not feedback, significantly alter functional connectivity MRI data.

Correlated gene expression and anatomical communication support synchronized brain activity in the mouse functional connectome

Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting-state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI. SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still primarily unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting-state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be used to streamline preclinical animal studies of disease.

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo.

Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols.

ADHD and Attentional Control: Impaired Segregation of Task Positive and Task Negative Brain Networks

In children with attention deficit hyperactivity disorder (ADHD) difficulty maintaining task focus may relate to the coordinated, negatively correlated activity between brain networks that support the initiation and maintenance of task sets (task positive networks) and networks that mediate internally directed processes (i.e., the default mode network). Here, resting-state functional connectivity MRI between these networks was examined in ADHD, across development, and in relation to attention. Children with ADHD had reduced negative connectivity between task positive and task negative networks (p = 0.002). Connectivity continues to become more negative between these networks throughout development (7–15 years of age) in children with ADHD (p = 0.005). Regardless of group status, females had increased negative connectivity (p = 0.003). In regards to attentional performance, the ADHD group had poorer signal detection (d′) on the continuous performance task (CPT) (p < 0.0001), more so on easy than difficult d′ trials (p < 0.0001). The reduced negative connectivity in children with ADHD also relates to their attention, where increased negative connectivity is related to better performance on the d′ measure of the CPT (p = 0.008). These results highlight and further strengthen prior reports underscoring the role of segregated system integrity in ADHD. Author Summary Maintaining task focus has been thought to relate to the coordinated activity between brain networks that support the initiation and maintenance of task sets (task positive networks) and networks that mediate internally directed processes (i.e., the default mode network). Here we find that segregation between these functional networks is impaired in children with ADHD, shows developmental lag, and is related to attentional impairments as measured by the continuous performance task. These results highlight and further strengthen prior reports underscoring the role of segregated system integrity in ADHD and its relationship to impairments in attention.