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Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers (QIBs) to measure changes in these features. Critical to the performance of a QIB in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method and metrics used to assess a QIB for clinical use. It is therefore, difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America (RSNA) and the Quantitative Imaging Biomarker Alliance (QIBA) with technical, radiological and statistical experts developed a set of technical performance analysis methods, metrics and study designs that provide terminology, metrics and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of QIB performance studies so that results from multiple studies can be compared, contrasted or combined.

12The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P ≤ 5 x 10 -8 ); 199 survived multiple testing correction (P ≤ 8.3 x 10 -10 ; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression and ADHD.One Sentence Summary: Common genetic variation is associated with inter-individual variation in the structure of the human cortex, both globally and within specific regions, and is shared with genetic risk factors for some neuropsychiatric disorders.The human cerebral cortex is the outer grey matter layer of the brain, which is implicated in multiple aspects of higher cognitive function. Its distinct folding pattern is characterised by convex (gyral) and concave (sulcal) regions. Computational brain mapping approaches use the consistent folding patterns across individual cortices to label brain regions(1). During fetal development excitatory neurons, the predominant neuronal cell-type in the cortex, are generated from neural progenitor cells in the developing germinal zone(2). The radial unit hypothesis(3) posits that the expansion of cortical surface area (SA) is driven by the proliferation of these neural progenitor cells, whereas thickness (TH) is determined by the number of neurogenic divisions. Variation in global and regional measures of cortical SA and TH are associated with neuropsychiatric disorders and psychological traits(4) ( Table S1). Twin and family-based brain imaging studies show that SA and TH measurements are highly heritable and are largely influenced by independent genetic factors(5). Despite extensive studies of genes impacting cortical structure in model organisms (6), our current understanding of genetic variation impacting human cortical size and patterning is limited to rare, highly penetrant variants (7,8). These variants often disrupt cortical development, leading to altered post-natal structure. However, little is known about how common genetic variants impact human cortical SA and TH.To address this, we conducted genome-wide association meta-analyses of cortical SA and TH measures in 51,662 individuals from 60 cohorts from around the world (Tables S2-S4). Cortical measures were extracted from structural brain MRI scan...

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Functional magnetic resonance imaging (fMRI) was used to compare brain activation to static facial displays versus dynamic changes in facial identity or emotional expression. Static images depicted prototypical fearful, angry and neutral expressions. Identity morphs depicted identity changes from one person to another, always with neutral expressions. Emotion morphs depicted expression changes from neutral to fear or anger, creating the illusion that the actor was 'getting scared' or 'getting angry' in real-time. Brain regions implicated in processing facial affect, including the amygdala and fusiform gyrus, showed greater responses to dynamic versus static emotional expressions, especially for fear. Identity morphs activated a dorsal fronto-cingulo-parietal circuit and additional ventral areas, including the amygdala, that also responded to the emotion morphs. Activity in the superior temporal sulcus discriminated emotion morphs from identity morphs, extending its known role in processing biologically relevant motion. The results highlight the importance of temporal cues in the neural coding of facial displays.

This report provides practical recommendations for the design and execution of Multi-Center functional Magnetic Resonance Imaging (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The paper was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multi-site aspects include: (1) establishing and verifying scan parameters including scanner types and magnetic fields, (2) establishing and monitoring of a scanner quality program, (3) developing task paradigms and scan session documentation, (4) establishing clinical and scanner training to ensure consistency over time, (5) developing means for uploading, storing, and monitoring of imaging and other data, (6) the use of a traveling fMRI expert and (7) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.

High-field (3 Tesla) functional magnetic resonance imaging (MRI) was used to investigate the cortical circuitry subserving pursuit tracking in humans and compare it to that for saccadic eye movements. Pursuit performance, relative to visual fixation, elicited activation in three areas known to contribute to eye movements in humans and in nonhuman primates: the frontal eye field, supplementary eye field, and intraparietal sulcus. It also activated three medial regions not previously identified in human neuroimaging studies of pursuit: the precuneus and the anterior and posterior cingulate cortices. All six areas were also activated during saccades. The spatial extent of activation was similar for saccades and pursuit in all but two regions: spatial extent was greater for saccades in the superior branch of the frontal eye field and greater for pursuit in posterior cingulate cortex. This set of activations for smooth pursuit parallels the network of oculomotor areas characterized in nonhuman primates and complements recent studies showing that common cortical networks subserve oculomotor functions and spatial attention in humans.

A remarkable feature of nerve cells is the complex and variable pattern of their axonal and dendritic branches. Quantitative studies of a simple part of the nervous system in mammals provide evidence that neuronal geometry and innervation are regulated by long-term trophic interactions between neurons and their targets. This trophic linkage may explain how nerve cells adjust their function to the needs of bodies that vary markedly in size and form.