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Background/Objectives : Determining how a patient with metastatic cancer is responding to therapy can be difficult for medical oncologists, especially with text-only radiology reports. In this investigation, we assess the clinical usefulness of a new algorithm-based analysis that provides spatial location and quantification for each detected lesion region of interest (ROI) and compare it to information included in radiology reports in the United States. Methods : Treatment response radiology reports for FDG PET/CT scans were retrospectively gathered from 228 patients with metastatic cancers. Each radiology report was assessed for the presence of both qualitative and quantitative information. A subset of patients ( N = 103) was further analyzed using an algorithm-based service that provides the clinician with comprehensive quantitative information, including change over time, of all detected ROI with visualization of anatomical location. For each patient, three medical oncologists from different practices independently rated the usefulness of the additional analysis overall and in four subcategories. Results : In the 228 radiology reports, quantitative information of size and uptake was provided for at least one lesion at one time point in 78% (size) and 95% (uptake) of patients. This information was reported for both analyzed time points (current scan and previous comparator) in 52% (size) and 66% (uptake) of patients. Only 7% of reports quantified the total number of lesions, and none of the reports quantified changes in all lesions for patients with more than a few lesions. In the assessment of the augmentative algorithm-based analysis, the majority of oncologists rated it as overall useful for 98% of patients (101/103). Within specific categories of use, the majority of oncologists voted to use it for making decisions regarding systemic therapy in 97% of patients, for targeted therapy decisions in 72% of patients, for spatial location information in 96% of patients, and for patient education purposes in 93% of patients. Conclusions : For patients with metastatic cancer, the algorithm-based analysis of all ROI would allow oncologists to better understand treatment response and support their work to more precisely optimize the patient's therapy.

Purpose: Automatic quantification of longitudinal changes in PET scans for lymphoma patients has proven challenging, as residual disease in interim-therapy scans is often subtle and difficult to detect. Our goal was to develop a longitudinally-aware segmentation network (LAS-Net) that can quantify serial PET/CT images for pediatric Hodgkin lymphoma patients., Materials and Methods: This retrospective study included baseline (PET1) and interim (PET2) PET/CT images from 297 patients enrolled in two Children's Oncology Group clinical trials (AHOD1331 and AHOD0831). LAS-Net incorporates longitudinal cross-attention, allowing relevant features from PET1 to inform the analysis of PET2. Model performance was evaluated using Dice coefficients for PET1 and detection F1 scores for PET2. Additionally, we extracted and compared quantitative PET metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in PET1, as well as qPET and ΔSUVmax in PET2, against physician measurements. We quantified their agreement using Spearman's ρ correlations and employed bootstrap resampling for statistical analysis., Results: LAS-Net detected residual lymphoma in PET2 with an F1 score of 0.606 (precision/recall: 0.615/0.600), outperforming all comparator methods (P<0.01). For baseline segmentation, LAS-Net achieved a mean Dice score of 0.772. In PET quantification, LAS-Net's measurements of qPET, ΔSUVmax, MTV and TLG were strongly correlated with physician measurements, with Spearman's ρ of 0.78, 0.80, 0.93 and 0.96, respectively. The quantification performance remained high, with a slight decrease, in an external testing cohort., Conclusion: LAS-Net demonstrated significant improvements in quantifying PET metrics across serial scans, highlighting the value of longitudinal awareness in evaluating multi-time-point imaging datasets.

Introduction: Early child development occurs within an interactive environment, initially dominated by parents or caregivers, and is heavily influenced by the dynamics of this social context. The current study probed the neurobiology of "family personality", or family functioning, in the context of parent-child dyadic interaction using a two-person neuroimaging modality., Methods: One hundred and five parent-child dyads (child mean age 5 years 4 months) were recruited. Functional near-infrared spectroscopy (fNIRS) hyperscanning was employed to measure neural synchrony while dyads completed a mildly stressful interactive task. Family functioning was measured through the Family Adaptability and Cohesion Scale IV (FACES-IV)., Results: Synchrony during stress was significantly greater than synchrony during both baseline and recovery conditions for all dyads. A significant interaction between neural synchrony in each task condition and familial balanced flexibility was found, such that higher levels of balanced flexibility were associated with greater changes in frontal cortex neural synchrony as dyads progressed through the three task conditions., Discussion: Parent-child dyads from families who display heightened levels of balanced flexibility are also more flexible in their engagement of neural synchrony when shifting between social conditions. This is one of the first studies to utilize a two-person imaging modality to explore the links between family functioning and interbrain synchrony between parents and their children., (© 2024 Wiley Periodicals LLC.)

Background: Radioactive tracer injections for breast cancer sentinel lymph node mapping can be painful. In this randomized trial, we compared four approaches to topical pain control for radiotracer injections., Methods: Breast cancer patients were randomized (9 April 2021-8 May 2022) to receive the institutional standard of ice prior to injection (n = 44), or one of three treatments: ice plus a vibrating distraction device (Buzzy ® ; n = 39), 4% lidocaine patch (n = 44), or 4% lidocaine patch plus ice plus Buzzy ® (n = 40). Patients completed the Wong-Baker FACES ® pain score (primary outcome) and a satisfaction with pain control received scale (secondary). Nuclear medicine technologists (n = 8) rated perceived pain control and ease of administration for each patient. At study conclusion, technologists rank-ordered treatments. Data were analyzed as intention-to-treat. Wilcoxon rank-sum tests were used to compare pain scores of control versus pooled treatment arms (primary) and then control to each treatment arm individually (secondary)., Results: There were no differences in pain scores between the control and treatment groups, both pooled and individually. Eighty-five percent of patients were 'satisfied/very satisfied' with treatment received, with no differences between groups. No differences in providers' perceptions of pain were observed, although providers perceived treatments involving Buzzy © more difficult to administer (p < 0.001). Providers rated lidocaine patch as the easiest, with ice being second., Conclusion: In this randomized trial, no differences in patient-reported pain or satisfaction with treatment was observed between ice and other topical treatments. Providers found treatments using Buzzy ® more difficult to administer. Given patient satisfaction and ease of administration, ice is a reasonable standard., (© 2024. Society of Surgical Oncology.)

Background: Self-regulation in early childhood develops within a social context. Variations in such development can be attributed to inter-individual behavioral differences, which can be captured both as facets of temperament and across a normal:abnormal dimensional spectrum. With increasing emphasis on irritability as a robust early-life transdiagnostic indicator of broad psychopathological risk, linkage to neural mechanisms is imperative. Currently, there is inconsistency in the identification of neural circuits that underlie irritability in children, especially in social contexts. This study aimed to address this gap by utilizing a functional magnetic resonance imaging (fMRI) paradigm to investigate pediatric anger/frustration using social stimuli., Methods: Seventy-three children (M = 6 years, SD = 0.565) were recruited from a larger longitudinal study on irritability development. Caregivers completed questionnaires assessing irritable temperament and clinical symptoms of irritability. Children participated in a frustration task during fMRI scanning that was designed to induce frustration through loss of a desired prize to an animated character. Data were analyzed using both general linear modeling (GLM) and independent components analysis (ICA) and examined from the temperament and clinical perspectives., Results: ICA results uncovered an overarching network structure above and beyond what was revealed by traditional GLM analyses. Results showed that greater temperamental irritability was associated with significantly diminished spatial extent of activation and low-frequency power in a network comprised of the posterior superior temporal sulcus (pSTS) and the precuneus (p < .05, FDR-corrected). However, greater severity along the spectrum of clinical expression of irritability was associated with significantly increased extent and intensity of spatial activation as well as low- and high-frequency neural signal power in the right caudate (p < .05, FDR-corrected)., Conclusions: Our findings point to specific neural circuitry underlying pediatric irritability in the context of frustration using social stimuli. Results suggest that a deliberate focus on the construction of network-based neurodevelopmental profiles and social interaction along the normal:abnormal irritability spectrum is warranted to further identify comprehensive transdiagnostic substrates of the irritability., (© 2023 Association for Child and Adolescent Mental Health.)

Smartphone sensors are used increasingly in the assessment of ataxias. To date, there is no specific consensus guidance regarding a priority set of smartphone sensor measurements, or standard assessment criteria that are appropriate for clinical trials. As part of the Ataxia Global Initiative Digital-Motor Biomarkers Working Group (AGI WG4), aimed at evaluating key ataxia clinical domains (gait/posture, upper limb, speech and oculomotor assessments), we provide consensus guidance for use of internal smartphone sensors to assess key domains. Guidance was developed by means of a literature review and a two stage Delphi study conducted by an Expert panel, which surveyed members of AGI WG4, representing clinical, research, industry and patient-led experts, and consensus meetings by the Expert panel to agree on standard criteria and map current literature to these criteria. Seven publications were identified that investigated ataxias using internal smartphone sensors. The Delphi 1 survey ascertained current practice, and systems in use or under development. Wide variations in smartphones sensor use for assessing ataxia were identified. The Delphi 2 survey identified seven measures that were strongly endorsed as priorities in assessing 3/4 domains, namely gait/posture, upper limb, and speech performance. The Expert panel recommended 15 standard criteria to be fulfilled in studies. Evaluation of current literature revealed that none of the studies met all criteria, with most being early-phase validation studies. Our guidance highlights the importance of consensus, identifies priority measures and standard criteria, and will encourage further research into the use of internal smartphone sensors to measure ataxia digital-motor biomarkers., (© 2023. The Author(s).)

Objective . Manual analysis of individual cancer lesions to assess disease response is clinically impractical and requires automated lesion tracking methodologies. However, no methodology has been developed for whole-body individual lesion tracking, across an arbitrary number of scans, and acquired with various imaging modalities. Approach . This study introduces a lesion tracking methodology and benchmarked it using 23 68 Ga-DOTATATE PET/CT and PET/MR images of eight neuroendocrine tumor patients. The methodology consists of six steps: (1) alignment of multiple scans via image registration, (2) body-part labeling, (3) automatic lesion-wise dilation, (4) clustering of lesions based on local lesion shape metrics, (5) assignment of lesion tracks, and (6) output of a lesion graph. Registration performance was evaluated via landmark distance, lesion matching accuracy was evaluated between each image pair, and lesion tracking accuracy was evaluated via identical track ratio. Sensitivity studies were performed to evaluate the impact of lesion dilation (fixed versus automatic dilation), anatomic location, image modalities (inter- versus intra-modality), registration mode (direct versus indirect registration), and track size (number of time-points and lesions) on lesion matching and tracking performance. Main results . Manual contouring yielded 956 lesions, 1570 lesion-matching decisions, and 493 lesion tracks. The median residual registration error was 2.5 mm. The automatic lesion dilation led to 0.90 overall lesion matching accuracy, and an 88% identical track ratio. The methodology is robust regarding anatomic locations, image modalities, and registration modes. The number of scans had a moderate negative impact on the identical track ratio (94% for 2 scans, 91% for 3 scans, and 81% for 4 scans). The number of lesions substantially impacted the identical track ratio (93% for 2 nodes versus 54% for ≥5 nodes). Significance . The developed methodology resulted in high lesion-matching accuracy and enables automated lesion tracking in PET/CT and PET/MR., (Creative Commons Attribution license.)

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

The ongoing stream of sensory experience is so complex and ever-changing that we tend to parse this experience at "event boundaries," which structures and strengthens memory. Memory processes undergo profound change across early childhood. Whether young children also divide their ongoing processing along event boundaries, and if those boundaries relate to memory, could provide important insight into the development of memory systems. In Study 1, 4-7-year-old children and adults segmented a cartoon, and we tested their memory. Children's event boundaries were more variable than adults' and differed in location and consistency of agreement. Older children's event segmentation was more adult-like than younger children's, and children who segmented events more like adults had better memory for those events. In Study 2, we asked whether these developmental differences in event segmentation had their roots in distinct neural representations. A separate group of 4-8-year-old children watched the same cartoon while undergoing an fMRI scan. In the right hippocampus, greater pattern dissimilarity across event boundaries compared to within events was evident for both child and adult behavioral boundaries, suggesting children and adults share similar event cognition. However, the boundaries identified by a data-driven Hidden Markov Model found that a different brain region-the left and right angular gyrus-aligned only with event boundaries defined by children. Overall, these data suggest that children's event cognition is reasonably well-developed by age 4 but continues to become more adult-like across early childhood. RESEARCH HIGHLIGHTS: Adults naturally break their experience into events, which structures and strengthens memory, but less is known about children's event perception and memory. Study 1 had adults and children segment and remember events from an animated show, and Study 2 compared those segmentations to other children's fMRI data. Children show better recognition and temporal order memory and more adult-like event segmentation with age, and children who segment more like adults have better memory. Children's and adults' behavioral boundaries mapped onto pattern similarity differences in hippocampus, and children's behavioral boundaries matched a data-driven model's boundaries in angular gyrus., (© 2023 John Wiley & Sons Ltd.)

The association between cognitive flexibility and related neural functioning has been inconsistent. This is particularly true in young children, where previous studies have found heterogenous results linking behavior and neural function, raising the possibility of unexplored moderators. The current study explored the moderating role of dimensional irritability in the association between cognitive flexibility task performance and prefrontal activation in young children. A total of 106 3- to 7-year-old children were recruited to complete a custom-designed, child-adapted, cognitive flexibility task, and 98 of them were included in the data analysis. The children's dorsolateral prefrontal cortex activation was monitored using functional near-infrared spectroscopy, and their levels of irritability were reported by parents using the MAP-DB Temper Loss subscale. Results indicated that the mean reaction time of the cognitive flexibility task was negatively correlated with concurrent prefrontal activation. No evidence was found for the association between task accuracy and prefrontal activation. Moreover, irritability moderated the association between the mean reaction time and prefrontal activation. Children high in irritability exhibited a stronger negative association between the mean reaction time and related prefrontal activation than children low in irritability. The moderating model suggested a novel affective-cognitive interaction to investigate the associations between cognitive task performance and their neural underpinnings.

Objective: Although emotion dysregulation has been defined as a maladaptive process of emotional experiences, there is no specific reference to the emotional valence of the dysregulation. To date, child psychiatry has focused primarily on dysregulation of negative affect. Here, we suggest that positive emotion dysregulation requires additional clinical and research attention., Method: First, we present a developmental approach to the study of positive emotion regulation within a temperament framework. Second, we describe emerging research findings regarding dysregulation of positive emotion in early childhood. Third, we integrate neuroscientific approaches to positive emotion regulation and introduce a framework for future investigations and clinical applications., Results: Dysregulation in positive affect can be examined from temperamental, developmental, clinical, and neuroscientific perspectives. Both temperamental surgency, which includes positive affect, and the proposed clinical extension, excitability, are associated with increased risk of externalizing symptoms and clinical impairment in youth., Conclusion: Studying the role of both temperamental surgency and clinically impairing positive affect, or excitability, in developmental psychopathology will help to elucidate the full spectrum of emotion dysregulation and to clarify the neural basis of dysregulation. A more comprehensive conceptualization of positively valanced emotion dysregulation will provide a more nuanced understanding of developmental risk and potential targets for intervention., Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Exposure to adversity is a well-documented risk factor for cognitive, behavioral, and mental health problems. In fact, the consequences of adversity may be intergenerational. A growing body of research suggests that maternal exposures to adversity, including those prior to childbirth, are associated with offspring biobehavioral development. In a sample of 36 mothers and their preschool-age children (mean child age = 4.21 ± 0.92 years), we used functional near-infrared spectroscopy to replicate and extend this work to include brain activation during inhibitory control in young children. We found that measures of maternal exposure to adversity, including cumulative, childhood, and preconception exposures, were significantly and positively associated with activation in the right frontopolar prefrontal cortex (PFC) and in the left temporal and parietal clusters during inhibitory control. In addition, and consistent with previous findings, children's increased negative affect and decreased effortful control were associated with increased right PFC activation during inhibitory control. These findings provide preliminary evidence that maternal and dispositional risk factors are linked to alterations in PFC functioning during the preschool years. Children of mothers with a history of exposure to adversity, as well as children who are less temperamentally regulated, may require increased neural resources to meet the cognitive demands of inhibitory control., (© 2022 Wiley Periodicals LLC.)

While substantial research supports the role of parent-child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent-child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent-child dyads first came to the laboratory when the child was 4-5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child's internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent-child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent-child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent-child dyad's ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors.

Deficits in self-regulation capacity have been linked to subsequent impairment and clinical symptomology across the lifespan. Prior work has identified difficulty regulating angry emotions (i.e., irritability) as a powerful transdiagnostic indicator of current and future clinical concerns. Less is known regarding how irritability intersects with cognitive features of self-regulation, in particular inhibitory control, despite its mental health relevance. A promising avenue for improving specificity of clinical predictions in early childhood is multi-method, joint consideration of irritability and inhibitory control capacities. To advance early identification of impairment and psychopathology risk, we contrast group- and variable-based models of neurodevelopmental vulnerability at the interface of irritability and inhibitory control in contexts of varied motivational and emotional salience. This work was conducted in a longitudinal study of children recruited at well-child visits in Midwestern pediatric clinics at preschool age (N = 223, age range = 3-7 years). Group-based models (clustering and regression of clusters on clinical outcomes) indicated significant heterogeneity of self-regulation capacity in this sample. Meanwhile, variable-based models (continuous multiple regression) evidenced associations with concurrent clinical presentation, future symptoms, and impairment across the broad spectrum of psychopathology. Irritability transdiagnostically indicated internalizing and externalizing problems, concurrently and longitudinally. In contrast, inhibitory control was uniquely associated with attention-deficit/hyperactivity symptoms. We present these findings to advance a joint consideration approach to two promising indicators of neurodevelopmental vulnerability and mental health risk. Models suggest that both emotional and cognitive self-regulation capacities can address challenges in characterizing the developmental unfolding of psychopathology from preschool to early childhood age., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Head motion during brain PET imaging can significantly degrade the quality of the reconstructed image, leading to reduced diagnostic value and inaccurate quantitation. A fully data-driven motion correction approach was recently demonstrated to produce highly accurate motion estimates (<1 mm) with high temporal resolution (≥1 Hz), which can then be used for a motion-corrected reconstruction. This can be applied retrospectively with no impact on the clinical image acquisition protocol. We present a reader-based evaluation and an atlas-based quantitative analysis of this motion correction approach within a clinical cohort. Methods: Clinical patient data were collected over 2019-2020 and processed retrospectively. Motion was estimated using image-based registration on reconstructions of ultrashort frames (0.6-1.8 s), after which list-mode reconstructions that were fully motion-corrected were performed. Two readers graded the motion-corrected and uncorrected reconstructions. An atlas-based quantitative analysis was performed. Paired Wilcoxon tests were used to test for significant differences in reader scores and SUVs between reconstructions. The Levene test was used to determine whether motion correction had a greater impact on quantitation in the presence of motion than when motion was low. Results: Fifty standard clinical 18 F-FDG brain PET datasets (age range, 13-83 y; mean ± SD, 59 ± 20 y; 27 women) from 3 scanners were collected. The reader study showed a significantly different, diagnostically relevant improvement by motion correction when motion was present ( P  = 0.02) and no impact in low-motion cases. Eight percent of all datasets improved from diagnostically unacceptable to acceptable. The atlas-based analysis demonstrated a significant difference between the motion-corrected and uncorrected reconstructions in cases of high motion for 7 of 8 regions of interest ( P < 0.05). Conclusion: The proposed approach to data-driven motion estimation and correction demonstrated a clinically significant impact on brain PET image reconstruction., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The ability to detect differences among similar events in our lives is a crucial aspect of successful episodic memory performance, which develops across early childhood. The neural substrate of this ability is supported by operations in the medial temporal lobe (MTL). Here, we used representational similarity analysis (RSA) to measure neural pattern similarity in hippocampus, perirhinal cortex, and parahippocampal cortex for 4- to 10-year-old children and adults during naturalistic viewing of clips from the same compared to different movies. Further, we assessed the role of prior exposure to individual movie clips on pattern similarity in the MTL. In both age groups, neural pattern similarity in hippocampus was lower for clips drawn from the same movies compared to those drawn from different movies, suggesting that related content activates processes focused on keeping representations with shared content distinct. However, children showed this only for movies with which they had prior exposures, whereas adults showed the effect regardless of any prior exposures to the movies. These findings suggest that children require repeated exposure to stimuli to show adult-like MTL functioning in distinguishing among similar events., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The intergenerational transmission of psychopathology is one of the strongest known risk factors for childhood disorder and may be a malleable target for prevention and intervention. Anxious parents have distinct parenting profiles that impact socioemotional development, and these parenting effects may result in broad alterations to the biological and cognitive functioning of their children. Better understanding the functional mechanisms by which parental risk is passed on to children can provide (1) novel markers of risk for socioemotional difficulties, (2) specific targets for intervention, and (3) behavioral and biological indices of treatment response. We propose a developmental model in which dyadic social dynamics serve as a key conduit in parent-to-child transmission of anxiety. Dyadic social dynamics capture the moment-to-moment interactions between parent and child that occur on a daily basis. In shaping the developmental trajectory from familial risk to actual symptoms, dyadic processes act on mechanisms of risk that are evident prior to, and in the absence of, any eventual disorder onset. First, we discuss dyadic synchrony or the moment-to-moment coordination between parent and child within different levels of analysis, including neural, autonomic, behavioral, and emotional processes. Second, we discuss how overt emotion modeling of distress is observed and internalized by children and later reflected in their own behavior. Thus, unlike synchrony, this is a more sequential process that cuts across levels of analysis. We also discuss maladaptive cognitive and affective processing that is often evident with increases in child anxiety symptoms. Finally, we discuss additional moderators (e.g., parent sex, child fearful temperament) that may impact dyadic processes. Our model is proposed as a conceptual framework for testing hypotheses regarding dynamic processes that may ultimately guide novel treatment approaches aimed at intervening on dyadically linked biobehavioral mechanisms before symptom onset., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Social information processing is vital for inferring emotional states in others, yet affective neuroscience has only begun to scratch the surface of how we represent emotional information in the brain. Most previous affective neuroscience work has used isolated stimuli such as static images of affective faces or scenes to probe affective processing. While this work has provided rich insight to the initial stages of emotion processing (encoding cues), activation to isolated stimuli provides limited insight into later phases of emotion processing such as interpretation of cues or interactions between cues and established cognitive schemas. Recent work has highlighted the potential value of using complex video stimuli to probe socio-emotional processing, highlighting the need to develop standardized video coding schemas as this exciting field expands. Toward that end, we present a standardized and open-source coding system for complex videos, two fully coded videos, and a video and code processing Python library. The EmoCodes manual coding system provides an externally validated and replicable system for coding complex cartoon stimuli, with future plans to validate the system for other video types. The emocodes  Python library provides automated tools for extracting low-level features from video files as well as tools for summarizing and analyzing the manual codes for suitability of use in neuroimaging analysis. Materials can be freely accessed at https://emocodes.org/. These tools represent an important step toward replicable and standardized study of socio-emotional processing using complex video stimuli., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00100-7., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Society for Affective Science 2022.)

The integration of neurodevelopmental perspectives into clinical science has identified irritability as an early dimensional marker of lifespan mental health risk. Elucidating the developmental patterning of irritable behavior is key to differentiating normative variation from risk markers. Accounting for dysregulation and contextual features of irritability is useful for differentiation at preschool age, laying the groundwork for even earlier characterization. We provide initial evidence for the validity of the Multidimensional Assessment Profile of Disruptive Behavior Temper Loss Scale, Infant-Toddler version in two independent samples of 12-18-month-olds from the US. We calibrated the measure using item response theory in a large representative sample, then validated within an independent sample. We characterized the developmental patterning of irritable behaviors and their dimensional spectrum, and demonstrated test-retest reliability, and convergent validity. The MAP-DB-IT is a standardized, dimensional survey assessing irritability that serves as a tool for characterizing the developmental expression of early mental health risk., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Emotion dysregulation is cross-diagnostic and impairing. Most research has focused on dysregulated expressions of negative affect, often measured as irritability, which is associated with multiple forms of psychopathology and predicts negative outcomes. However, the Research Domain Criteria (RDoC) include both negative and positive valence systems. Emerging evidence suggests that dysregulated expressions of positive affect, or excitability, in early childhood predict later psychopathology and impairment above and beyond irritability. Typically, irritability declines from early through middle childhood; however, the developmental trajectory of excitability is unknown. The impact of excitability across childhood on later emotion dysregulation is also yet unknown. In a well-characterized, longitudinal sample of 129 children studied from ages 3 to 5.11 years through 14 to 19 years, enriched for early depression and disruptive symptoms, we assessed the trajectory of irritability and excitability using multilevel modeling and how components of these trajectories impact later emotion dysregulation. While irritability declines across childhood, excitability remains remarkably stable both within and across the group. Overall levels of excitability (excitability intercept) predict later emotion dysregulation as measured by parent and self-report and predict decreased functional magnetic resonance imaging activity in cognitive emotion regulation regions during an emotion regulation task. Irritability was not related to any dysregulation outcome above and beyond excitability., Competing Interests: Conflicts of Interest. None.

Background: A major challenge in prenatal drug exposure research concerns the balance of measurement quality with sample sizes necessary to address confounders. To inform the selection of optimal exposure measures for the HEALthy Brain and Child Development (HBCD) Study, we employed integrated analysis to determine how different methods used to characterize prenatal tobacco exposure influence the detection of exposure-related risk, as reflected in normal variations in birth weight., Methods: Participants were N = 2323 mother-infant dyads derived from 7 independent developmental cohorts harmonized on measures of exposure, outcome (birthweight), and covariates. We compared estimates of PTE-related effects on birthweight derived from linear regression models when PTE was categorized dichotomously based on any fetal exposure (30% exposed; 69% not exposed); versus categorically, based on common patterns of maternal smoking during pregnancy (never smoked 69%; quit smoking 16%; smoked intermittently 2%; smoked persistently 13%). We secondarily explored sex differences in PTE-birthweight associations across these categorization methods., Results: When PTE was categorized dichotomously, exposure was associated with a - 125-g difference in birthweight (95% C.I. -173.7 - -76.6, p < .0001). When PTE was characterized categorically based on maternal smoking patterns, however, exposure was associated with either no difference in birthweight if mothers quit smoking by the end of the first trimester (B = -30.6, 95% C.I. -88.7-27.4, p = .30); or a - 221.8 g difference in birthweight if mothers did not [95% C.I. (-161.7 to -282.0); p < .001]. Qualitative sex differences were also detected though PTE x sex interactions did not reach statistical significance. Maternal smoking cessation during pregnancy was associated with a 239.3 g increase in birthweight for male infants, and a 114.0 g increase in birthweight for females infants (p = .07)., Conclusions: Categorization of PTE based on patterns of maternal smoking rather than the presence or absence of exposure alone revealed striking nuances in estimates of exposure-related risk. The described method that captures both between-individual and within-individual variability in prenatal drug exposure is optimal and recommended for future developmental investigations such as the HBCD Study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose. To investigate image intensity histograms as a potential source of useful imaging biomarkers in both a clinical example of detecting immune-related colitis (irColitis) in 18 F-FDG PET/CT images of immunotherapy patients and an idealized case of classifying digital reference objects (DRO). Methods. Retrospective analysis of bowel 18 F-FDG uptake in N = 40 patients receiving immune checkpoint inhibitors was conducted. A CNN trained to segment the bowel was used to generate the histogram of bowel 18 F-FDG uptake, and percentiles of the histogram were considered as potential metrics for detecting inflammation associated with irColitis. A model of the colon was also considered using cylindrical DRO. Classification of DRO with different intensity distributions was undertaken under varying geometry and noise settings. Results. The most predictive biomarker of irColitis was the 95th percentile of the bowel SUV histogram (SUV 95% ). Patients later diagnosed with irColitis had a significantly higher increase in SUV 95% from baseline to first on-treatment PET than patients who did not experience irColitis (p = 0.02). An increase in SUV 95% > + 40% separated pre-irColitis change from normal variability with a sensitivity of 75% and specificity of 88%. Furthermore, histogram percentiles were ideal metrics for classifying 'hot center' and 'cold center' DRO, and were robust to varying DRO geometry and noise, and to the presence of spoiler volumes unrelated to the detection task. Conclusions. The 95th percentile of the bowel SUV histogram was the optimal metric for detecting irColitis on 18 F-FDG PET/CT. Image intensity histograms are a promising source of imaging biomarkers for clinical tasks., (© 2021 IOP Publishing Ltd.)

Children reared in socioeconomically disadvantaged environments are at risk for academic, cognitive, and behavioral problems. Mounting evidence suggests that childhood adversities, encountered at disproportionate rates in contexts of socioeconomic risk, shape the developing brain in ways that explain disparities. Circuitries that subserve neurocognitive functions related to memory, attention, and cognitive control are especially affected. However, most work showing altered neural function has focused on middle childhood and adolescence. Understanding alterations in brain development during foundational points in early childhood is a key next step. To address this gap, we examined functional near-infrared-spectroscopy-based neural activation during a working memory (WM) task in young children aged 4-7 years (N = 30) who varied in socioeconomic risk exposure. Children who experienced greater disadvantage (lower income to needs ratio and lower Hollingshead index) exhibited lower activation in the lateral prefrontal cortex than children who experienced less to no disadvantage. Variability in prefrontal cortex activation, but not behavioral performance on the WM task, was associated with worse executive functioning in children as reported by parents. These findings add to existing evidence that exposure to early adversity, such as socioeconomic risk, may lead to foundational changes in the developing brain, which increases risk for disparities in functioning across multiple cognitive and social domains., (© 2021 Wiley Periodicals LLC.)

Social deficits in autism spectrum disorder (ASD) have been linked to atypical activation of the mentalizing network. This work, however, has been limited by a focus on the brain activity of a single person during computerized social tasks rather than exploring brain activity during in vivo interactions. The current study assessed neural synchronization during a conversation as a mechanism for social impairment in adults with ASD (n = 24) and matched controls (n = 26). Functional near-infrared spectroscopy (fNIRS) data were collected from the prefrontal cortex (PFC) and tempoparietal junction (TPJ). Participants self-reported on their social communication and videos of the interaction were coded for utterances and conversational turns. As expected, controls showed more neural synchrony than participants with ASD in the TPJ. Also as expected, controls showed less social communication impairment than participants with ASD. However, participants with ASD did not have fewer utterances compared with control subjects. Overall, less neural synchrony in the TPJ was associated with higher social impairment and marginally fewer utterances. Our findings advance our understanding of social difficulties in ASD by linking them to decreased neural synchronization of the TPJ. LAY SUMMARY: The coordination of brain responses is important for efficient social interactions. The current study explored the coordination of brain responses in neurotypical adults and adults with ASD to investigate if difficulties in social interactions are related to difficulties coordinating brain responses in ASD. We found that participants with ASD had more difficulties coordinating brain responses during a conversation with an interacting partner. Additionally, we found that the level of coordination in brain responses was linked to problems with social communication., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Developmental studies have identified differences in prefrontal and subcortical affective structures between children and adults, which correspond with observed cognitive and behavioral maturations from relatively simplistic emotional experiences and expressions to more nuanced, complex ones. However, developmental changes in the neural representation of emotions have not yet been well explored. It stands to reason that adults and children may demonstrate observable differences in the representation of affect within key neurological structures implicated in affective cognition. Forty-five participants (25 children; 20 adults) passively viewed positive, negative, and neutral clips from popular films while undergoing functional magnetic resonance imaging (fMRI). Using representational similarity analysis (RSA) to measure variability in neural pattern similarity, we found developmental differences between children and adults in the amygdala, nucleus accumbens (NAcc), and ventromedial prefrontal cortex (vmPFC), such that children generated less pattern similarity within subcortical structures relative to the vmPFC; a phenomenon not replicated among their older counterparts. Furthermore, children generated valence-specific differences in representational patterns across regions; these valence-specific patterns were not found in adults. These results may suggest that affective representations grow increasingly dissimilar over development as individuals mature from visceral affective responses to more evaluative analyses., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: To demonstrate the utility of deep learning enhancement (DLE) to achieve diagnostic quality low-dose positron emission tomography (PET)/magnetic resonance (MR) imaging., Methods: Twenty subjects with known Crohn disease underwent simultaneous PET/MR imaging after intravenous administration of approximately 185 MBq of 18F-fluorodeoxyglucose (FDG). Five image sets were generated: (1) standard-of-care (reference), (2) low-dose (ie, using 20% of PET counts), (3) DLE-enhanced low-dose using PET data as input, (4) DLE-enhanced low-dose using PET and MR data as input, and (5) DLE-enhanced using no PET data input. Image sets were evaluated by both quantitative metrics and qualitatively by expert readers., Results: Although low-dose images (series 2) and images with no PET data input (series 5) were nondiagnostic, DLE of the low-dose images (series 3 and 4) achieved diagnostic quality images that scored more favorably than reference (series 1), both qualitatively and quantitatively., Conclusions: Deep learning enhancement has the potential to enable a 90% reduction of radiotracer while achieving diagnostic quality images., Competing Interests: A.P. has received payments as consultant from Sanofi Genzyme. D.H.K. is a shareholder for Elucent and Cellectar. The University of Wisconsin-Madison Department of Radiology receives research support from GE Healthcare. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Parent-child synchrony-parent-child interaction patterns characterized by contingent social responding, mutual responsivity, and co-regulation-has been robustly associated with adaptive child outcomes. Synchrony has been investigated in both behavioral and biological frameworks. While it has been demonstrated that adversity can influence behavioral parent-child synchrony, the neural mechanisms by which this disruption occurs are understudied. The current study examined the association between adversity, parent-child behavioral synchrony, and parent-child neural synchrony across lateral prefrontal cortical regions using functional near-infrared spectroscopy hyperscanning during a parent-child interaction task that included a mild stress induction followed by a recovery period. Participants included 115 children (ages 4-5) and their primary caregivers. Parent-child behavioral synchrony was quantified as the amount time the dyad was synchronous (e.g., reciprocal communication, coordinated behaviors) during the interaction task. Parent-child neural synchrony was examined as the hemodynamic concordance between parent and child lateral PFC activation. Adversity was examined across two, empirically-derived domains: sociodemographic risk (e.g., family income) and familial risk (e.g., household chaos). Adversity, across domains, was associated with decreased parent-child behavioral synchrony across task conditions. Sociodemographic risk was associated with decreased parent-child neural synchrony in the context of experimentally-induced stress. These findings link adversity to decreased parent-child behavioral and neural synchrony., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High Temperamental Negative Affectivity in early childhood has been found to predict later emotion dysregulation. While much work has been conducted to separately probe bio-behavioral systems associated with Negative Affectivity, very little work has examined the relations among multiple systems across age. In this study, we use multi-modal methods to index neurobiological systems associated with Negative Affectivity in 53 4-7-year-old children. Prefrontal activation during emotion regulation was measured using functional near-infrared spectroscopy over the lateral prefrontal cortex (PFC) while children played a game designed to elicit frustration in Social (Happy and Angry faces) and Nonsocial contexts. Gaze behaviors while free-viewing Happy and Angry faces were also measured. Finally, Negative Affectivity was indexed using a score composite based on factor analysis of parent-reported temperament. Using mixed-effects linear models, we found an age-dependent association between Negative Affectivity and both PFC activation during frustration and fixation duration on the mouth area of Happy faces, such that older children high in Negative Affectivity spent less time looking at the mouths of Happy faces and had lower PFC activation in response to frustration (ps<0.034). These results provide further insight to how Negative Affectivity may be associated with changes in affective neurobiological systems across early childhood., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare the measurement of glucose uptake in primary invasive breast cancer using simultaneous, time-of-flight breast PET/MRI with prone time-of-flight PET/CT., Materials and Methods: In this prospective study, women with biopsy-proven invasive breast cancer undergoing preoperative breast MRI from 2016 to 2018 were eligible. Participants who had fasted underwent prone PET/CT of the breasts approximately 60 minutes after injection of 370 MBq (10 mCi) fluorine 18 fluorodeoxyglucose ( 18 F-FDG) followed by prone PET/MRI using standard clinical breast MRI sequences performed simultaneously with PET acquisition. Volumes of interest were drawn for tumors and contralateral normal breast fibroglandular tissue to calculate standardized uptake values (SUVs). Spearman correlation, Wilcoxon signed ranked test, Mann-Whitney test, and Bland-Altman analyses were performed., Results: Twenty-three women (mean age, 50 years; range, 33-70 years) were included. Correlation between tumor uptake values measured with PET/MRI and PET/CT was strong ( r s = 0.95-0.98). No difference existed between modalities for tumor maximum SUV (SUV max ) normalized to normal breast tissue SUV mean (normSUV max ) ( P = .58). The least amount of measurement bias was observed with normSUV max , +3.86% (95% limits of agreement: -28.92, +36.64)., Conclusion: These results demonstrate measurement agreement between PET/CT, the current reference standard for tumor glucose uptake quantification, and simultaneous time-of-flight breast 18 F-FDG PET/MRI. Keywords: Breast, Comparative Studies, PET/CT, PET/MR Supplemental material is available for this article. © RSNA, 2021See also the commentary by Mankoff and Surti in this issue., Competing Interests: Disclosures of Conflicts of Interest: A.M.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author paid for virtual lecture (8/21/20) by Wisconsin Association of Hematology and Oncology and Wisconsin Oncology Network Virtual Annual Conference; author receives royalties from Elsevier for book chapters (Diagnostic Imaging: Breast). Other relationships: The Department of Radiology at the University of Wisconsin School of Medicine and Public Health receives research support from GE Healthcare. M.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. L.H.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. K.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. J.M.J. disclosed no relevant relationships. J.K. disclosed no relevant relationships. S.B.P. disclosed no relevant relationships. T.J.B. disclosed no relevant relationships. S.A.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The University of Wisconsin - Madison, Department of Radiology receives research support from GE Healthcare. None of this support was specifically designated to this project or its authors. A.B.M. Activities related to the present article: institution received NIH/NIBIB grant EB026708. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. R.M.S. Activities related to the present article: institution received NIH/NIBIB grant EB026708. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare., (2021 by the Radiological Society of North America, Inc.)

Background: Research to date has largely conceptualized irritability in terms of intraindividual differences. However, the role of interpersonal dyadic processes has received little consideration. Nevertheless, difficulties in how parent-child dyads synchronize during interactions may be an important correlate of irritably in early childhood. Innovations in developmentally sensitive neuroimaging methods now enable the use of measures of neural synchrony to quantify synchronous responses in parent-child dyads and can help clarify the neural underpinnings of these difficulties. We introduce the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS:BioSync) as a paradigm for exploring parent-child neural synchrony as a potential biological mechanism for interpersonal difficulties in preschool psychopathology., Methods: Using functional near-infrared spectroscopy (fNIRS) 4- to 5-year-olds (N = 116) and their mothers completed the DB-DOS:BioSync while assessing neural synchrony during mild frustration and recovery. Child irritability was measured using a latent irritability factor that was calculated from four developmentally sensitive indicators., Results: Both the mild frustration and the recovery contexts resulted in neural synchrony. However, less neural synchrony during the recovery context only was associated with more child irritability., Conclusions: Our results suggest that recovering after a frustrating period might be particularly challenging for children high in irritability and offer support for the use of the DB-DOS:BioSync task to elucidate interpersonal neural mechanisms of developmental psychopathology., (© 2019 Association for Child and Adolescent Mental Health.)

Purpose: Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18 F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression., Patients and Methods: Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382). 18 F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI., Results: Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUV hetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUV total ) was seen at the time of progression, as measured by 18 F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI., Conclusion: We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.

Purpose: To automatically detect lymph nodes involved in lymphoma on fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET/CT images using convolutional neural networks (CNNs)., Materials and Methods: In this retrospective study, baseline disease of 90 patients with lymphoma was segmented on 18 F-FDG PET/CT images (acquired between 2005 and 2011) by a nuclear medicine physician. An ensemble of three-dimensional patch-based, multiresolution pathway CNNs was trained using fivefold cross-validation. Performance was assessed using the true-positive rate (TPR) and number of false-positive (FP) findings. CNN performance was compared with agreement between physicians by comparing the annotations of a second nuclear medicine physician to the first reader in 20 of the patients. Patient TPR was compared using Wilcoxon signed rank tests., Results: Across all 90 patients, a range of 0-61 nodes per patient was detected. At an average of four FP findings per patient, the method achieved a TPR of 85% (923 of 1087 nodes). Performance varied widely across patients (TPR range, 33%-100%; FP range, 0-21 findings). In the 20 patients labeled by both physicians, a range of 1-49 nodes per patient was detected and labeled. The second reader identified 96% (210 of 219) of nodes with an additional 3.7 per patient compared with the first reader. In the same 20 patients, the CNN achieved a 90% (197 of 219) TPR at 3.7 FP findings per patient., Conclusion: An ensemble of three-dimensional CNNs detected lymph nodes at a performance nearly comparable to differences between two physicians' annotations. This preliminary study is a first step toward automated PET/CT assessment for lymphoma.© RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: A.J.W. Activities related to the present article: disclosed money paid to institution for research support by GE Healthcare. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. M.W.K. disclosed no relevant relationships. S.B.P. disclosed no relevant relationships. M.H. disclosed no relevant relationships. R.J. Activities related to the present article: disclosed grant money paid to institution by the National Cancer Institute, in part supported by the UW Carbone Cancer Center. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed patent issued by WARF and patent pending with AIQ Solutions. L.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid for consultancy by Roche, Genentech. Other relationships: disclosed no relevant relationships. T.J.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: institution receives research support from GE Healthcare., (2020 by the Radiological Society of North America, Inc.)

Previous research shows that forming memories of not only whom we have previously encountered but also the feedback of those encounters supports adaptive behavior. However, there are dynamic changes throughout childhood in declarative memory systems, leaving open the question about the precise timing for the emergence and maturation of memory for social interactions. In this study, we characterized memory for dynamic social interactions during a computerized task in children ranging between 4 and 6 years of age. Specifically, we probed memory for the characters children interacted with, the decisions they made, and the valanced-feedback from those interactions. We found that while there were differences in discriminating between old and new characters, there were no age-related differences in the ability to remember which decision a child made or the feedback from that decision when a character was successfully identified. These findings support a model by which basic foundations of social memory develop early in childhood; however, the number of social memories and the incorporation of feedback into these memories may be limited in early childhood., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In cognitive neuroscience, measurements of "resting baseline" are often considered stable across age and used as a reference point against which to judge cognitive state. The task-based approach-comparing resting baseline to task conditions-implies that resting baseline is an equalizer across participants and-in the case of studies of developmental changes in cognition-across age groups. In contrast, network neuroscience explicitly examines the development of "resting state" networks across age, at odds with the idea of a consistent resting baseline. Little attention has been paid to how cognition during rest may shift across development, particularly in children under the age of eight. Childhood is marked by striking maturation of neural systems, including a protracted developmental period for cognitive control systems. To grow and shape these cognitive systems, children have a developmental imperative to engage their neural circuitry at every possible opportunity. Thus, periods of "rest" without specific instructions may require additional control for children as they fight against developmental expectation to move, speak, or otherwise engage. We therefore theorize that the child brain does not rest in a manner consistent with the adult brain as longer rest periods may represent increased cognitive control. To shape this theory, we first review the extant literature on neurodevelopment across early childhood within the context of cognitive development. Next, we present nascent evidence for a destabilized baseline for comparisons across age. Finally, we present recommendations for designing, analyzing, and interpreting tasks conducted with young children as well as for resting state. Future work must aim to tease apart the cognitive context under which we examine functional brain development in young children and take considerations into account unique to each age., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [ 124 I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [ 124 I]CLR1404 PET/CT (aka CLR124)., Procedures: Adult patients with new or suspected recurrence of high-grade primary or metastatic brain tumors (N = 27) were injected with [ 124 I]CLR1404 followed by PET/CT at 6, 24, and 48 h. Standard uptake values (SUV) and TBR values were calculated for all time points. Uptake of [ 124 I]CLR1404 was qualitatively assessed, compared with magnetic resonance imaging (MRI), and correlated with clinical outcome. Final diagnosis (N = 25) was established based on surgically resected tissue or long-term follow-up., Results: Positive uptake with high TBR was detected in all but one patient with a final diagnosis of primary/recurrent brain tumor (12/13) and in less than half of patients with treatment-related changes (5/12). Concordance between [ 124 I]CLR1404 uptake and contrast enhancement on MRI was seen in < 40 %, with no concordance between T 2 -hyperintensities and uptake. No significant difference in overall outcome was found between patients with and without [ 124 I]CLR1404 uptake., Conclusions: The uptake pattern in these patients suggests a very high sensitivity of [ 124 I]CLR1404 PET/CT for diagnosing tumor tissue; however, tumor specificity needs to be further defined. Relative lack of concordance with standard MRI characteristics suggests that [ 124 I]CLR1404 PET/CT provides additional information about brain tumors compared to MRI alone, potentially improving clinical decision-making.

There is surprisingly little empirical evidence supporting theoretical and anecdotal claims regarding the spontaneous production of prototypic facial expressions used in numerous emotion recognition studies. Proponents of innate prototypic expressions believe that this lack of evidence may be due to ethical restrictions against presenting powerful elicitors in the lab. The current popularity of internet platforms designed for public sharing of videos allows investigators to shed light on this debate by examining naturally-occurring facial expressions outside the laboratory. An Internet prank ("Scary Maze") has provided a unique opportunity to observe children reacting to a consistent fear- and surprise-inducing stimulus: The unexpected presentation of a "scary face" during an online maze game. The purpose of this study was to examine children's facial expressions in this naturalistic setting. Emotion ratings of non-facial behaviour (provided by untrained undergraduates) and anatomically-based facial codes were obtained from 60 videos of children (ages 4-7) found on YouTube. Emotion ratings were highest for fear and surprise. Correspondingly, children displayed more facial expressions of fear and surprise than for other emotions (e.g. anger, joy). These findings provide partial support for the ecological validity of fear and surprise expressions. Still prototypic expressions were produced by fewer than half the children.

Standardized developmentally based assessment systems have transformed the capacity to identify transdiagnostic behavioral markers of mental disorder risk in early childhood, notably, clinically significant irritability and externalizing behaviors. However, behavior-based instruments that both differentiate risk for persistent psychopathology from normative misbehavior, and are feasible for community clinicians to implement, are in nascent phases of development. Young children's facial expressions during frustration challenges may form the basis for novel assessments tools that are flexible, quick, and easy to implement as markers of psychopathology to complement validated questionnaires. However, the accuracy of facial expressions to correctly classify young children falling above and below clinical cut-offs is unknown. Our goal was to test how facial expressions during frustration, defined by different facial muscular movements, related to individual differences in irritability and externalizing behaviors and discriminated children with clinically significant levels from peers. Participants were 79 children (ages 3-7) who completed a short, moderately frustrating computer task while facial expressions were recorded. Only negative facial expressions that included eye constriction related to irritability and externalizing behaviors and were clinically discriminating. Moreover, these expressions significantly discriminated children with and without clinically significant irritability and externalizing symptoms with high Area Under the Curve (AUC) values (> .75) indicating good clinical utility. In contrast, expressions without eye constriction showed no clinical utility. The presence of negative expressions with eye constriction in response to a short frustration prompt may serve as an indicator of early psychopathology, raising the potential for novel assessment tools that may enhance precision of early identification., (Copyright © 2019. Published by Elsevier Ltd.)

Irritability is a substrate of more than one dozen clinical syndromes. Thus, identifying when it is atypical and interfering with functioning is crucial to the prevention of mental disorder in the earliest phase of the clinical sequence. Advances in developmentally based measurement of irritability have enabled differentiation of normative irritable mood and tantrums from indicators of concern, beginning in infancy. However, developmentally sensitive assessments of irritability-related impairment are lacking. We introduce the Early Childhood Irritability-Related Impairment Interview (E-CRI), which assesses impairment associated with irritable mood and tantrums across contexts. Reliability and validity are established across two independent samples varied by developmental period: the Emotional Growth preschool sample (EmoGrow; N = 151, M = 4.82 years) and the When to Worry infant/toddler sample (W2W; N = 330, M = 14 months). We generated a well-fitting two-factor E-CRI model, with tantrum- and irritable mood-related impairment factors. The E-CRI exhibited good interrater, test-retest, and longitudinal reliability. Construct and clinical validity were also demonstrated. In both samples, E-CRI factors showed association to internalizing and externalizing problems, and to caregiver-reported concern in W2W. Tantrum-related impairment demonstrated stronger and more consistent explanatory value across outcomes, while mood-related impairment added explanatory utility for internalizing problems. The E-CRI also showed incremental utility beyond variance explained by the Family Life Impairment Scale (FLIS) survey indicator of developmental impairment. The E-CRI holds promise as an indicator of impairment to inform identification of typical versus atypical patterns reflecting early emerging irritability-related syndromes in the initial phase of the clinical sequence., Competing Interests: Conflict of Interest Statement The authors declare that there are no conflicts of interest., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose of Review: The main goal of the article is to familiarize the reader with commonly and uncommonly used nuclear medicine procedures that can significantly contribute to improved patient care. The article presents examples of specific modality utilization in the chest including assessment of lung ventilation and perfusion, imaging options for broad range of infectious and inflammatory processes, and selected aspects of oncologic imaging. In addition, rapidly developing new techniques utilizing molecular imaging are discussed., Recent Findings: The article describes nuclear medicine imaging modalities including gamma camera, SPECT, PET, and hybrid imaging (SPECT/CT, PET/CT, and PET/MR) in the context of established and emerging clinical applications. Areas of potential future development in nuclear medicine are discussed with emphasis on molecular imaging and implementation of new targeted tracers used in diagnostics and therapeutics (theranostics)., Summary: Nuclear medicine and molecular imaging provide many unique and novel options for the diagnosis and treatment of pulmonary diseases. This article reviews current applications for nuclear medicine and molecular imaging and selected future applications for radiopharmaceuticals and targeted molecular imaging techniques., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Springer Science+Business Media, LLC, part of Springer Nature 2020.)

The vast individual differences in the developmental origins of risk and resilience pathways combined with sophisticated capabilities of big data science increasingly point to the imperative of large, neurodevelopmental consortia to capture population heterogeneity and key variations in developmental trajectories. At the same time, such large-scale population-based designs involving multiple independent sites also must weigh competing demands. For example, the need for efficient, scalable assessment strategies must be balanced with the need for nuanced, developmentally sensitive phenotyping optimized for linkage to neural mechanisms and specification of common and distinct exposure pathways. Standardized epidemiologic batteries designed for this purpose such as PhenX (consensus measures for Pheno types and e X posures) and the National Institutes of Health (NIH) Toolbox provide excellent "off the shelf" assessment tools that are well-validated and enable cross-study comparability. However, these standardized toolkits can also constrain ability to leverage advances in neurodevelopmental measurement over time, at times disproportionately advantaging established measures. In addition, individual consortia often expend exhaustive effort "reinventing the wheel," which is inefficient and fails to fully maximize potential synergies with other like initiatives. To address these issues, this paper lays forth an early childhood neurodevelopmental assessment strategy, guided by a set of principles synthesizing developmental and pragmatic considerations generated by the Neurodevelopmental Workgroup of the HEALthy Brain and Child Development (HBCD) Planning Consortium. These principles emphasize characterization of both risk- and resilience-promoting processes. Specific measurement recommendations to HBCD are provided to illustrate application. However, principles are intended as a guiding framework to transcend any particular initiative as a broad neurodevelopmentally informed, early childhood assessment strategy for large-scale consortia science., (© Springer Nature Switzerland AG 2020.)

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

Deliberate emotion regulation, the ability to willfully modulate emotional experiences, is shaped through interpersonal scaffolding and forecasts later functioning in multiple domains. However, nascent deliberate emotion regulation in early childhood is poorly understood due to a paucity of studies that simulate interpersonal scaffolding of this skill and measure its occurrence in multiple modalities. Our goal was to identify neural and behavioral components of early deliberate emotion regulation to identify patterns of competent and deficient responses. A novel probe was developed to assess deliberate emotion regulation in young children. Sixty children (age 4-6 years) were randomly assigned to deliberate emotion regulation or control conditions. Children completed a frustration task while lateral prefrontal cortex (LPFC) activation was recorded via functional near-infrared spectroscopy (fNIRS). Facial expressions were video recorded and children self-rated their emotions. Parents rated their child's temperamental emotion regulation. Deliberate emotion regulation interpersonal scaffolding predicted a significant increase in frustration-related LPFC activation not seen in controls. Better temperamental emotion regulation predicted larger LPFC activation increases post- scaffolding among children who engaged in deliberate emotion regulation interpersonal scaffolding. A capacity to increase LPFC activation in response to interpersonal scaffolding may be a crucial neural correlate of early deliberate emotion regulation., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individual differences in temperament have been theorized to be supported by differential recruitment of key neural regions, resulting in the distinct patterns of behavior observed throughout life. Although a compelling model, its rigorous and systematic testing is lacking, particularly within the heightened neuroplasticity of early childhood. The current study tested a model of the link between temperament, the brain, and behavior for cognitive flexibility in a sample of 4-5-year-old children (N = 123) using functional near-infrared spectroscopy (fNIRS) to assess prefrontal cortex (PFC) activation. Structural Equation Modeling (SEM) was used to explore the link between survey reports of temperamental effortful control, and both performance-based and neuroimaging measures of cognitive flexibility. Results indicated that greater parent-reported temperamental effortful control was associated with better performance on a cognitive flexibility task, and less activation of the DLPFC in preschoolers. These findings support the theorized model of the interrelatedness between temperamental tendencies, behavior, and brain activation and suggest that better temperamentally regulated children use the DLPFC more efficiently for cognitive flexibility., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Whole-body assessments of 18 F-NaF positron emission tomography (PET)/computed tomography (CT) provide promising quantitative imaging biomarkers of metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether the distribution of metastases across anatomic regions is prognostic of progression-free survival., Patients and Methods: Fifty-four mCRPC patients with osseous metastases received baseline NaF PET/CT. Patients received chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 38). Semiautomated analysis using Quantitative Total Bone Imaging software extracted imaging metrics for the whole, axial, and appendicular skeleton as well as 11 skeletal regions. Five PET metrics were extracted for each region: number of lesions (N L ), standardized maximum uptake value (SUV max ), average uptake (SUV mean ), sum of uptake (SUV total ), and diseased fraction of the skeleton (volume fraction). Progression included that discovered by clinical, biochemical, or radiographic means. Univariate and multivariate Cox proportional hazard regression analyses were performed between imaging metrics and progression-free survival, and were assessed according to their hazard ratios (HR) and concordance (C)-indices., Results: The strongest univariate models of progression-free survival were pelvic N L and SUV max with HR = 1.80 (N L : false discovery rate adjusted P = .001, SUV max : adjusted P = .001). Three other region-specific metrics (axial N L : HR = 1.59, adjusted P = .02, axial SUV max : HR = 1.61, adjusted P = .02, and skull SUV max : HR = 1.58, adjusted P = .04) were found to be stronger prognosticators relative to their whole-body counterparts. Multivariate model including region-specific metrics (C-index = 0.727) outperformed that of whole-body metrics (C-index = 0.705). The best performance was obtained when region-specific and whole-body metrics were included (C-index = 0.742)., Conclusion: Quantitative characterization of metastatic spread by anatomic location on NaF PET/CT enhances potential prognostication. Further study is warranted to optimize the prognostic and predictive value of NaF PET/CT in mCRPC patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bone flare has been observed on 99m Tc-MDP bone scans of patients with metastatic castration-resistant prostate cancer (mCRPC). This exploratory study investigates bone flare in mCRPC patients receiving androgen receptor (AR) inhibitors using 18 F-NaF PET/CT., Methods: Twenty-nine mCRPC patients undergoing AR-inhibiting therapy (abiraterone, orteronel, enzalutamide) received NaF PET/CT scans at baseline, week 6, and week 12 of treatment. SUV metrics were extracted globally for each patient (SUV) and for each individual lesion (iSUV). Bone flare was defined as increasing SUV metrics or lesion number at week 6 followed by subsequent week 12 decrease. Differences in metrics across timepoints were compared using Wilcoxon tests. Cox proportional hazard regression was conducted between global metrics and progression-free survival (PFS)., Results: Total SUV was most sensitive for flare detection and was identified in 14/23 (61%) patients receiving CYP17A1-inhibitors (abiraterone, orteronel), and not identified in any of six patients receiving enzalutamide. The appearance of new lesions did not account for initial increases in SUV metrics. iSUV metrics followed patient-level trends: bone flare positive patients showed a median of 72% (range: 0-100%) of lesions with total iSUV flare. Increasing mean SUV at week 6 correlated with extended PFS (HR = 0.58, p = 0.02)., Conclusion: NaF PET bone flare was present on 61% of mCRPC patients in the first 6 weeks of treatment with CYP17A1-inhibitors. Characterization provided in this study suggests favorable PFS in patients showing bone flare. This characterization of NaF flare is important for guiding treatment assessment schedules to better distinguish between patients showing bone flare and those truly progressing, and should be performed for all emerging mCRPC treatments and imaging agents.